Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases

. 2015 Feb 25 ; 13 () : 10. [epub] 20150225

Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu úvodníky, úvodní články

Perzistentní odkaz   https://www.medvik.cz/link/pmid25889983
Odkazy

PubMed 25889983
PubMed Central PMC4414002
DOI 10.1186/s12958-015-0001-8
PII: 10.1186/s12958-015-0001-8
Knihovny.cz E-zdroje

In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

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“IVF - the past, current development and its future” 2014 [www.rbej.com/series/IVF]¬Edited by Antonin Bukovsky.

Salaria N. IVF: Past, current and future developments. http://blogs.biomedcentral.com/on-health/2014/11/24/ivf-past-current-and-future-developments/. 2014.

Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol (Oxf) 2008;68:499–509. doi: 10.1111/j.1365-2265.2007.03073.x. PubMed DOI

Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360:606–14. doi: 10.1056/NEJMcp0808697. PubMed DOI PMC

Ameratunga D, Weston G, Osianlis T, Catt J, Vollenhoven B. In vitro fertilisation (IVF) with donor eggs in post-menopausal women: are there differences in pregnancy outcomes in women with premature ovarian failure (POF) compared with women with physiological age-related menopause? J Assist Reprod Genet. 2009;26:511–4. doi: 10.1007/s10815-009-9351-5. PubMed DOI PMC

Sills ES, Brady AC, Omar AB, Walsh DJ, Salma U, Walsh AP. IVF for premature ovarian failure: first reported births using oocytes donated from a twin sister. Reprod Biol Endocrinol. 2010;8:31. doi: 10.1186/1477-7827-8-31. PubMed DOI PMC

Gleicher N, Kushnir VA, Weghofer A, Barad DH. The “graying” of infertility services: an impending revolution nobody is ready for. Reprod Biol Endocrinol. 2014;12:63. doi: 10.1186/1477-7827-12-63. PubMed DOI PMC

Schatten H, Sun QY, Prather R. The impact of mitochondrial function/dysfunction on IVF and new treatment possibilities for infertility. Reprod Biol Endocrinol. 2014;12:111. doi: 10.1186/1477-7827-12-111. PubMed DOI PMC

Bhartiya D, Hinduja I, Patel H, Bhilawadikar R. Making gametes from pluripotent stem cells - a promising role for very small embryonic-like stem cells. Reprod Biol Endocrinol. 2014;12:114. doi: 10.1186/1477-7827-12-114. PubMed DOI PMC

Bukovsky A, Svetlikova M, Caudle MR. Oogenesis in cultures derived from adult human ovaries. Reprod Biol Endocrinol. 2005;3:17 http://www.rbej.com/content/3/1/17. PubMed PMC

Erickson BH. Development and senescence of the postnatal bovine ovary. J Anim Sci. 1966;25:800–5. PubMed

Block E. Quantitative morphological investigations of the follicular system in women. Variations at different ages. Acta Anat (Basel) 1952;14:108–23. doi: 10.1159/000140595. PubMed DOI

Gougeon A, Echochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early- growing follicles in aging women. Biol Reprod. 1994;50:653–63. doi: 10.1095/biolreprod50.3.653. PubMed DOI

Ingram DL. Atresia. In: Zuckerman S, editor. The Ovary. London: Academic Press; 1962. pp. 247–73.

Bukovsky A, Caudle MR, Keenan JA, Wimalasena J, Upadhyaya NB, Van Meter SE. Is irregular regression of corpora lutea in climacteric women caused by age-induced alterations in the “tissue control system”? Am J Reprod Immunol. 1996;36:327–41. doi: 10.1111/j.1600-0897.1996.tb00183.x. PubMed DOI

Mathe G. Immunity aging. I. The chronic perduration of the thymus acute involution at puberty? Or the participation of the lymphoid organs and cells in fatal physiologic decline? Biomed Pharmacother. 1997;51:49–57. doi: 10.1016/S0753-3322(97)87726-8. PubMed DOI

Bukovsky A. Immune maintenance of self in morphostasis of distinct tissues, tumor growth, and regenerative medicine. Scand J Immunol. 2011;73:159–89. doi: 10.1111/j.1365-3083.2010.02497.x. PubMed DOI

Cameo P, Srisuparp S, Strakova Z, Fazleabas AT. Chorionic gonadotropin and uterine dialogue in the primate. Reprod Biol Endocrinol. 2004;2:50. doi: 10.1186/1477-7827-2-50. PubMed DOI PMC

Schumacher A, Costa SD, Zenclussen AC. Endocrine factors modulating immune responses in pregnancy. Front Immunol. 2014;5:196. doi: 10.3389/fimmu.2014.00196. PubMed DOI PMC

Bukovsky A, Presl J. Ovarian function and the immune system. Med Hypotheses. 1979;5:415–36. doi: 10.1016/0306-9877(79)90108-7. PubMed DOI

Warner J. Dad’s Age Raises Down Syndrome Risk, Too. WebMD. 2003; http://www.webmd.com/infertility-and-reproduction/news/20030701/dad-age-down-syndrome.

Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008;22:908–17. doi: 10.1101/gad.1640708. PubMed DOI PMC

Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB. Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol. 2004;2:20 http://www.rbej.com/content/2/1/20. PubMed PMC

Bukovsky A, Keenan JA, Caudle MR, Wimalasena J, Upadhyaya NB, Van Meter SE. Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis. Am J Reprod Immunol. 1995;33:323–40. doi: 10.1111/j.1600-0897.1995.tb00901.x. PubMed DOI

Bukovsky A, Caudle MR, Svetlikova M, Wimalasena J, Ayala ME, Dominguez R. Oogenesis in adult mammals, including humans: a review. Endocrine. 2005;26:301–16. doi: 10.1385/ENDO:26:3:301. PubMed DOI

Bukovsky A, Caudle MR. Immunoregulation of follicular renewal, selection, POF, and menopause in vivo, vs. neo-oogenesis in vitro, POF and ovarian infertility treatment, and a clinical trial. Reprod Biol Endocrinol. 2012;10:97. doi: 10.1186/1477-7827-10-97. PubMed DOI PMC

Bukovsky A, Caudle MR, Svetlikova M. Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro. Cell Cycle. 2008;7:3577–83. doi: 10.4161/cc.7.22.7101. PubMed DOI

Wartenberg H. Germ cell migration induced and guided by somatic cell interaction. Bibl Anat. 1983;24:67–76. PubMed

Dyce PW, Wen L, Li J. In vitro germline potential of stem cells derived from fetal porcine skin. Nat Cell Biol. 2006;8:384–90. doi: 10.1038/ncb1388. PubMed DOI

Dyce PW. Differentiation of newborn mouse skin derived stem cells into germ-like cells in vitro. J Vis Exp. 2013; doi:10.3791/50486: http://www.ncbi.nlm.nih.gov/pubmed/?term=23892454. PubMed PMC

Bukovsky A, Caudle MR, Gupta SK, Svetlikova M, Selleck-White R, Ayala ME, et al. Mammalian neo-oogenesis and expression of meiosis-specific protein SCP3 in adult human and monkey ovaries. Cell Cycle. 2008;7:683–6. doi: 10.4161/cc.7.5.5453. PubMed DOI

Bukovsky A, Caudle MR, Carson RJ, Gaytan F, Huleihel M, Kruse A, et al. Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine. Aging. 2009;1:157–81. PubMed PMC

Bukovsky A. How can female germline stem cells contribute to the physiological Neo-oogenesis in mammals and why menopause occurs? Microsc Microanal. 2011;17:498–505. doi: 10.1017/S143192761000036X. PubMed DOI

Bukovsky A. Ovarian stem cell niche and follicular renewal in mammals. Anat Rec (Hoboken ) 2011;294:1284–306. doi: 10.1002/ar.21422. PubMed DOI

Bukovsky A, Caudle MR. Mammalian neo-Oogenesis from Ovarian Stem Cells in Vivo and in Vitro. In: Schatten H, editor. Cell and Molecular Biology and Imaging of Stem Cells. Hoboken: Wiley; 2014. pp. 67–136.

Bukovsky A, Caudle MR, Keenan JA, Upadhyaya NB, Van Meter S, Wimalasena J et al. Association of mesenchymal cells and immunoglobulins with differentiating epithelial cells. BMC Dev Biol. 2001;1:11 http://www.biomedcentral.com/1471-213X/1/11. PubMed PMC

Skinner SM, Lee VH, Kieback DG, Jones LA, Kaplan AL, Dunbar BS. Identification of a meiotically expressed carbohydrate antigen in ovarian carcinoma: I. Immunohistochemical localization. Anticancer Res. 1997;17:901–6. PubMed

Cooper GM. Meiosis and Fertilization. In: Geoffrey M Cooper, editor. The Cell: A Molecular Approach. Sunderland (MA): Sinauer Associate; 2000. p. http://www.ncbi.nlm.nih.gov/books/NBK9901/.

Bukovsky A, Ayala ME, Dominguez R, Svetlikova M, Selleck-White R. Bone marrow derived cells and alternative pathways of oogenesis in adult rodents. Cell Cycle. 2007;6:2306–9. doi: 10.4161/cc.6.18.4707. PubMed DOI

Motta PM, Makabe S, Naguro T, Correr S. Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy. Arch Histol Cytol. 1994;57:369–94. doi: 10.1679/aohc.57.369. PubMed DOI

Bukovsky A, Gupta SK, Bansal P, Chakravarthy S, Chaudhary M, Svetlikova M, et al. Production of monoclonal antibodies against recombinant human zona pellucida glycoproteins: utility in immunolocalization of respective zona proteins in ovarian follicles. J Reprod Immunol. 2008;78:102–14. doi: 10.1016/j.jri.2007.10.004. PubMed DOI

Niikura Y, Niikura T, Tilly JL. Aged mouse ovaries possess rare premeiotic germ cells that can generate oocytes following transplantation into a young host environment. Aging (Albany NY) 2009;1:971–8. PubMed PMC

Bukovsky A, Caudle MR. Immunology: Animal Models. In: Ekerdt DJ, editor. Encyclopedia of Aging. New York: Macmillan Reference USA; 2002. pp. 691–5.

Bukovsky A, Virant-Klun I. Adult Stem Cells in the Human Ovary. In: Simon C, Pellicer A, editors. Stem Cells in Reproductive Medicine: Basic Science & Therapeutic Potential. London: Informa Healthcare; 2007. pp. 53–69.

Tachibana M, Sparman M, Sritanaudomchai H, Ma H, Clepper L, Woodward J, et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009;461:367–72. doi: 10.1038/nature08368. PubMed DOI PMC

Tachibana M, Amato P, Sparman M, Woodward J, Sanchis DM, Ma H, et al. Towards germline gene therapy of inherited mitochondrial diseases. Nature. 2013;493:627–31. doi: 10.1038/nature11647. PubMed DOI PMC

Zhang J. Revisiting germinal vesicle transfer as a treatment for aneuploidy in infertile women with diminished ovarian reserve. J Assist Reprod Genet. 2014;31(PMID):25515532. PubMed PMC

Paull D, Emmanuele V, Weiss KA, Treff N, Stewart L, Hua H, et al. Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants. Nature. 2013;493:632–7. doi: 10.1038/nature11800. PubMed DOI PMC

Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. PubMed

Gupta SK. Role of zona pellucida glycoproteins during fertilization in humans. J Reprod Immunol. 2015;108:90–97. doi: 10.1016/j.jri.2014.08.006. PubMed DOI

Yang SH, Son WY, Yoon SH, Ko Y, Lim JH. Correlation between in vitro maturation and expression of LH receptor in cumulus cells of the oocytes collected from PCOS patients in HCG-primed IVM cycles. Hum Reprod. 2005;20:2097–103. doi: 10.1093/humrep/dei045. PubMed DOI

Erickson GF, Wang C, Hsueh AJ. FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium. Nature. 1979;279:336–8. doi: 10.1038/279336a0. PubMed DOI

Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433:760–4. doi: 10.1038/nature03260. PubMed DOI

Katcher HL. Studies that shed new light on aging. Biochemistry (Mosc) 2013;78:1061–70. doi: 10.1134/S0006297913090137. PubMed DOI

Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013;153:828–39. doi: 10.1016/j.cell.2013.04.015. PubMed DOI PMC

Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. 2014;344:630–4. doi: 10.1126/science.1251141. PubMed DOI PMC

Mendelsohn AR, Larrick JW. Systemic factors mediate reversible age-associated brain dysfunction. Rejuvenation Res. 2014;17:525–8. doi: 10.1089/rej.2014.1643. PubMed DOI

Laviano A. Young blood. N Engl J Med. 2014;371:573–5. doi: 10.1056/NEJMcibr1407158. PubMed DOI

Patel VK, Demontis F. GDF11/myostatin and aging. Aging (Albany NY) 2014;6:351–2. PubMed PMC

Demontis F, Patel VK, Swindell WR, Perrimon N. Intertissue control of the nucleolus via a myokine-dependent longevity pathway. Cell Rep. 2014;7:1481–94. doi: 10.1016/j.celrep.2014.05.001. PubMed DOI PMC

Kaiser J. Aging. ‘Rejuvenation factor’ in blood turns back the clock in old mice. Science. 2014;344:570–1. doi: 10.1126/science.344.6184.570. PubMed DOI

Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014;20:659–63. doi: 10.1038/nm.3569. PubMed DOI PMC

Sample I. Infusions of young blood may reverse effects of ageing, studies suggest. The Guardian. 2014; Ageing: http://www.theguardian.com/science/2014/may/04/young-blood-reverse-ageing-mice-studies.

Thompson H. Young blood to be used in ultimate rejuvenation trial. NewScientist. 2014; http://www.newscientist.com/article/mg22329831.400-young-blood-to-be-used-in-ultimate-rejuvenation-trial.html#.VNbJmi7fHwM.

Zimmer C. Young Blood May Hold Key to Reversing Aging. The New York Times. 2014; May 4: http://www.nytimes.com/2014-05/05/science/young-blood-may-hold-key-to-reversing-aging.html.

Fight Aging! Posted by Reason. 2014; https://www.fightaging.org/archives/2014-08/human-trials-of-young-blood-transfused-into-old-individuals.php.

Bukovsky A. The role of resident monocytes and vascular pericytes in the stem cell niche and regenerative medicine. Stem Cell Stud. 2011;1:126–47 http://www.pagepress.org/journals/index.php/scs/article/view/scs.2011.e20/pdf.

Berger TG, Steinhoff M. Pruritus in elderly patients–eruptions of senescence. Semin Cutan Med Surg. 2011;30:113–7. doi: 10.1016/j.sder.2011.04.002. PubMed DOI PMC

Gougeon A. Intragonadal regulation of human follicular genesis: facts and hypotheses. Ann Endocrinol (Paris) 1994;55:63–73. PubMed

Chang EM, Song HS, Lee DR, Lee WS, Yoon TK. In vitro maturation of human oocytes: Its role in infertility treatment and new possibilities. Clin Exp Reprod Med. 2014;41:41–6. doi: 10.5653/cerm.2014.41.2.41. PubMed DOI PMC

Yu W, Zheng H, Lin W, Tajima A, Zhang Y, Zhang X, et al. Estrogen promotes Leydig cell engulfment by macrophages in male infertility. J Clin Invest. 2014;124:2709–21. doi: 10.1172/JCI59901. PubMed DOI PMC

Gaytan F, Bellido C, Morales C, Reymundo C, Aguilar E, Van Rooijen N. Effects of macrophage depletion at different times after treatment with ethylene dimethane sulfonate (EDS) on the regeneration of Leydig cells in the adult rat. J Androl. 1994;15:558–64. PubMed

Seta N, Kuwana M. Derivation of multipotent progenitors from human circulating CD14+ monocytes. Exp Hematol. 2010;38:557–63. doi: 10.1016/j.exphem.2010.03.015. PubMed DOI

Turek PJ. Sperm production. The Turek Clinic. 2015; http://theturekclinic.com/services/male-fertility-infertility-doctor-treatments-issues-zero-sperm-count-male-doctors/spermatogenesis-production/.

Kubota Y, Umegaki K, Kobayashi K, Tanaka N, Kagota S, Nakamura K, et al. Anti-hypertensive effects of Brazilian propolis in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 2004;31(Suppl 2):S29–30. doi: 10.1111/j.1440-1681.2004.04113.x. PubMed DOI

Kitamura H, Naoe Y, Kimura S, Miyamoto T, Okamoto S, Toda C, et al. Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice: Possible involvement of immune cells in mesenteric adipose tissue. Adipocyte. 2013;2:227–36. doi: 10.4161/adip.25608. PubMed DOI PMC

Tao Y, Wang D, Hu Y, Huang Y, Yu Y, Wang D. The immunological enhancement activity of propolis flavonoids liposome in vitro and in vivo. Evid Based Complement Alternat Med. 2014;2014:483513. PubMed PMC

Fan Y, Ma L, Zhang W, Wang J, Chen Y, Gao Y, et al. The design of propolis flavone microemulsion and its effect on enhancing the immunity and antioxidant activity in mice. Int J Biol Macromol. 2014;65:200–7. doi: 10.1016/j.ijbiomac.2014.01.041. PubMed DOI

Missima F, Sforcin JM. Green brazilian propolis action on macrophages and lymphoid organs of chronically stressed mice. Evid Based Complement Alternat Med. 2008;5:71–5. doi: 10.1093/ecam/nel112. PubMed DOI PMC

Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol. 2007;113:1–14. doi: 10.1016/j.jep.2007.05.012. PubMed DOI

Pagliarone AC, Orsatti CL, Bufalo MC, Missima F, Bachiega TF, Junior JP, et al. Propolis effects on pro-inflammatory cytokine production and Toll-like receptor 2 and 4 expression in stressed mice. Int Immunopharmacol. 2009;9:1352–6. doi: 10.1016/j.intimp.2009.08.005. PubMed DOI

Gui J, Mustachio LM, Su DM, Craig RW. Thymus size and age-related thymic involution: early programming, sexual dimorphism, progenitors and stroma. Aging Dis. 2012;3:280–90. PubMed PMC

Rifa’i M, Widodo N. Significance of propolis administration for homeostasis of CD4(+)CD25(+) immunoregulatory T cells controlling hyperglycemia. Springerplus. 2014;3:526. doi: 10.1186/2193-1801-3-526. PubMed DOI PMC

Aral CA, Kesim S, Greenwell H, Kara M, Cetin A, Yakan B. Alveolar bone protective and hypoglycemic effects of systemic propolis treatment in experimental periodontitis and diabetes mellitus. J Med Food. 2015;18:195–201. doi: 10.1089/jmf.2013.3137. PubMed DOI PMC

El-Sharkawy EE, Kames AO, Sayed SM, Nisr NA, Wahba NM, Elsherif WM, et al. The ameliorative effect of propolis against methoxychlor induced ovarian toxicity in rat. Exp Toxicol Pathol. 2014;66:415–21. doi: 10.1016/j.etp.2014.06.003. PubMed DOI

Russo A, Troncoso N, Sanchez F, Garbarino JA, Vanella A. Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and exogenous reactive oxygen species. Life Sci. 2006;78:1401–6. doi: 10.1016/j.lfs.2004.10.085. PubMed DOI

Yousef MI, Kamel KI, Hassan MS, El-Morsy AM. Protective role of propolis against reproductive toxicity of triphenyltin in male rabbits. Food Chem Toxicol. 2010;48:1846–52. doi: 10.1016/j.fct.2010.04.018. PubMed DOI

Capucho C, Sette R, De Souza PF, De Castro MJ, Pigoso AA, Barbieri R, et al. Green Brazilian propolis effects on sperm count and epididymis morphology and oxidative stress. Food Chem Toxicol. 2012;50:3956–62. doi: 10.1016/j.fct.2012.08.027. PubMed DOI

Collodel G, Moretti E, Del Vecchio MT, Biagi M, Cardinali R, Mazzi L, et al. Effect of chocolate and Propolfenol on rabbit spermatogenesis and sperm quality following bacterial lipopolysaccharide treatment. Syst Biol Reprod Med. 2014;60:217–26. doi: 10.3109/19396368.2014.911392. PubMed DOI

Cedikova M, Miklikova M, Stachova L, Grundmanova M, Tuma Z, Vetvicka V, et al. Effects of the czech propolis on sperm mitochondrial function. Evid Based Complement Alternat Med. 2014;2014:248768. doi: 10.1155/2014/248768. PubMed DOI PMC

Rizk SM, Zaki HF, Mina MA. Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food Chem Toxicol. 2014;67:176–86. doi: 10.1016/j.fct.2014.02.031. PubMed DOI

Wikipedia. Three-parent baby. Wikipedia,The Free Encyclopedia. 2014; http://en.wikipedia.org/wiki/Three-parent_baby.

Atkinson HG, Apperley JF, Dawson K, Goldman JM, Winston RM. Successful pregnancy after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Lancet. 1994;344:199. doi: 10.1016/S0140-6736(94)92804-5. PubMed DOI

Bukovsky A, Michael SD, Presl J. Cell-mediated and neural control of morphostasis. Med Hypotheses. 1991;36:261–8. doi: 10.1016/0306-9877(91)90146-P. PubMed DOI

Gougeon A. Is neo-oogenesis in the adult ovary, a realistic paradigm? Gynecol Obstet Fertil. 2010;38:398–401. doi: 10.1016/j.gyobfe.2010.04.013. PubMed DOI

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