A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers. The discovery, which appeared in the journal Science, changes the long-standing belief that an embryo will automatically become female unless androgens, or male hormones, in the embryo make it male.
Senior author said all early-stage mammalian embryos, regardless of their sex, contain structures for both male and female reproductive tracts. For a mouse or human to end up with the reproductive tract of one sex after birth, the other tract has to disintegrate.
"I learned in graduate school that androgens are needed to maintain the male reproductive tract, but our work finds that maintenance of the male reproductive tract can be achieved without androgen," senior author said.
The evidence comes from a mouse model created by the group. The mice lack COUP-TFII in an embryonic structure that develops into distinct male and female reproductive ducts. To the surprise of researchers female mouse embryos without COUP-TFII displayed both male and female ducts. Control females with COUP-TFII appropriately exhibited only the female duct.
Since the team did not find any evidence of androgen production in female mice without COUP-TFII, they concluded that the presence of the male reproductive tract in female embryos lacking COUP-TFII occurs without androgen.
The study suggests that COUP-TFII has to be present to block the growth of male reproductive tracts. Without COUP-TFII, the mice are born intersex, or having both male and female reproductive tracts.
"This work is just the beginning and many interesting questions remain unanswered," senior author said. "We will continue to study how the embryo develops a functional reproductive system."
The group plans to use mouse models to examine how birth defects of the reproductive system originate. These birth defects lead to disorders of sexual development (DSD), which include common defects, such as cryptorchidism, or undescended testicles, as well as the genetic disorders Klinefelter Syndrome and Turner Syndrome.