PGE2 inhibits spermatogonia differentiation in zebrafish: interaction with Fsh and an androgen

Abstract

Changes in zebrafish testicular gene expression induced by follicle-stimulating hormone (Fsh) or anti-Mullerian hormone (Amh) suggested that Amh inhibition and Fsh stimulation of spermatogenesis involved up and downregulation, respectively, of prostaglandin (PG) signaling. We found that Sertoli cells contacting type A undifferentiated (A und ) and differentiating (A diff ) spermatogonia expressed a key enzyme of PG production (Ptgs2); previous work showed that Sertoli cells contacting A diff and B spermatogonia and spermatocytes showed ptges3b expression, an enzyme catalyzing PGE 2 production. In primary testis tissue cultures, PGE 2 , but not PGD 2 or PGF 2α , reduced the mitotic activity of A diff and their development into B spermatogonia. Vice versa , inhibiting PG production increased the mitotic activity of A diff and B spermatogonia. Studies with pharmacological PG receptor antagonists suggest that an Ep4 receptor mediates the inhibitory effects on the development of spermatogonia, and cell-sorting experiments indicated this receptor is expressed mainly by testicular somatic cells. Combined inhibition of PG and steroid production moreover reduced the mitotic activity of A und spermatogonia and led to their partial depletion, suggesting that androgens (and/or other testicular steroids), supported by PGE 2 , otherwise prevent depletion of A und . Androgens also decreased testicular PGE 2 production, increased the transcript levels of the enzyme-catabolizing PGs and decreased PGE 2 receptor ptger4b transcript levels. Also Fsh potentially reduced, independent of androgens, PGE 2 production by decreasing ptges3b transcript levels. Taken together, our results indicate that PGE 2 , via Ep4 receptors, favors self-renewal in conjunction with androgens and, independent of Fsh and androgens, inhibits differentiating divisions of spermatogonia.