Nature Neuroscience 9, 220 - 226 (2006)
Published online: 1 January 2006; | doi:10.1038/nn1624
Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogensJulie Bakker1, Christelle De Mees2, Quentin Douhard1, Jacques Balthazart1, Philippe Gabant2, Josiane Szpirer2
& Claude Szpirer21
Center for Cellular & Molecular Neurobiology, University of Liège, Avenue de l'Hôpital 1, B36, 4000 Liège, Belgium. 2
Laboratoire de Biologie du Développement, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, 12 Rue Profs. Jeener & Brachet, B-6041 Gosselies (Charleroi), Belgium.
Correspondence should be addressed to Julie Bakker jbakker@ulg.ac.be Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mutant mice (Afp-/-) now finally allows us to resolve this longstanding controversy concerning the role of AFP in brain sexual differentiation, and thus to determine whether prenatal estrogens contribute to the development of the female brain. Here we show that the brain and behavior of female Afp-/- mice were masculinized and defeminized. However, when estrogen production was blocked by embryonic treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione, the feminine phenotype of these mice was rescued. These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens.
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