1. The Bone Morphogenetic Protein 15 Up-Regulates the Anti-Müllerian Hormone Receptor Expression in Granulosa Cells
- Author
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Jean-Yves Picard, J. Folch, Anthony Estienne, Stéphane Fabre, B. Lahoz, Renato Fanchin, Peggy Jarrier, Chrystèle Racine, Alice Pierre, Danielle Monniaux, Nathalie di Clemente, J.L. Alabart, U 1133, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Unidad de Producción y Sanidad Animal, Centro de Investigacion y Technologia Agroalimentaria de Aragon (CITA), Instituto Agroalimentario de Aragón, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Agence Nationale pour la Recherche (grant ANR-12-BSV1–0034–01 to Nathalie di Clemente, grant ANR-10-BLAN-1608–01 to Stéphane Fabre), Agence de la Biomédecine (grant to Renato Fanchin), Région Centre, INRA, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,cellule de granulosa ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Growth Differentiation Factor 9 ,Bone Morphogenetic Protein 4 ,Biochemistry ,mullerian-inhibitory substance ,Ovinos ,0302 clinical medicine ,Endocrinology ,Ovarian Follicle ,bone morphogenetic protein ,Promoter Regions, Genetic ,Regulation of gene expression ,030219 obstetrics & reproductive medicine ,Up-Regulation ,medicine.anatomical_structure ,producción y sanidad animal ,hormone antimullérienne ,Bone morphogenetic protein 4 ,Hormone receptor ,Reproductividad ,Female ,Bone Morphogenetic Protein 15 ,hormones, hormone substitutes, and hormone antagonists ,Autre (Sciences du Vivant) ,Adult ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,endocrine system ,medicine.medical_specialty ,Receptors, Peptide ,Biology ,Growth differentiation factor-9 ,Bone morphogenetic protein ,Young Adult ,03 medical and health sciences ,Internal medicine ,Anti-Müllerian hormone receptor ,medicine ,Animals ,Humans ,Ovarian follicle ,protéine morphogénétique ,Granulosa Cells ,Sheep ,Bone morphogenetic protein 15 ,urogenital system ,Biochemistry (medical) ,Genética ,030104 developmental biology ,Gene Expression Regulation ,Receptors, Transforming Growth Factor beta - Abstract
Anti-Müllerian hormone (AMH) is produced by the granulosa cells (GCs) of growing follicles and inhibits follicular development. This study aimed to investigate the regulation of the AMH-specific receptor gene (AMHR2) expression in GCs by bone morphogenetic protein 15 (BMP15), BMP4 and growth differentiation factor 9 (GDF9). Their effects on AMHR2 and AMH mRNAs were studied in luteinized human GCs (hGCs) and in ovine GCs (oGCs) from small antral follicles. The effects of BMPs on human AMHR2 and AMH promoter reporter activities were analyzed in transfected oGCs. The in vivo effect of BMP15 on GCs AMHR2 and AMH expression was investigated by using Lacaune and Rasa Aragonesa hyperprolific ewes carrying loss-of-function mutations in BMP15. mRNAs were quantified by real-time RT-PCR. Promoter reporter constructs activities were quantified by the measurement of their luciferase activity. BMP15 and BMP4 enhanced AMHR2 and AMH expression in hGCs and in oGCs whereas GDF9 had no effect. In oGCs, GDF9 increased BMP15 effect on AMH expression. Consistent with these results, BMP15 and BMP4, but not GDF9, enhanced AMHR2 promoter activity in oGCs, whereas GDF9 increased BMP15 effect on AMH promoter activity. Moreover, oGCs from both BMP15 mutant ewes had reduced AMHR2 mRNA levels but unchanged AMH expression compared to wild-type ewes. Altogether, these results suggest that the mechanisms of action of BMP15 on AMHR2 and AMH expression are different, and that by stimulating AMHR2 and AMH expression in GCs BMP15 enhances AMH inhibitory actions in GCs.
- Published
- 2016