FOXL2 activates P450 aromatase gene transcription: towards a better characterization of the early steps of mammalian ovarian development.
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-betaA 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(-/-).
Pannetier
Maëlle
M
Biologie du Développement et de la Reproduction - UMR 1198 INRA-ENVA, Bât. J Poly, 78350 Jouy-en-Josas, France.
Fabre
Stéphane
S
Batista
Frank
F
Kocer
Ayhan
A
Renault
Lauriane
L
Jolivet
Geneviève
G
Mandon-Pépin
Béatrice
B
Cotinot
Corinne
C
Veitia
Reiner
R
Pailhoux
Eric
E
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D029404:Activin Receptors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006041:Goats; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D010053:Ovary / Q000166:cytology / Q000196:embryology* / Q000254:growth & development* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D013577:Syndrome; D014158:Transcription, Genetic
D051858:Forkhead Transcription Factors; D011960:Receptors, Estrogen; D007265:Inhibins; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D029404:Activin Receptors