FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development

    1. Eric Pailhoux
    1. Biologie du Développement et de la Reproduction – UMR 1198 INRA-ENVA, Bât. J Poly, 78350 Jouy-en-Josas, France
    2. 1Physiologie de la Reproduction et des Comportements – UMR 6175 INRA-CNRS-Université de Tours, Haras Nationaux, 37380 Nouzilly, France
    3. 2INSERM U709 Génomique et Epigénétique des Pathologies Placentaires (Ex. U361), Hôpital Cochin, Pavillon Baudelocque, 123 Bd de Port Royal, 75014 Paris, France
    1. (Requests for offprints should be addressed to E Pailhoux; Email: eric.pailhoux{at}


    Previous studies have equated FOXL2 as a crucial actor in the ovarian differentiation process in different vertebrate species. Its transcriptional extinction in the polled intersex syndrome (PIS) leads primarily to a drastic decrease of aromatase (CYP19) expression in the first steps of goat ovarian development. In this study, we provide a better characterization of early ovarian development in goat, and we provide experimental evidence demonstrating that FOXL2 represents a direct transcriptional activator of the CYP19 gene through its ovarian-specific promoter 2. Moreover, the ovarian location of FOXL2 and CYP19 proteins, together with their expression profiles in the female gonads, stress the involvement of FOXL2 co-factor(s) for regulating CYP19 transcription. Expressional analyses show that activin-βA can be considered as a strong candidate for being one of these FOXL2 co-factors. Finally, we discuss evidence for a role of activin and estrogens in somatic and germinal cell proliferation occurring before germ cell meiosis. This period, of 20 days in goat, seems to have no equivalent in mouse. This species-specific difference could explain the phenotype discrepancy observed between XX goat PIS−/− and XX mouse Foxl2−/−.

    • Revision received 3 February 2006
    • Accepted 17 February 2006
    • Made available online as an Accepted Preprint 21 February 2006
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