An Evolutionary Perspective on Adult Female Germline Stem Cell Function from Flies to Humans

 

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Abstract

The concept that oogenesis continues into reproductive life has been well established in nonmammalian species. Recent studies of mice and women indicate that oocyte formation is also not, as traditionally believed, restricted to the fetal or perinatal periods. Analogous to de novo oocyte formation in flies and fish, newly formed oocytes in adult mammalian ovaries arise from germline stem cells (GSCs) or, more specifically, oogonial stem cells (OSCs). Studies of mice have confirmed that isolated OSCs, once delivered back into adult ovaries, are capable of generating fully functional eggs that fertilize to produce healthy embryos and offspring. Parallel studies of OSCs recently purified from ovaries of reproductive-age women indicate that these cells closely resemble their mouse ovary–derived counterparts, although the fertilization competency of oocytes generated by human OSCs awaits clarification. Despite the ability of OSCs to produce new oocytes during adulthood, oogenesis will still ultimately cease with age, contributing to ovarian failure. The causal mechanisms behind these events in mammals are unknown, but studies of flies have revealed that GSC niche dysfunction plays a critical role in age-related oogenic failure. Such insights derived from evaluation of nonmammalian species, in which postnatal oogenesis has been studied in depth, may aid in development of new strategies to alleviate ovarian failure and infertility in mammals.

• References

• 1 Kirilly D, Xie T. The Drosophila ovary: an active stem cell community. Cell Res 2007; 17 (1) 15-25
  CrossrefPubMedGoogle Scholar
• 2 Zhao R, Xuan Y, Li X, Xi R. Age-related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila . Aging Cell 2008; 7 (3) 344-354
  CrossrefPubMedGoogle Scholar
• 3 Nakamura S, Kobayashi K, Nishimura T, Higashijima S, Tanaka M. Identification of germline stem cells in the ovary of the teleost medaka. Science 2010; 328 (5985) 1561-1563
  CrossrefPubMedGoogle Scholar
• 4 Nakamura S, Kobayashi K, Nishimura T, Tanaka M. Ovarian germline stem cells in the teleost fish, medaka (Oryzias latipes). Int J Biol Sci 2011; 7 (4) 403-409
  PubMedGoogle Scholar
• 5 Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004; 428 (6979) 145-150
  CrossrefPubMedGoogle Scholar
• 6 Johnson J, Bagley J, Skaznik-Wikiel M , et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 2005; 122 (2) 303-315
  CrossrefPubMedGoogle Scholar
• 7 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 Online) 2009; 1 (12) 971-978
  PubMedGoogle Scholar
• 8 Zou K, Yuan Z, Yang Z , et al. Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol 2009; 11 (5) 631-636
  CrossrefPubMedGoogle Scholar
• 9 Wang N, Tilly JL. Epigenetic status determines germ cell meiotic commitment in embryonic and postnatal mammalian gonads. Cell Cycle 2010; 9 (2) 339-349
  CrossrefPubMedGoogle Scholar
• 10 Pacchiarotti J, Maki C, Ramos T , et al. Differentiation potential of germ line stem cells derived from the postnatal mouse ovary. Differentiation 2010; 79 (3) 159-170
  CrossrefPubMedGoogle Scholar
• 11 White YAR, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 2012; 18 (3) 413-421
  CrossrefPubMedGoogle Scholar
• 12 Zuckerman S. The number of oocytes in the mature ovary. Recent Prog Horm Res 1951; 6: 63-108
  PubMedGoogle Scholar
• 13 Packer C, Tatar M, Collins A. Reproductive cessation in female mammals. Nature 1998; 392 (6678) 807-811
  CrossrefPubMedGoogle Scholar
• 14 Schulze C. Morphological characteristics of the spermatogonial stem cells in man. Cell Tissue Res 1979; 198 (2) 191-199
  PubMedGoogle Scholar
• 15 Lin H. The stem-cell niche theory: lessons from flies. Nat Rev Genet 2002; 3 (12) 931-940
  CrossrefPubMedGoogle Scholar
• 16 Brinster RL. Male germline stem cells: from mice to men. Science 2007; 316 (5823) 404-405
  CrossrefPubMedGoogle Scholar
• 17 de Cuevas M, Matunis EL. The stem cell niche: lessons from the Drosophila testis. Development 2011; 138 (14) 2861-2869
  CrossrefPubMedGoogle Scholar
• 18 Tilly JL, Niikura Y, Rueda BR. The current status of evidence for and against postnatal oogenesis in mammals: a case of ovarian optimism versus pessimism?. Biol Reprod 2009; 80 (1) 2-12
  CrossrefPubMedGoogle Scholar
• 19 Woods DC, Tilly JL. The next (re)generation of human ovarian biology and female fertility: is current science tomorrow's practice?. Fertil Steril 2012; 98 (1) 3-10
  CrossrefPubMedGoogle Scholar
• 20 Tworzydlo W, Kloc M, Bilinski SM. Female germline stem cell niches of earwigs are structurally simple and different from those of Drosophila melanogaster. J Morphol 2010; 271 (5) 634-640
  PubMedGoogle Scholar
• 21 Wong MD, Jin Z, Xie T. Molecular mechanisms of germline stem cell regulation. Annu Rev Genet 2005; 39: 173-195
  CrossrefPubMedGoogle Scholar
• 22 Waskar M, Li Y, Tower J. Stem cell aging in the Drosophila ovary. AGE 2005; 27: 201-212
  CrossrefPubMedGoogle Scholar
• 23 Pan L, Chen S, Weng C , et al. Stem cell aging is controlled both intrinsically and extrinsically in the Drosophila ovary. Cell Stem Cell 2007; 1: 470-478
  CrossrefPubMedGoogle Scholar
• 24 Nystul T, Spradling A. Regulation of epithelial stem cell replacement and follicle formation in the Drosophila ovary. Genetics 2010; 184 (2) 503-515
  CrossrefPubMedGoogle Scholar
• 25 Song X, Zhu CH, Doan C, Xie T. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches. Science 2002; 296 (5574) 1855-1857
  CrossrefPubMedGoogle Scholar
• 26 Spradling AC. Germline cysts: communes that work. Cell 1993; 72 (5) 649-651
  CrossrefPubMedGoogle Scholar
• 27 Lin H, Yue L, Spradling AC. The Drosophila fusome, a germline-specific organelle, contains membrane skeletal proteins and functions in cyst formation. Development 1994; 120 (4) 947-956
  PubMedGoogle Scholar
• 28 de Cuevas M, Lee JK, Spradling AC. α-spectrin is required for germline cell division and differentiation in the Drosophila ovary. Development 1996; 122 (12) 3959-3968
  PubMedGoogle Scholar
• 29 Lin H, Spradling AC. Fusome asymmetry and oocyte determination in Drosophila . Dev Genet 1995; 16 (1) 6-12
  CrossrefPubMedGoogle Scholar
• 30 David J, Cohet Y, Foluillet P. The variability between individuals as a measure of senescence: a study of the number of eggs laid and the percentage of hatched eggs in the case of Drosophila melanogaster . Exp Gerontol 1975; 10 (1) 17-25
  CrossrefPubMedGoogle Scholar
• 31 Xie T, Spradling AC. A niche maintaining germ line stem cells in the Drosophila ovary. Science 2000; 290 (5490) 328-330
  CrossrefPubMedGoogle Scholar
• 32 Song X, Call GB, Kirilly D, Xie T. Notch signaling controls germline stem cell niche formation in the Drosophila ovary. Development 2007; 134 (6) 1071-1080
  CrossrefPubMedGoogle Scholar
• 33 Dejima K, Kanai MI, Akiyama T, Levings DC, Nakato H. Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans. J Biol Chem 2011; 286 (19) 17103-17111
  CrossrefPubMedGoogle Scholar
• 34 Hayashi Y, Kobayashi S, Nakato H. Drosophila glypicans regulate the germline stem cell niche. J Cell Biol 2009; 187 (4) 473-480
  CrossrefPubMedGoogle Scholar
• 35 Wallace RA, Selman K. Ultrastructural aspects of oogenesis and oocyte growth in fish and amphibians. J Electron Microsc Tech 1990; 16 (3) 175-201
  CrossrefPubMedGoogle Scholar
• 36 Selman K, Wallace R, Sarka A, Qi X. Stages of oocyte development in the zebrafish, Brachydanio rerio . J Morphol 1993; 218: 203-224
  CrossrefPubMedGoogle Scholar
• 37 Grier H. Ovarian germinal epithelium and folliculogenesis in the common snook, Centropomus undecimalis (Teleostei: centropomidae). J Morphol 2000; 243 (3) 265-281
  CrossrefPubMedGoogle Scholar
• 38 Lo Nostro F, Grier H, Andreone L, Guerrero GA. Involvement of the gonadal germinal epithelium during sex reversal and seasonal testicular cycling in the protogynous swamp eel, Synbranchus marmoratus Bloch 1795 (Teleostei, Synbranchidae). J Morphol 2003; 257 (1) 107-126
  CrossrefPubMedGoogle Scholar
• 39 Abascal FJ, Medina A. Ultrastructure of oogenesis in the bluefin tuna, Thunnus thynnus . J Morphol 2005; 264 (2) 149-160
  CrossrefPubMedGoogle Scholar
• 40 Draper BW, McCallum CM, Moens CB. nanos1 is required to maintain oocyte production in adult zebrafish. Dev Biol 2007; 305 (2) 589-598
  CrossrefPubMedGoogle Scholar
• 41 Grier HJ, Uribe MC, Parenti LR. Germinal epithelium, folliculogenesis, and postovulatory follicles in ovaries of rainbow trout, Oncorhynchus mykiss (Walbaum, 1792) (Teleostei, protacanthopterygii, salmoniformes). J Morphol 2007; 268 (4) 293-310
  CrossrefPubMedGoogle Scholar
• 42 Leu DH, Draper BW. The ziwi promoter drives germline-specific gene expression in zebrafish. Dev Dyn 2010; 239 (10) 2714-2721
  CrossrefPubMedGoogle Scholar
• 43 Yoshizaki G, Ichikawa M, Hayashi M , et al. Sexual plasticity of ovarian germ cells in rainbow trout. Development 2010; 137 (8) 1227-1230
  CrossrefPubMedGoogle Scholar
• 44 Underwood JL, Hestand III RS, Thompson BZ. Gonad regeneration in grass carp following bilateral gonadectomy. Prog Fish-Cult 1986; 48: 54-56
  PubMedGoogle Scholar
• 45 Kersten CA, Krisfalusi M, Parsons JE, Cloud JG. Gonadal regeneration in masculinized female or steroid-treated rainbow trout (Oncorhynchus mykiss). J Exp Zool 2001; 290 (4) 396-401
  CrossrefPubMedGoogle Scholar
• 46 White YAR, Woods DC, Wood AW. A transgenic zebrafish model of targeted oocyte ablation and de novo oogenesis. Dev Dyn 2011; 240 (8) 1929-1937
  CrossrefPubMedGoogle Scholar
• 47 Everett NB. The present status of the germ-cell problem in vertebrates. Biol Rev Camb Philos Soc 1945; 20: 40-45
  PubMedGoogle Scholar
• 48 Pearl R, Schoppe WF. Studies on the physiology of reproduction in the domestic fowl. J Exp Zool 1921; 34: 101-118
  PubMedGoogle Scholar
• 49 Zuckerman S. Beyond the Ivory Tower. The Frontiers of Public and Private Science. New York, NY: Taplinger; 1971: 22-34
  Google Scholar
• 50 Arai H. On the postnatal development of the ovary (albino rat), with especial reference to the number of ova. Am J Anat 1920; 27: 405-462
  CrossrefPubMedGoogle Scholar
• 51 Allen E. Ovogenesis during sexual maturity. Am J Anat 1923; 31: 439-470
  CrossrefPubMedGoogle Scholar
• 52 Davenport CB. Regeneration of ovaries in mice. J Exp Zool 1925; 42: 1-12
  CrossrefPubMedGoogle Scholar
• 53 Butcher EO. The origin of definitive ova in the white rat (Mus norvegicus albinus). Anat Rec 1927; 37: 13-29
  CrossrefPubMedGoogle Scholar
• 54 Parkes AS, Fielding U, Brambell WR. Ovarian regeneration in the mouse after complete double ovariectomy. Proc R Soc Lond Biol Sci 1927; 101: 328-354
  CrossrefPubMedGoogle Scholar
• 55 Pansky B, Mossman HW. The regenerative capacity of the rabbit ovary. Anat Rec 1953; 116 (1) 19-51
  CrossrefPubMedGoogle Scholar
• 56 Vermande-Van Eck GJ. Neo-ovogenesis in the adult monkey; consequences of atresia of ovocytes. Anat Rec 1956; 125 (2) 207-224
  CrossrefPubMedGoogle Scholar
• 57 Artem'eva NS. Regenerative capacity of the rat ovary after compensatory hypertrophy. Bull Exp Biol Med 1961; 51: 76-81
  CrossrefPubMedGoogle Scholar
• 58 Nichols SM, Bavister BD, Brenner CA, Didier PJ, Harrison RM, Kubisch HM. Ovarian senescence in the rhesus monkey (Macaca mulatta). Hum Reprod 2005; 20 (1) 79-83
  PubMedGoogle Scholar
• 59 Gosden RG. Germline stem cells in the postnatal ovary: is the ovary more like a testis?. Hum Reprod Update 2004; 10 (3) 193-195
  CrossrefPubMedGoogle Scholar
• 60 Greenfeld C, Flaws JA. Renewed debate over postnatal oogenesis in the mammalian ovary. Bioessays 2004; 26 (8) 829-832
  CrossrefPubMedGoogle Scholar
• 61 Hoyer PB. Can the clock be turned back on ovarian aging?. Sci SAGE KE 2004; 2004 (10) pe11
  PubMedGoogle Scholar
• 62 Telfer EE. Germline stem cells in the postnatal mammalian ovary: a phenomenon of prosimian primates and mice?. Reprod Biol Endocrinol 2004; 2: 24
  CrossrefPubMedGoogle Scholar
• 63 Albertini DF. Micromanagement of the ovarian follicle reserve—do stem cells play into the ledger?. Reproduction 2004; 127 (5) 513-514
  CrossrefPubMedGoogle Scholar
• 64 Byskov AG, Faddy MJ, Lemmen JG, Andersen CY. Eggs forever?. Differentiation 2005; 73 (9–10) 438-446
  CrossrefPubMedGoogle Scholar
• 65 Skaznik-Wikiel M, Tilly JC, Lee H-J , et al. Serious doubts over “Eggs forever?”. Differentiation 2007; 75 (2) 93-99
  CrossrefPubMedGoogle Scholar
• 66 Gougeon A. Neo-oogenesis in the postnatal ovary: fantasy or reality? [in French]. Gynecol Obstet Fertil 2005; 33 (10) 819-823
  CrossrefPubMedGoogle Scholar
• 67 Powell K. Going against the grain. PLoS Biol 2007; 5 (12) e338
  CrossrefPubMedGoogle Scholar
• 68 Gu W, Tekur S, Reinbold R , et al. Mammalian male and female germ cells express a germ cell-specific Y-Box protein, MSY2. Biol Reprod 1998; 59 (5) 1266-1274
  CrossrefPubMedGoogle Scholar
• 69 Yang J, Medvedev S, Yu J , et al. Absence of the DNA-/RNA-binding protein MSY2 results in male and female infertility. Proc Natl Acad Sci U S A 2005; 102 (16) 5755-5760
  CrossrefPubMedGoogle Scholar
• 70 Telfer EE, McLaughlin M, Ding C, Thong KJ. A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Hum Reprod 2008; 23 (5) 1151-1158
  CrossrefPubMedGoogle Scholar
• 71 Telfer EE, McLaughlin M. In vitro development of ovarian follicles. Semin Reprod Med 2011; 29 (1) 15-23
  Article in Thieme ConnectPubMedGoogle Scholar
• 72 Sadri-Ardekani H, Mizrak SC, van Daalen SK , et al. Propagation of human spermatogonial stem cells in vitro. JAMA 2009; 302 (19) 2127-2134
  CrossrefPubMedGoogle Scholar
• 73 Sadri-Ardekani H, Akhondi MA, van der Veen F, Repping S, van Pelt AM. In vitro propagation of human prepubertal spermatogonial stem cells. JAMA 2011; 305 (23) 2416-2418
  CrossrefPubMedGoogle Scholar
• 74 Ko K, Schöler HR. Embryonic stem cells as a potential source of gametes. Semin Reprod Med 2006; 24 (5) 322-329
  Article in Thieme ConnectPubMedGoogle Scholar
• 75 Nagano MC. In vitro gamete derivation from pluripotent stem cells: progress and perspective. Biol Reprod 2007; 76 (4) 546-551
  CrossrefPubMedGoogle Scholar
• 76 Nicholas CR, Chavez SL, Baker VL, Reijo Pera RA. Instructing an embryonic stem cell-derived oocyte fate: lessons from endogenous oogenesis. Endocr Rev 2009; 30 (3) 264-283
  CrossrefPubMedGoogle Scholar
• 77 Telfer EE, Albertini DF. The quest for human ovarian stem cells. Nat Med 2012; 18 (3) 353-354
  CrossrefPubMedGoogle Scholar
• 78 Woods DC, White Y, Tilly JL. Purification of oogonial stem cells from adult mouse and human ovaries: an assessment of the literature and a view toward the future. Reprod Sci 2013; 20 (1) 7-15
  CrossrefPubMedGoogle Scholar