n adult female mice, switching off one gene seems to start turning the ovaries into testicles and triggers the production of male hormones at normal male levels, scientists say.
The curious findings have led two researchers to remark in a published paper that, biologically speaking, females may be engaged in a lifelong “battle to suppress their inner male.”
Both papers appear in the Dec. 11 issue of the research journal Cell.
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In adult female mice, switching off one gene starts turning the ovaries into testicles that produce male hormones, scientists say. Above, John Couse, biologist in the National Institute of Environmental Health Sciences and author of a previous study on rodent "sex reversal," holds a female mouse. (Image courtesy U.S. Nat'l Inst. of Environmental Health Sciences)
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The new results echo a previous study that found that female ovarian tissues in mice start to convert to male-like tissues in the absence of signals from estrogen, a female sex hormone. That study appeared in the Dec. 17, 1999 issue of the journal Science.
In the newer research, N. Henriette Uhlenhaut of the European Molecular Biology Laboratory in Heidelberg, Germany, and colleagues were studying genes that during development are responsible for converting glands called gonads into either ovaries or testicles, depending on the sex.
Ovaries produce eggs, the female sex cells, while testicles produce sperm.
Uhlenhaut and colleagues genetically engineered mice in which the activity of a called Fox2L could be chemically suppressed in the ovaries.
Fox2L, in turn, is a regulator gene that influences the level of activity of an array of other genes. Among other things, it keeps in check genes that tend to promote testicle development, according to Uhlenhaut’s group.
Switching off Fox2L had the immediate effect of increasing the level of activity of some of these “testis-specific” genes, the scientists reported. Critical among these, they identified one called Sox9.
Concomitant with the boost in Sox9 activity was a “reprogramming” of certain ovarian cell lineages into what appeared to be testis cell lineages, Uhlenhaut and colleagues found. Meanwhile, the modified ovaries began producing normal male-like levels of the hormone testosterone.
“Our results show that maintenance of the ovarian phenotype [form] is an active process throughout life,” the scientists wrote.
It’s unclear whether the findings would translate to humans, but because mice share over 90 percent of their genes with humans, it very often happens that mouse processes have parallels in humans.
It would seem “testicular development is actively repressed throughout the life of females,” added Andrew Sinclair and Craig Smith of the Murdoch Children’s Research Institute in Melbourne, Australia, in a paper published in the same issue of Cell. Sinclair and Smith—the researchers who in their article metaphorically suggested an “inner male” may lurk within all females—also noted the findings go against “conventional wisdom” that the ovary and testis are “terminally differentiated,” or irreversibly developed to their mature state.
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