title: Intra-cellular mechanism of Anti-Müllerian hormone (AMH) in regulation of follicular development.
abstract: Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily and plays a crucial role in testicular and ovarian functions. In clinical practice, AMH is used as a diagnostic and/or prognostic marker in women in association with ovulation induction and in various pathophysiological conditions. Despite widespread clinical use of AMH, our mechanistic understanding of AMH actions in regulating follicular development is limited. Using a mouse model, we in this study report that in vivo AMH treatment while stalls follicular development and inhibits ovulation, also prevents follicular atresia. We further show that these AMH actions are mediated through induction of two miRNAs, miR-181a and miR-181b, which regulate various aspects of FSH signaling and follicular growth, ultimately affecting downstream gene expression and folliculogenesis. We also report that in this mouse model AMH pre-treatment prior to superovulation improves oocyte yield. These studies, therefore, offer new mechanistic insight into AMH actions in folliculogenesis and point toward potential utilization of AMH as a therapeutic agent.
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Hayes
authors.affiliation: Center for Human Reproduction, New York, NY 10021, USA; Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Kushnir
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Ma
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Anindita
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Hen
authors.initials: H
authors.lastname: Prizant
authors.affiliation: Center for Human Reproduction, New York, NY 10021, USA; The Rockefeller University, New York, NY 10065, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gleicher
authors.affiliation: Division of Endocrinology & Metabolism, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA; Center for Human Reproduction, New York, NY 10021, USA. Electronic address: Aritro_Sen@urmc.rochester.edu.
authors.forename: Aritro
authors.initials: A
authors.lastname: Sen
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005496:Follicular Atresia / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013480:Superovulation / Q000187:drug effects
chemical_list: D006023:Glycoproteins; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone
keywords: AMH; FSH; Follicular development; miR-181a; miR-181b