Hypogonadism is an endocrine disorder characterized by inadequate serum testosterone production by the Leydig cells of the testis. It is triggered by alterations in the hypothalamic-pituitary-gonadal axis. Erectile dysfunction (ED) is another common disorder in men that involves an alteration in erectile response-organic, relational, or psychological. The incidence of hypogonadism and ED is common in men aged over 40 years. Hypogonadism (including late-onset hypogonadism) and ED may be linked to several environmental factors-induced oxidative stresses. The factors mainly include exposure to pesticides, radiation, air pollution, heavy metals and other endocrine-disrupting chemicals. These environmental risk factors may induce oxidative stress and lead to hormonal dysfunctions. To better understand the subject, the study used many keywords, including "hypogonadism", "late-onset hypogonadism", "testosterone", "erectile dysfunction", "reactive oxygen species", "oxidative stress", and "environmental pollution" in major online databases, such as SCOPUS and PUBMED to extract relevant scientific information. Based on these parameters, this review summarizes a comprehensive insight into the important environmental issues that may have a direct or indirect association with hypogonadism and ED in men. The study concludes that environmental factors-induced oxidative stress may cause infertility in men. The hypothesis and outcomes were reviewed critically, and the mechanistic approaches are applied through oxidant-sensitive pathways. This study also provides reccomendations on future therapeutic interventions and protective measures against such adverse environmental factors-induced hypogonadism and ED.

Department of Animal Morphology Physiology and Genetics Faculty of AgriSciences Mendel University in Brno 61300 Brno Czech Republic

Department of Animal Physiology Faculty of Biotechnology and Food Sciences Slovak University of Agriculture in Nitra 94976 Nitra Slovakia

Department of Applied Physics School of Science Aalto University 00076 Espoo Finland

Department of Biotechnology School of Engineering and Technology Sharda University Greater Noida 201310 India

Department of Life Science and Bioinformatics Assam University Silchar 788011 India

Department of Obstetrics and Gynecology Silchar Medical College and Hospital Silchar 788014 India

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Jungwirth A., Giwercman A., Tournaye H., Diemer T., Kopa Z., Dohle G., Krausz C. European Association of Urology guidelines on male infertility: The 2012 update. Eur. Urol. 2012;62:324–332. doi: 10.1016/j.eururo.2012.04.048. PubMed DOI

Tüttelmann F., Nieschlag E. Classification of andrological disorders. In: Nieschlag E., Behre H.M., Nieschlag S., editors. Andrology, Male Reproductive Health and Dysfucntion. 3rd ed. Springer; Berlin/Heidelberg, Germany: 2010. pp. 87–92.

Salonia A., Rastrelli G., Hackett G., Seminara S.B., Huhtaniemi I.T., Rey R.A., Hellstorm W.J.G., Palmert M.R., Corona G., Dohle G.R., et al. Paediatric and adult-onset hypogonadism. Nat. Rev. Dis. Primers. 2019;5:38. doi: 10.1038/s41572-019-0087-y. PubMed DOI PMC

Sizar O., Schwartz J. Hypogonadism. Stat Pearls Publishing; Treasure Island, FL, USA: 2019.

Kim K.M. Late-onset hypogonadism. Korean J. Fam. Pract. 2013;3:245–254.

European Association of Urology Guidelines on Male Hypogonadism. [(accessed on 15 February 2021)]; Available online: http://uroweb.org/wp-content/uploads/EAU-Guidelines-Male-Hypogonadism-2015.pdf.

Huhtaniemi I. Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment. Asian J. Androl. 2014;16:192–202. doi: 10.4103/1008-682X.122336. PubMed DOI PMC

Huhtaniemi I., Makinen J.I., Perheentupa A., Raitakari O.T. Late-onset hypogonadism in men. Experience form Turku Male Aging Study (TuMAS) Hormones. 2008;7:36–45. doi: 10.14310/horm.2002.1111036. PubMed DOI

Yan Y.Y. Awareness and knowledge of andropause among Chinese males in Hong Kong. Am. J. Men’s Health. 2009;4:231–236. doi: 10.1177/1557988309335154. PubMed DOI

Guay A., Seftel A.D., Traish A. Hypogonadism in men with erectile dysfunction may be related to a host of chronic illness. Int. J. Impot. Res. 2010;22:9–19. doi: 10.1038/ijir.2009.46. PubMed DOI

Shamloul R., Ghanem H. Erectile dysfunction. Lancet. 2013;381:153–165. doi: 10.1016/S0140-6736(12)60520-0. PubMed DOI

Agarwal A., Nandipati K.C., Sharma R.K., Zippe C.D., Raina R. Role of oxidative stress in the pathophysiological mechanisms of erectile dysfunction. J. Androl. 2006;27:335–347. doi: 10.2164/jandrol.05136. PubMed DOI

Yafi F.A., Jenkins L., Albersen M., Corona G., Isidori A.M., Goldfarb S., Maggi M., Nelson C.J., Parish S., Salonia A., et al. Erectile dysfunction. Nat. Rev. Dis. Primers. 2016;2:16003. doi: 10.1038/nrdp.2016.3. PubMed DOI PMC

Rew K.T., Heidelbaugh J.J. Erectile dysfunction. Am. Fam. Phys. 2016;94:820–827. PubMed

Darbandi M., Darbandi S., Agarwal A., Sengupta P., Durairajanayagam D., Henkel R., Sadeghi M.R. Reactive oxygen species and male reproductive hormones. Reprod. Biol. Endocrinol. 2018;16:87. doi: 10.1186/s12958-018-0406-2. PubMed DOI PMC

Burton G.J., Jauniaux E. Oxidative stress. Best Pract. Res. Clin. Obstet. Gynecol. 2011;25:287–299. doi: 10.1016/j.bpobgyn.2010.10.016. PubMed DOI PMC

Darbandi S., Darbandi M. Lifestyle modifications on further reproductive problems. Cresco J. Reprod. Sci. 2016;1:1–2.

Zirkin B.R., Chen H. Regulation of Leydig cell steroidogenic function during aging. Biol. Reprod. 2000;63:977–981. doi: 10.1095/biolreprod63.4.977. PubMed DOI

Turner T.T., Bang H.J., Lysiak J.J. Experimental testicular torsion: Reperfusion blood flow and subsequent testicular venous plasma testosterone concentrations. Urology. 2005;65:390–394. doi: 10.1016/j.urology.2004.09.033. PubMed DOI

Cartledge J., Minhas S., Eardley I. The role of nitric oxide in penile erection. Expert Opin. Pharmacother. 2001;2:95–107. doi: 10.1517/14656566.2.1.95. PubMed DOI

Jones R.W.A., Rees R.W., Minhas S., Ralph D., Persad R.A., Jeremy J.Y. Oxygen free radicals and the penis. Expert Opin. Pharmacother. 2002;3:889–897. doi: 10.1517/14656566.3.7.889. PubMed DOI

Jeremy J.Y., Jones R.A., Koupparis A.J., Hotston M., Persad R., Angelini G.D., Shukla N. Reactive oxygen species and erectile dysfunction: Possible role of NADPH oxidase. Int. J. Impot. Res. 2007;19:265–280. doi: 10.1038/sj.ijir.3901523. PubMed DOI

Fattahi E., Parivar K., Jorsaraei S.G.A., Moghadamnia A.A. The effects of diazinon on testosterone, FSH and LH levels and testicular tissue in mice. Int. J. Reprod. Biomed. 2009;7:59–64.

Kesari K.K., Kumar S., Behari J. Effects of radiofrequency electromagnetic wave exposure from cellular phones on the reproductive pattern in male wistar rats. Appl. Biochem. Biotechnol. 2011;164:546–559. doi: 10.1007/s12010-010-9156-0. PubMed DOI

Wang X., Yang Y., Li J., Bai Y., Tang Y., Han Y. Effects of fine particulate matter (PM2.5) on erectile function and its potential mechanism in rats. Urology. 2016;102:e9–e265. doi: 10.1016/j.urology.2016.08.034. PubMed DOI

Alaee S., Talaiekhozani A., Rezaei S., Alaee K., Yousefian E. Cadmium and male fertility. J. Int. Reprod. Biol. 2014;2:62–69.

Rahman M.S., Pang M.G. Understanding the molecular mechanisms of bisphenol A action in spermatozoa. Clin. Exp. Reprod. Med. 2019;46:99–106. doi: 10.5653/cerm.2019.00276. PubMed DOI PMC

Smith L.B., Walker W.H. The regulation of spermatogenesis by androgens. Semin. Cell Dev. Biol. 2014;30:2–13. doi: 10.1016/j.semcdb.2014.02.012. PubMed DOI PMC

Clavijo R.I., Hsiao W. Update on male reproductive endocrinology. Trans. Androl. Urol. 2018;7:367–372. doi: 10.21037/tau.2018.03.25. PubMed DOI PMC

Tsai M.-Y., Yeh S.-D., Wang R.-S., Yeh S., Zhang C., Lin H.-Y., Tzeng C.-R., Chang C. Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. Proc. Natl. Acad. Sci. USA. 2006;103:18975–18980. doi: 10.1073/pnas.0608565103. PubMed DOI PMC

Joshi S.C., Mathur R., Gulati N. Testicular toxicity of chlorpyrifos (an organophosphate pesticide) in albino rat. Toxicol. Ind. Health. 2007;23:439. doi: 10.1177/0748233707080908. PubMed DOI

Chinoy N.J., Bhattacharya S. Effects of chronic administration of aluminium chloride on reproductive function of testis and some accessory sex organs of male mice. Ind. J. Environ. Toxicol. 1997;7:12–22.

Johnson L., Thompson D.L., Jr., Varner D.D. Role of Sertoli cell number and function on regulation of spermatogenesis. Anim. Reprod. Sci. 2008;105:23–51. doi: 10.1016/j.anireprosci.2007.11.029. PubMed DOI

Cheng C.Y., Wong E.W.P., Lie P.P.Y., Li M.W.M., Su L., Siu E.R., Yan H.H.N., Mannu J., Mathur P.P., Bonanomi M., et al. Environmental toxicants and male reproductive functions. Spermatogenesis. 2010;1:2–13. doi: 10.4161/spmg.1.1.13971. PubMed DOI PMC

Li M.W.M., Mruk D.D., Cheng C.Y. Gap junctions and blood-testis barriers. Adv. Exp. Med. Biol. 2012;763:260–280. doi: 10.1007/978-1-4614-4711-5_13. PubMed DOI PMC

Siu E.R., Mruk D.D., Porto C.S., Cheng C.Y. Cadmium-induced testicular injury. Toxicol. Appl. Pharmacol. 2009;238:240–249. doi: 10.1016/j.taap.2009.01.028. PubMed DOI PMC

Mruk D.D., Cheng C.Y. Environmental contaminants: Is male reproductive health at risk? Spermatogenesis. 2011;1:283–290. doi: 10.4161/spmg.1.4.18328. PubMed DOI PMC

Pointis G., Gilleron J., Carette D., Segretain D. Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility. Spermatogenesis. 2011;1:303–317. doi: 10.4161/spmg.1.4.18392. PubMed DOI PMC

Pierantoni R., Cobellis G., Meccariello R., Fasano S. Evolutionary aspects of cellular communication in the vertebrate hypothalamo-hypophysio-gonadal axis. Int. Rev. Cytol. 2002;218:69–141. doi: 10.1016/s0074-7696(02)18012-0. PubMed DOI

Madhukar D., Rajender S. hormonal treatment of male infertility: Promises and pitfalls. J. Androl. 2009;30:95–112. doi: 10.2164/jandrol.108.005694. PubMed DOI

Magon N., Singh S., Saxena A., Sahay R. Growth hormone in male infertility. Indian J. Endocrinol. Metab. 2011;15:248–249. doi: 10.4103/2230-8210.84877. PubMed DOI PMC

Gangwar P.K., Sankhwar S.N., Pant S., Krishna A., Singh B.P., Mahdi A.A., Singh R. Increased gonadotropins and prolactin are linked to infertility in males. Bioinformation. 2020;16:176–182. doi: 10.6026/97320630016176. PubMed DOI PMC

Lu C., Yang W., Chen M., Liu T., Yang J., Tan P., Li L., Hu X., Fan C., Hu Z., et al. Inhibin A inhibits follicle-stimulating hormone (FSH) action by supressing its receptor expression in cultured rat granulosa cells. Mol. Cell Endocrinol. 2009;298:48–56. doi: 10.1016/j.mce.2008.09.039. PubMed DOI

Vermeulen A. Androgens in the aging male. J. Clin. Endocrinol. Metab. 1991;73:221–224. doi: 10.1210/jcem-73-2-221. PubMed DOI

Morley J.E., Kaiser F.E., Perry H.M., III, Patrick P., Morley P.M., Stauber P.M., Vellas B., Baumgartenr R.N., Garry P.J. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997;46:410–413. doi: 10.1016/S0026-0495(97)90057-3. PubMed DOI

Seidman S.N. Testosterone deficiency and mood in aging men: Pathogenic and therapeutic interactions. World J. Biol. Psychiatry. 2003;4:14–20. doi: 10.3109/15622970309167905. PubMed DOI

Chong H., Pangas S.A., Bernard D.J., Wang E., Gitch J., Chen W., Draper L.B., Cox E.T., Woodruff T.K. Structure and expression of a membrane component of the inhibin receptor system. Endocrinology. 2000;141:2600–2607. doi: 10.1210/endo.141.7.7540. PubMed DOI

Andreassen M., Juul A., Feldt-Rasmussen U., Jorgensen N. Semen quality in patients with pituitary disease and adult-onset hypogonadotropic hypogonadism. Endocr. Connect. 2018;7:523–533. doi: 10.1530/EC-18-0061. PubMed DOI PMC

Harris I.D., Fronczak C., Roth L., Meacham R.B. Fertility and the aging male. Rev. Urol. 2011;13:e184–e190. PubMed PMC

Schwartz D., Mayaux M.J., Spira A., Moscato M.L., Jouannet P., Czyglik F., David G. Semen characteristics as a function of age in 833 fertile men. Fertil. Steril. 1983;39:530–535. doi: 10.1016/S0015-0282(16)46946-3. PubMed DOI

Hellstorm W.J.G., Sikka S.C. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J. Urol. 2006;176:1529–1533. doi: 10.1016/j.juro.2006.06.004. PubMed DOI

Elzanaty S., Erenpreiss J., Becker C. Seminal plasma albumin: Origin and relation to the male reproductive parameters. Andrologia. 2007;39:60–65. doi: 10.1111/j.1439-0272.2007.00764.x. PubMed DOI

Tang W.H., Zhuang X.J., Shu R.M., Guan D., Ji Y.D., Zhang B.L., Wang C.G., Zhuang L.H., Yang Z., Hong K., et al. The prevalence of erectile dysfunction among subjects with late-onset hypogonadism: A population-based study in China. Int. J. Clin. Exp. Med. 2015;8:13901–13910. PubMed PMC

Wu F.C.W., Tajar A., Beynon J.M., Pye S.R., Silman A.J., Finn J.D., O’Neill T.W., Bartfai G., Casanueva F.F., Forti G., et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N. Engl. J. Med. 2010;363:123–135. doi: 10.1056/NEJMoa0911101. PubMed DOI

Vishwanathan V., Eugster E.A. Etiology and treatment of hypogonadism in adolescents. Pediatr. Clin. N. Am. 2011;58:1181–1200. doi: 10.1016/j.pcl.2011.07.009. PubMed DOI PMC

Brauner R., Neve M., Allali S., Trivin C., Lottmann H., Bashaamboo A., McElreavey K. Clinical, biological and genetic analysis of anorchia in 26 boys. PLoS ONE. 2011;6:e23292. doi: 10.1371/journal.pone.0023292. PubMed DOI PMC

Rodprasert W., Virtanen H.E., Makela J.-A., Toppari J. Hypogonadism and cryptorchidism. Front. Endocrinol. 2020;10:906. doi: 10.3389/fendo.2019.00906. PubMed DOI PMC

Kumar P., Kumar N., Thakur D.S., Patidar A. Male hypogonadism: Symptoms and treatment. J. Adv. Pharm. Technol. Res. 2010;1:297–301. doi: 10.4103/0110-5558.72420. PubMed DOI PMC

Achermann J.C., Gu W.X., Kotlar T.J., Meeks J.J., Sabacan L.P., Seminara S.B., Habiby R.L., Hindmarsh P.C., Bick D.P., Sherins R.J., et al. Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay. J. Clin. Endocrinol. Metab. 1999;84:4497–4500. doi: 10.1210/jc.84.12.4497. PubMed DOI

Lawrence K.L., Stewart F., Larson B.M. Approaches to male hypogonadism in primary care. Nurse Pract. 2017;42:32–37. doi: 10.1097/01.NPR.0000511774.51873.da. PubMed DOI PMC

Pelusi C., Gasparini D.I., Bianchi N., Pasquali R. Endocrine dysfunction in hereditary hemochromatosis. J. Endocrinol. Investig. 2016;39:837–847. doi: 10.1007/s40618-016-0451-7. PubMed DOI

Osta R.E., Grandpre N., Monnin N., Hubert J., Koscinski I. Hypogonadotropic hypogonadism in men with hereditary hemochromatosis. Basic Clin. Androl. 2017;27:13. doi: 10.1186/s12610-017-0057-8. PubMed DOI PMC

Leichtmann-Bardoogo Y., Cohen L.A., Weiss A., Marohn B., Schubert S., Meinhardt A., Meyron-Holtz E.G. Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload. Am. J. Physiol. Endocrinol. Metab. 2012;302:1519–1530. doi: 10.1152/ajpendo.00007.2012. PubMed DOI

Nieschlag E. Late-onset hypogonadism: A concept comes of age. Andrologia. 2019;8:1506–1511. doi: 10.1111/andr.12719. PubMed DOI

Scaglione F., Donde S., Hassan T.A., Jannini E.A. Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction: Pharmacology and clinical impact of the sildenafil citrate orodispersible tablet formulation. Clin. Ther. 2017;39:370–377. doi: 10.1016/j.clinthera.2017.01.001. PubMed DOI

Shridharani A.N., Brant W.O. The treatment of erectile dysfunction in patients with neurogenic disease. Transl. Androl. Urol. 2016;5:88–101. doi: 10.3978/j.issn.2223-4683.2016.01.07. PubMed DOI PMC

Irfan M., Hussain N.H.N., Noor N.M., Mohamed M., Sidi H., Ismail S.B. Epidemiology of male sexual dysfunction in Asian and European regions: A systematic review. Am. J. Mens Health. 2020;14:1557988320937200. doi: 10.1177/1557988320937200. PubMed DOI PMC

Dowsett G.W., Lyons A., Duncan D., Wassersug R.J. Flexibility in men’s sexual practices in response to iatrogenic erectile dysfunction after prostate cancer treatment. Sex. Med. 2014;2:115–120. doi: 10.1002/sm2.32. PubMed DOI PMC

Baba K., Yajima M., Carrier S., Morgan D.M., Nunes L., Lue T.F., Iwamoto T. Delayed testosterone replacement restores nitric oxide synthase-containing nerve fibres and the erectile response in rat penis. BJU Int. 2000;85:953–958. doi: 10.1046/j.1464-410x.2000.00598.x. PubMed DOI

Soran H., Wu F.C.W. Endocrine causes of erectile dysfunction. Int. J. Androl. 2005;28:28–34. doi: 10.1111/j.1365-2605.2005.00596.x. PubMed DOI

Lunenfeld B., Mskhalaya G., Kalinchenko S., Tishova Y. Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism in men—A suggested update. Aging Male. 2013;16:143–150. doi: 10.3109/13685538.2013.853731. PubMed DOI

Attia A.A., Hassan F.A., Kamel M.I., Ayoub M.R. Quality of life in erectile dysfunction patients and their partners responding to tadalafil versus sildenafil citrate. Egypt. J. Dermatol. Venerol. 2013;33:32–36. doi: 10.7123/01.EJDV.0000431583.00793.33. DOI

Bai W.J., Li H.J., Jin J.J., Xu W.P., Sebastian S., Wang X.F. A randomized clinical trial investigating treatment choice in Chinese men receiving sildenafil citrate and tadalafil for treating erectile dysfunction. Asian J. Androl. 2017;19:500–504. doi: 10.4103/1008-682X.175782. PubMed DOI PMC

Selvin E., Burnett A.L., Platz E.A. Prevalence and risk factors for erectile dysfunction in the US. Am. J. Med. 2007;120:151–157. doi: 10.1016/j.amjmed.2006.06.010. PubMed DOI

Sand M.S., Fisher W., Rosen R., Heiman J., Eardly I. Erectile dysfunction and constructs of masculinity and quality of life in the multinational Men’s Attitudes to Life Events and Sexuality (MALES) study. J. Sex. Med. 2008;5:583–594. doi: 10.1111/j.1743-6109.2007.00720.x. PubMed DOI

Corona G., Boddi V., Balercia G., Rastrelli G., De Vita G., Sforza A., Forti G., Mannucci E., Maggi M. The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. J. Sex. Med. 2010;4:1547–1556. doi: 10.1111/j.1743-6109.2009.01698.x. PubMed DOI

Hafez E.S.E., Hafez S.D. Erectile dysfunction: Anatomical parameters, etiology, diagnosis, and therapy. Arch. Androl. 2005;51:15–31. doi: 10.1080/1485010490475147. PubMed DOI

Makhlouf A.A., Mohamed M.A., Seftel A.D., Neiderberger C. Hypogonadism is associated with overt depression in men with erectile dysfuncion. Int. J. Impot. Res. 2008;20:157–161. doi: 10.1038/sj.ijir.3901576. PubMed DOI

Vermeulen A. Environment, human reproduction, menopause, and andropause. Environ. Health Perspect. 1993;101:91–100. doi: 10.1289/ehp.93101s291. PubMed DOI PMC

Roychoudhury S., Bhattacharjee R. Environmental issues resulting in andropause and hypogonadism. In: Sikka S.C., Hellstrorm W.J.G., editors. Bioenvironmental Issues Affecting Men’s Reproductive and Sexual Health. 1st ed. Academic Press; Cambridge, MA, USA: 2018. pp. 262–273.

Park S. Genetic factors and environmental factors affecting male infertility. Int. Res. J. Adv. Eng. Sci. 2016;1:115–118.

Da Ros C.T., Graziottin T.M. Environmental issues resulting in hypogonadism in Brazilian men. In: Sikka S.C., Hellstrorm W.J.G., editors. Bioenvironmental Issues Affecting Men’s Reproductive and Sexual Health. 1st ed. Academic Press; Cambridge, MA, USA: 2018. pp. 33–40.

Tallon L.A., Manjourides J., Pun V.C., Mittleman M.A., Kioumourtzoglou M.A., Coull B., Suh H. Erectile dysfunction and exposure to ambient Air pollution in a nationally representative cohort of older. Men Environ. Health. 2017;16:12. doi: 10.1186/s12940-017-0216-6. PubMed DOI PMC

Hafez E.M., Issa S.Y., AI-Mazroua M.K., Ibrahim K.T., Rahman S.M.A. The neonicotinoid insecticide imidacloprid: A male reproductive system toxicity inducer-human and experimental study. Toxicol. Open Access. 2016;1:109. doi: 10.4172/2476-2067.1000109. DOI

Wilson V.S., Blystone C.R., Hotchkiss A.K., Rider C.V., Gray L.E., Jr. Diverse mechanisms of anti-androgen action: Impact on male rat reproductive tract development. Int. J. Androl. 2008;31:178–187. doi: 10.1111/j.1365-2605.2007.00861.x. PubMed DOI

Kaur R.P., Gupta V., Christopher A.F., Bansal P. Potential pathways of pesticide action on erectile function—A contributory factor in male infertility. Asian Pac. J. Reprod. 2015;4:322–330. doi: 10.1016/j.apjr.2015.07.012. DOI

Toman R., Tunegová M. Selenium, cadmium and diazinon insecticide in tissues of rats after peroral exposure. Potr. Slovak J. Food Sci. 2017;11:718–724. doi: 10.5219/827. DOI

Krockova J., Massanyi P., Toman R., Danko J., Roychoudhury S. In vivo and in vitro effect of bendiocarb on rabbit testicular structure and spermatozoa motility. J. Environ. Sci. Health. 2012;47:1301–1311. doi: 10.1080/10934529.2012.672136. PubMed DOI

Slimani S., Boulakoud M.S., Abdennour C. Pesticide exposure and reproductive biomarkers among male farmers from north-east Algeria. Ann. Biol. Res. 2011;2:290–297.

Brook J.S., Brook D.W., Rosa M.D.L., Whiteman M., Johnson E., Montoya I. Adolescent illegal drug use: The impact of personality, family, and environmental factors. J. Behav. Med. 2001;24:183–203. doi: 10.1023/A:1010714715534. PubMed DOI

Lushchak V.I., Matviishyan T.M., Husak V.V., Storey J.M., Storey K.B. Pesticide toxicity: A mechanistic approach. EXCLI J. 2018;17:1101–1136. doi: 10.17179/excli2018-1710. PubMed DOI PMC

Costa C., Virag R. The endothelial-erectile dysfunction connection: An essential update. J. Sex. Med. 2009;6:2390–2404. doi: 10.1111/j.1743-6109.2009.01356.x. PubMed DOI

Traish A.M., Park K., Dhir V., Kim N.N., Moreland R.B., Goldstein I. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology. 1999;140:1861–1868. doi: 10.1210/endo.140.4.6655. PubMed DOI

ElMazoudy R.H., Attia A.A. Endocrine-disrupting and cytotoxic potential of anticholinesterase insecticide, diazinon in reproductive toxicity of male mice. J. Hazard. Mater. 2012;209–210:111–120. doi: 10.1016/j.jhazmat.2011.12.073. PubMed DOI

Lafuente A., Cabaleiro T., Caride A., Esquifino A.I. Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats. Food Chem. Toxicol. 2008;46:1570–1575. doi: 10.1016/j.fct.2007.12.017. PubMed DOI

Lafuente A., Gonzalez-Carracedo A., Romero A., Cano P., Esquifino A.I. Effect of nitric oxide on prolactin secretion and hypothalamic biogenic amine contents. Life Sci. 2004;74:1681–1690. doi: 10.1016/j.lfs.2003.09.041. PubMed DOI

Svechnikov K., Izzo G., Landreh L., Weisser J., Soder O. Endocrine disruptors and Leydig cell function. J. Biomed. Biotechnol. 2010;2010:684504. doi: 10.1155/2010/684504. PubMed DOI PMC

Leong C.T., D’Souza U.J.A., Iqbal M., Mustapha Z.A. Lipid peroxidation and decline in antioxidant status as one of the toxicity measures of diazinon in the testis. Redox Rep. 2013;18:155–164. doi: 10.1179/1351000213Y.0000000054. PubMed DOI PMC

Bedwal R.S., Nair N., Mathur R.S. Effects of zinc deficiency and toxicity on reproductive organs, pregnancy and lactation—A review. Trace Elem. Med. 1991;8:89–100.

Farag A.T., Radwan A.H., Sorour F., Okazy A.E., El-Agamy E., El-Sebae A.E. Chlorpyrifos induced reproductive toxicity in male mice. Reprod. Toxicol. 2010;29:80–85. doi: 10.1016/j.reprotox.2009.10.003. PubMed DOI

Khokhar J.Y., Tyndale R.F. Rat brain CYP2B-enzymatic activation of chlorpyrifos to the oxon mediates cholinergic neurotoxicity. Toxicol. Sci. 2012;126:325–335. doi: 10.1093/toxsci/kfs029. PubMed DOI

Adedara I.A., Owoeye O., Ajayi B.O., Awogbindin I.O., Rocha J.B.T., Farombi E.O. Diphenyl diselenide abrogates chlorpyrifos-induced hypothalamic-pituitary-testicular axis impairment in rats. Biochem. Biophys. Res. Commun. 2018;503:171–176. doi: 10.1016/j.bbrc.2018.05.205. PubMed DOI

Sai L., Li X., Liu Y., Guo Q., Xie L., Yu G., Bo C., Zhang Z., Li L. Effects of chlorpyrifos on reproductive toxicology of male rats. Environ. Toxicol. 2014;29:1083–1088. doi: 10.1002/tox.21838. PubMed DOI

Slimen S., Saloua E.F., Najoua G. Oxidative stress and cytotoxic potential of anticholinesterase insecticide, malathion in reproductive toxicology of male adolescent mice after acute exposure. Iran. J. Basic Med. Sci. 2014;17:522–530. PubMed PMC

Janssens L., Stoks R. Chlorpyrifos-induced oxidative damage is reduced under warming and predation risk: Explaining antagonistic interactions with a pesticide. Environ. Pollut. 2017;226:79–88. doi: 10.1016/j.envpol.2017.04.012. PubMed DOI

Mandal T.K., Das N.S. Correlation of testicular toxicity and oxidative stress induced by chlorpyrifos in rats. Hum. Exp. Toxicol. 2011;30:1529–1539. doi: 10.1177/0960327110392400. PubMed DOI

Mandal T.K., Das N.S. Testicular gametogenic and steroidogenic activities in chlorpyrifos insecticide-treated rats: A correlational study with testicular oxidative stress and role of antioxidant enzyme defence systems in Sprague-Dawley rats. Andrologia. 2012;44:102–115. doi: 10.1111/j.1439-0272.2010.01110.x. PubMed DOI

Peiris D.C., Dhanushka T. Low doses of chlorpyrifos interfere with spermatogenesis of rats through reduction of sex hormones. Environ. Sci. Pollut. Res. Int. 2017;24:20859–20867. doi: 10.1007/s11356-017-9617-x. PubMed DOI

Watkins S.S., Koob G.F., Markou A. Neural mechanisms underlying nicotine addiction: Acute positive reinforcement and withdrawal. Nicotine Tob. Res. 2000;2:19–37. doi: 10.1080/14622200050011277. PubMed DOI

Ala-Eldin E.A., El-Safei D.A., Abouhashem N.S. Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats. Environ. Sci. Pollut. Res. 2017;24:1532–1543. doi: 10.1007/s11356-016-7912-6. PubMed DOI

Sharma P., Huq A.U., Singh R. Cypermethrin-induced reproductive toxicity in the rat is preserved by resveratrol. J. Hum. Reprod. Sci. 2014;7:99–106. doi: 10.4103/0974-1208.138867. PubMed DOI PMC

Civen M., Brown C.B. The effect of organophosphate insecticides on adrenal corticosterone formation. Pestic. Biochem. Phys. 1947;4:254–259. doi: 10.1016/0048-3575(74)90108-4. DOI

Chattopadhyay A., Sarkar M., Biswas N.M. Dose-dependent effect of copper chloride on male reproductive function in immature rats. Kathmandu Univ. Med. J. 2005;3:392–400. PubMed

Joshi S.C., Bansal B., Jasuja N.D. Evaluation of reproductive and developmental toxicity of cypermethrin in male albino rats. Toxicol. Environ. Chem. 2011;93:593–602. doi: 10.1080/02772248.2010.537441. DOI

Wang X.-Z., Liu S.-S., Sun Y., Wu J.-Y., Zhou Y.-L., Zhang J.-H. Beta-cypermethrin impairs reproductive function in male mice by inducing oxidative stress. Theriogenology. 2009;72:599–611. doi: 10.1016/j.theriogenology.2009.04.016. PubMed DOI

Wang Q., Wang H.-X., Shen J.-Y., Zhang R., Hong J.-W., Li Z., Chen G., Li M.-X., Ding Z., Li J., et al. The anti-androgenic effects of cypermethrin mediated by non-classical testosterone pathway activation of mitogen-activated protein kinase cascade in mouse Sertoli cells. Ecotoxicol. Environ. Saf. 2019;177:58–65. doi: 10.1016/j.ecoenv.2019.03.109. PubMed DOI

Solati J., Hajikhani R., Zaeim R.T. Effects of cypermethrin on sexual behaviour and plasma concentrations of pituitary-gonadal hormones. Int. J. Fertil. Steril. 2010;4:23–28.

Avendano C., Mata A., Sarmiento C.A.S., Doncel G.F. Use of laptop computers connected to internet through Wi-Fi decreases human sperm motility and increases sperm DNA fragmentation. Fertil. Steril. 2012;97:39–45. doi: 10.1016/j.fertnstert.2011.10.012. PubMed DOI

Kesari K., Kumar S., Behari J. Mobile phone usage and male infertility in Wistar rats. Indian J. Exp. Biol. 2010;48:987–992. PubMed

Kesari K.K., Kumar S., Nirala J., Siddiqui M.H., Behari J. Biophysical evaluation of radiofrequency electromagnetic field effects on male reproductive pattern. Cell Biochem. Biophys. 2013;65:85–96. doi: 10.1007/s12013-012-9414-6. PubMed DOI

McGill J.J., Agarwal A. The impact of cell phone, laptop computer, and microwave oven usage on male fertility. In: du Plessis S.S., Agarwal A., Sabanegh E.S. Jr., editors. Male Infertility: A Complete Guide to Lifestyle and Environmental Factors. Springer; New York, NY, USA: 2014. pp. 161–177. DOI

Kesari K.K., Agarwal A., Henkel R. Radiations and male fertility. Reprod. Biol. Endocrinol. 2018;16:118. doi: 10.1186/s12958-018-0431-1. PubMed DOI PMC

Yu G., Tang Z., Chen H., Wang L., Cao H., Wang G., Xing J., Shen H., Chen Q., Li D., et al. Long-term exposure to 4G smartphone radiofrequency electromagneticradiation diminished male reproductive potential by directly disruptingSpock3–MMP2-BTB axis in the testes of adult rats. Sci. Total Environ. 2020;698:133860. doi: 10.1016/j.scitotenv.2019.133860. PubMed DOI

Daniell H.W., Clark J.C., Pereira S.E., Niazi Z.A., Ferguson D.W., Dunn S.R., Figueroa M.L., Stratte P.T. Hypogonadism following prostate-bed radiation therapy for prostate carcinoma. Cancer. 2001;91:1889–1895. doi: 10.1002/1097-0142(20010515)91:10<1889::AID-CNCR1211>3.0.CO;2-U. PubMed DOI

Incrocci L. Radiotherapy for prostate cancer and sexual health. Transl. Androl. Urol. 2015;4:124–130. PubMed PMC

Huyghe E., Matsuda T., Daudin M., Chevreau C., Bachaud J.M., Plante P., Bujan L., Thonneau P. Fertility after testicular cancer treatments: Results of a large multicenter study. Cancer. 2004;100:732–737. doi: 10.1002/cncr.11950. PubMed DOI

Brydøy M., Fosså S.D., Klepp O., Bremnes R.M., Wist E.A., Wentzel-Larsen T., Dahl O. Paternity following treatment for testicular cancer. J. Natl. Cancer Inst. 2005;97:1580–1588. doi: 10.1093/jnci/dji339. PubMed DOI

Huddart R.A., Norman A., Moynihan C., Horwich A., Parker C., Nicholls E., Dearnaley D.P. Fertility, gonadal and sexual function in survivors of testicular cancer. Br. J. Cancer. 2005;93:200–207. doi: 10.1038/sj.bjc.6602677. PubMed DOI PMC

Pasqualotto F.F., Agarwal A. Impact of cancers and treatment on male fertility: Radiation effects on spermatogenesis. In: Mulhall J.P., Applegarth L.D., Oates R.D., Schlegel P.N., editors. Fertility Preservation in Male Cancer Patients. Cambridge University Press; Cambridge, UK: 2013. pp. 104–109.

Arnon J., Meirow D., Lewis-Roness H., Ornoy A. Genetic and teratogenic effects of cancer treatments on gametes and embryos. Hum. Reprod. Update. 2001;7:394–403. doi: 10.1093/humupd/7.4.394. PubMed DOI

Meistrich M.L. The effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil. Steril. 2013;100:1180–1186. doi: 10.1016/j.fertnstert.2013.08.010. PubMed DOI PMC

Martin R.H., Hildebrand K., Yamamoto J. An increased frequency of human sperm chromosomal abnormalities after radiotherapy. Mutat. Res. 1986;174:219–225. doi: 10.1016/0165-7992(86)90155-7. PubMed DOI

Behari J. General, Applied and Systems Toxicology. Wiley; Hoboken, NJ, USA: 2009. Biological correlates of low-level electromagnetic-field exposure; p. 109. DOI

Kesari K.K., Behari J. Evidence for mobile phone radiation exposure effects on reproductive pattern of male rats: Role of ROS. Electromagn. Biol. Med. 2012;31:13–222. doi: 10.3109/15368378.2012.700292. PubMed DOI

Kumar S., Nirala J.P., Behari J., Paulraj R. Effect of electromagnetic irradiation produced by 3G mobile phone on male rat reproductive system in a simulated scenario. Indian J. Exp. Biol. 2014;52:890–897. PubMed

Zilberlicht A., Weiner-Megnazi Z., Sheinfeld Y., Grach B., Lahav-Baratz S., Dirnfeld M. Habits of cell phone usage and sperm quality–Does it warrant attention? Reprod. Biomed. 2015;31:421–426. doi: 10.1016/j.rbmo.2015.06.006. PubMed DOI

Agarwal A., Deepinder F., Sharma R.K. Effect of cell phone usage on semen analysis in men attending infertility clinic: An observational study. Fertil. Steril. 2008;89:124–128. doi: 10.1016/j.fertnstert.2007.01.166. PubMed DOI

Roychoudhury S., Jedlicka J., Ondruska L., Bulla J., Massanyi P., Kolesarova A. Does 50 Hz extra low frequency electromagnetic field affect rabbit spermatozoa motility in vitro? Res. J. Biotechnol. 2008;3:244–249.

Roychoudhury S., Jedlicka J., Parkanya V., Ondruska L., Massanyi P., Bulla J. Influence of a 50 Hz extra low frequency electromagnetic field on spermatozoa motility and fertilization rates in rabbits. J. Environ. Sci. Health A Tox. Hazard. Subst. Environ. Eng. 2009;44:1041–1047. doi: 10.1080/10934520902997029. PubMed DOI

Lukac N., Massanyi P., Roychoudhury S., Capcarova M., Tvrda E., Knazicka Z., Kolesarova A., Danko J. In vitro effects of radiofrequency electromagnetic waves on bovine spermatozoa motility. J. Environ. Sci. Health. 2011;46:1417–1423. doi: 10.1080/10934529.2011.607037. PubMed DOI

Jaffar F.H.F., Osman K., Ismail H.N., Chin K.Y., Ibrahim S.F. Adverse effects of wifi–Radiation on male reproductive system: A systematic review. Tohoku J. Exp. Med. 2019;248:169–179. doi: 10.1620/tjem.248.169. PubMed DOI

Saygin M., Asci H., Ozmen O., Cankara F.N., Dincoglu D., Ilhan I. Impact of 2.45 GHz microwave radiation on testicular inflammatory pathway biomarkers in young rats: Role of gallic acid. Environ. Toxicol. 2016;31:1771–1784. doi: 10.1002/tox.22179. PubMed DOI

Jonwal C., Sisodia R., Saxena V.K., Kesari K.K. Effect of 2.45GHz microwave radiation on fertility pattern in male mice. Gen. Physiol. Biophys. 2018;37:453–460. doi: 10.4149/gpb_2017059. PubMed DOI

Meena R., Kumari K., Kumar J., Rajamani P., Verma H.N., Kesari K.K. Therapeutic approaches of melatonin in microwave radiations-induced oxidative stress-mediated toxicity on male fertility pattern of Wistar rats. Electromagn. Biol. Med. 2013:1–11. doi: 10.3109/15368378.2013.781035. PubMed DOI

Lin Y.Y., Wu T., Liu J.Y., Gao P., Li K.C., Guo Q.Y., Yuan M., Lang H.Y., Zeng L.H., Guo G.Z. 1950MHz radio frequency electromagnetic radiation inhibits testosterone secretion of mouse Leydig cells. Int. J. Environ. Res. Public Health. 2017;15:17. doi: 10.3390/ijerph15010017. PubMed DOI PMC

Qin F., Cao H., Yuan H., Guo W., Pei H., Cao Y., Tong J. 1800MHz radiofrequency fields inhibitstestosteroneproduction viaCaMKI /RORα pathway. Reprod. Toxicol. 2018 doi: 10.1016/j.reprotox.2018.08.014. PubMed DOI

Song B., Wang F., Wang W. Effect of aqueous extract from Morindaofficinalis F. C. Howon microwave-induced hypothalamic-pituitary-testis axis impairment in male Sprague-Dawley rats. Evid. Based Complement. Alternat. Med. 2015;2015 doi: 10.1155/2015/360730. PubMed DOI PMC

Walker W.H. Non-classical actions of testosterone and spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol.Sci. 2010;365:1557–1569. doi: 10.1098/rstb.2009.0258. PubMed DOI PMC

Ramaswamy S., Weinbauer G.F. Endocrine control of spermatogenesis: Role of FSH and LH/testosterone. Spermatogenesis. 2014;4:e996025. doi: 10.1080/21565562.2014.996025. PubMed DOI PMC

Zhang Y., Guo X., Li T., Zhang M., Feng Y., Li W., Zhu X., Gu R., Zhou L. Effect and safety evaluation of XETHRU X4 radar radiation on sexual hormone levels in mice. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. 2019;2019:1318–1320. doi: 10.1109/EMBC.2019.8857733. PubMed DOI

Shahin S., Singh S.P., Chaturvedi C.M. 2.45 GHz microwave radiation induced oxidative and nitrosativestress mediated testicular apoptosis: Involvement of a p53 dependent bax-caspase-3 mediated pathway. Environ. Toxicol. 2018;33:931–945. doi: 10.1002/tox.22578. PubMed DOI

Kesari K.K., Behari J. Microwave exposure affecting reproductive system in male rats. Appl. Biochem. Biotechnol. 2010;162:416–428. doi: 10.1007/s12010-009-8722-9. PubMed DOI

Condell R.A., Tappel A.L. Evidence for suitability of glutathione peroxidase as a protective enzyme: Studies of oxidative damage, restoration and proteolysis. Arch. Biochem. Biophy. 1993;223:407. doi: 10.1016/0003-9861(83)90604-5. PubMed DOI

Russo A., Troncoso N., Sanchez F., Vanella A. Propolis protects human spermatozoa from DNA damage caused by benzopyrene and exogenous reactive oxygen species. Life Sci. 2006;78:1401–1406. doi: 10.1016/j.lfs.2004.10.085. PubMed DOI

Aitken R.J., Baker M.A. Oxidative stress, sperm survival and fertility control. Mol. Cell. Endocrinol. 2006;250:66–69. doi: 10.1016/j.mce.2005.12.026. PubMed DOI

Kalia S., Bansal M.P. P53 is involved in inducing testicular apoptosis in mice by the altered redox status following tertiary butyl hydroperoxide treatment. Chem. Biol. Interact. 2008;174:193–200. doi: 10.1016/j.cbi.2008.06.004. PubMed DOI

Li D., Ueta E., Kimura T., Yamamoto T., Osaki T. Reactive oxygen species (ROS) control the expression of Bcl-2 family proteins by regulating their phosphorylation and ubiquitination. Cancer Sci. 2004;95:644–650. doi: 10.1111/j.1349-7006.2004.tb03323.x. PubMed DOI PMC

Mishra D.P., Pal R., Shaha C. Changes in cytosolic Ca2+ levels regulate Bcl-xSandBcl-xL expression in spermatogenic cells during apoptotic death. J. Biol. Chem. 2006;281:2133–2143. doi: 10.1074/jbc.M508648200. PubMed DOI

Chandra J., Samali A., Orrenius S. Triggering and modulation of apo-ptosis by oxidative stress. Free Radic. Biol. Med. 2000;29:323–333. doi: 10.1016/S0891-5849(00)00302-6. PubMed DOI

Lazebnik Y.A., Kaufmann S.H., Desnoyers S., Poirier G.G., Earnshaw W.C. Cleavageofpoly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 1994;371:346–347. doi: 10.1038/371346a0. PubMed DOI

Rowley M.J., Leach D.R., Warner G.A., Heller C.G. Effect of graded doses of ionizing radiation on the human testis. Radiat. Res. 1974;59:665–678. doi: 10.2307/3574084. PubMed DOI

Nichols R.C., Hu C., Bahary J.P., Zeitzer K.L., Souhami L., Leibenhaut M.H., Rotman M., Gore E.M., Balogh A.G., McGowan D., et al. Serum testosterone changes in patients treated with radiation therapy alone for prostate cancer on NRG oncology RTOG 9408. Adv. Radiat. Oncol. 2017;2:608–614. doi: 10.1016/j.adro.2017.07.004. PubMed DOI PMC

Ishiyama H., Teh B.S., Paulino A.C., Yogeswarern S., Mai W., Xu B., Butler E.B. Serum testosterone level after intensity-modulated radio therapy in low-risk prostate cancer patients: Does testicular dose correlate with testosterone level? J. Radiat. Oncol. 2012;1:173–177. doi: 10.1007/s13566-012-0007-1. DOI

Pickles T., Graham P., Members of the British Columbia Cancer Agency Prostate Cohort Outcomes Initiative What happens to testosterone after prostate radiation mono therapy, and does it matter? J. Urol. 2002;167:2448–2452. doi: 10.1016/S0022-5347(05)65002-1. PubMed DOI

Pompe R.S., Karakiewicz P.I., Zaffuto E., Smith A., Bandini M., Marchioni M., Tian Z., Ley-Bannurah S., Schiffmann J., Delouya G., et al. External beam radiotherapy affects serum testosterone in patients with localized prostate cancer. J. Sex. Med. 2017;14:876–882. doi: 10.1016/j.jsxm.2017.04.675. PubMed DOI

Filchenkov G.N., Popoff E.H., Naumov A.D. The low dose gamma ionizing radiation impact upon cooperativity of androgen specific proteins. J. Environ. Radioact. 2013 doi: 10.1016/j.jenvard.2013.02.002. PubMed DOI

Zagars G.K., Pollack A. Serum testosterone levels after external beam radiation for clinically localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 1997;39:85–89. doi: 10.1016/S0360-3016(97)00311-8. PubMed DOI

Zagars G.K. Management of stage I seminoma: Radiotherapy. In: Horwich A., editor. Testicular Cancer, Investigation and Management. Chapman & Hall Medical; London, UK: 1991. pp. 83–107.

Shapiro E., Kinsella T.J., Makuch R.W., Fraass B.A., Glatstein E., Rosenberg S.A., Sherins R.J. Effects of fractionated irradiation on endocrine aspects of testicular function. J. Clin. Oncol. 1985;3:1232–1239. doi: 10.1200/JCO.1985.3.9.1232. PubMed DOI

Oberley-Deegan R.E., Steffan J.J., Rove K.O., Pate K.M., Weaver M.W., Spasojevic I., Frederick B., Raben D., Meacham R.B., Crapo J.D., et al. The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer irradiation. PLoS ONE. 2012;7:e44178. doi: 10.1371/journal.pone.0044178. PubMed DOI PMC

Kimura M., Rabbani Z.N., Zodda A.R., Yan H., Jackson I.L., Polascik T.J., Donatucci C.F., Moul J.W., Vujaskovic Z., Koontz B.F. Role of oxidative stress in a rat model of radiation-induced erectile dysfunction. J. Sex. Med. 2012;9:1535–1549. doi: 10.1111/j.1743-6109.2012.02716.x. PubMed DOI

Ji H.J., Wang D.M., Wu Y.P., Niu Y.Y., Jia L.L., Liu B.W., Feng Q.J., Feng M.L. Wuzi Yanzong pill, a Chinese poly herbal formula, alleviates testicular damage in mice induced by ionizing radiation. BMC Complement. Altern. Med. 2016;16:509. doi: 10.1186/s12906-016-1481-6. PubMed DOI PMC

Ezz M.K., Ibrahim N.K., Said M.M., Farrag M.A. The beneficial radioprotective effect of tomato seed oil against gamma radiation–induced damage in male rats. J. Diet Suppl. 2018;15:923–938. doi: 10.1080/19390211.2017.1406427. PubMed DOI

Bala S., Chugh N.A., Bansal S.C., Garg M.L., Koul A. Protective role of Aloe vera against X-ray induced testicular dysfunction. Andrologia. 2016:1–12. doi: 10.1111/and.12697. PubMed DOI

Chatterjee A., Kosmacek E.A., Oberly-Deegan R.E. MnTE-2-PyP treatment, or NOX4 inhibition, protects against radiation-, induced damage in mouse primary prostate fibroblasts by inhibiting the TGF-Beta 1 signaling pathway. Radiat. Res. 2017;187:367–381. doi: 10.1667/RR14623.1. PubMed DOI PMC

Gorbunov N.V., Sharma P. Protracted oxidative alterations in the mechanism of hematopoietic acute radiation syndrome. Antioxidants. 2015;4:134–152. doi: 10.3390/antiox4010134. PubMed DOI PMC

Batinic-Haberle I., Benov L., Spasojevic I., Fridovich I. The ortho effect makes manganese(III) meso-tetrakis(N-methylpyridinium-2-yl) porphyrin a powerful and potentially useful superoxide dismutase mimic. J. Biol. Chem. 1998;273:24521–24528. doi: 10.1074/jbc.273.38.24521. PubMed DOI

Beckman J.S., Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly. Am. J. Physiol. 1996;271:C1424–C1427. doi: 10.1152/ajpcell.1996.271.5.C1424. PubMed DOI

Zou M., Martin C., Ullrich V. Tyrosine nitration as a mechanism of selective inactivation of prostacyclin synthase by peroxynitrite. Biol. Chem. 1997;378:707–713. doi: 10.1515/bchm.1997.378.7.707. PubMed DOI

Khan M.A., Thompsom C.S., Mumtaz F.H., Mikhailidis D.P., Morgan R.J., Bruckdorfer R.K., Naseem K.M. The effect of nitric oxide and peroxynitrate on rabbit cavernosal smooth muscle relaxation. World J. Urol. 2001;19:220–224. doi: 10.1007/s003450000162. PubMed DOI

Steers W.D. Pharmacologic treatment of erectile dysfunction. Rev. Urol. 2002;4:S17–S25. PubMed PMC

Manisalidis I., Stavropoulou E., Stavropoulos A., Bezirtzoglou E. Environmental and health impacts of air pollution: A review. Front. Public Health. 2002;8:14. doi: 10.3389/fpubh.2020.00014. PubMed DOI PMC

Wang L., Luo D., Liu X., Zhu J., Wang F., Li B., Li L. Effects of PM2.5 exposure on reproductive system and its mechanisms. Chemosphere. 2021;264:128436. doi: 10.1016/j.chemosphere.2020.128436. PubMed DOI

El-Maraghy S.A., Nasssar N.N. Modulatory effects of lipoic acid and selenium against cadmium-induced biochemical alterations in testicular steroidogenesis. Biochem. Mol. Toxicol. 2011;25:15–25. doi: 10.1002/jbt.20354. PubMed DOI

Alkhedaide A., Alsheri Z.S., Sabry A., Abdel-Gaffer T., Soliman M.M., Attia S. Protective effect of grape seed extract against cadmium-induced testicular dysfunction. Mol. Med. Rep. 2016;13:3101–3109. doi: 10.3892/mmr.2016.4928. PubMed DOI PMC

Zhang Q., Zou P., Zhan H., Zhang M., Zhang M., Ge R.S., Huang Y. Dihydrolipoamide dehydrogenase and cAMP are associated with cadmium mediated Leydig cell damage. Toxicol. Lett. 2011;205:183–189. doi: 10.1016/j.toxlet.2011.06.003. PubMed DOI

Kresovich J.K., Argos M., Turyk M.E. Associations of lead and cadmium with sex hormones in adult males. Environ. Res. 2015;142:25–33. doi: 10.1016/j.envres.2015.05.026. PubMed DOI

El-Magd M.A., Kahilo K.A., Nasr N.E., Kamal T., Shukry M., Saleh A.A. A potential mechanism associated with lead-induced testicular toxicity in rats. Andrologia. 2017;49 doi: 10.1111/and.12750. PubMed DOI

Cacciola G., Chioccarelli T., Fasano S., Pierantoni R., Cobellis G. Estrogens and spermiogenesis: New insights from type 1 cannabinoid receptor knockout mice. Int. J. Endocrinol. 2013;2013:501350. doi: 10.1155/2013/501350. PubMed DOI PMC

Carreau S., Hess R.A. Oestrogens and spermatogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2010;365:1517–1535. doi: 10.1098/rstb.2009.0235. PubMed DOI PMC

Carreau S., de Vienne C., Galeraud-Denis I. Aromatase and estrogens in man reproduction: A review and latest advances. Adv. Med. Sci. 2008;53:139–144. doi: 10.2478/v10039-008-0022-z. PubMed DOI

Elmallah M.I.Y., Elkhadragy M.F., Al-Olayan E.M., Moneim A.E.A. Protective effect of Fragaria ananassa crude extract on cadmium-induced lipid peroxidation, antioxidant enzymes suppression, and apoptosis in rat testes. Int. J. Mol. Sci. 2017;18:957. doi: 10.3390/ijms18050957. PubMed DOI PMC

Mouro V.G.S., de Melo F.C.S.A., Martins A.L.P., Gomes M.L.M., de Oliveria J.M., de Freitas M.B.D., Demuner A.J., Leite J.P.V., de Matta S.L.P. Euterpe oleracea (Martius) oil reverses testicular alterations caused after cadmium administration. Biol. Trace Elem. Res. 2020;197:555–570. doi: 10.1007/s12011-019-02004-x. PubMed DOI

Chatterjee P.K., Anantharaya V.N.M., Shiva R.K., Kumar N.A., Shetty S.B., Budihal S.V., Bhat M.R., Kunal Pre- and post-treatment effects: Estimation of serum testosterone and lipid peroxidation levels on Moringaolifera extract induced cadmium exposed rats. Pharmacogn. J. 2017;9:846–849. doi: 10.5530/pj.2017.6.132. DOI

Ekhoye E.I., Olerimi S.M., Ehebha S.E. Comparison of the deleterious effects of yajiandcadmium chloride on testicular physio morphological and oxidative stress status: The gonado protective effects of an omega-3 fatty acid. Clin. Exp. Reprod. Med. 2020;47:168–179. doi: 10.5653/cerm.2019.03517. PubMed DOI PMC

Koriem K.M.M., Fathi G.E., Salem H.A., Akram N.H., Gamil S.A. Protective role of pectin against cadmium induced testiculartoxicity and oxidative stress in rats. Toxicol. Mech. Method. 2013 doi: 10.3109/15376516.2012.748857. PubMed DOI

Choong G., Liu Y., Templeton D.M. Interplay of calcium and cadmium in mediating cadmium toxicity. Chem. Biol. Interact. 2014;211:54–65. doi: 10.1016/j.cbi.2014.01.007. PubMed DOI

Marzec-Wróblewska U., Kaminski P., Lakota P. Influence of chemical elements on mammalian spermatozoa. Folia Biol. 2012;58:7–15. PubMed

Khanna S., Mitra S., Lakhera P.C., Khandelwal S. N-acetylcysteine effectively mitigates cadmium induced oxidative damage and cell death in Leydig cells in vitro. Drug Chem. Toxicol. 2016;39:74–80. doi: 10.3109/01480545.2015.1028068. PubMed DOI

Kelainy E.G., Laila I.M.I., Ibrahim S.R. The effect of ferulic acid against lead-induced oxidative stress and DNA damage in kidney and testes of rats. Environ. Sci. Pollut. Res. 2019;26:31675–31684. doi: 10.1007/s11356-019-06099-6. PubMed DOI

Dorostghoal M., Seyyednejad S.M., Nejad M.N.T. Cichorium intybus L. extract ameliorates testicular oxidative stress induced by lead acetate in male rats. Clin. Exp. Reprod. Med. 2020;47:161–167. doi: 10.5653/cerm.2019.03496. PubMed DOI PMC

Olayaki L.A., Alagbonsi I.A., Abdulrahim A.H., Adeyami W.J., Bakare M., Omeiza M. Melatonin prevents and ameliorates lead-induced gonado toxicity through antioxidative and hormonal mechanisms. Toxicol. Ind. Health. 2018;34:596–608. doi: 10.1177/0748233718773508. PubMed DOI

Wen L., Jiang X., Sun J., Li X., Li X., Tian L., Li Y. Cyanidin-3-O-glucoside promotes the biosynthesis of progesterone throughthe protection of mitochondrial function in Pb-exposed rat leydig cells. Food Chem. Toxicol. 2018;112:427–434. doi: 10.1016/j.fct.2017.10.008. PubMed DOI

El-Sayed Y.S., El-Neweshy M.S. Impact of lead toxicity on male ratreproduction at hormonal and histopathological levels. Toxicol. Environ. Chem. 2010;4:765–774. doi: 10.1080/02772240902984453. DOI

Rubio J., Riqueros M.I., Gasco M., Yucra S., Miranda S., Gonzales G.F. Lepidiummeyenii (Maca) reversed the lead acetate induced-damage on reproductive function in male rats. Food Chem. Toxicol. 2006;44:1114–1122. doi: 10.1016/j.fct.2006.01.007. PubMed DOI

Kasperczyk A., Kasperczyk S., Horak S., Ostalowska A., Grucka- Mamczar E., Romuk E., Olejek A., Birkner E. Assessment of semen function and lipid peroxidation among lead exposed men. Toxicol. Appl. Pharmacol. 2008;228:378–384. doi: 10.1016/j.taap.2007.12.024. PubMed DOI

Ghaffari M.A., Motlagh B. In vitro effect of lead, silver, tin, mercury, indium and bismuth on human sperm creatine kinase activity: A presumable mechanism for men infertility. Iran. Biomed. J. 2011;15:38–43. PubMed PMC

Abdel-Wahhab M.A., Aly S.E. Antioxidant property of Nigella sativa (Black cumin) and Syzygium aromaticum (Cloves) in rats during aflatoxicosis. J. Appl. Toxicol. 2005;25:218–223. doi: 10.1002/jat.1057. PubMed DOI

Nita M., Grybowski A. The role of reactive oxygen species and oxidative stress in the patho mechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid. Med. Cell. Longev. 2016;2016:3164734. doi: 10.1155/2016/3164734. PubMed DOI PMC

Ercal N., Gurer-Orhan H., Aykin-Burns N. Toxic metals and oxidative stress part I: Mechanisms involved in metal-induced oxidative damage. Curr. Top. Med. Chem. 2001;1:529–539. doi: 10.2174/1568026013394831. PubMed DOI

Szweda P.A., Friguet B., Szweda L.I. Proteolysis, free radicals, and aging. Free Radic. Biol. Med. 2002;33:29–36. doi: 10.1016/S0891-5849(02)00837-7. PubMed DOI

Silbergeld E.K., Waalkes M., Rice J.M. Lead as a carcinogen: Experimental evidence and mechanisms of action. Am. J. Ind. Med. 2000;38:316–323. doi: 10.1002/1097-0274(200009)38:3<316::AID-AJIM11>3.0.CO;2-P. PubMed DOI

US Environmental Protection Agency (EPA) Particulate Matter (PM) Pollution. [(accessed on 20 January 2021)]; Available online: https://www.epa.gov/pm-pollution.

Brook R.D., Franklin B., Cascio W., Hong Y., Howard G., Lipsett M., Luepker R., Mittleman M., Samet J., Smith S.C., Jr., et al. Expert panel on population and prevention science of the American Heart Association: Air pollution and cardiovascular disease: A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation. 2004;109:2655–2671. doi: 10.1161/01.CIR.0000128587.30041.C8. PubMed DOI

Kloner R.A., Speakman M. Erectile dysfunction and atherosclerosis. Curr. Atheroscler. Rep. 2002;4:397–401. doi: 10.1007/s11883-002-0078-3. PubMed DOI

Ying Z., Xu X., Bai Y., Zhong J., Chen M., Liang Y., Zhao J., Liu D., Morishita M., Sun Q., et al. Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: A role for hypothalamic inflammation. Environ. Health Perspect. 2014;122:79–86. doi: 10.1289/ehp.1307151. PubMed DOI PMC

Qiu L., Chen M., Wang X., Qin X., Chen S., Qian Y., Liu Z., Cao Q., Ying Z. Exposure to concentrated ambient PM2.5 compromises spermatogenesis in a mouse model: Role of suppression of hypothalamus-pituitary-gonads axis. Toxicol. Sci. 2018;162:318–326. doi: 10.1093/toxsci/kfx261. PubMed DOI PMC

Jeng H.A., Yu L. Alteration of sperm quality and hormone levels by polycyclic aromatic hydrocarbons on airborne particulate particles. J. Environ. Sci. Health A Tox. Hazard Subst. Environ. Eng. 2008;43:675–681. doi: 10.1080/10934520801959815. PubMed DOI

Corradi P.F., Corradi R.B., Greene L.W. Physiology of the hypothalamic pituitary gonadal axis in the male. Urol. Clin. N. Am. 2016;43:151–162. doi: 10.1016/j.ucl.2016.01.001. PubMed DOI

Yang Y., Yang T., Liu S., Cao Z., Zhao Y., Su X., Liao Z., Teng X., Hua J. Concentrated ambient PM2.5 exposure affects mice sperm quality and testosterone biosynthesis. PeerJ. 2019;7:e8109. doi: 10.7717/peerj.8109. PubMed DOI PMC

Albersen M., Orabi H., Lue T.F. Evaluation and treatment of erectile dysfunction in the aging male: A mini review. Gerontology. 2012;58:3–14. doi: 10.1159/000329598. PubMed DOI

Vanhoutte P.M. Ageing and endothelial dysfunction. Eur. Heart J. Suppl. 2002;4:A8–A17. doi: 10.1016/S1520-765X(02)90068-4. DOI

Aitken R.J., Baker M.A. Reactive oxygen species generation by human spermatozoa: A continuing enigma. Int. J. Androl. 2002;25:191–194. doi: 10.1046/j.1365-2605.2002.03521.x. PubMed DOI

Mishra D.P., Shaha C. Estrogen-induced spermatogenic cell apoptosis occurs via the mitochondrial pathway: Role of superoxide and nitric oxide. J. Biol. Chem. 2005;280:6181–6196. doi: 10.1074/jbc.M405970200. PubMed DOI

Iremashvili V., Brackett N.L., Lynne C.M. Impact of spinal cord injury. In: Parekattil S., Agarwal A., editors. Male Infertility. 1st ed. Springer; New York, NY, USA: 2012. pp. 337–345.

Brackett N.L., Ferrell S.M., Aballa T.C., Amador M.J., Lynne C.M. Semen quality in spinal cord injured men: Does it progressively decline postinjury? Arch. Phys. Med. Rehabil. 1998;79:625–628. doi: 10.1016/S0003-9993(98)90034-X. PubMed DOI

Gillon G., Barnea O. Erection mechanism of the penis: A model-based analysis. J. Urol. 2002;168:2711–2715. doi: 10.1016/S0022-5347(05)64249-8. PubMed DOI

Wang W., Deng Z., Feng Y., Liao F., Feng S., Wang X. PM2.5 induced apoptosis in endothelial cell through the activation of p53-bax-caspase pathway. Chemosphere. 2017;177:135–143. doi: 10.1016/j.chemosphere.2017.02.144. PubMed DOI

Künzli N., Jerrett M., Garcia-Esteban R., Basagaña X., Beckermann B., Gilliland F., Medina M., Peters J., Hodis H.N., Mack W.J. Ambient air pollution and the progression of atherosclerosis in adults. PLoS ONE. 2010;5:e9096. doi: 10.1371/annotation/21f6b02b-e533-46ca-9356-86a0eef8434e. PubMed DOI PMC

Xie L.N., Wang X.C., Dong X.J., Su L.Q., Zhu H.J., Wang C., Zhang D.P., Liu F.Y., Hou S.S., Dong B., et al. Concentration, spatial distribution, and health risk assessment of PFASs in serum of teenagers, tap water and soil near a Chinese fluorochemical industrial plant. Environ. Int. 2021;146:106166. doi: 10.1016/j.envint.2020.106166. PubMed DOI

Castellini C., Totaro M., Parisi A., D’Andrea S., Lucente L., Cordeschi G., Francavilla S., Francevilla F., Barbonetti A. Bisphenol A and male fertility: Myths and realities. Front. Endocrinol. 2020;11:353. doi: 10.3389/fendo.2020.00353. PubMed DOI PMC

Pan G., Hanaoka T., Yoshimura M., Zhang S., Wang P., Tsukino H., Inoue K., Nakazawa H., Tsugane S., Takahasi K. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): A cross-sectional study in China. Environ. Health Perspect. 2006;114:1643–1648. doi: 10.1289/ehp.9016. PubMed DOI PMC

Leong J.Y., Blachman-Braun R., Patel A.S., Patel P., Ramasamy R. Association between polychlorinated biphenyl 153 exposure and serum testosterone levels: Analysis of the National Health and Nutrition Examination Survey. Transl. Androl. Urol. 2019;8:666–672. doi: 10.21037/tau.2019.11.26. PubMed DOI PMC

Lopez-Espinosa M.J., Fletcher T., Armstrong B., Genser B., Dhatariya K., Mondal D., Ducatman A., Leonardi G. Association of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with age of puberty among children living near a chemical plant. Environ. Sci. Technol. 2011;45:8160–8166. doi: 10.1021/es1038694. PubMed DOI

Li D., Zhou Z., Qing D., He Y., Wu T., Miao M., Wang J., Weng X., Ferber J.R., Herrinton L.J., et al. Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. Hum. Reprod. 2010;255:19–27. doi: 10.1093/humrep/dep381. PubMed DOI

Groves-Kirkby N. BPA worsens male sexual function. Nat. Rev. Urol. 2010;7:60. doi: 10.1038/nrurol.2009.246. DOI

Hanaoka. T., Kawamura N., Hara K., Tsugane S. Urinary bisphenol A and plasma hormone concentrations in male workers exposed to bisphenol A diglycidyl ether and mixed organic solvents. Occup. Environ. Med. 2002;59:625–628. doi: 10.1136/oem.59.9.625. PubMed DOI PMC

Xi W., Lee C.K., Yeung W.S., Giesy J.P., Wong M.H., Zhang X., Hecker M., Wong C.K. Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus-pituitary-gonadal axis of CD-1 mice. Reprod. Toxicol. 2011;31:409–417. doi: 10.1016/j.reprotox.2010.12.002. PubMed DOI

Nakamura D., Yanagiba Y., Duan Z., Ito Y., Okamura A., Asaeda N., Tagawa Y., Li C., Taya K., Zhang S.Y., et al. Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. Toxicol. Lett. 2010;194:16–25. doi: 10.1016/j.toxlet.2010.02.002. PubMed DOI

Sanocka D., Kurpisz M. Reactive oxygen species and sperm cells. Reprod. Biol. Endocrinol. 2004;2:12. doi: 10.1186/1477-7827-2-12. PubMed DOI PMC

Ullah A., Pirzada M., Jahan S., Ullah H., Turi N., Ullah W., Siddiqui M.F., Zakria M., Lodhi K.Z., Khan M.M. Impact of low-dose chronic exposure to bisphenol A and its analogue bisphenol B, bisphenol F and bisphenol S on hypothalamic-pituitary-testicular activities in adult rats: A focus on the possible hormonal mode of action. Food Chem. Toxicol. 2018;121:24–36. doi: 10.1016/j.fct.2018.08.024. PubMed DOI

Ha M., Guan X., Wei L., Li P., Yang M., Liu C. Di-(2-ethylhexyl) phthalate inhibits testosterone level through disturbed hypothalamic-pituitary-testis axis and ERK-mediated 5α-Reductase 2. Sci. Total Environ. 2016;563–564:566–575. doi: 10.1016/j.scitotenv.2016.04.145. PubMed DOI

Akingbemi B.T., Youker R.T., Sottas C.M., Ge R., Katz E., Klinefelter G.R., Zirkin B.R., Hardy M.P. Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate. Biol. Reprod. 2001;65:1252–1259. doi: 10.1095/biolreprod65.4.1252. PubMed DOI

Barlow N.J., Philips S.L., Wallace D.G., Sar M., Gaido K.W., Foster P.M.D. Quantitatve changes in gene expression in fetal rat testes following exposure to di(n-butyl) phthalate. Toxicol. Sci. 2003;73:431–441. doi: 10.1093/toxsci/kfg087. PubMed DOI

Sedha S., Kumar S., Shukla S. Role of oxidative stress in male reproductive dysfunctions with reference to phthalate compounds. Urol. J. 2015;12:2304–2316. PubMed

Meroni S.B., Galardo M.N., Rindone G., Gorga A., Riera M.F., Cigorraga S.B. Molecular mechanisms and signaling pathways involved in Sertoli cell proliferation. Front. Endocrinol. 2019;10:224. doi: 10.3389/fendo.2019.00224. PubMed DOI PMC

Zoeller R.T., Brown T.R., Doan L.L., Gore A.C., Skakkebaek N.E., Soto A.M., Woodruff T.J., Vom Saal F.S. Endocrine-disrupting chemicals and public health protection: A statement of principles from The Endocrine Society. Endocrinology. 2012;153:4097–4110. doi: 10.1210/en.2012-1422. PubMed DOI PMC

Meeker J.D., Barr D.B., Hauser R. Pyrethroid insecticide metabolites are associated with serum hormone levels in adult men. Reprod. Toxicol. 2009;27:155–160. doi: 10.1016/j.reprotox.2008.12.012. PubMed DOI PMC

Sansone A., Romanelli F., Gianfrilli D., Lenzi A. Endocrine evaluation of erectile dysfunction. Endocrine. 2014;46:423–430. doi: 10.1007/s12020-014-0254-6. PubMed DOI

Seftel A.D., Kathrins M., Niederberger C. Critical update of the 2010 endocrine society clinical practice guidelines for male hypogonadism: A systematic analysis. Mayo Clin. Proc. 2015;90:1104–1115. doi: 10.1016/j.mayocp.2015.06.002. PubMed DOI

Traish A.M., Miner M.M., Morgentaler A., Zitzmann M. Testosterone deficiency. Am. J. Med. 2011;124:578–587. doi: 10.1016/j.amjmed.2010.12.027. PubMed DOI

Talsness C.E., Andrade A.J., Kuriyama S.N., Taylor J.A., vom Saal F.S. Components of plastic: Experimental studies in animals and relevance for human health. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009;364:2079–2096. doi: 10.1098/rstb.2008.0281. PubMed DOI PMC

Fromme H., Tittlemier S.A., Volkel W., Wilhelm M., Twardella D. Perfluorinated compounds--exposure assessment for the general population in Western countries. Int. J. Hyg. Environ. Health. 2009;212:239–270. doi: 10.1016/j.ijheh.2008.04.007. PubMed DOI

Joensen U.N., Veyrand B., Antignac J.P., Blomberg Jensen M., Petersen J.H., Marchand P., Skakkebaek N.E., Andersson A.M., Le Bizec B., Jorgensen N. PFOS (perfluorooctanesulfonate) in serum is negatively associated with testosterone levels, but not with semen quality, in healthy men. Hum. Reprod. 2013;28:599–608. doi: 10.1093/humrep/des425. PubMed DOI

Kraugerud M., Zimmer K.E., Ropstad E., Verhaegen S. Perfluorinated compounds differentially affect steroidogenesis and viability in the human adrenocortical carcinoma (H295R) in vitro cell assay. Toxicol. Lett. 2011;205:62–68. doi: 10.1016/j.toxlet.2011.05.230. PubMed DOI

Zhao B., Chu Y., Hardy D.O., Li X.K., Ge R.S. Inhibition of 3beta- and 17beta-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluoro octane acid. J. Steroid Biochem. Mol. Biol. 2010;118:13–17. doi: 10.1016/j.jsbmb.2009.09.010. PubMed DOI

Lu H., Zhang H., Gao J., Li Z., Bao S., Chen X., Wang Y., Ge R., Ye L. Effects of perfluorooctanoic acid on stem Leydig cell functions in the rat. Environ. Pollut. 2019;250:206–215. doi: 10.1016/j.envpol.2019.03.120. PubMed DOI

Eggert A., Cisneros-Montalvo S., Anandan S., Musilli S., Stukenborg J.B., Adamsson A., Nurmio M., Toppari J. The effects of perfluorooctanoic acid (PFOA) on fetal and adult rat testis. Reprod. Toxicol. 2019;90:68–76. doi: 10.1016/j.reprotox.2019.08.005. PubMed DOI

Wielsoe M., Long M., Ghisari M., Bonefeld-Jorgensen E.C. Perfluoro alkylated substances (PFAS) affect oxidative stress biomarkers in vitro. Chemosphere. 2015;129:239–245. doi: 10.1016/j.chemosphere.2014.10.014. PubMed DOI

Zeng Z., Song B., Xiao R., Zeng G., Gong J., Chen M., Xu P., Zhang P., Shen M., Yi H. Assessing the human health risk of perfluorooctane sulfonate by in vivo and in vitro studies. Environ. Int. 2019;126:598–610. doi: 10.1016/j.envint.2019.03.002. PubMed DOI

Ivanciuc. T., Ivanciuc O., Klein D.J. Modeling the bioconcentration factors and bioaccumulation factors of polychlorinated biphenyls with posetic quantitative super-structure/activity relationships (QSSAR) Mol. Divers. 2006;10:133–145. doi: 10.1007/s11030-005-9003-3. PubMed DOI

Murugesan P., Muthusamy T., Balasubramanian K., Arunakaran J. Polychlorinated biphenyl (Aroclor 1254) inhibits testosterone biosynthesis and antioxidant enzymes in cultured rat Leydig cells. Reprod. Toxicol. 2008;25:447–454. doi: 10.1016/j.reprotox.2008.04.003. PubMed DOI

Lyche J.L., Oskam I.C., Skaare J.U., Reksen O., Sweeney T., Dahl E., Farstad W., Ropstad E. Effects of gestational and lactational exposure to low doses of PCBs 126 and 153 on anterior pituitary and gonadal hormones and on puberty in mice. Reprod. Toxicol. 2004;19:87–95. doi: 10.1016/j.reprotox.2004.05.005. PubMed DOI

Okino S.T., Whitlock J.P. The aromatic hydrocarbon receptor, transcription, and endocrine aspects of dioxin action. Vitam. Horm. 2000;59:241–264. doi: 10.1016/s0083-6729(00)59009-8. PubMed DOI

Chen H., Cangello D., Benson S., Folmer J., Zhu H., Trush M.A., Zirkin B.R. Age-related increase in mitochondrial superoxide generation in the testosterone-producing cells of Brown Norway rat testes: Relationship to reduced steroidogenic function? Exp. Gerontol. 2001;36:1361–1373. doi: 10.1016/S0531-5565(01)00118-8. PubMed DOI

Cao L., Leers-Sucheta S., Azhar S. Aging alters the functional expression of enzymatic and non-enzymatic anti-oxidant defense systems in testicular rat Leydig cells. J. Steroid Biochem. Mol. Biol. 2004;88:61–67. doi: 10.1016/j.jsbmb.2003.10.007. PubMed DOI

Toppari. J., Larsen J.C., Christiansen P. Male reproductive health and environmental xenoestrogens. Environ. Health Perspect. 1996;104:741–803. doi: 10.1289/ehp.96104s4741. PubMed DOI PMC

Wolff M.S., Camann D., Gammon M., Stellman S.D. Proposed PCB congener groupings for epidemiological studies. Environ. Health Perspect. 1997;105:13–14. doi: 10.1289/ehp.9710513. PubMed DOI PMC

Melis M.R., Argiolas A. Nitric oxide donors induce penile erection and yawning when injected in the central nervous system of male rats. Eur. J. Pharmacol. 1995;294:1–9. doi: 10.1016/0014-2999(95)00508-0. PubMed DOI

Lugg J.A., Rajfer J., González-Cadavid N.F. Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology. 1995;136:1495–1501. doi: 10.1210/endo.136.4.7534702. PubMed DOI

Mills T.M. Vasoconstriction and vasodilation in erectile physiology. Curr. Urol. Rep. 2002;3:477–483. doi: 10.1007/s11934-002-0101-9. PubMed DOI

Polsky J.Y., Aronson K.J., Heaton J.P., Adams M.A. Pesticides and polychlorinated biphenyls as potential risk factors for erectile dysfunction. J. Androl. 2007;28:28–37. doi: 10.2164/jandrol.106.000851. PubMed DOI

Sadeghi A., Farokhi F., Shalijar-Jalali A., Najafi G. Protective effect of vitamin E on sperm quality and in vitro fertilizing potential and testosterone concentration in polyvinyl chloride treated male rats. Vet. Res. Forum. 2020;11:257–263. doi: 10.30466/vrf.2019.911842206. PubMed DOI PMC

Lamb D.J. An approach that someday may boost testosterone biosynthesis in males with late-onset hypogonadism (low testosterone) Proc. Natl. Acad. Sci. USA. 2019;116:22904–22906. doi: 10.1073/pnas.1916719116. PubMed DOI PMC

Ankerst D.P., Hoefler J., Bock S., Goodman P.J., Vickers A., Hernandez J., Sokoll L.J., Sanda M.G., Wei J.T., Leach R.J., et al. Prostate cancer prevention trial risk calculator 2.0 for the prediction of low-vs-high grade prostate cancer. Urology. 2014;83:1362–1368. doi: 10.1016/j.urology.2014.02.035. PubMed DOI PMC

Francomano D., Bruzziches R., Barbaro G., Lenzi A., Aversa A. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: A pilot study. J. Endocrinol. Investig. 2014;37:401–411. doi: 10.1007/s40618-014-0066-9. PubMed DOI

Ide V., Vanderschueren D., Antonio L. Treatment of men with central hypogonadism: Alternatives for testosterone replacement therapy. Int. J. Mol. Sci. 2021;22:21. doi: 10.3390/ijms22010021. PubMed DOI PMC

Sharma R., Oni O.A., Gupta K., Sharma M., Sharma R., Singh V., Parashara D., Kamalakar S., Dawn B., Chen G. Normalization of testosterone levels after testosterone replacement therapy is associated with decreased incidence of atrial fibrillation. J. Am. Heart. Assoc. 2017:e004880. doi: 10.1161/JAHA.116.004880. PubMed DOI PMC

Li S., Zhao Y., Yang Y., Wang X., Nie M., Wu X., Mao J. Metabolic effects of testosterone replacement therapy in patients with type 2 diabetes mellitus or metabolic syndrome: A meta-analysis. Int. J. Endocrinol. 2020;2020:4732021. doi: 10.1155/2020/4732021. PubMed DOI PMC

Dean J.D., McMahon C.G., Guay A.T., Morgentaler A., Althof S.E., Becher E.F., Bivalacqua T.J., Burnett A.L., Buvat J., Meliegy A.E., et al. The international society for sexual medicine’s process of care for the assessment and management of testosterone deficiency in adult men. J. Sex. Med. 2015;12:1660–1686. doi: 10.1111/jsm.12952. PubMed DOI

Khera M., Adaikan G., Buvat J., Carrier S., El-Meliegy A., Hatzimouratidis K., McCoullough A., Morgentaler A., Torres L.O., Salonia A. Diagnosis and treatment of testosterone deficiency: Recommendations from the fourth international consultation for sexual medicine (ICSM 2015) J. Sex. Med. 2016;13:1787–1804. doi: 10.1016/j.jsxm.2016.10.009. PubMed DOI

Üçer O., Gümüş B. The treatment of late-onset hypogonadism. Turk. J. Urol. 2014;40:170–179. doi: 10.5152/tud.2013.97752. PubMed DOI PMC

Rodriguez K.M., Pastuzak A.W. A history of penile implants. Transl. Androl. Urol. 2017;6:S851–S857. doi: 10.21037/tau.2017.04.02. PubMed DOI PMC

Gonçalves L., de Souza R.R., Maifrino L.B., Caperuto É.C., Carbone P.O., Rodrigues B., Gama E.F. Resistance exercise and testosterone treatment alters the proportion of numerical density of capillaries of the left ventricle of aging Wistar rats. Aging Male. 2014;17:243–247. doi: 10.3109/13685538.2014.919252. PubMed DOI

Hayes L.D., Sculthorpe N., Herbert P., Baker J.S., Hullin D.A., Kilduff L.P., Grace F.M. Resting steroid hormone concentrations in lifetime exercisers and lifetime sedentary males. Aging Male. 2015;18:22–26. doi: 10.3109/13685538.2014.977246. PubMed DOI

Drugs FDA FDA-Approved Drugs. U.S Food and Drug Administration. [(accessed on 15 March 2021)]; Available online: https://www.fda.gov/scripts/cder/daf/

Guiliano F., Peña B.M., Mishra A., Smith M.D. Efficacy results and quality-of-life measures in men receiving sildenafil citrate for the treatment of erectile dysfunction. Qual. Life Res. 2001;10:359–369. doi: 10.1023/A:1012270220064. PubMed DOI

Janini E.A., Isidori A.M., Gravina G.L., Aversa A., Balercia G., Bocchio M., Boscaro M., Carini C., Corona G., Fabbari A., et al. The ENDOTRIAL study: A spontaneous, open-label, randomized, multicenter, crossover study on the efficacy of sildenafil, tadalafil, and vardenafil in the treatment of erectile dysfunction. J. Sex. Med. 2009;6:2547–2560. doi: 10.1111/j.1743-6109.2009.01375.x. PubMed DOI

Kim E.D., Owen R.C., White G.S., Elkelany O.O., Rahnema C.D. Endovascular treatment of vasculogenic erectile dysfunction. Asian J. Androl. 2015;17:40–43. doi: 10.4103/1008-682X.143752. PubMed DOI PMC

Sanchez-Borrego R., Molero F., Castaño R., Castelo-Branco C., Honrado M., Jurado A.R., Laforet E., Prieto R., Cabello F., Larrazabal M., et al. Spanish consensus on sexual health in men and women over 50. Maturitas. 2014;78:138–145. doi: 10.1016/j.maturitas.2014.02.020. PubMed DOI

Urology Care Foundation, American Urological Association Erectile Dysfunction: Diagnosis. [(accessed on 20 March 2021)]; Available online: www.urologyhealth.org.

Coulson C., Jenkins J. Complementary and alternative medicine utilisation in NHS and private clinic settings: A United Kingdom survey of 400 infertility patients. J. Exp. Clin. Assist. Reprod. 2005;2:5. doi: 10.1186/1743-1050-2-5. PubMed DOI PMC

Yadav R., Yadav A., Kumar A., Singh J.P. Understanding of andropause and its ayurvedic management: Conceptual study. IAMJ. 2019;7:446–450.

Singh S.K., Rajoria K. Review of andropause in ayurveda, rasayan, vajikarana and panchakarma perspective. RRJoAsYN. 2014;1:19–26.

George A., Liske E. Acceptance of herbal medicine in andrology. In: Henkel R., Agarwal A., editors. Herbal Medicine in Andrology an Evidence-Based Update. 1st ed. Academic Press; Cambridge, MA, USA: 2021. pp. 215–255. DOI

Sengupta P., Agarwal A., Pogrebetskaya M., Roychoudhury S., Durairajanayagam D., Henkel R. Role of Withania somnifera (Ashwagandha) in the management of male infertility. Reprod. Biomed. 2017;36:311–326. doi: 10.1016/j.rbmo.2017.11.007. PubMed DOI

Lohiya N.K., Balasubramanian K., Ansari A.S. Indian folklore medicine in managing men’s health and wellness. Andrologia. 2016;48:894–907. doi: 10.1111/and.12680. PubMed DOI

Amano T., Imao T., Takemae K. Clinical efficacy of Japanese herbal medicine (Kampo) in patients with late-onset hypogonadism. Aging Male. 2010;13:166–173. doi: 10.3109/13685530903536684. PubMed DOI

Choi S.W., Jeon S.H., Kwon E.B., Zhu G.Q., Lee K.W., Choi J.B., Jeong H.C., Kim K.S., Bae S.R., Bae W.J., et al. Effect of Korean herbal formula (modified ojayeonjonghwan) on androgen receptor expression in an aging rat model of late onset hypogonadism. World J. Mens Health. 2019;37:105–112. doi: 10.5534/wjmh.180051. PubMed DOI PMC

Zhang Z.J., Ji S.Y., Dong W., Zhang Y.N., Zhang E.H., Bin Z. A herbal medicine, saikokaryokotsuboreito, improves serum testosterone levels and affects sexual behavior of in old male mice. Aging Male. 2015;18:106–111. doi: 10.3109/13685538.2014.963042. PubMed DOI

Roychoudhury S., Chakraborty S., Das A., Guha P., Agarwal A., Henkel R. Herbal medicine used to treat andrological problems: Asian and Indian subcontinent: Ginkgo biloba, Curcuma longa, and Camellia sinensis. In: Henkel R., Agarwal A., editors. Herbal Medicine in Andrology an Evidence-Based Update. 1st ed. Academic Press; Cambridge, MA, USA: 2021. pp. 129–146. DOI

Roychoudhury S., Agarwal A., Cho C.L. Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod. Biomed. 2017;34:487–498. doi: 10.1016/j.rbmo.2017.02.006. PubMed DOI

Lee J.K.C., Tan R.B.W., Chung E. Erectile dysfunction treatment and traditional medicine—Can East and West medicine coexist? Transl. Androl. Urol. 2017;6:91–100. doi: 10.21037/tau.2016.11.13. PubMed DOI PMC

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