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Review
. 2015 Aug 1;142(15):2554-63.
doi: 10.1242/dev.125211.

The developmental origins of the mammalian ovarian reserve

Kathryn J Grive  1 , Richard N Freiman  2
Affiliations
Review

The developmental origins of the mammalian ovarian reserve

Kathryn J Grive et al. Development. .

Abstract

The adult mammalian ovary is devoid of definitive germline stem cells. As such, female reproductive senescence largely results from the depletion of a finite ovarian follicle pool that is produced during embryonic development. Remarkably, the crucial nature and regulation of follicle assembly and survival during embryogenesis is just coming into focus. This developmental pathway involves the coordination of meiotic progression and the breakdown of germ cell cysts into individual oocytes housed within primordial follicles. Recent evidence also indicates that genetic and environmental factors can specifically perturb primordial follicle assembly. Here, we review the cellular and molecular mechanisms by which the mammalian ovarian reserve is established, highlighting the presence of a crucial checkpoint that allows survival of only the highest-quality oocytes.

Keywords: Cyst breakdown; Meiosis; Oocyte; Ovary; Primordial follicle.

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Figures

Fig. 1.
Fig. 1.
Fetal origins of the adult ovarian reserve. Primordial follicles are produced from a pool of primordial germ cells, which are localized to the somatic gonad during gestation and undergo mitotic divisions to form germ cell cysts. These cysts then undergo ‘breakdown’ to form the primordial follicle pool, which comprises oocytes surrounded by a layer of somatic pre-granulosa cells. During sexual maturation, primordial follicles can mature into the primary and secondary follicle stages, eventually acquiring a fluid-filled antral space. After the onset of puberty, matured follicles can be activated by a surge of luteinizing hormone, which promotes further maturation of the oocyte and subsequent ovulation.
Fig. 2.
Fig. 2.
Comparative timelines of primordial follicle formation in mouse and humans. Representative timelines of cyst formation, meiotic onset and primordial follicle formation in mice and humans. Primordial germ cells colonize the somatic gonad at about E10.5 in mice and ∼5 weeks gestation in humans. These cells undergo mitotic divisions, form cysts, and then cease mitosis and enter meiosis I around E13.5 in mice and between 10 and 12 weeks gestation in humans. Finally, these cysts break down via apoptosis of germ cells to form the primordial follicle pool. Whereas this event takes place around the time of birth in mice, it begins during mid-gestation (around 16 weeks) in humans. Abbreviations: E, embryonic day; PND, post-natal day.
Fig. 3.
Fig. 3.
Regulators of primordial follicle development. Red text and arrow indicate factors that promote the transition between germline cyst and primordial follicles, whereas blue text and arrows indicates inhibitors of primordial follicle formation. Abbreviations: FSH, follicle stimulating hormone; TE, transposable element.
See this image and copyright information in PMC

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