Hematopoietic prostaglandin D synthase (H-Pgds) is expressed in the early embryonic gonad and participates to the initial nuclear translocation of the SOX9 protein.

In mammals, the Prostaglandin D(2) (PGD(2) ) signaling pathway is involved in male gonadal development, regulating Sox9 gene expression and SOX9 protein subcellular localization through lipocalin prostaglandin D synthase (L-Pgds) activity. Nevertheless, because L-Pgds is downstream of Sox9, its expression cannot explain the initial nuclear translocation of the SOX9 protein. Here, we show that another source of PGD(2) , hematopoietic-Pgds (H-Pgds) enzyme is expressed in somatic and germ cells of the embryonic gonad of both sexes, as early as embryonic day (E) 10.5, before the onset of L-Pgds expression. Inhibition of H-Pgds activity by the specific HQL-79 inhibitor leads to impaired nuclear translocation of SOX9 protein in E11.5 Sertoli cells. Furthermore, analysis of H-Pgds(-/-) male embryonic gonads confirms abnormal subcellular localization of SOX9 protein at the E11.5 early stage of mouse testicular differentiation suggesting a role for H-Pgds-produced PGD(2) in the initial nuclear translocation of SOX9.

[Prostaglandin D2: new roles in the embryonic and pathological gonad]. / La prostaglandine D2: nouveaux rôles dans la gonade embryonnaire et pathologique.

Prostaglandin D2 (PGD2) belongs to the superfamily of ubiquitous signalling molecules, the prostaglandins ; these bind to specific G-coupled transmembrane receptors, inducing various transduction pathways. Prostaglandins PGE2 and PGF2alpha have several identified functions during ovulation, fecondation and embryo implantation. However, the roles of PGD2 within the male or female reproductive organs are still largely unknown, even though the PGD2-producing enzyme, prostaglandin D synthase (PGDS), is detected in these organs. In this study, we summarize recent data highlighting new functions of PGD2 in the onset of testicular embryogenesis and in the growth inhibition of ovarian cancer cells. In both cases, PGD2 acts by activating the function of the Sertoli cell differentiating factor SOX9.

Hematopoietic-Prostaglandin D2 synthase through PGD2 production is involved in the adult ovarian physiology.

BACKGROUND: The prostaglandin D2 (PGD2) pathway is involved in numerous biological processes and while it has been identified as a partner of the embryonic sex determining male cascade, the roles it plays in ovarian function remain 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 situ hybridization were performed. Then, to evaluate 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 of H-Pgds mRNA in the granulosa cells from the primary to pre-ovulatory follicles. We provide evidence of the role of H-Pgds-produced PGD2 signaling in the FSH signaling through increased FshR 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 through inhibition of granulosa cell proliferation in the growing follicles. CONCLUSIONS: Together, these results show PGD2 signaling to interfere with FSH action within granulosa cells, thus identifying an important and unappreciated role for PGD2 signaling in modulating the balance of proliferation, differentiation and steroidogenic activity of granulosa cells.