Oocyte maturation: the coming of age of a germ cell

Abstract

Normal female fertility relies on proper development of the oocyte. This growth culminates just prior to ovulation, when oocyte maturation occurs. Oocyte maturation refers to a release of meiotic arrest that allows oocytes to advance from prophase I to metaphase II of meiosis. This precisely regulated meiotic progression is essential for normal ovulation and subsequent fertilization, and involves changes in the delicate balance between factors promoting meiotic arrest and others that are stimulating maturation. Most of the inhibitory mechanisms appear to involve the upregulation of intracellular cyclic adenosine monophosphate levels. These processes may include direct transport of the nucleotide into oocytes via gap junctions, G protein-mediated stimulation of adenylyl cyclase, and inhibition of intracellular phosphodiesterases. In contrast, potential factors that play roles in triggering oocyte maturation include gonadotropins (e.g., follicle-stimulating factor and luteinizing hormone), growth factors (e.g., amphiregulin and epiregulin), sterols (e.g., follicular fluid-derived meiosis-activating sterol), and steroids (e.g., testosterone progesterone, and estradiol). Delineating the complex interactions between these positive and negative components is critical for determining the role that oocyte maturation plays in regulating follicle development and ovulation, and may lead to novel methods that can be used to modulate these processes in women with both normal and aberrant fertility.

Figure 1

(A) Schematic model of follicle structure and gonadotropin-mediated cumulus cell expansion. Oocytes are directly surrounded by cumulus granulosa cells. These in turn are surrounded by mural granulosa cells, followed by layers of theca cells. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulate expansion of cumulus granulosa cells, loss of gap junctions, and oocyte maturation (depicted by loss of gray nucleus). (B) Model for gonadotropin-induced oocyte maturation. LH stimulates both steroid and growth factor production by theca and mural granulosa cells. These growth factors, including amphiregulin and epiregulin, then act in a paracrine fashion on cumulus granulosa cells, possibly to produce meiosis-activating sterol (MAS), steroids, or other unknown factors that can promote oocyte maturation. FF-MAS, follicular fluid-derived meiosis-activating sterol.

Figure 2

Steroidogenic pathway from the cholesterol precursor lanosterol to the sex steroids testosterone and estradiol. Sterols and steroids that have been shown to promote mouse oocyte maturation in vitro are enclosed in a box, whereas steroids known to trigger oocyte maturation in frogs (in addition to testosterone) are enclosed in a circle. FF-MAS, follicular fluid-derived meiosis-activating sterol; CYP, cytochrome P450 enzyme; DHEA, dehydroepiandrosterone; HSD, hydroxysteroid dehydrogenase.