Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway: New roles for an old timer

Abstract

A large amount of information has accumulated over the past decade on how gonadotropins, steroid hormones and growth factors regulate development of the mammalian ovarian follicle. Moreover, the bi-directional communication between mammalian oocytes and their surrounding somatic (granulosa) cells has also been shown to be crucial for this process. The intra-ovarian factors, or more specifically, the intra-oocyte signaling pathways that control oocyte growth and early follicular development are largely unknown, however. Based on both in vitro studies and in vivo functional studies using gene-modified mouse models, this review focuses on the key features of the phosphatidylinositol 3 kinase (PI3K) pathway in growing mouse oocytes and on the novel functions of the oocyte PI3K pathway in controlling mammalian oocyte growth and follicular development that have come to light only recently. We propose that the PI3K pathway in the oocyte, which is activated by granulosa cell-produced Kit ligand (KL) via the oocyte-surface receptor Kit, may serve as an intra-oocyte network that regulates both oocyte growth and the early development of ovarian follicles.

Differential expression of matrix metalloproteinases during stimulated ovarian recrudescence in Siberian hamsters (Phodopus sungorus)

“…Despite these correlations, other studies do not clearly identify a role for MMPs during ovulation or corpus luteum function. Use of a broadspectrum inhibitor of MMPs, GM6001, reduced, but did not prevent ovulation, and did not alter corpus luteum development in wild type and plasminogen activator deficient mice (Liu et al, 2006;Wahlberg et al, 2007). Similarly, no significant changes in MMP-2 and MMP-9 were noted in human or equine ovaries prior to ovulation (Lind et al, 2006;Riley et al, 2004), and the absence of MMP-9 and MMP-13 in fertile mice suggests that these MMPs are not essential for ovulation (Hägglund et al, 1999;Johnson et al, 1999).…”

Mammalian foetal ovarian development: consequences for health and disease

“…Normal follicular development also requires cell-to-cell communication between the oocyte and the granulosa cells, as well as between the granulosa and the theca cells (Eppig 2001, Skinner 2005. Earlier studies implicated Kit ligand and c-Kit as intraovarian factors acting via phosphatidylinositol-3-kinase to control oocyte growth and early follicular development (reviewed in Liu et al (2006)). …”

Mechanisms of Ovarian Atresia Induced by Xenobiotic Exposures

“…The PI3K signaling pathway has recently been demonstrated to be critical for maintaining the viability of primordial follicles that comprise the ovarian reserve (Jagarlamudi et al, 2009;Liu et al, 2006;Rajareddy et al, 2007;Reddy et al, 2005;. Kit Ligand (KL), a growth factor expressed in the granulosa cells of primordial follicles (Ismail et al, 1996), binds to the oocyte-expressed receptor, c-KIT (Horie et al, 1991;Manova et al, 1990;Orr-Urtreger et al, 1990).…”

“…This pathway also plays a "gatekeeper" role in determining the entry or the primordial oocyte into the growing follicular pool (Jagarlamudi et al, 2009;Liu et al, 2006;Rajareddy et al, 2007;Reddy et al, 2005;. The forkhead transcription factor family member, FOXO3, is negatively regulated by AKT.…”