Activation of estrogen receptor alpha disrupts differentiation of the reproductive organs in chicken embryos

Abstract

Gonadal estrogen plays an important role in the differentiation of a female phenotype in birds. Exogenous compounds that interfere with estrogen signaling, for instance by binding to the estrogen receptors alpha and beta (ERα and ERβ), are therefore potential disruptors of sexual differentiation in birds. The ERα agonist propyl-pyrazole-triol (PPT), the ERα antagonist methyl piperidino pyrazole (MPP) and the ERβ agonist diarylproprionitrile (DPN) were used in the present study to explore the roles of the ERs in normal and disrupted sex differentiation in the chicken embryo. Activation of ERα by PPT caused disturbed differentiation of the reproductive organs in both sexes. In male embryos, PPT caused left-side ovotestis formation and retention of the Müllerian ducts. In female embryos, PPT caused retention of the right Müllerian duct (which normally regresses) and malformation of both Müllerian ducts. PPT also induced hepatic expression of mRNA for the estrogen-regulated egg yolk protein apoVLDL II. Notably, none of these effects were observed following treatment with DPN. ERα-inactivation by MPP counteracted the action of PPT but had little effect by its own. Our results indicate that ERα plays an important role in sex differentiation of the reproductive tract in female chicken embryos and show that ERα can mediate xenoestrogen-induced disturbances of sex differentiation.