title: BMP15 regulates the inhibin/activin system independently of ovulation rate control in sheep.
abstract: Polymorphisms in the gene encoding bone morphogenetic protein 15 (BMP15) have been associated with multiple ovulations in sheep. As BMP15 regulates inhibin expression in rodents, we assumed that the ovarian inhibin/activin system could mediate part of the effect of BMP15 mutations in the regulation of ovulation rate in sheep. To answer this question, we have studied the effects of two natural loss-of-function mutations of BMP15 on the expression of components of this system. The FecXRand the FecXGrmutations, when present respectively in Rasa Aragonesa ewes at the heterozygous state and in Grivette ewes at the homozygous state, were associated with a twofold increase in ovulation rate. There were only small differences between mutant and wild-type ewes for mRNA expression of INHA, INHBA, ACVR1B, ACVR2A, FST or TGFBR3 in granulosa cells and inhibin A or activin A concentrations in follicular fluid. Moreover, the effects of mutations differed between breeds. In cultures of granulosa cells from wild-type ewes, BMP15, acting alone or in synergy with GDF9, stimulated INHA, INHBA and FST expression, but inhibited the expression of TGFBR3 Activin A did not affect INHBA expression, but inhibited the expression of ACVR2A also. The complexity of the inhibin/activin system, including positive and antagonistic elements, and the differential regulation of these elements by BMP15 and activin can explain that the effects of BMP15 mutations differ when present in different genetic backgrounds. In conclusion, the ovarian inhibin/activin system is unlikely to participate in the increase of ovulation rate associated with BMP15 mutations in sheep.
authors.affiliation: UMR85 PRC, INRA, CNRS, IFCEUniversité de Tours, Nouzilly, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Estienne
authors.affiliation: Unidad de Producción y Sanidad AnimalCentro de Investigación y Tecnología Agroalimentaria de Aragón (CITA), Instituto Agroalimentario de Aragón - IA2 (CITA-Universidad de Zaragoza), Zaragoza, España.
authors.forename: Belén
authors.initials: B
authors.lastname: Lahoz
authors.affiliation: UMR85 PRC, INRA, CNRS, IFCEUniversité de Tours, Nouzilly, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Jarrier
authors.affiliation: GenPhySEUniversité de Toulouse, INRA, INPT, ENVT, Castanet Tolosan, France.
authors.forename: Loys
authors.initials: L
authors.lastname: Bodin
authors.affiliation: Unidad de Producción y Sanidad AnimalCentro de Investigación y Tecnología Agroalimentaria de Aragón (CITA), Instituto Agroalimentario de Aragón - IA2 (CITA-Universidad de Zaragoza), Zaragoza, España.
authors.forename: José
authors.initials: J
authors.lastname: Folch
authors.affiliation: Unidad de Producción y Sanidad AnimalCentro de Investigación y Tecnología Agroalimentaria de Aragón (CITA), Instituto Agroalimentario de Aragón - IA2 (CITA-Universidad de Zaragoza), Zaragoza, España.
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Alabart
authors.affiliation: GenPhySEUniversité de Toulouse, INRA, INPT, ENVT, Castanet Tolosan, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Fabre
authors.affiliation: UMR85 PRC, INRA, CNRS, IFCEUniversité de Tours, Nouzilly, France Danielle.Monniaux@inra.fr.
authors.forename: Danielle
authors.initials: D
authors.lastname: Monniaux
mesh_terms: D028341:Activins / Q000235:genetics*; D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology; D055429:Growth Differentiation Factor 9 / Q000235:genetics; D007265:Inhibins / Q000235:genetics*; D009154:Mutation; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology*; D010060:Ovulation / Q000235:genetics*; D012756:Sheep
chemical_list: D055430:Bone Morphogenetic Protein 15; D055429:Growth Differentiation Factor 9; D028341:Activins; D007265:Inhibins