Abstract
The mammalian ovary consists of a large number of dormant immature follicles, each containing a single oocyte and located on the periphery of the ovary. With each reproductive cycle, a group of immature follicles is sequentially activated to resume growth, and pituitary gonadotropins and ovarian steroid and peptide hormones cooperate to ensure further growth and development. A single dominant follicle eventually emerges, ovulates, and then involutes to allow the selection of the next group of follicles. While hormones are known to control the later stages of folliculogenesis, little is known about the pathways that activate individual immature primordial follicles in the dormant follicle pool. We advance a new hypothesis: that follicle activation is dependent on the physical environment of the ovary in addition to well-established hormonal cues. This novel perspective on ovarian function may provide new avenues to study follicle dynamics and identify therapeutic targets for ovarian dysfunction.
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Tingen C, Kim A, Woodruff TK. The primordial pool of follicles and nest breakdown in mammalian ovaries. Mol Hum Reprod. 2009;15:795–803.
Edson MA, Nagaraja AK, Matzuk MM. The mammalian ovary from genesis to revelation. Endocr Rev. 2009;30:624–712.
Park JY, Su YQ, Ariga M, Law E, Jin SL, Conti M. EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science. 2004;303:682–4.
Freimann S, Ben-Ami I, Dantes A, Ron-El R, Amsterdam A. EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells. Biochem Biophys Res Commun. 2004;324:829–34.
Mehlmann LM. Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation. Reproduction. 2005;130:791–9.
Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, et al. Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum Reprod Update. 2010;16:395–414.
Pangas SA, Saudye H, Shea LD, Woodruff TK. Novel approach for the three-dimensional culture of granulosa cell-oocyte complexes. Tissue Eng. 2003;9:1013–21.
Kreeger PK, Deck JW, Woodruff TK, Shea LD. The in vitro regulation of ovarian follicle development using alginate-extracellular matrix gels. Biomaterials. 2006;27:714–23.
Xu M, Kreeger PK, Shea LD, Woodruff TK. Tissue-engineered follicles produce live, fertile offspring. Tissue Eng. 2006;12:2739–46.
Xu M, Barrett SL, West-Farrell E, et al. In vitro grown human ovarian follicles from cancer patients support oocyte growth. Hum Reprod. 2009;24:2531–40.
Xu M, West-Farrell ER, Stouffer RL, Shea LD, Woodruff TK, Zelinski MB. Encapsulated three-dimensional culture supports development of nonhuman primate secondary follicles. Biol Reprod. 2009;81:587–94.
Barrett SL, Shea LD, Woodruff TK. Noninvasive index of cryorecovery and growth potential for human follicles in vitro. Biol Reprod. 2010;82:1180–9.
West ER, Xu M, Woodruff TK, Shea LD. Physical properties of alginate hydrogels and their effects on in vitro follicle development. Biomaterials. 2007;28:4439–48.
West-Farrell ER, Xu M, Gomberg MA, Chow YH, Woodruff TK, Shea LD. The mouse follicle microenvironment regulates antrum formation and steroid production: alterations in gene expression profiles. Biol Reprod. 2009;80:432–9.
Xu M, West E, Shea LD, Woodruff TK. Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development. Biol Reprod. 2006;75:916–23.
Kreeger PK, Woodruff TK, Shea LD. Murine granulosa cell morphology and function are regulated by a synthetic Arg-Gly-Asp matrix. Mol Cell Endocrinol. 2003;205:1–10.
Shikanov A, Xu M, Woodruff TK, Shea LD. Interpenetrating fibrin-alginate matrices for in vitro ovarian follicle development. Biomaterials. 2009;30:5476–85.
Smith MF, Ricke WA, Bakke LJ, Dow MP, Smith GW. Ovarian tissue remodeling: role of matrix metalloproteinases and their inhibitors. Mol Cell Endocrinol. 2002;191:45–56.
Berkholtz CB, Shea LD, Woodruff TK. Extracellular matrix functions in follicle maturation. Semin Reprod Med. 2006;24:262–9.
Hughesdon PE. Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called “hyperthecosis”. Obstet Gynecol Surv. 1982;37:59–77.
Ma X, Fan L, Meng Y, et al. Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome. Mol Hum Reprod. 2007;30:527–35.
Tasab M, Batten MR, Buleid NJ. Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen. EMBO J. 2000;19:2204–11.
Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P. Laparoscopic ‘drilling’ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2007:CD001122.
Acknowledgements
The authors are grateful for technical input from Dr. Jenny Hirshfield-Cytron, Dr. Frank Miller, Dr. Ariella Shikanov, and Rachel Smith. This research was supported by the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NIH grant numbers: U54HD041857) and the National Institutes of Health (Grant Numbers: UL1DE019587, PL1EB008542). Editorial assistance was provided by Stacey C. Tobin, PhD.
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Follicle development is controlled by hormones, the 3D relationship between oocyte and somatic cells and the physical environment of the ovary.
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Woodruff, T.K., Shea, L.D. A new hypothesis regarding ovarian follicle development: ovarian rigidity as a regulator of selection and health. J Assist Reprod Genet 28, 3–6 (2011). https://doi.org/10.1007/s10815-010-9478-4
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DOI: https://doi.org/10.1007/s10815-010-9478-4