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Published in: Reproductive Biology and Endocrinology 1/2003

Open Access 01-12-2003 | Debate

Ovarian follicle counts – not as simple as 1, 2, 3

Author: Jonathan L Tilly

Published in: Reproductive Biology and Endocrinology | Issue 1/2003

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Excerpt

The functional life span of the ovaries is dictated in large part by the number of oocytes present, a number that is known to decline precipitously during both fetal development and postnatal life. Furthermore, studies from numerous laboratories have shown that exposure of the ovaries to a variety of pathological insults, such as anti-cancer therapies and environmental toxicants, accelerates oocyte and follicle depletion, consequently hastening the time at which ovarian failure is observed. Accordingly, over the past several years a tremendous amount of research effort has been expended to uncover the genetic and molecular mechanisms responsible for determining the size of the follicle reserve endowed at birth as well as the rate at which this stockpile of follicles is subsequently depleted [reviewed in [1, 2]]. Since, however, there are no known serum markers that can be used to accurately estimate the number of follicles in the ovaries – in particular follicles at the earliest stages of development (primordial, primary, small preantral) – some type of histomorphometric evaluation of the ovary is generally employed. …
Literature
1.
go back to reference Tilly JL: Commuting the death sentence: how oocytes strive to survive. Nat Rev Mol Cell Biol. 2001, 2: 838-848. 10.1038/35099086.CrossRefPubMed Tilly JL: Commuting the death sentence: how oocytes strive to survive. Nat Rev Mol Cell Biol. 2001, 2: 838-848. 10.1038/35099086.CrossRefPubMed
2.
go back to reference Pru JK, Tilly JL: Programmed cell death in the ovary: insights and future prospects using genetic technologies. Mol Endocrinol. 2001, 15: 845-853.CrossRefPubMed Pru JK, Tilly JL: Programmed cell death in the ovary: insights and future prospects using genetic technologies. Mol Endocrinol. 2001, 15: 845-853.CrossRefPubMed
3.
go back to reference Pepling ME, Spradling AC: Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol. 2001, 234: 339-351. 10.1006/dbio.2001.0269.CrossRefPubMed Pepling ME, Spradling AC: Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol. 2001, 234: 339-351. 10.1006/dbio.2001.0269.CrossRefPubMed
4.
go back to reference Canning J, Takai Y, Tilly JL: Evidence for genetic modifiers of ovarian follicular endowment and development from studies of five inbred mouse strains. Endocrinology. 2003, 144: 9-12. 10.1210/en.2002-220988.CrossRefPubMed Canning J, Takai Y, Tilly JL: Evidence for genetic modifiers of ovarian follicular endowment and development from studies of five inbred mouse strains. Endocrinology. 2003, 144: 9-12. 10.1210/en.2002-220988.CrossRefPubMed
5.
go back to reference Hirshfield AN, Midgley AR: Morphometric analysis of follicular development in the rat. Biol Reprod. 1978, 19: 597-605.CrossRefPubMed Hirshfield AN, Midgley AR: Morphometric analysis of follicular development in the rat. Biol Reprod. 1978, 19: 597-605.CrossRefPubMed
6.
go back to reference Flaws JA, Abbud R, Mann RJ, Nilson JH, Hirshfield AN: Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. Biol Reprod. 1997, 57: 1233-1237.CrossRefPubMed Flaws JA, Abbud R, Mann RJ, Nilson JH, Hirshfield AN: Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. Biol Reprod. 1997, 57: 1233-1237.CrossRefPubMed
7.
go back to reference Flaws JA, Hirshfield AN, Hewitt JA, Babus JK, Furth PA: Effect of Bcl-2 on the primordial follicle endowment in the mouse ovary. Biol Reprod. 2001, 64: 1153-1159.CrossRefPubMed Flaws JA, Hirshfield AN, Hewitt JA, Babus JK, Furth PA: Effect of Bcl-2 on the primordial follicle endowment in the mouse ovary. Biol Reprod. 2001, 64: 1153-1159.CrossRefPubMed
8.
go back to reference Bucci TJ, Bolon B, Warbritton AR, Chen JJ, Heindel JJ: Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies. Reprod Toxicol. 1997, 11: 689-696. 10.1016/S0890-6238(97)00034-8.CrossRefPubMed Bucci TJ, Bolon B, Warbritton AR, Chen JJ, Heindel JJ: Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies. Reprod Toxicol. 1997, 11: 689-696. 10.1016/S0890-6238(97)00034-8.CrossRefPubMed
9.
go back to reference Bolon B, Bucci TJ, Warbritton AR, Chen JJ, Mattison DR, Heindel JJ: Differential follicle counts as a screen for chemically induced ovarian toxicity in mice: results from continuous breeding bioassays. Fundam Appl Toxicol. 1997, 39: 1-10. 10.1006/faat.1997.2338.CrossRefPubMed Bolon B, Bucci TJ, Warbritton AR, Chen JJ, Mattison DR, Heindel JJ: Differential follicle counts as a screen for chemically induced ovarian toxicity in mice: results from continuous breeding bioassays. Fundam Appl Toxicol. 1997, 39: 1-10. 10.1006/faat.1997.2338.CrossRefPubMed
10.
go back to reference Rucker EB, Dierisseau P, Wagner KU, Garrett L, Wynshaw-Boris A, Flaws JA, Hennighausen L: Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol. 2000, 14: 1038-1052.CrossRefPubMed Rucker EB, Dierisseau P, Wagner KU, Garrett L, Wynshaw-Boris A, Flaws JA, Hennighausen L: Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol. 2000, 14: 1038-1052.CrossRefPubMed
11.
go back to reference Benedict JC, Lin TM, Loeffler IK, Peterson RE, Flaws JA: Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci. 2000, 56: 383-388. 10.1093/toxsci/56.2.382.CrossRef Benedict JC, Lin TM, Loeffler IK, Peterson RE, Flaws JA: Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci. 2000, 56: 383-388. 10.1093/toxsci/56.2.382.CrossRef
12.
go back to reference Tomic D, Brodie SG, Deng C, Hickey RJ, Babus JK, Malkas LH, Flaws JA: Smad 3 may regulate follicular growth in the mouse ovary. Biol Reprod. 2002, 66: 917-923.CrossRefPubMed Tomic D, Brodie SG, Deng C, Hickey RJ, Babus JK, Malkas LH, Flaws JA: Smad 3 may regulate follicular growth in the mouse ovary. Biol Reprod. 2002, 66: 917-923.CrossRefPubMed
13.
go back to reference Ratts VS, Flaws JA, Kolp R, Sorenson CM, Tilly JL: Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology. 1995, 136: 3665-3668.PubMed Ratts VS, Flaws JA, Kolp R, Sorenson CM, Tilly JL: Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology. 1995, 136: 3665-3668.PubMed
14.
go back to reference Bergeron L, Perez GI, Mcdonald G, Shi L, Sun Y, Jurisicova A, Varmuza S, Latham KE, Flaws JA, Salter J, et al: Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev. 1998, 12: 1304-1314.PubMedCentralCrossRefPubMed Bergeron L, Perez GI, Mcdonald G, Shi L, Sun Y, Jurisicova A, Varmuza S, Latham KE, Flaws JA, Salter J, et al: Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev. 1998, 12: 1304-1314.PubMedCentralCrossRefPubMed
15.
go back to reference Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL: Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat Genet. 1999, 21: 200-203. 10.1038/5985.CrossRefPubMed Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL: Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat Genet. 1999, 21: 200-203. 10.1038/5985.CrossRefPubMed
16.
go back to reference Morita Y, Perez GI, Maravei DV, Tilly KI, Tilly JL: Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro. Mol Endocrinol. 1999, 13: 841-850.CrossRefPubMed Morita Y, Perez GI, Maravei DV, Tilly KI, Tilly JL: Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro. Mol Endocrinol. 1999, 13: 841-850.CrossRefPubMed
17.
go back to reference Robles R, Morita Y, Mann KK, Perez GI, Yang S, Matikainen T, Sherr DH, Tilly JL: The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse. Endocrinology. 2000, 141: 450-453.CrossRefPubMed Robles R, Morita Y, Mann KK, Perez GI, Yang S, Matikainen T, Sherr DH, Tilly JL: The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse. Endocrinology. 2000, 141: 450-453.CrossRefPubMed
18.
go back to reference Morita Y, Perez GI, Paris F, Miranda S, Ehleiter D, Haimovitz-Friedman A, Fuks Z, Xie Z, Reed JC, Schuchman EH, et al: Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med. 2000, 6: 1109-1114. 10.1038/80442.CrossRefPubMed Morita Y, Perez GI, Paris F, Miranda S, Ehleiter D, Haimovitz-Friedman A, Fuks Z, Xie Z, Reed JC, Schuchman EH, et al: Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med. 2000, 6: 1109-1114. 10.1038/80442.CrossRefPubMed
19.
go back to reference Matikainen T, Perez GI, Zheng TS, Kluzak TR, Rueda BR, Flavell RA, Tilly JL: Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. Endocrinology. 2001, 142: 2468-2480.PubMed Matikainen T, Perez GI, Zheng TS, Kluzak TR, Rueda BR, Flavell RA, Tilly JL: Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. Endocrinology. 2001, 142: 2468-2480.PubMed
20.
go back to reference Morita Y, Maravei DV, Bergeron L, Wang S, Perez GI, Tsutsumi O, Taketani Y, Asano M, Horai R, Korsmeyer SJ, et al: Caspase-2 deficiency rescues female germ cells from death due to cytokine insufficiency but not meiotic defects caused by ataxia telangiectasia-mutated (Atm) gene inactivation. Cell Death Differ. 2001, 8: 614-620. 10.1038/sj.cdd.4400845.CrossRefPubMed Morita Y, Maravei DV, Bergeron L, Wang S, Perez GI, Tsutsumi O, Taketani Y, Asano M, Horai R, Korsmeyer SJ, et al: Caspase-2 deficiency rescues female germ cells from death due to cytokine insufficiency but not meiotic defects caused by ataxia telangiectasia-mutated (Atm) gene inactivation. Cell Death Differ. 2001, 8: 614-620. 10.1038/sj.cdd.4400845.CrossRefPubMed
21.
go back to reference Matikainen T, Perez GI, Jurisicova A, Schlezinger JJ, Ryu H-Y, Pru JK, Sakai T, Korsmeyer SJ, Casper RF, Sherr DH, et al: Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat Genet. 2001, 28: 355-360. 10.1038/ng575.CrossRefPubMed Matikainen T, Perez GI, Jurisicova A, Schlezinger JJ, Ryu H-Y, Pru JK, Sakai T, Korsmeyer SJ, Casper RF, Sherr DH, et al: Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat Genet. 2001, 28: 355-360. 10.1038/ng575.CrossRefPubMed
22.
go back to reference Malamed S, Gibney JA, Ojeda SR: Ovarian innervation develops before initiation of folliculogenesis in the rat. Cell Tiss Res. 1992, 270: 87-93.CrossRef Malamed S, Gibney JA, Ojeda SR: Ovarian innervation develops before initiation of folliculogenesis in the rat. Cell Tiss Res. 1992, 270: 87-93.CrossRef
23.
go back to reference Doerr JK, Hollis EA, Sipes IG: Species differences in the ovarian toxicity of 1,3-butadiene epoxies in B6C3F1 mice and Sprague-Dawley rats. Toxicology. 1996, 113: 128-136. 10.1016/0300-483X(96)03437-3.CrossRefPubMed Doerr JK, Hollis EA, Sipes IG: Species differences in the ovarian toxicity of 1,3-butadiene epoxies in B6C3F1 mice and Sprague-Dawley rats. Toxicology. 1996, 113: 128-136. 10.1016/0300-483X(96)03437-3.CrossRefPubMed
24.
go back to reference Morita Y, Manganaro TF, Tao X-J, Martimbeau S, Donahoe PK, Tilly JL: Requirement for phosphatidylinositol-3'-kinase in cytokine-mediated germ cell survival during fetal oogenesis in the mouse. Endocrinology. 1999, 140: 941-949.PubMed Morita Y, Manganaro TF, Tao X-J, Martimbeau S, Donahoe PK, Tilly JL: Requirement for phosphatidylinositol-3'-kinase in cytokine-mediated germ cell survival during fetal oogenesis in the mouse. Endocrinology. 1999, 140: 941-949.PubMed
25.
go back to reference Vitt UA, McGee EA, Hayashi M, Hsueh AJW: In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. Endocrinology. 2000, 141: 3814-3820.PubMed Vitt UA, McGee EA, Hayashi M, Hsueh AJW: In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. Endocrinology. 2000, 141: 3814-3820.PubMed
26.
go back to reference Thompson KE, Sipes IG, Greenstein BD, Hoyer PB: 17β-Estradiol affords protection against 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in Fischer-344 rats. Endocrinology. 2002, 143: 1058-1065.PubMed Thompson KE, Sipes IG, Greenstein BD, Hoyer PB: 17β-Estradiol affords protection against 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in Fischer-344 rats. Endocrinology. 2002, 143: 1058-1065.PubMed
27.
go back to reference Durlinger ALL, Gruijters MJG, Kramer P, Karels B, Ingraham HA, Nachtigal MW, HThUilenbroek J, Grootegoed JA, Themmen APN: Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology. 2002, 143: 1076-1084.PubMed Durlinger ALL, Gruijters MJG, Kramer P, Karels B, Ingraham HA, Nachtigal MW, HThUilenbroek J, Grootegoed JA, Themmen APN: Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology. 2002, 143: 1076-1084.PubMed
28.
go back to reference Takai Y, Canning J, Perez GI, Pru JK, Schlezinger JJ, Sherr DH, Kolesnick RN, Yuan J, Flavell RA, Korsmeyer SJ, et al: Bax, caspase-2 and caspase-3 are required for ovarian follicle loss caused by 4-vinylcyclohexene diepoxide exposure of female mice in vivo. Endocrinology. 2003, 144: 69-74. 10.1210/en.2002-220814.CrossRefPubMed Takai Y, Canning J, Perez GI, Pru JK, Schlezinger JJ, Sherr DH, Kolesnick RN, Yuan J, Flavell RA, Korsmeyer SJ, et al: Bax, caspase-2 and caspase-3 are required for ovarian follicle loss caused by 4-vinylcyclohexene diepoxide exposure of female mice in vivo. Endocrinology. 2003, 144: 69-74. 10.1210/en.2002-220814.CrossRefPubMed
Metadata
Title
Ovarian follicle counts – not as simple as 1, 2, 3
Author
Jonathan L Tilly
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2003
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-1-11

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