2023-11-02 18:04:00
The discovery published this Thursday, November 2 in the prestigious journal Science immediately found an echo at the international level.
All microphones are aimed at the team which has just provided the proof awaited for 30 years that, like what happens to male sexual development, there is indeed a specific determinant of orientation towards sex. feminine.
Contrary to what we have long believed, we do not become a woman, because we do not have “what it takes” to become a man, in this case a gene called Sry.
This is the (very simplified) summary of the studies carried out by five European teams, led by the Nice team of Marie-Christine Chaboissier (Institut de Biologie Valrose).
The scientist, already known worldwide for her work on sex determination and fertility, returns to the chronicle of this discovery: “When Sry, the gene determining the development of the testicles, was discovered in 1990, we thought that we would immediately identify the other important players in sexual determination, and the development of the ovaries in particular. In reality , it took more than 30 years to finally discover this much sought-following determinant. And ironically, it is a variant (different form, Editor’s note) of a so-called tumor suppressor gene, WT1, involved in diseases rare kidney, discovered in…1991, the same year as Sry, the testicular determinant.”
If it took so many years to reach this conclusion, it is partly because this research had to rely on extremely cutting-edge molecular genetic techniques, recently developed.
Frasier Syndrome
But how did we come to prove that a gene involved in kidney disease and responsible for abnormalities in the kidney was also “in control” of sexual orientation? “As was the case for the male determinant, we were guided by discoveries made in patients with “troubles” of sexual development”replies the scientist.
Among them, people with so-called Frasier syndrome. “These patients are of male genetic sex, since they are XY, but they have female-type genitalia and develop, when they are older, kidney disease, a reason which leads them to consult. The analysis of their genome has highlighted an imbalance between two genetic variants named -KTS and +KTS, originating from the WT1 gene.”
To analyze the role of these +KTS and -KTS isoforms in the development of the sexual organs (ovary or testicle), Elodie Gregoire, engineer in Marie-Christine Chaboissier’s team, used genetically modified mouse models. expressing only one of these two isoforms.
“It was thus possible to demonstrate that the absence of -KTS prevents all development of the ovary. In contrast, overexpression of -KTS activates ovarian development, preventing the activation of the Sry gene in the XY gonad. This gonad therefore does not become a testicle but an ovary. And this deregulation leads to Frasier syndrome.”
An important step in the knowledge of sexual development has been reached, which should also allow progress in the understanding of diseases associated with problems of sexual differentiation. “For more than 50% of them, we are unaware of the causes.” This discovery should shed light on its exploration.
What gender?
In most mammals, sex is determined during fertilization. The mother transmits the X sex chromosome while the father transmits an X or Y chromosome. Thus the XX embryo becomes a female while an XY individual becomes a male through the process called “sex determination”. This process allows the undifferentiated gonad to develop into an ovary or testis, thus initiating all sexual development of the individual.
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