Scientists have shown that this single gene, which is found on a non-sex chromosome, is solely responsible for keeping the ovary as an ovary in adults and acts by directly suppressing the male-promoting gene Sox9. Using genetic tricks to turning off the gene Foxl2 in adult female mice, scientists made a dramatic change to cell types in the ovary, making them more closely resemble those in a testis. The cells produced testosterone and organised into structures resembling those responsible for sperm production (although sperm was not produced).
The research has wide-ranging implications for reproductive medicine and challenges several long held assumptions about sex determination; that female development happens by default, is fixed and relies solely on the X and Y chromosome. The Foxl2 gene was thought to be important for normal ovary development and for female fertility, but until now its role in maintaining the adult ovary, was unknown.
Dr Robin Lovell Badge, from the Medical Research Council’s, National Institute for Medical Research said:
“We take it for granted that we maintain the sex we are born with, including whether we have testes or ovaries. But this work shows that the activity of a single gene, Foxl2, is all that prevents adult ovary cells turning into cells found in testes. If it is possible to make these changes in adult humans it may eventually remove the need for surgery in gender reassignment treatment. If this does become possible, it’s likely that while treated individuals would make the right hormones for their new sex, fertility would be lost”.
Dr Mathias Treier, Group Leader at the European Molecular Biology Laboratory said:
“We were surprised by the results. We expected the mice to stop producing oocytes (eggs), but what happened was much more dramatic: somatic cells which support the developing egg took on the characteristics of the cells which usually support developing sperm, and the gender-specific hormone-producing cells also switched from a female to a male cell type.”
These findings could help to understand and eventually treat certain conditions affecting fertility and sexual development, such as the masculinising effects of menopause seen in some women and some cases of premature ovarian failure. It also offers for the first time the suggestion that fertility treatment options might be available for sex differentiation conditions in children with intersex conditions.
Notes to editors:
1. “Somatic Sex Reprogramming of Adult Ovaries to Testes by FOXL2 Ablation” will be published in the Journal Cell.
2. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century
3. The European Molecular Biology Laboratory is a basic research institute funded by public research monies from 20 member states (Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom) and associate member state Australia. Research at EMBL is conducted by approximately 80 independent groups covering the spectrum of molecular biology. The Laboratory has five units: the main Laboratory in Heidelberg, and Outstations in Hinxton (the European Bioinformatics Institute), Grenoble, Hamburg, and Monterotondo near Rome. The cornerstones of EMBL’s mission are: to perform basic research in molecular biology; to train scientists, students and visitors at all levels; to offer vital services to scientists in the member states; to develop new instruments and methods in the life sciences and to actively engage in technology transfer activities. EMBL’s International PhD Programme has a student body of about 170. The Laboratory also sponsors an active Science and Society programme. Visitors from the press and public are welcome.
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