Embryonic estrogens induce hypothalamic progesterone receptor expression to support brain feminization in birds

Embryonic estrogens are known to demasculinize the avian brain, but whether they actively promote brain feminization has remained unresolved. Here, transcriptomic analyses of the embryonic hypothalamus in Japanese quail identified progesterone receptor ( PGR ) as the principal estrogen-responsive gene showing female-biased expression. PGR expression required estrogen receptor activation and endogenous estrogen synthesis, and both progesterone and estrogens were detected in the female embryonic hypothalamus during the critical period of brain sexual differentiation. Embryonic treatment with the PGR antagonist PF-02413873 impaired adult egg laying without affecting male-typical sexual behavior. Together, these findings support a developmental hormonal cascade in which embryonic estrogens induce hypothalamic PGR expression, enabling progesterone signaling that may contribute to brain feminization in birds.