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 D2 (PGD2) 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 PGD2, 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 PGD2 in the initial nuclear translocation of SOX9. Developmental Dynamics 240:2335–2343, 2011. © 2011 Wiley-Liss, Inc.