Résumé
Background : The prostaglandin D2 (PGD2) pathway is involved in numerous biological processes and while it hasbeen identified as a partner of the embryonic sex determining male cascade, the roles it plays in ovarian functionremain largely unknown. PGD2 is secreted by two prostaglandin D synthases (Pgds); the male-specific lipocalin (L)-Pgds and the hematopoietic (H)-Pgds.Methods : To study the expression of the Pgds in the adult ovary, in situhybridization were performed. Then, toevaluate the role of H-Pgds produced PGD2 in the ovarian physiology, adult female mice were treated with HQL-79, a specific inhibitor of H-Pgds enzymatic activity. The effects on expression of the gonadotrophin receptors FshR and LhR, steroidogenic genes Cyp11A1, StAR and on circulating progesterone and estradiol, were observed. Results : We report the localization ofH-PgdsmRNA in the granulosa cells from the primary to pre-ovulatoryfollicles. We provide evidence of the role of H-Pgds-produced PGD2 signaling in the FSH signaling throughincreasedFshR and LhR receptor expression. This leads to the activation of steroidogenic Cyp11A1 and StAR gene expression leading to progesterone secretion, independently on other prostanoid-synthetizing mechanisms. We also identify a role whereby H-Pgds-produced PGD2 is involved in the regulation of follicular growth throughinhibition of granulosa cell proliferation in the growing follicles.Conclusions : Together, these results show PGD2 signaling to interfere with FSH action within granulosa cells, thusidentifying an important and unappreciated role for PGD2 signaling in modulating the balance of proliferation,differentiation and steroidogenic activity of granulosa cells.