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Fetal estrogens are not involved in sex determination but critical for early ovarian differentiation in rabbits
Inactivation of the aromatase gene in rabbits demonstrates the fundamental role of oestrogens in the establishment of the germ cell reserve in the fetal ovary.
Published on 19 November 2021

AROMATASE is encoded by the CYP19A1 gene and is the cytochrome enzyme responsible for estrogen synthesis in vertebrates. In most mammals, a peak of CYP19A1 gene expression occurs in the fetal XX gonad when sexual differentiation is initiated.
To elucidate the role of this peak, we produced 3 lines of TALEN genetically edited CYP19A1 knockout (KO) rabbits that were devoid of any estradiol production.
All the KO XX rabbits developed as females with aberrantly small ovaries in adulthood, an almost empty reserve of primordial follicles, and very few large antrum follicles. Ovulation never occurred.
Our histological, immunohistological, and transcriptomic analyses showed that the estradiol surge in the XX fetal rabbit gonad is not essential to its determination as an ovary, or for meiosis. However, it is mandatory for the high proliferation and differentiation of both somatic and germ cells, and consequently for establishment of the ovarian reserve.
Jolivet G, Daniel-Carlier N, Harscoët E, Airaud E, Dewaele A, Pierson C, Giton F, Boulanger L, Daniel N, Mandon-Pépin B, Pannetier M, Pailhoux E, 2021, Fetal estrogens are not involved in sex determination but critical for early ovarian differentiation in rabbits. Endocrinology. https://doi.org/10.1210/endocr/bqab210