title: Loss of R-spondin1 and Foxl2 amplifies female-to-male sex reversal in XX mice.
abstract: In vertebrates, 2 main genetic pathways have been shown to regulate ovarian development. Indeed, a loss of function mutations in Rspo1 and Foxl2 promote partial female-to-male sex reversal. In mice, it has been shown that the secreted protein RSPO1 is involved in ovarian differentiation and the transcription factor FOXL2 is required for follicular formation. Here, we analysed the potential interactions between these 2 genetic pathways and have shown that while Rspo1 expression seems to be independent of Foxl2 up-regulation, Foxl2 expression partly depends of Rspo1 signalisation. This suggests that different Foxl2-positive somatic cell lineages exist within the ovaries. In addition, a combination of both mutated genes in XX Foxl2(-/-)/Rspo1(-/-) gonads promotes sex reversal, detectable at earlier stages than in XX Rspo1(-/-) mutants. Ectopic development of the steroidogenic lineage is more pronounced in XX Foxl2(-/-)/Rspo1(-/-) gonads than in XX Rspo1(-/-) embryos, suggesting that Foxl2 is involved in preventing ectopic steroidogenesis in foetal ovaries.
authors: INRA, UMR 1198, Biologie du Développement et de la Reproduction, Jouy-en-Josas, France.
authors: A
authors: A
authors: Auguste
authors: A-A
authors: AA
authors: Chassot
authors: E P
authors: EP
authors: Grégoire
authors: L
authors: L
authors: Renault
authors: M
authors: M
authors: Pannetier
authors: M
authors: M
authors: Treier
authors: Eric
authors: E
authors: Pailhoux
authors: M-C
authors: MC
authors: Chaboissier
mesh_terms: D000818:Animals; D012734:Disorders of Sex Development / Q000235:genetics; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D010053:Ovary / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012733:Sex Differentiation / Q000235:genetics / Q000502:physiology; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; C518903:RSPO1 protein, mouse; D019699:Thrombospondins