Implications of Polycystic Ovary Syndrome on Oocyte Development

Overview

Journal Semin Reprod Med

Specialty Reproductive Medicine

Date 2008 Jan 9

PMID 18181083

Citations 43

Authors

Daniel A Dumesic

David H Abbott

Affiliations

Soon will be listed here.

Abstract

Human follicle development requires the recruitment of primordial follicles into a cohort of growing follicles from which one follicle is selected to ovulate a mature oocyte. During this developmental process, complex endocrine and intraovarian paracrine signals create a changing intrafollicular hormonal milieu. With this microenvironment, appropriate cumulus cell-oocyte signaling governs oocyte developmental competence, defined as the ability of the oocyte to complete meiosis and undergo fertilization, embryogenesis, and term development. Many of these mechanisms are perturbed in polycystic ovary syndrome (PCOS), a heterogeneous syndrome characterized by ovarian hyperandrogenism, hyperinsulinemia from insulin resistance, and reduced fecundity. In addition to these endocrinopathies, PCOS also is characterized by paracrine dysregulation of follicle development by intraovarian proteins of the transforming growth factor-beta family. Consequently, PCOS patients undergoing ovarian stimulation for in vitro fertilization are at increased risks of impaired oocyte developmental competence, implantation failure, and pregnancy loss. Recent data demonstrate links between endocrine/paracrine factors and oocyte gene expression in PCOS and suggest that new clinical strategies to optimize developmental competence of PCOS oocytes should target correction of the entire follicle growth and oocyte development process.

Citing Articles

Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Their Ratios in Women with Polycystic Ovary Syndrome and Healthy Controls.

Butler A, Nandakumar M, Sathyapalan T, Brennan E, Atkin S Int J Mol Sci. 2025; 26(1.

PMID: 39796177 PMC: 11720512. DOI: 10.3390/ijms26010321.

Identification of transcriptome characteristics of granulosa cells and the possible role of UBE2C in the pathogenesis of premature ovarian insufficiency.

Liu D, Guan X, Liu W, Jia Y, Zhou H, Xi C J Ovarian Res. 2023; 16(1):203.

PMID: 37848988 PMC: 10580542. DOI: 10.1186/s13048-023-01266-3.

Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis.

Chen X, Lan Y, Yang L, Liu Y, Li H, Zhu X Front Endocrinol (Lausanne). 2022; 13:978280.

PMID: 36105396 PMC: 9465241. DOI: 10.3389/fendo.2022.978280.

Ovarian expression of follicle stimulating hormone and activin receptors genes in a prenatally-androgenized rat model of polycystic ovary syndrome in adulthood.

Noroozzadeh M, Jahromi M, Gholami H, Amiri M, Ramezani Tehrani F Mol Biol Rep. 2022; 49(8):7765-7771.

PMID: 35668149 DOI: 10.1007/s11033-022-07601-z.

Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development.

Kawai T, Richards J, Shimada M Commun Biol. 2021; 4(1):1334.

PMID: 34824385 PMC: 8617273. DOI: 10.1038/s42003-021-02849-w.

References

Vitt U, Hayashi M, Klein C, Hsueh A . Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. Biol Reprod. 2000; 62(2):370-7. DOI: 10.1095/biolreprod62.2.370. View

Elvin J, Yan C, Matzuk M . Oocyte-expressed TGF-beta superfamily members in female fertility. Mol Cell Endocrinol. 2000; 159(1-2):1-5. DOI: 10.1016/s0303-7207(99)00185-9. View

Albertini D, Sanfins A, Combelles C . Origins and manifestations of oocyte maturation competencies. Reprod Biomed Online. 2003; 6(4):410-5. DOI: 10.1016/s1472-6483(10)62159-1. View

Dumesic D, Schramm R, Bird I, Peterson E, Paprocki A, Zhou R . Reduced intrafollicular androstenedione and estradiol levels in early-treated prenatally androgenized female rhesus monkeys receiving follicle-stimulating hormone therapy for in vitro fertilization. Biol Reprod. 2003; 69(4):1213-9. DOI: 10.1095/biolreprod.102.015164. View

Zheng P, Si W, Bavister B, Yang J, Ding C, Ji W . 17Beta-estradiol and progesterone improve in-vitro cytoplasmic maturation of oocytes from unstimulated prepubertal and adult rhesus monkeys. Hum Reprod. 2003; 18(10):2137-44. DOI: 10.1093/humrep/deg410. View

Webber L, Stubbs S, Stark J, Trew G, Margara R, Hardy K . Formation and early development of follicles in the polycystic ovary. Lancet. 2003; 362(9389):1017-21. DOI: 10.1016/s0140-6736(03)14410-8. View

Weenen C, Laven J, von Bergh A, Cranfield M, Groome N, Visser J . Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004; 10(2):77-83. DOI: 10.1093/molehr/gah015. View

Kjotrod S, von During V, Carlsen S . Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study. Hum Reprod. 2004; 19(6):1315-22. DOI: 10.1093/humrep/deh248. View

Phy J, Conover C, Abbott D, Zschunke M, Walker D, Session D . Insulin and messenger ribonucleic acid expression of insulin receptor isoforms in ovarian follicles from nonhirsute ovulatory women and polycystic ovary syndrome patients. J Clin Endocrinol Metab. 2004; 89(7):3561-6. DOI: 10.1210/jc.2003-031888. View

10.

Rice S, Ojha K, Whitehead S, Mason H . Stage-specific expression of androgen receptor, follicle-stimulating hormone receptor, and anti-Müllerian hormone type II receptor in single, isolated, human preantral follicles: relevance to polycystic ovaries. J Clin Endocrinol Metab. 2006; 92(3):1034-40. DOI: 10.1210/jc.2006-1697. View

11.

Franks S, Mason H, Willis D . Follicular dynamics in the polycystic ovary syndrome. Mol Cell Endocrinol. 2000; 163(1-2):49-52. DOI: 10.1016/s0303-7207(99)00239-7. View

12.

Schneyer A, Fujiwara T, Fox J, Welt C, Adams J, Messerlian G . Dynamic changes in the intrafollicular inhibin/activin/follistatin axis during human follicular development: relationship to circulating hormone concentrations. J Clin Endocrinol Metab. 2000; 85(9):3319-30. DOI: 10.1210/jcem.85.9.6767. View

13.

Jakimiuk A, Weitsman S, NAVAB A, Magoffin D . Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and steroidogenic enzyme messenger ribonucleic acids are overexpressed in thecal and granulosa cells from polycystic ovaries. J Clin Endocrinol Metab. 2001; 86(3):1318-23. DOI: 10.1210/jcem.86.3.7318. View

14.

Norman R, Milner C, Groome N, Robertson D . Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome. Hum Reprod. 2001; 16(4):668-72. DOI: 10.1093/humrep/16.4.668. View

15.

Knight P, Glister C . Potential local regulatory functions of inhibins, activins and follistatin in the ovary. Reproduction. 2001; 121(4):503-12. DOI: 10.1530/rep.0.1210503. View

16.

Gandolfi T, Gandolfi F . The maternal legacy to the embryo: cytoplasmic components and their effects on early development. Theriogenology. 2001; 55(6):1255-76. DOI: 10.1016/s0093-691x(01)00481-2. View

17.

Yan C, Wang P, DeMayo J, Demayo F, Elvin J, Carino C . Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol. 2001; 15(6):854-66. DOI: 10.1210/mend.15.6.0662. View

18.

Dumesic D, Damario M, Session D, Famuyide A, Lesnick T, Thornhill A . Ovarian morphology and serum hormone markers as predictors of ovarian follicle recruitment by gonadotropins for in vitro fertilization. J Clin Endocrinol Metab. 2001; 86(6):2538-43. DOI: 10.1210/jcem.86.6.7605. View

19.

Eldar-Geva T, Spitz I, Groome N, Margalioth E, Homburg R . Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome. Hum Reprod. 2001; 16(12):2552-6. DOI: 10.1093/humrep/16.12.2552. View

20.

Nelson V, Qin K, Rosenfield R, Wood J, Penning T, Legro R . The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001; 86(12):5925-33. DOI: 10.1210/jcem.86.12.8088. View