Battle of the sexes: When the female embryo takes control

2017

Challenge

The consensus of sexual differentiation, which has been held for over half a century, contends that the female reproductive system forms passively by default, whereas the male reproductive system arises as a result of the active action of testicular hormones.

Advance

IRP researchers led by Humphrey Hung-Chang Yao, Ph.D., challenged the female-by-default theory with a series of experiments in genetically female mouse embryos that lacked a protein called COUP-TFII, which regulates numerous genes important for development. The team discovered that female embryos actively promote the elimination of the male reproductive tract through the action of COUP-TFII.

Impact

The findings alter the long-standing view that an embryo will automatically become female unless male hormones called androgens in the embryo make it male. This study also fills a void in our understanding of the mechanism of sexual differentiation and provides a unique animal model for investigating disorders of sex development in humans.

Publications

Zhao F, Franco HL, Rodriguez KF, Brown PR, Tsai MJ, Tsai SY, Yao HHC. (2017). Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science. Aug 18;357:717-720.