Prostaglandin D2 (PGD2) signalling and male germ cell : differentiation in the mouse embryonic testis

The sex determination and subsequent germ cell differentiation is highly ordered process that starts at embryonic stage and completes at adult life. In the embryonic gonads Sry expression followed by Sox9 expression initiates testis development while in the absence of Sry expression, genes associated to female fate initiate ovary development. The germ cells that migrated towards newly formed gonads continue extensive proliferation until they commit to the male or female pathway. The fate decision of germ cells as male or female does not depend only on germ cell chromosomal sex but also on gonadal micro-environment. If germ cells enter into female gonad, they have to stop proliferation, pass through mitotic arrest and enter into meiosis; then arrest into prophase I. While if germ cells enter into male gonad, they have to stop proliferation and enter into mitotic arrest. Here we show that during embryonic sex determination, Prostaglandin D2 (PGD2) produced by each of the two enzymes: L-Pgds and H-Pgds in somatic cells and germ cells of testis participates in male germ cell differentiation program. PGD2 signalling supports mitotic arrest by activating the expression and nuclear localization of cell cycle inhibitor P21cip1 and by repressing pluripotency markers and PGD2 has negative effects on Stra8 expression. In addition PGD2 supports activation of male specific gene Nanos2. Hence these data suggest that PGD2 signalling through DP2 receptor is required for proper male germ cell differentiation.