The crucial role that oestrogens play in male reproduction has been generally accepted; however, the exact mechanism of their action is not entirely clear and there is still much more to be clarified. The oestrogen response is mediated through oestrogen receptors, as well as classical oestrogen receptors' variants, and their specific co-expression plays a critical role. The importance of oestrogen signalling in male fertility is indicated by the adverse effects of selected oestrogen-like compounds, and their interaction with oestrogen receptors was proven to cause pathologies. The aims of this review are to summarise the current knowledge on oestrogen signalling during spermatogenesis and sperm maturation and discuss the available information on oestrogen receptors and their splice variants. An overview is given of species-specific differences including in humans, along with a detailed summary of the methodology outcome, including all the genetically manipulated models available to date. This review provides coherent information on the recently discovered mechanisms of oestrogens' and oestrogen receptors' effects and action in both testicular somatic and germ cells, as well as in mature sperm, available for mammals, including humans.

Department of Zoology Faculty of Science Charles University Vinicna 7 12844 Prague 2 Czech Republic

Group of Reproductive Biology Institute of Biotechnology CAS v v i BIOCEV Prumyslova 595 25250 Vestec Czech Republic

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Hess R.A. Estrogen in the adult male reproductive tract: A review. Reprod. Biol. Endocrinol. 2003;1:52. doi: 10.1186/1477-7827-1-52. PubMed DOI PMC

Free M.J., Jaffe R.A. Collection of rete testis fluid from rats without previous efferent duct ligation. Biol. Reprod. 1979;20:269–278. doi: 10.1095/biolreprod20.2.269. PubMed DOI

Hess R.A., Bunick D., Bahr J.M. Sperm, a source of estrogen. Environ. Heal. Perspect. 1995;103:59–62. doi: 10.1289/ehp.95103s759. PubMed DOI PMC

Faccio L., Da Silva A.S., Tonin A.A., Franca R.T., Gressler L.T., Copetti M.M., Oliveira C.B., Sangoi M.B., Moresco R.N., Bottari N.B., et al. Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by trypanosoma evansi. Exp. Parasitol. 2013;135:110–115. doi: 10.1016/j.exppara.2013.06.008. PubMed DOI

Kelch R.P., Jenner M.R., Weinstein R., Kaplan S.L., Grumbach M.M. Estradiol and testosterone secretion by human, simian, and canine testes, in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome. J. Clin. Investig. 1972;51:824–830. doi: 10.1172/JCI106877. PubMed DOI PMC

Abraham G.E., Odell W.D., Swerdloff R.S., Hopper K. Simultaneous radioimmunoassay of plasma FSH, LH, progesterone, 17-hydroxyprogesterone, and estradiol-17 β during the menstrual cycle. J. Clin. Endocrinol. Metab. 1972;34:312–318. doi: 10.1210/jcem-34-2-312. PubMed DOI

Lubahn D.B., Moyer J.S., Golding T.S., Couse J.F., Korach K.S., Smithies O. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc. Natl. Acad. Sci. USA. 1993;90:11162–11166. doi: 10.1073/pnas.90.23.11162. PubMed DOI PMC

Cooper T.G., Noonan E., von Eckardstein S., Auger J., Baker H.W., Behre H.M., Haugen T.B., Kruger T., Wang C., Mbizvo M.T., et al. World health organization reference values for human semen characteristics. Hum. Reprod. Update. 2010;16:231–245. doi: 10.1093/humupd/dmp048. PubMed DOI

Pflieger-Bruss S., Schuppe H.C., Schill W.B. The male reproductive system and its susceptibility to endocrine disrupting chemicals. Andrologia. 2004;36:337–345. doi: 10.1111/j.1439-0272.2004.00641.x. PubMed DOI

Schagdarsurengin U., Western P., Steger K., Meinhardt A. Developmental origins of male subfertility: Role of infection, inflammation, and environmental factors. Semin. Immunopathol. 2016;38:765–781. doi: 10.1007/s00281-016-0576-y. PubMed DOI

Contractor R.G., Foran C.M., Li S., Willett K.L. Evidence of gender-and tissue-specific promoter methylation and the potential for ethinylestradiol-induced changes in japanese medaka (Oryzias latipes) estrogen receptor and aromatase genes. J. Toxicol. Environ. Health. Part A. 2004;67:1–22. doi: 10.1080/15287390490253633. PubMed DOI

Mirbahai L., Chipman J.K. Epigenetic memory of environmental organisms: A reflection of lifetime stressor exposures. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2014;764–765:10–17. doi: 10.1016/j.mrgentox.2013.10.003. PubMed DOI

Schagdarsurengin U., Steger K. Epigenetics in male reproduction: Effect of paternal diet on sperm quality and offspring health. Nat. Rev. Urol. 2016;13:584–595. doi: 10.1038/nrurol.2016.157. PubMed DOI

Aschim E.L., Saether T., Wiger R., Grotmol T., Haugen T.B. Differential distribution of splice variants of estrogen receptor β in human testicular cells suggests specific functions in spermatogenesis. J. Steroid Biochem. Mol. Biol. 2004;92:97–106. doi: 10.1016/j.jsbmb.2004.05.008. PubMed DOI

Flouriot G., Brand H., Denger S., Metivier R., Kos M., Reid G., Sonntag-Buck V., Gannon F. Identification of a new isoform of the human estrogen receptor-α (HER-α) that is encoded by distinct transcripts and that is able to repress HER-α activation function 1. EMBO J. 2000;19:4688–4700. doi: 10.1093/emboj/19.17.4688. PubMed DOI PMC

Friend K.E., Resnick E.M., Ang L.W., Shupnik M.A. Specific modulation of estrogen receptor mRNA isoforms in rat pituitary throughout the estrous cycle and in response to steroid hormones. Mol. Cell. Endocrinol. 1997;131:147–155. doi: 10.1016/S0303-7207(97)00098-1. PubMed DOI

Fuqua S.A., Fitzgerald S.D., Chamness G.C., Tandon A.K., McDonnell D.P., Nawaz Z., O’Malley B.W., McGuire W.L. Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res. 1991;51:105–109. PubMed

Hanstein B., Liu H., Yancisin M.C., Brown M. Functional analysis of a novel estrogen receptor-β isoform. Mol. Endocrinol. 1999;13:129–137. PubMed

Inoue S., Ogawa S., Horie K., Hoshino S., Goto W., Hosoi T., Tsutsumi O., Muramatsu M., Ouchi Y. An estrogen receptor β isoform that lacks exon 5 has dominant negative activity on both ERα and ERβ. Biochem. Biophys. Res. Commun. 2000;279:814–819. doi: 10.1006/bbrc.2000.4010. PubMed DOI

Lambard S., Galeraud-Denis I., Saunders P.T., Carreau S. Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors. J. Mol. Endocrinol. 2004;32:279–289. doi: 10.1677/jme.0.0320279. PubMed DOI

Lewandowski S., Kalita K., Kaczmarek L. Estrogen receptor β. Potential functional significance of a variety of mRNA isoforms. FEBS Lett. 2002;524:1–5. doi: 10.1016/S0014-5793(02)03015-6. PubMed DOI

Lu B., Leygue E., Dotzlaw H., Murphy L.J., Murphy L.C. Functional characteristics of a novel murine estrogen receptor-β isoform, estrogen receptor-β 2. J. Mol. Endocrinol. 2000;25:229–242. doi: 10.1677/jme.0.0250229. PubMed DOI

Lu B., Leygue E., Dotzlaw H., Murphy L.J., Murphy L.C., Watson P.H. Estrogen receptor-β mRNA variants in human and murine tissues. Mol. Cell. Endocrinol. 1998;138:199–203. doi: 10.1016/S0303-7207(98)00050-1. PubMed DOI

Ogawa S., Inoue S., Watanabe T., Orimo A., Hosoi T., Ouchi Y., Muramatsu M. Molecular cloning and characterization of human estrogen receptor βCX: A potential inhibitor ofestrogen action in human. Nucleic Acids Res. 1998;26:3505–3512. doi: 10.1093/nar/26.15.3505. PubMed DOI PMC

Peng B., Lu B., Leygue E., Murphy L.C. Putative functional characteristics of human estrogen receptor-β isoforms. J. Mol. Endocrinol. 2003;30:13–29. doi: 10.1677/jme.0.0300013. PubMed DOI

Petersen D.N., Tkalcevic G.T., Koza-Taylor P.H., Turi T.G., Brown T.A. Identification of estrogen receptor β2, a functional variant of estrogen receptor β expressed in normal rat tissues. Endocrinology. 1998;139:1082–1092. doi: 10.1210/endo.139.3.5840. PubMed DOI

Price R.H., Jr., Lorenzon N., Handa R.J. Differential expression of estrogen receptor β splice variants in rat brain: Identification and characterization of a novel variant missing exon 4. Brain Res. Mol. Brain Res. 2000;80:260–268. doi: 10.1016/S0169-328X(00)00135-2. PubMed DOI

Wang Z., Zhang X., Shen P., Loggie B.W., Chang Y., Deuel T.F. A variant of estrogen receptor-α, HER-α36: Transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling. Proc. Natl. Acad. Sci. USA. 2006;103:9063–9068. doi: 10.1073/pnas.0603339103. PubMed DOI PMC

Barone I., Brusco L., Fuqua S.A. Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin. Cancer Res. 2010;16:2702–2708. doi: 10.1158/1078-0432.CCR-09-1753. PubMed DOI PMC

Hirata S., Shoda T., Kato J., Hoshi K. Isoform/variant mRNAs for sex steroid hormone receptors in humans. Trends. Endocrinol. Metab. 2003;14:124–129. doi: 10.1016/S1043-2760(03)00028-6. PubMed DOI

Luconi M., Forti G., Baldi E. Genomic and nongenomic effects of estrogens: Molecular mechanisms of action and clinical implications for male reproduction. J. Steroid Biochem. Mol. Biol. 2002;80:369–381. doi: 10.1016/S0960-0760(02)00041-9. PubMed DOI

Nilsson S., Makela S., Treuter E., Tujague M., Thomsen J., Andersson G., Enmark E., Pettersson K., Warner M., Gustafsson J.A. Mechanisms of estrogen action. Physiol. Rev. 2001;81:1535–1565. PubMed

Paterni I., Granchi C., Katzenellenbogen J.A., Minutolo F. Estrogen receptors α (ERα) and β (ERβ): Subtype-selective ligands and clinical potential. Steroids. 2014;90:13–29. doi: 10.1016/j.steroids.2014.06.012. PubMed DOI PMC

Filardo E., Quinn J., Pang Y., Graeber C., Shaw S., Dong J., Thomas P. Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. Endocrinology. 2007;148:3236–3245. doi: 10.1210/en.2006-1605. PubMed DOI

Funakoshi T., Yanai A., Shinoda K., Kawano M.M., Mizukami Y. G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochem. Biophys. Res. Commun. 2006;346:904–910. doi: 10.1016/j.bbrc.2006.05.191. PubMed DOI

Revankar C.M., Cimino D.F., Sklar L.A., Arterburn J.B., Prossnitz E.R. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science. 2005;307:1625–1630. doi: 10.1126/science.1106943. PubMed DOI

Sakamoto H., Matsuda K., Hosokawa K., Nishi M., Morris J.F., Prossnitz E.R., Kawata M. Expression of G protein-coupled receptor-30, a g protein-coupled membrane estrogen receptor, in oxytocin neurons of the rat paraventricular and supraoptic nuclei. Endocrinology. 2007;148:5842–5850. doi: 10.1210/en.2007-0436. PubMed DOI

Filardo E.J., Graeber C.T., Quinn J.A., Resnick M.B., Giri D., DeLellis R.A., Steinhoff M.M., Sabo E. Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin. Cancer Res. 2006;12:6359–6366. doi: 10.1158/1078-0432.CCR-06-0860. PubMed DOI

Hazell G.G., Yao S.T., Roper J.A., Prossnitz E.R., O’Carroll A.M., Lolait S.J. Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues. J. Endocrinol. 2009;202:223–236. doi: 10.1677/JOE-09-0066. PubMed DOI PMC

Plante B.J., Lessey B.A., Taylor R.N., Wang W., Bagchi M.K., Yuan L., Scotchie J., Fritz M.A., Young S.L. G protein-coupled estrogen receptor (GPER) expression in normal and abnormal endometrium. Reprod. Sci. 2012;19:684–693. doi: 10.1177/1933719111431000. PubMed DOI PMC

Wang C., Prossnitz E.R., Roy S.K. Expression of g protein-coupled receptor 30 in the hamster ovary: Differential regulation by gonadotropins and steroid hormones. Endocrinology. 2007;148:4853–4864. doi: 10.1210/en.2007-0727. PubMed DOI

Fietz D., Ratzenbock C., Hartmann K., Raabe O., Kliesch S., Weidner W., Klug J., Bergmann M. Expression pattern of estrogen receptors α and β and g-protein-coupled estrogen receptor 1 in the human testis. Histochem. Cell Biol. 2014;142:421–432. doi: 10.1007/s00418-014-1216-z. PubMed DOI

Oliveira P.F., Alves M.G., Martins A.D., Correia S., Bernardino R.L., Silva J., Barros A., Sousa M., Cavaco J.E., Socorro S. Expression pattern of G protein-coupled receptor 30 in human seminiferous tubular cells. Gen. Comp. Endocrinol. 2014;201:16–20. doi: 10.1016/j.ygcen.2014.02.022. PubMed DOI

Rago V., Romeo F., Giordano F., Maggiolini M., Carpino A. Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes. Reprod. Biol. Endocrinol. 2011;9:135. doi: 10.1186/1477-7827-9-135. PubMed DOI PMC

Hewitt S.C., Deroo B.J., Korach K.S. Signal transduction. A new mediator for an old hormone? Science. 2005;307:1572–1573. doi: 10.1126/science.1110345. PubMed DOI

Sirianni R., Chimento A., Ruggiero C., De Luca A., Lappano R., Ando S., Maggiolini M., Pezzi V. The novel estrogen receptor, G protein-coupled receptor 30, mediates the proliferative effects induced by 17β-estradiol on mouse spermatogonial GC-1 cell line. Endocrinology. 2008;149:5043–5051. doi: 10.1210/en.2007-1593. PubMed DOI

Prossnitz E.R., Arterburn J.B., Smith H.O., Oprea T.I., Sklar L.A., Hathaway H.J. Estrogen signaling through the transmembrane g protein-coupled receptor GPR30. Annu. Rev. Physiol. 2008;70:165–190. doi: 10.1146/annurev.physiol.70.113006.100518. PubMed DOI

Toran-Allerand C.D., Guan X., MacLusky N.J., Horvath T.L., Diano S., Singh M., Connolly E.S.J., Nethrapalli I.S., Tinnikov A.A. Er-x: A novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. J. Neurosci. 2002;22:8391–8401. PubMed PMC

Kampa M., Notas G., Pelekanou V., Troullinaki M., Andrianaki M., Azariadis K., Kampouri E., Lavrentaki K., Castanas E. Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERX) Steroids. 2012;77:959–967. doi: 10.1016/j.steroids.2012.02.011. PubMed DOI

Qiu J., Bosch M.A., Tobias S.C., Grandy D.K., Scanlan T.S., Ronnekleiv O.K., Kelly M.J. Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase c. J. Neurosci. 2003;23:9529–9540. PubMed PMC

Micevych P.E., Dewing P. Membrane-initiated estradiol signaling regulating sexual receptivity. Front. Endocrinol. 2011;2:26. doi: 10.3389/fendo.2011.00026. PubMed DOI PMC

Banerjee S., Chambliss K.L., Mineo C., Shaul P.W. Recent insights into non-nuclear actions of estrogen receptor α. Steroids. 2014;81:64–69. doi: 10.1016/j.steroids.2013.11.002. PubMed DOI

Marino M., Galluzzo P., Ascenzi P. Estrogen signaling multiple pathways to impact gene transcription. Curr. Genom. 2006;7:497–508. doi: 10.2174/138920206779315737. PubMed DOI PMC

Lucas T.F., Siu E.R., Esteves C.A., Monteiro H.P., Oliveira C.A., Porto C.S., Lazari M.F. 17β-estradiol induces the translocation of the estrogen receptors ESR1 and ESR2 to the cell membrane, MAPK3/1 phosphorylation and proliferation of cultured immature rat sertoli cells. Biol. Reprod. 2008;78:101–114. doi: 10.1095/biolreprod.107.063909. PubMed DOI

Cowley S.M., Hoare S., Mosselman S., Parker M.G. Estrogen receptors α and β form heterodimers on DNA. J. Biol. Chem. 1997;272:19858–19862. doi: 10.1074/jbc.272.32.19858. PubMed DOI

Hammes S.R., Levin E.R. Extranuclear steroid receptors: Nature and actions. Endocr. Rev. 2007;28:726–741. doi: 10.1210/er.2007-0022. PubMed DOI

Ho K.J., Liao J.K. Nonnuclear actions of estrogen. Arterioscler. Thromb. Vasc. Biol. 2002;22:1952–1961. doi: 10.1161/01.ATV.0000041200.85946.4A. PubMed DOI

Kelly M.J., Levin E.R. Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol. Metab. 2001;12:152–156. doi: 10.1016/S1043-2760(01)00377-0. PubMed DOI

Acconcia F., Ascenzi P., Bocedi A., Spisni E., Tomasi V., Trentalance A., Visca P., Marino M. Palmitoylation-dependent estrogen receptor α membrane localization: Regulation by 17β-estradiol. Mol. Biol. Cell. 2005;16:231–237. doi: 10.1091/mbc.E04-07-0547. PubMed DOI PMC

Li L., Haynes M.P., Bender J.R. Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells. Proc. Natl. Acad. Sci. USA. 2003;100:4807–4812. doi: 10.1073/pnas.0831079100. PubMed DOI PMC

Marquez D.C., Chen H.W., Curran E.M., Welshons W.V., Pietras R.J. Estrogen receptors in membrane lipid rafts and signal transduction in breast cancer. Mol. Cell. Endocrinol. 2006;246:91–100. doi: 10.1016/j.mce.2005.11.020. PubMed DOI

Norfleet A.M., Thomas M.L., Gametchu B., Watson C.S. Estrogen receptor-α detected on the plasma membrane of aldehyde-fixed GH3/B6/F10 rat pituitary tumor cells by enzyme-linked immunocytochemistry. Endocrinology. 1999;140:3805–3814. PubMed

Pappas T.C., Gametchu B., Watson C.S. Membrane estrogen receptors identified by multiple antibody labeling and impeded-ligand binding. FASEB J. 1995;9:404–410. PubMed

Pedram A., Razandi M., Levin E.R. Nature of functional estrogen receptors at the plasma membrane. Mol. Endocrinol. 2006;20:1996–2009. doi: 10.1210/me.2005-0525. PubMed DOI

Razandi M., Alton G., Pedram A., Ghonshani S., Webb P., Levin E.R. Identification of a structural determinant necessary for the localization and function of estrogen receptor α at the plasma membrane. Mol. Cell. Biol. 2003;23:1633–1646. doi: 10.1128/MCB.23.5.1633-1646.2003. PubMed DOI PMC

Razandi M., Pedram A., Greene G.L., Levin E.R. Cell membrane and nuclear estrogen receptors (ERS) originate from a single transcript: Studies of ERα and ERβ expressed in chinese hamster ovary cells. Mol. Endocrinol. 1999;13:307–319. doi: 10.1210/mend.13.2.0239. PubMed DOI

Razandi M., Pedram A., Merchenthaler I., Greene G.L., Levin E.R. Plasma membrane estrogen receptors exist and functions as dimers. Mol. Endocrinol. 2004;18:2854–2865. doi: 10.1210/me.2004-0115. PubMed DOI

Pedram A., Razandi M., Sainson R.C., Kim J.K., Hughes C.C., Levin E.R. A conserved mechanism for steroid receptor translocation to the plasma membrane. J. Biol. Chem. 2007;282:22278–22288. doi: 10.1074/jbc.M611877200. PubMed DOI

Acconcia F., Ascenzi P., Fabozzi G., Visca P., Marino M. S-palmitoylation modulates human estrogen receptor-α functions. Biochem. Biophys. Res. Commun. 2004;316:878–883. doi: 10.1016/j.bbrc.2004.02.129. PubMed DOI

Galluzzo P., Caiazza F., Moreno S., Marino M. Role of ERβ palmitoylation in the inhibition of human colon cancer cell proliferation. Endocr. Cancer. 2007;14:153–167. doi: 10.1677/ERC-06-0020. PubMed DOI

Wang Z., Zhang X., Shen P., Loggie B.W., Chang Y., Deuel T.F. Identification, cloning, and expression of human estrogen receptor-α36, a novel variant of human estrogen receptor-α66. Biochem. Biophys. Res. Commun. 2005;336:1023–1027. doi: 10.1016/j.bbrc.2005.08.226. PubMed DOI

Wang C., Liu Y., Cao J.M. G protein-coupled receptors: Extranuclear mediators for the non-genomic actions of steroids. Int. J. Mol. Sci. 2014;15:15412–15425. doi: 10.3390/ijms150915412. PubMed DOI PMC

Cavaco J.E., Laurentino S.S., Barros A., Sousa M., Socorro S. Estrogen receptors α and β in human testis: Both isoforms are expressed. Syst. Biol. Reprod. Med. 2009;55:137–144. doi: 10.3109/19396360902855733. PubMed DOI

Enmark E., Pelto-Huikko M., Grandien K., Lagercrantz S., Lagercrantz J., Fried G., Nordenskjold M., Gustafsson J.A. Human estrogen receptor β-gene structure, chromosomal localization, and expression pattern. J.Clin. Endocrinol. Metab. 1997;82:4258–4265. doi: 10.1210/jc.82.12.4258. PubMed DOI

Fisher J.S., Millar M.R., Majdic G., Saunders P.T., Fraser H.M., Sharpe R.M. Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood. J. Endocrinol. 1997;153:485–495. doi: 10.1677/joe.0.1530485. PubMed DOI

Gunawan A., Cinar M.U., Uddin M.J., Kaewmala K., Tesfaye D., Phatsara C., Tholen E., Looft C., Schellander K. Investigation on association and expression of ESR2 as a candidate gene for boar sperm quality and fertility. Reprod. Domest. Anim. 2012;47:782–790. doi: 10.1111/j.1439-0531.2011.01968.x. PubMed DOI

Gunawan A., Kaewmala K., Uddin M.J., Cinar M.U., Tesfaye D., Phatsara C., Tholen E., Looft C., Schellander K. Association study and expression analysis of porcine ESR1 as a candidate gene for boar fertility and sperm quality. Anim. Reprod. Sci. 2011;128:11–21. doi: 10.1016/j.anireprosci.2011.08.008. PubMed DOI

Han Y., Feng H.L., Sandlow J.I., Haines C.J. Comparing expression of progesterone and estrogen receptors in testicular tissue from men with obstructive and nonobstructive azoospermia. J. Androl. 2009;30:127–133. doi: 10.2164/jandrol.108.005157. PubMed DOI

Lekhkota O., Brehm R., Claus R., Wagner A., Bohle R.M., Bergmann M. Cellular localization of estrogen receptor-α (ERα) and -β (ERβ) mRNA in the boar testis. Histochem. Cell Biol. 2006;125:259–264. doi: 10.1007/s00418-005-0008-x. PubMed DOI

Makinen S., Makela S., Weihua Z., Warner M., Rosenlund B., Salmi S., Hovatta O., Gustafsson J.A. Localization of oestrogen receptors α and β in human testis. Mol. Hum. Reprod. 2001;7:497–503. doi: 10.1093/molehr/7.6.497. PubMed DOI

Mutembei H.M., Pesch S., Schuler G., Hoffmann B. Expression of oestrogen receptors α and β and of aromatase in the testis of immature and mature boars. Reprod. Domest. Anim. 2005;40:228–236. doi: 10.1111/j.1439-0531.2005.00586.x. PubMed DOI

Otto C., Fuchs I., Kauselmann G., Kern H., Zevnik B., Andreasen P., Schwarz G., Altmann H., Klewer M., Schoor M., et al. Gpr30 does not mediate estrogenic responses in reproductive organs in mice. Biol. Reprod. 2009;80:34–41. doi: 10.1095/biolreprod.108.071175. PubMed DOI

Pelletier G., El-Alfy M. Immunocytochemical localization of estrogen receptors α and β in the human reproductive organs. J. Clin. Endocrinol. Metab. 2000;85:4835–4840. PubMed

Pelletier G., Labrie C., Labrie F. Localization of oestrogen receptor α, oestrogen receptor β and androgen receptors in the rat reproductive organs. J. Endocrinol. 2000;165:359–370. doi: 10.1677/joe.0.1650359. PubMed DOI

Pentikainen V., Erkkila K., Suomalainen L., Parvinen M., Dunkel L. Estradiol acts as a germ cell survival factor in the human testis in vitro. J. Clin. Endocrinol. Metab. 2000;85:2057–2067. doi: 10.1210/jc.85.5.2057. PubMed DOI

Saunders P.T., Fisher J.S., Sharpe R.M., Millar M.R. Expression of oestrogen receptor β (ERβ) occurs in multiple cell types, including some germ cells, in the rat testis. J. Endocrinol. 1998;156:R13–R17. doi: 10.1677/joe.0.156R013. PubMed DOI

Saunders P.T., Millar M.R., Macpherson S., Irvine D.S., Groome N.P., Evans L.R., Sharpe R.M., Scobie G.A. ERβ1 and the ERβ2 splice variant (ERβcx/β2) are expressed in distinct cell populations in the adult human testis. J. Clin. Endocrinol. Metab. 2002;87:2706–2715. doi: 10.1210/jcem.87.6.8619. PubMed DOI

Saunders P.T., Sharpe R.M., Williams K., Macpherson S., Urquart H., Irvine D.S., Millar M.R. Differential expression of oestrogen receptor α and β proteins in the testes and male reproductive system of human and non-human primates. Mol. Hum. Reprod. 2001;7:227–236. doi: 10.1093/molehr/7.3.227. PubMed DOI

Van Pelt A.M., de Rooij D.G., van der Burg B., van der Saag P.T., Gustafsson J.A., Kuiper G.G. Ontogeny of estrogen receptor-β expression in rat testis. Endocrinology. 1999;140:478–483. doi: 10.1210/en.140.1.478. PubMed DOI

Zhou Q., Nie R., Prins G.S., Saunders P.T., Katzenellenbogen B.S., Hess R.A. Localization of androgen and estrogen receptors in adult male mouse reproductive tract. J. Androl. 2002;23:870–881. PubMed

Snyder M.A., Smejkalova T., Forlano P.M., Woolley C.S. Multiple ERβ antisera label in ERβ knockout and null mouse tissues. J. Neurosci. Methods. 2010;188:226–234. doi: 10.1016/j.jneumeth.2010.02.012. PubMed DOI PMC

Bois C., Delalande C., Nurmio M., Parvinen M., Zanatta L., Toppari J., Carreau S. Age- and cell-related gene expression of aromatase and estrogen receptors in the rat testis. J. Mol. Endocrinol. 2010;45:147–159. doi: 10.1677/JME-10-0041. PubMed DOI

Lucas T.F., Lazari M.F., Porto C.S. Differential role of the estrogen receptors ESR1 and ESR2 on the regulation of proteins involved with proliferation and differentiation of sertoli cells from 15-day-old rats. Mol. Cell. Endocrinol. 2014;382:84–96. doi: 10.1016/j.mce.2013.09.015. PubMed DOI

Chimento A., Sirianni R., Delalande C., Silandre D., Bois C., Ando S., Maggiolini M., Carreau S., Pezzi V. 17 β-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ERα. Mol. Cell. Endocrinol. 2010;320:136–144. doi: 10.1016/j.mce.2010.01.035. PubMed DOI

Chimento A., Sirianni R., Zolea F., Bois C., Delalande C., Ando S., Maggiolini M., Aquila S., Carreau S., Pezzi V. Gper and ESRS are expressed in rat round spermatids and mediate oestrogen-dependent rapid pathways modulating expression of cyclin B1 and Bax. Int. J. Androl. 2011;34:420–429. doi: 10.1111/j.1365-2605.2010.01100.x. PubMed DOI

Lucas T.F., Pimenta M.T., Pisolato R., Lazari M.F., Porto C.S. 17β-estradiol signaling and regulation of sertoli cell function. Spermatogenesis. 2011;1:318–324. doi: 10.4161/spmg.1.4.18903. PubMed DOI PMC

Chimento A., Sirianni R., Casaburi I., Ruggiero C., Maggiolini M., Ando S., Pezzi V. 17β-estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line. Mol. Cell. Endocrinol. 2012;355:49–59. doi: 10.1016/j.mce.2012.01.017. PubMed DOI

Lucas T.F., Royer C., Siu E.R., Lazari M.F., Porto C.S. Expression and signaling of G protein-coupled estrogen receptor 1 (GPER) in rat sertoli cells. Biol. Reprod. 2010;83:307–317. doi: 10.1095/biolreprod.110.084160. PubMed DOI

Royer C., Lucas T.F., Lazari M.F., Porto C.S. 17β-estradiol signaling and regulation of proliferation and apoptosis of rat sertoli cells. Biol. Reprod. 2012;86:108. doi: 10.1095/biolreprod.111.096891. PubMed DOI

Prossnitz E.R., Hathaway H.J. What have we learned about gper function in physiology and disease from knockout mice? J. Steroid Biochem. Mol. Biol. 2015;153:114–126. doi: 10.1016/j.jsbmb.2015.06.014. PubMed DOI PMC

Kumar A., Dumasia K., Deshpande S., Balasinor N.H. Direct regulation of genes involved in sperm release by estrogen and androgen through their receptors and coregulators. J. Steroid Biochem. Mol. Biol. 2017 doi: 10.1016/j.jsbmb.2017.02.017. PubMed DOI

Kumar A., Dumasia K., Gaonkar R., Sonawane S., Kadam L., Balasinor N.H. Estrogen and androgen regulate actin-remodeling and endocytosis-related genes during rat spermiation. Mol. Cell. Endocrinol. 2015;404:91–101. doi: 10.1016/j.mce.2014.12.029. PubMed DOI

Xu J., Qiu Y., DeMayo F.J., Tsai S.Y., Tsai M.J., O’Malley B.W. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science. 1998;279:1922–1925. doi: 10.1126/science.279.5358.1922. PubMed DOI

Gehin M., Mark M., Dennefeld C., Dierich A., Gronemeyer H., Chambon P. The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and P/CIP. Mol. Cell. Biol. 2002;22:5923–5937. doi: 10.1128/MCB.22.16.5923-5937.2002. PubMed DOI PMC

Robyr D., Wolffe A.P., Wahli W. Nuclear hormone receptor coregulators in action: Diversity for shared tasks. Mol. Endocrinol. 2000;14:329–347. doi: 10.1210/mend.14.3.0411. PubMed DOI

Cravatt B.F., Demarest K., Patricelli M.P., Bracey M.H., Giang D.K., Martin B.R., Lichtman A.H. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc. Natl. Acad. Sci. USA. 2001;98:9371–9376. doi: 10.1073/pnas.161191698. PubMed DOI PMC

Grimaldi P., Orlando P., Di Siena S., Lolicato F., Petrosino S., Bisogno T., Geremia R., De Petrocellis L., Di Marzo V. The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis. Proc. Natl. Acad. Sci. USA. 2009;106:11131–11136. doi: 10.1073/pnas.0812789106. PubMed DOI PMC

Maccarrone M., Barboni B., Paradisi A., Bernabo N., Gasperi V., Pistilli M.G., Fezza F., Lucidi P., Mattioli M. Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction. J. Cell Sci. 2005;118:4393–4404. doi: 10.1242/jcs.02536. PubMed DOI

Rossato M., Ion Popa F., Ferigo M., Clari G., Foresta C. Human sperm express cannabinoid receptor CB1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J. Clin. Endocrinol. Metab. 2005;90:984–991. doi: 10.1210/jc.2004-1287. PubMed DOI

Rossi G., Gasperi V., Paro R., Barsacchi D., Cecconi S., Maccarrone M. Follicle-stimulating hormone activates fatty acid amide hydrolase by protein kinase a and aromatase-dependent pathways in mouse primary sertoli cells. Endocrinology. 2007;148:1431–1439. doi: 10.1210/en.2006-0969. PubMed DOI

Grimaldi P., Pucci M., Di Siena S., Di Giacomo D., Pirazzi V., Geremia R., Maccarrone M. The faah gene is the first direct target of estrogen in the testis: Role of histone demethylase LSD1. Cell. Mol. Life Sci. 2012;69:4177–4190. doi: 10.1007/s00018-012-1074-6. PubMed DOI PMC

Hernandez-Perez O., Ballesteros L.M., Rosado A. Binding of 17β-estradiol to the outer surface and nucleus of human spermatozoa. Arch. Androl. 1979;3:23–29. doi: 10.3109/01485017908985044. PubMed DOI

Cheng C.Y., Boettcher B., Rose R.J., Kay D.J., Tinneberg H.R. The binding of sex steroids to human spermatozoa. An autoradiographic study. Int. J. Androl. 1981;4:1–17. doi: 10.1111/j.1365-2605.1981.tb00685.x. PubMed DOI

Cheng C.Y., Boettcher B., Rose R.J. Lack of cytosol and nuclear estrogen receptors in human spermatozoa. Biochem. Biophys. Res. Commun. 1981;100:840–846. doi: 10.1016/S0006-291X(81)80250-1. PubMed DOI

Durkee T.J., Mueller M., Zinaman M. Identification of estrogen receptor protein and messenger ribonucleic acid in human spermatozoa. Am. J. Obstet. Gynecol. 1998;178:1288–1297. doi: 10.1016/S0002-9378(98)70335-7. PubMed DOI

Rago V., Siciliano L., Aquila S., Carpino A. Detection of estrogen receptors ER-α and ER-β in human ejaculated immature spermatozoa with excess residual cytoplasm. Reprod. Biol. Endocrinol. 2006;4:36. doi: 10.1186/1477-7827-4-36. PubMed DOI PMC

Solakidi S., Psarra A.M., Nikolaropoulos S., Sekeris C.E. Estrogen receptors α and β (ERα and ERβ) and androgen receptor (AR) in human sperm: Localization of ERβ and ar in mitochondria of the midpiece. Hum. Reprod. 2005;20:3481–3487. doi: 10.1093/humrep/dei267. PubMed DOI

Denger S., Reid G., Kos M., Flouriot G., Parsch D., Brand H., Korach K.S., Sonntag-Buck V., Gannon F. ERα gene expression in human primary osteoblasts: Evidence for the expression of two receptor proteins. Mol. Endocrinol. 2001;15:2064–2077. doi: 10.1210/mend.15.12.0741. PubMed DOI

Aquila S., Sisci D., Gentile M., Middea E., Catalano S., Carpino A., Rago V., Ando S. Estrogen receptor ERα and ERβ are both expressed in human ejaculated spermatozoa: Evidence of their direct interaction with phosphatidylinositol-3-OH kinase/AKT pathway. J. Clin. Endocrinol. Metab. 2004;89:1443–1451. doi: 10.1210/jc.2003-031681. PubMed DOI

Rago V., Aquila S., Panza R., Carpino A. Cytochrome p450arom, androgen and estrogen receptors in pig sperm. Reprod. Biol. Endocrinol. 2007;5:23. doi: 10.1186/1477-7827-5-23. PubMed DOI PMC

Sebkova N., Cerna M., Ded L., Peknicova J., Dvorakova-Hortova K. The slower the better: How sperm capacitation and acrosome reaction is modified in the presence of estrogens. Reproduction. 2012;143:297–307. doi: 10.1530/REP-11-0326. PubMed DOI

Luconi M., Muratori M., Forti G., Baldi E. Identification and characterization of a novel functional estrogen receptor on human sperm membrane that interferes with progesterone effects. J. Clin. Endocrinol. Metab. 1999;84:1670–1678. doi: 10.1210/jcem.84.5.5670. PubMed DOI

Antal M.C., Krust A., Chambon P., Mark M. Sterility and absence of histopathological defects in nonreproductive organs of a mouse ERβ-null mutant. Proc. Natl. Acad. Sci. USA. 2008;105:2433–2438. doi: 10.1073/pnas.0712029105. PubMed DOI PMC

Dupont S., Krust A., Gansmuller A., Dierich A., Chambon P., Mark M. Effect of single and compound knockouts of estrogen receptors α (ERα) and β (ERβ) on mouse reproductive phenotypes. Development. 2000;127:4277–4291. PubMed

Eddy E.M., Washburn T.F., Bunch D.O., Goulding E.H., Gladen B.C., Lubahn D.B., Korach K.S. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology. 1996;137:4796–4805. PubMed

Krege J.H., Hodgin J.B., Couse J.F., Enmark E., Warner M., Mahler J.F., Sar M., Korach K.S., Gustafsson J.A., Smithies O. Generation and reproductive phenotypes of mice lacking estrogen receptor β. Proc. Natl. Acad. Sci. USA. 1998;95:15677–15682. doi: 10.1073/pnas.95.26.15677. PubMed DOI PMC

Levin E.R. Integration of the extranuclear and nuclear actions of estrogen. Mol. Endocrinol. 2005;19:1951–1959. doi: 10.1210/me.2004-0390. PubMed DOI PMC

Fisher C.R., Graves K.H., Parlow A.F., Simpson E.R. Characterization of mice deficient in aromatase (ARKO) because of targeted disruption of the CYP19 gene. Proc. Natl. Acad. Sci. USA. 1998;95:6965–6970. doi: 10.1073/pnas.95.12.6965. PubMed DOI PMC

Robertson K.M., O’Donnell L., Jones M.E., Meachem S.J., Boon W.C., Fisher C.R., Graves K.H., McLachlan R.I., Simpson E.R. Impairment of spermatogenesis in mice lacking a functional aromatase (CYP 19) gene. Proc. Natl. Acad. Sci. USA. 1999;96:7986–7991. doi: 10.1073/pnas.96.14.7986. PubMed DOI PMC

Dumasia K., Kumar A., Kadam L., Balasinor N.H. Effect of estrogen receptor-subtype-specific ligands on fertility in adult male rats. J. Endocrinol. 2015;225:169–180. doi: 10.1530/JOE-15-0045. PubMed DOI

Honda S., Harada N., Ito S., Takagi Y., Maeda S. Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the Cyp19 gene. Biochem. Biophys. Res. Commun. 1998;252:445–449. doi: 10.1006/bbrc.1998.9672. PubMed DOI

Robertson K.M., Simpson E.R., Lacham-Kaplan O., Jones M.E. Characterization of the fertility of male aromatase knockout mice. J. Androl. 2001;22:825–830. PubMed

Dudek P., Picard D. Genomics of signaling crosstalk of estrogen receptor α in breast cancer cells. PLoS ONE. 2008;3:e1859. doi: 10.1371/journal.pone.0001859. PubMed DOI PMC

Lee K.H., Hess R.A., Bahr J.M., Lubahn D.B., Taylor J., Bunick D. Estrogen receptor α has a functional role in the mouse rete testis and efferent ductules. Biol. Reprod. 2000;63:1873–1880. doi: 10.1095/biolreprod63.6.1873. PubMed DOI

Mahato D., Goulding E.H., Korach K.S., Eddy E.M. Estrogen receptor-α is required by the supporting somatic cells for spermatogenesis. Mol. Cell. Endocrinol. 2001;178:57–63. doi: 10.1016/S0303-7207(01)00410-5. PubMed DOI

Joseph A., Hess R.A., Schaeffer D.J., Ko C., Hudgin-Spivey S., Chambon P., Shur B.D. Absence of estrogen receptor α leads to physiological alterations in the mouse epididymis and consequent defects in sperm function. Biol. Reprod. 2010;82:948–957. doi: 10.1095/biolreprod.109.079889. PubMed DOI PMC

Joseph A., Shur B.D., Ko C., Chambon P., Hess R.A. Epididymal hypo-osmolality induces abnormal sperm morphology and function in the estrogen receptor α knockout mouse. Biol. Reprod. 2010;82:958–967. doi: 10.1095/biolreprod.109.080366. PubMed DOI PMC

Nanjappa M.K., Hess R.A., Medrano T.I., Locker S.H., Levin E.R., Cooke P.S. Membrane-localized estrogen receptor 1 is required for normal male reproductive development and function in mice. Endocrinology. 2016;157:2909–2919. doi: 10.1210/en.2016-1085. PubMed DOI PMC

Sinkevicius K.W., Laine M., Lotan T.L., Woloszyn K., Richburg J.H., Greene G.L. Estrogen-dependent and -independent estrogen receptor-α signaling separately regulate male fertility. Endocrinology. 2009;150:2898–2905. doi: 10.1210/en.2008-1016. PubMed DOI PMC

Shaha C. Estrogens and spermatogenesis. Adv. Exp. Med. Biol. 2008;636:42–64. PubMed

Delbes G., Levacher C., Pairault C., Racine C., Duquenne C., Krust A., Habert R. Estrogen receptor β-mediated inhibition of male germ cell line development in mice by endogenous estrogens during perinatal life. Endocrinology. 2004;145:3395–3403. doi: 10.1210/en.2003-1479. PubMed DOI

Gould M.L., Hurst P.R., Nicholson H.D. The effects of oestrogen receptors α and β on testicular cell number and steroidogenesis in mice. Reproduction. 2007;134:271–279. doi: 10.1530/REP-07-0025. PubMed DOI

Antal M.C., Petit-Demouliere B., Meziane H., Chambon P., Krust A. Estrogen dependent activation function of ERβ is essential for the sexual behavior of mouse females. Proc. Natl. Acad. Sci. USA. 2012;109:19822–19827. doi: 10.1073/pnas.1217668109. PubMed DOI PMC

Maneix L., Antonson P., Humire P., Rochel-Maia S., Castaneda J., Omoto Y., Kim H.J., Warner M., Gustafsson J.A. Estrogen receptor β exon 3-deleted mouse: The importance of non-ere pathways in ERβ signaling. Proc. Natl. Acad. Sci. USA. 2015;112:5135–5140. doi: 10.1073/pnas.1504944112. PubMed DOI PMC

Isensee J., Meoli L., Zazzu V., Nabzdyk C., Witt H., Soewarto D., Effertz K., Fuchs H., Gailus-Durner V., Busch D., et al. Expression pattern of G protein-coupled receptor 30 in lacz reporter mice. Endocrinology. 2009;150:1722–1730. doi: 10.1210/en.2008-1488. PubMed DOI

Balasinor N.H., D'Souza R., Nanaware P., Idicula-Thomas S., Kedia-Mokashi N., He Z., Dym M. Effect of high intratesticular estrogen on global gene expression and testicular cell number in rats. Reprod. Biol. Endocrinol. 2010;8:72. doi: 10.1186/1477-7827-8-72. PubMed DOI PMC

Sharpe R.M., Skakkebaek N.E. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993;341:1392–1395. doi: 10.1016/0140-6736(93)90953-E. PubMed DOI

O’Donnell L., Robertson K.M., Jones M.E., Simpson E.R. Estrogen and spermatogenesis. Endocr. Rev. 2001;22:289–318. doi: 10.1210/edrv.22.3.0431. PubMed DOI

Smith E.P., Boyd J., Frank G.R., Takahashi H., Cohen R.M., Specker B., Williams T.C., Lubahn D.B., Korach K.S. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 1994;331:1056–1061. doi: 10.1056/NEJM199410203311604. PubMed DOI

Carani C., Qin K., Simoni M., Faustini-Fustini M., Serpente S., Boyd J., Korach K.S., Simpson E.R. Effect of testosterone and estradiol in a man with aromatase deficiency. N. Engl. J. Med. 1997;337:91–95. doi: 10.1056/NEJM199707103370204. PubMed DOI

Herrmann B.L., Saller B., Janssen O.E., Gocke P., Bockisch A., Sperling H., Mann K., Broecker M. Impact of estrogen replacement therapy in a male with congenital aromatase deficiency caused by a novel mutation in the Cyp19 gene. J. Clin. Endocrinol. Metab. 2002;87:5476–5484. doi: 10.1210/jc.2002-020498. PubMed DOI

Prossnitz E.R., Barton M. Signaling, physiological functions and clinical relevance of the G protein-coupled estrogen receptor gper. Prostaglandins Lipid Mediat. 2009;89:89–97. doi: 10.1016/j.prostaglandins.2009.05.001. PubMed DOI PMC

Clarke M., Pearl C.A. Alterations in the estrogen environment of the testis contribute to declining sperm production in aging rats. Syst. Biol. Reprod. Med. 2014;60:89–97. doi: 10.3109/19396368.2014.885995. PubMed DOI

Hamden K., Silandre D., Delalande C., Elfeki A., Carreau S. Protective effects of estrogens and caloric restriction during aging on various rat testis parameters. Asian J. Androl. 2008;10:837–845. doi: 10.1111/j.1745-7262.2008.00430.x. PubMed DOI

Chieffi P., Colucci D’Amato L., Guarino F., Salvatore G., Angelini F. 17 β-estradiol induces spermatogonial proliferation through mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) activity in the lizard (podarcis s. Sicula) Mol. Reprod. Dev. 2002;61:218–225. doi: 10.1002/mrd.1151. PubMed DOI

Chieffi P., Colucci-D’Amato G.L., Staibano S., Franco R., Tramontano D. Estradiol-induced mitogen-activated protein kinase (extracellular signal-regulated kinase 1 and 2) activity in the frog (rana esculenta) testis. J. Endocrinol. 2000;167:77–84. doi: 10.1677/joe.0.1670077. PubMed DOI

Dumasia K., Kumar A., Deshpande S., Sonawane S., Balasinor N.H. Differential roles of estrogen receptors, ESR1 and ESR2, in adult rat spermatogenesis. Mol. Cell. Endocrinol. 2016;428:89–100. doi: 10.1016/j.mce.2016.03.024. PubMed DOI

D'Souza R., Pathak S., Upadhyay R., Gaonkar R., D’Souza S., Sonawane S., Gill-Sharma M., Balasinor N.H. Disruption of tubulobulbar complex by high intratesticular estrogens leading to failed spermiation. Endocrinology. 2009;150:1861–1869. doi: 10.1210/en.2008-1232. PubMed DOI

Upadhyay R.D., Kumar A.V., Ganeshan M., Balasinor N.H. Tubulobulbar complex: Cytoskeletal remodeling to release spermatozoa. Reprod. Biol. Endocrinol. 2012;10:27. doi: 10.1186/1477-7827-10-27. PubMed DOI PMC

Yanagimachi R. Mammalian fertilization. In: Knobil E., Neill J.D., editors. The Physiology of Reproduction. Raven Press; New York, NY, USA: 1994. pp. 189–317.

Adeoya-Osiguwa S.A., Markoulaki S., Pocock V., Milligan S.R., Fraser L.R. 17β-estradiol and environmental estrogens significantly affect mammalian sperm function. Hum. Reprod. 2003;18:100–107. doi: 10.1093/humrep/deg037. PubMed DOI

Bathla H., Guraya S.S., Sangha G.K. Role of estradiol in the capacitation and acrosome reaction of hamster epididymal spermatozoa in the isolated uterus of mice incubated in vitro. Indian J. Phys. Pharmacol. 1999;43:211–217. PubMed

Ded L., Dostalova P., Dorosh A., Dvorakova-Hortova K., Peknicova J. Effect of estrogens on boar sperm capacitation in vitro. Reprod. Biol. Endocrinol. 2010;8:87. doi: 10.1186/1477-7827-8-87. PubMed DOI PMC

Fraser L.R., Beyret E., Milligan S.R., Adeoya-Osiguwa S.A. Effects of estrogenic xenobiotics on human and mouse spermatozoa. Hum. Reprod. 2006;21:1184–1193. doi: 10.1093/humrep/dei486. PubMed DOI

He Y.F., Yue L.M., He Y.P., Zhang J.H., Zheng J., Gao X.P. Effects of estrogen on acrosome reaction and intracellular calcium in human spermatozoa and the possible mechanism concerned. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005;36:500–502. PubMed

Luconi M., Bonaccorsi L., Forti G., Baldi E. Effects of estrogenic compounds on human spermatozoa: Evidence for interaction with a nongenomic receptor for estrogen on human sperm membrane. Mol. Cell. Endocrinol. 2001;178:39–45. doi: 10.1016/S0303-7207(01)00416-6. PubMed DOI

Mohamed el S.A., Park Y.J., Song W.H., Shin D.H., You Y.A., Ryu B.Y., Pang M.G. Xenoestrogenic compounds promote capacitation and an acrosome reaction in porcine sperm. Theriogenology. 2011;75:1161–1169. doi: 10.1016/j.theriogenology.2010.11.028. PubMed DOI

Vigil P., Toro A., Godoy A. Physiological action of oestradiol on the acrosome reaction in human spermatozoa. Andrologia. 2008;40:146–151. doi: 10.1111/j.1439-0272.2007.00814.x. PubMed DOI

Ded L., Sebkova N., Cerna M., Elzeinova F., Dostalova P., Peknicova J., Dvorakova-Hortova K. In vivo exposure to 17β-estradiol triggers premature sperm capacitation in cauda epididymis. Reproduction. 2013;145:255–263. doi: 10.1530/REP-12-0472. PubMed DOI

Shanle E.K., Xu W. Endocrine disrupting chemicals targeting estrogen receptor signaling: Identification and mechanisms of action. Chem. Res. Toxicol. 2011;24:6–19. doi: 10.1021/tx100231n. PubMed DOI PMC

Brzozowski A.M., Pike A.C., Dauter Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J.A., Carlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997;389:753–758. doi: 10.1038/39645. PubMed DOI

Pike A.C., Brzozowski A.M., Hubbard R.E., Bonn T., Thorsell A.G., Engstrom O., Ljunggren J., Gustafsson J.A., Carlquist M. Structure of the ligand-binding domain of oestrogen receptor β in the presence of a partial agonist and a full antagonist. EMBO J. 1999;18:4608–4618. doi: 10.1093/emboj/18.17.4608. PubMed DOI PMC

Troisi R., Hatch E.E., Titus-Ernstoff L., Hyer M., Palmer J.R., Robboy S.J., Strohsnitter W.C., Kaufman R., Herbst A.L., Hoover R.N. Cancer risk in women prenatally exposed to diethylstilbestrol. Int. J. Cancer. 2007;121:356–360. doi: 10.1002/ijc.22631. PubMed DOI

Wilcox A.J., Baird D.D., Weinberg C.R., Hornsby P.P., Herbst A.L. Fertility in men exposed prenatally to diethylstilbestrol. N. Engl. J. Med. 1995;332:1411–1416. doi: 10.1056/NEJM199505253322104. PubMed DOI

Newbold R.R. Lessons learned from perinatal exposure to diethylstilbestrol. Toxicol. Appl. Pharmacol. 2004;199:142–150. doi: 10.1016/j.taap.2003.11.033. PubMed DOI

Newbold R.R., Hanson R.B., Jefferson W.N., Bullock B.C., Haseman J., McLachlan J.A. Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol. Carcinogenesis. 2000;21:1355–1363. doi: 10.1093/carcin/21.5.355. PubMed DOI

Filipiak E., Walczak-Jedrzejowska R., Oszukowska E., Guminska A., Marchlewska K., Kula K., Slowikowska-Hilczer J. Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat’s testis. Folia Histochem. Cytobiol. 2009;47:S113–S120. doi: 10.2478/v10042-009-0049-4. PubMed DOI

Gupta C. Reproductive malformation of the male offspring following maternal exposure to estrogenic chemicals. Proc. Soc. Exp. Biol. Med. 2000;224:61–68. doi: 10.1046/j.1525-1373.2000.22402.x. PubMed DOI

Kyselova V., Peknicova J., Boubelik M., Buckiova D. Body and organ weight, sperm acrosomal status and reproduction after genistein and diethylstilbestrol treatment of CD1 mice in a multigenerational study. Theriogenology. 2004;61:1307–1325. doi: 10.1016/j.theriogenology.2003.07.017. PubMed DOI

Li Y., Hamilton K.J., Lai A.Y., Burns K.A., Li L., Wade P.A., Korach K.S. Diethylstilbestrol (DES)-stimulated hormonal toxicity is mediated by ERα alteration of target gene methylation patterns and epigenetic modifiers (DNMT3A, MBD2, AND HDAC2) in the mouse seminal vesicle. Environ. Health Perspect. 2014;122:262–268. doi: 10.1289/ehp.1307351. PubMed DOI PMC

Takemura H., Shim J.Y., Sayama K., Tsubura A., Zhu B.T., Shimoi K. Characterization of the estrogenic activities of zearalenone and zeranol in vivo and in vitro. J. Steroid Biochem. Mol. Biol. 2007;103:170–177. doi: 10.1016/j.jsbmb.2006.08.008. PubMed DOI

Yang J.Y., Wang G.X., Liu J.L., Fan J.J., Cui S. Toxic effects of zearalenone and its derivatives α-zearalenol on male reproductive system in mice. Reprod. Toxicol. 2007;24:381–387. doi: 10.1016/j.reprotox.2007.05.009. PubMed DOI

Zatecka E., Ded L., Elzeinova F., Kubatova A., Dorosh A., Margaryan H., Dostalova P., Korenkova V., Hoskova K., Peknicova J. Effect of zearalenone on reproductive parameters and expression of selected testicular genes in mice. Reprod. Toxicol. 2014;45:20–30. doi: 10.1016/j.reprotox.2014.01.003. PubMed DOI

Adibnia E., Razi M., Malekinejad H. Zearalenone and 17 β-estradiol induced damages in male rats reproduction potential; evidence for ERα and ERβ receptors expression and steroidogenesis. Toxicon. 2016;120:133–146. doi: 10.1016/j.toxicon.2016.08.009. PubMed DOI

17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice

Missing Information from the Estrogen Receptor Puzzle: Where Are They Localized in Bull Reproductive Tissues and Spermatozoa?

New Insight into Sperm Capacitation: A Novel Mechanism of 17β-Estradiol Signalling