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Female is not 'default sex' of embryos

21 August 2017
Appeared in BioNews 914

A protein that controls removal of male reproductive tissue in female mice embryos has been discovered. 

The protein is critical to the correct growth of the female reproductive system, and overturns the longstanding theory that development of the female reproductive system is a passive process which spontaneously occurs when the male hormone androgen is not present.

'We were just shocked,' said co-author Dr Humphrey Hung-Chang Yao of the National Institute of Environmental Health Sciences (NIEHS).

The study overturns the 'female-by-default' theory, which has been held for over half a century. At the start of mammalian reproductive development, both male, sperm-carrying reproductive tracts and female, egg-delivering reproductive tracts are present. Depending on the sex of the embryo, one set of tracts usually disintegrates as development proceeds.

The team were researching how reproductive tissues communicate with early tract linings in female mouse embryos. Suspecting that a protein called COUP-TFII was involved, the team genetically modified female mice embryos to lack the gene responsible for producing it. To their surprise, the male reproductive tracts did not disintegrate in these embryos, and they were born intersex with both male and female reproductive tracts.

After ruling out the possibility that androgen was present in the mutant female mice, they concluded that COUP-TFII is required for active removal of the male tracts.

COUP-TFII is also found in many other tissues and is crucial for the survival of mice embryos. It may also be implicated in other complex disorders. While their study uses a mouse model of reproductive development, it is thought that the process is very similar in humans.

The team say the study could aid in studies of sex development disorders such as cryptorchidism (undescended testicles), Klinefelter Syndrome and Turner Syndrome.

'Individuals with [sex development disorders] may have developmental challenges due to the presence of intersex organ systems,' said Dr Kenneth Korach, head of the NIEHS Reproductive and Developmental Biological Laboratory, 'With its highly novel approach and unexpected findings, Yao's research has important implications for understanding the potential causes of these conditions.'

'This work is just the beginning and many interesting questions remain unanswered,' lead author Dr Fei Zhao said, 'We will continue to study how the embryo develops a functional reproductive system.'

Although the findings give some indication of how COUP-TFII controls disintegration of the male reproductive tracts, more research is needed. In particular the team want to investigate the interaction between COUP-TFII and male hormones such as androgen, as well as looking for other proteins involved in the process.

The study was published in the journal Science.

Ductal sex determination
Science |  18 August 2017
Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice
Science |  18 August 2017
Embryos kill off male tissue to become female
Science News |  17 August 2017
Female mouse embryos actively remove male reproductive systems
NIH |  17 August 2017
NIH study shows how sex-specific reproductive systems arise
UPI |  17 August 2017
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