Estrogen Receptor 1 (ESR1) Agonist Induces Ovarian Differentiation and Aberrant Müllerian Duct Development in the Chinese Soft-shelled Turtle, .

Estrogens play critical roles in ovarian and reproductive organ development, but the molecular signaling pathways in non-mammalian vertebrates are not well understood. Studies of reptiles have indicated that administration of exogenous estrogens during embryonic development causes ovarian differentiation and presumptive male to female sex-reversal. The Chinese soft-shelled turtle, , belongs to the family Trionychidae and exhibits genotypic sex determination system with ZZ/ZW sex chromosomes. In order to assess the role of estrogens and their signaling pathway on sex determination and differentiation, eggs were given a single administration of endogenous estrogen,17β-estradiol (E2) or a synthetic estrogen receptor 1 (ESR1) agonist, 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) during gonadal differentiation, and the subsequent effects were examined during a final developmental stage prior to hatching. The administration of both E2 and PPT induced ovarian differentiation in genetic male embryos. Intriguingly, PPT but not E2 induced the Müllerian duct enlargement and aberrant glandular development. These data suggest that ovarian differentiation and reproductive tract anomalies induced by the exogenous estrogen exposure act through ESR1 in the Chinese soft-shelled turtles.