Attention of transsexuals: it is enough to block one gene for sex change
Scientists at the European Laboratory of Molecular Biology, working under the leadership of Mathias Treier, have found that knocking out the Foxl2 gene leads to the fact that the ovaries of adult mice acquire the characteristics of male sex glands and begin to produce testosterone. The results of their work, published in the December issue of the journal Cell in the article "Somatic Sex Reprogramming of Adult Ovaries to Tests by FOXL2 Ablation", indicate that in adulthood, the constant functioning of the Foxl2 gene is necessary to maintain the female phenotype of the body, and can help to understand the mechanisms underlying female infertility.
A few years ago, the same group of authors cloned for the first time the Foxl2 gene, a transcription factor localized on somatic chromosomes. When this gene was knocked out, the ovaries in young female mice began to develop, but subsequently atrophied. This gene is expressed throughout the life of the organism, so the authors decided to check what happens if it is knocked out in the body of adult animals with normally formed ovaries.
When planning the experiment, they expected that knocking out this gene would lead to degeneration of oocytes (immature eggs), but in general the body would retain all the physiological signs of the female sex. Instead, the animals had a complete transdifferentiation of the ovaries into the testes. The most surprising was the fact that the "orientation" was changed not by germ cells, but by fully differentiated somatic cells of the ovaries.
Trayer suggests that the different behavior of the Foxl2 gene during development and in adulthood is due to the fact that it regulates the work of other genes that play important roles in the process of organ differentiation. It is believed that during the formation of the body, the main signal suppressing the "male" development program is the activity of the Wnt4 gene. However, at the end of the formation of female genitalia, this gene ceases to function. The expression of the Foxl2 gene throughout the life of the female body indicates its need to maintain female physiology.
The transformation of ovarian cells into testicular cells had no effect on the appearance of the animals. Trayer explains this by saying that the development of secondary sexual characteristics is impossible at this stage of animal development. However, the transformation of two types of ovarian cells into testicular cells occurred within just 48 hours after knocking out the gene. In this regard, a very interesting question arises: how could the chromatin rearrangement necessary for such a complex transformation take place in this short period of time?
Mice capable of changing the sex of their reproductive organs in adulthood are a valuable experimental model. The fact that transdifferentiation of organs occurs in an adult organism allows researchers to analyze the genetic hierarchy of the process of development of genital cells at the molecular level. Violations of the functioning of the Foxl2 gene are observed in female infertility, so experts believe that a new experimental model will allow us to study the role of this gene in the production of sex hormones and the realization of female reproductive function.
The fact that a fully differentiated adult organ under certain conditions is able to undergo such radical changes is in itself a very surprising fact. Ten years ago, researchers were firmly convinced that a fully formed organ was no longer capable of such changes, but the results of recent work, including the discovery by Shinya Yamanaka of a complex of four factors that make it possible to turn a somatic cell into a pluripotent one, have greatly shaken this confidence.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: One gene keeps ovaries female.
14.12.2009