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Inactivation of the aromatase gene in rabbits reveals the fundamental role of oestrogens in establishing ovarian reserve during fetal life in non-rodent mammals

For a long time we have known that oestrogens play a major role in the differentiation of ovaries in mammals, however, their precise role during fetal differentiation is poorly known and differs among species. Scientists from the BREED Unit (SAPS, INRAE, Jouy-en-Josas) showed that in rabbits, as in humans, ostrogen synthesis in the ovaries begins early-on during fetal life.

The first step of this study was to obtain rabbits devoid of oestrogen synthesis following the introduction of a stop mutation using the TALEN technique in the CYP19A1 gene coding for aromatase, an enzyme responsible for the synthesis of oestrogens. The article then describes the phenotype of female gonads during their differentiation, from the "undifferentiated gonad stage" until they become adults. Thus, the total absence of oestrogen production by the fetal gonad with the XX genotype did not modify the ovarian destiny of this gonad but led to a massive and definite reduction in stored germ cells, constituting the ovarian reserve.

The study underlines the importance of autocrine regulations in the foetal gonad, suggesting that in utero exposition to anti-ostrogenic molecules (endocrine disruptors and other environmental factors) could alter the reproductive capacity of the individual to be born, by reducing the oocyte reserve.

Scientific:

• Geneviève Jolivet, UMR BREED, INRAE, genevieve.jolivet@inrae.fr