Differential Regulation of Progesterone and Estradiol Production by Mouse Cumulus and Mural Granulosa Cells by a Factor(s) Secreted by the Oocyte

Abstract

Mouse oocytes secrete a factor(s) that inhibits progesterone and enhances estradiol production by cumulus granulosa cells. The purpose of this study was to investigate the mechanisms by which the production of these steroids is modulated. Mouse oocyte-cumulus cell complexes (intact) and complexes from which the oocytes were removed microsurgically (oocytectomized; OOX) were cultured for up to 48 h in the presence of FSH (150 ng/ml) and testosterone (5 x 10(-7) M). For these experiments, all cells were obtained from antral follicles of 24- to 26-day-old mice primed with eCG. Intact complexes produced primarily estradiol, with significant accumulation occurring between 24 and 48 h. In contrast, OOX complexes produced little estradiol but, starting at 18 h of culture, released significantly more progesterone than did intact complexes. Progesterone accumulation in cocultures of denuded oocytes with either OOX complexes or monolayers of mural granulosa cells was significantly reduced compared to that with OOX complexes or mural granulosa cells cultured alone. If dibutyryl cAMP replaced FSH in the cocultures, similar results were obtained, suggesting that the oocyte-secreted steroid-regulating factor acts downstream of the generation of cAMP to inhibit progesterone production. Since estradiol can inhibit progesterone production by granulosa cells, we investigated the possibility that the increased progesterone released by OOX complexes was secondary to the lower estradiol production. Intact complexes cultured in the presence of the nonaromatizable androgen, 5 alpha-dihydrotestosterone, or steroidal (4-hydroxyandrostenedione) or non-steroidal (CGS 16949A) aromatase inhibitors produced little estradiol; however, progesterone production by these complexes was no different from that of estradiol-producing intact complexes. These results suggest that the steroid-regulating factor(s) secreted by occytes acts to regulate granulosa cell production of estradiol and progesterone by independent mechanisms.

Sperm transport and retention at the fertilization site is orchestrated by a chemical guidance and oviduct movement

“…However, there are several in vitro studies suggesting progesterone as a spermattractant candidate. After ovulation, the cumulus cells secrete progesterone (Vanderhyden & Tonary 1995, Chian et al 1999, Yamashita et al 2003, Guidobaldi et al 2008, which may form a concentration gradient by diffusion along and beyond the cumulus matrix (Teves et al 2006, Guidobaldi et al 2008, Oren-Benaroya et al 2008. A gradient of a picomolar concentration of progesterone chemoattracts only capacitated spermatozoa, those ready to fertilize the egg (Teves et al 2006).…”

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

“…Data are described as median (range). a p < 0.05 compared to <35; b p < 0.05 compared to [35][36][37][38][39] …”

“…Although not fully defined yet, cumulus GCs express characteristics distinct from mural GCs, which are steroidogenically more active [37,38]. Cumulus cells communicate with each other and with the oocyte through specialized gap junctions that allow metabolic exchange and transport of signaling molecules for appropriate follicular development [35,36,39].…”

PACAP-mediated sperm–cumulus cell interaction promotes fertilization

“…Progesterone is presumably responsible for the stimulation of sperm motility by the PACAP-treated fluid because an increased amount of progesterone was detected when the cumulus-oocyte complexes were treated with PACAP. Studies have demonstrated that human, mouse, porcine, and rabbit cumulus cells synthesize and secrete progesterone (Osman et al 1989, Vanderhyden & Tonary 1995, Chian et al 1999, Yamashita et al 2003, Guidobaldi et al 2008. In addition, human sperm express a cell surface receptor for progesterone (Luconi et al 2004).…”