Roles of ERα and ERβ in Normal and Disrupted Sex Differentiation in Japanese Quail

Sammanfattning: Exposure to xenoestrogens during development has been shown to impair sexual differentiation in various species. The major aim of this thesis was to elucidate the respective roles of the two estrogen receptors ERα and ERβ in normal and disrupted differentiation of sex organs and copulatory behavior in the Japanese quail (Coturnix japonica). The expression of ERα mRNA was much stronger than that of ERβ mRNA in the gonads and Müllerian ducts (embryonic oviducts) in early embryos. By contrast, ERβ seemed to be predominantly expressed in regions of the embryonic brain that are associated with male sexual behavior. Embryos were exposed to the selective ERα agonists propyl-pyrazole-triol (PPT) and 16α-lactone-estradiol (16α-LE2). The estrogens 17β-estradiol (E2) and 17α-ethynylestradiol (EE2), which activate both ERα and ERβ, were used as positive controls. All substances impaired reproductive organ differentiation. The effects observed included oviductal malformations in females and partial development of oviducts in males. All substances also induced testis feminization (ovotestis) in male embryos. The male copulatory behavior was severely impaired by the positive controls but was unaffected by PPT and 16α-LE2 at doses that disrupted sex organ differentiation. A higher dose of 16α-LE2 significantly suppressed the behavior. However, it is possible that this effect was caused by cross-activation of ERβ. The substances also induced hepatic expression of mRNA encoding the egg-yolk proteins vitellogenin II and very low-density apolipoprotein II, which are commonly used as indicators of estrogen exposure. In conclusion, the results suggest that ERα is important for female reproductive organ differentiation. Excess activation of ERα by xenoestrogens impairs differentiation in both females and males and induces hepatic expression of egg-yolk proteins. The results also indicate that ERα alone cannot mediate demasculinization of male copulatory behavior in quail, although further studies are needed to test this hypothesis.