The Bone Morphogenetic Protein 15 Up-Regulates the Anti-Müllerian Hormone Receptor Expression in Granulosa Cells

Context: Anti-Mullerian hormone (AMH) is produced by the granulosa cells (GCs) of growing follicles and inhibits follicular development. Objective: This study aimed to investigate the regulation of the AMH-specific type 2 receptor (AMHR2) gene expression in GCs by bone morphogenetic protein (BMP)15, BMP4 and growth differentiation factor (GDF)9. Design, Setting, and Patients: Their effects on AMHR2 and AMH mRNAs were studied in luteinized human GCs 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. Main Outcome Measures: mRNAs were quantified by real-time RT-PCR. Promoter reporter constructs activities were quantified by the measurement of their luciferase activity. Results: BMP15 and BMP4 enhanced AMHR2 and AMH expression ...