Unveiling the critical role of androgen receptor signaling in avian sexual development

Gonadal hormone activities mediated by androgen and estrogen receptors, along with cell-autonomous mechanisms arising from the absence of sex-chromosome dosage compensation, are key factors in avian sexual development. In this study, we generate androgen receptor (AR) knockout chickens (AR^−/−) to explore the role of androgen signaling in avian sexual development. Despite developing sex-typical gonads and gonadal hormone production, AR^−/− males and females are infertile. While few somatic sex-specific traits persist (body size, spurs, and tail feathers), crucial sexual attributes such as comb, wattles and sexual behaviors remain underdeveloped in both sexes. Testosterone treatment of young AR^−/− males fails to induce crow behavior, comb development, or regression of the bursa of Fabricius, which are testosterone-dependent phenotypes. These findings highlight the significance of androgen receptor mechanisms in fertility and sex-specific traits in chickens, challenging the concept of a default sex in birds and emphasizing the dominance of androgen signaling in avian sexual development.