Hormonal control of somatic cell oocyte interactions during ovarian follicle development

Abstract

In the mammalian ovarian follicle, paracrine signaling between the oocyte and somatic granulosa cells is bidirectional but the structural basis and physiological regulations of communication between gametic and somatic compartments remain unknown. The present experiments were designed to test the hypothesis that follicle stimulating hormone (FSH) regulates the ability of granulosa cells to make connections with the oocyte. We show that in prepubertal unprimed mice and mice carrying a targeted deletion of the FSHbeta subunit gene, granulosa cells exhibit orientation towards the oocyte manifest by the elaboration of transzonal projections (TZPs) and "apical" centrosome positioning at sites of granulosa-zona contact. In vivo FSH treatment results in a retraction of TZPs. Coincident with TZP retraction induced by FSH are changes in oocyte transcriptional activity and meiotic competence, which suggests one means by which the oocyte-granulosa cell dialogue may be modulated during development of ovarian follicles.

Cumulus cell contact during oocyte maturation in mice regulates meiotic spindle positioning and enhances developmental competence

“…As an obvious substrate for cell interactions, it is somewhat surprising that so little is known about TZP remodeling especially with respect to the acquisition of developmental competence after IVM. TZPs are ubiquitous amongst mammals [1][2][3] and have been widely implicated in paracrine signaling within the COC [12,17,19,20,45]. However, the fate and function of TZPs during oocyte maturation under in vivo or in vitro conditions has evaded definition for signaling mechanisms other than those of paracrine or junctional varieties [15,22,29,32].…”

“…Moreover, LatB induced a reversible change in GV position from a cortical to central location and targeted TZPs due to their f-actin content, suggesting a direct link between TZP integrity and oocyte polarity has been demonstrated. Hormone stimulation of the COC is likely to regulate TZP integrity [12] and gonadotropin supplementation to culture media enhanced cortical actin assembly and stabilized cortical GV positioning in hamster COCs [33]. Recently, several studies have addressed the mechanisms that regulate GV position and its relationship to spindle morphogenesis.…”

“…At ovulation, oocyte derived signaling molecules such as GDF9 and BMP-15 effect expansion of the compact cumulus mass through a process that confers enhanced developmental competence in oocytes of certain mammals [21,46]. Gonadotropins like follicle stimulating hormone (FSH) have profound effects on the stability and cytoskeletal composition of TZPs in the developing mammalian follicle [12]. TZPs are dynamic and undergo alterations composition and function at various stages of oogenesis [2] but exactly how cell contact or culture conditions impact nuclear and cytoplasmic maturation remains unclear [29].…”

Epigenetic regulation during mammalian oogenesis

“…Before reviewing these, it is important to point out that the production of epigenetically competent oocytes is a by-product of the germ cell's life history within the ovary. The coordination of folliculogenesis with oogenesis clearly requires a balance of cellular interactions between the ovarian somatic components and the oocyte and the feedback interactions that are mediated by hormones and growth factors within the hypothalamic-pituitary-gonadal axis (Combelles et al 2004). How circadian rhythms participate in this complex multicellular dialogue is only now being uncovered (Karman and Tischkau 2006) and is beyond the purview of this paper.…”

“…That the germinal vesicle is modified at the level of chromatin patterning has been studied in many mammals, and generally these alterations in the location and extent of heterochromatization are linked to timely changes in transcription that assure large scale repression prior to fertilization. Interestingly, it is at the later stages of oocyte growth that heterochromatization is initiated, a time when both oocyte imprints are established (Obata and Kono 2002) and hormone regulated oocyte-granulosa interactions are diminished (Combelles et al 2004). Finally, while often overlooked, a large degree of cortical differentiation is required in the oocyte for its successful transition into embryogenesis.…”