title: Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary.
abstract: Recruitment of primordial follicles is essential for female fertility; however, the exact mechanisms regulating this process are largely unknown. Earlier studies using anti-Müllerian hormone (AMH)-deficient mice suggested that AMH is involved in the regulation of primordial follicle recruitment. We tested this hypothesis in a neonatal ovary culture system, in which ovaries from 2-d-old C57Bl/6J mice were cultured for 2 or 4 d in the absence or presence of AMH. Ovaries from 2-d-old mice contain multiple primordial follicles, some naked oocytes, and no follicles at later stages of development. We observed that in the cultured ovaries, either nontreated or AMH-treated, follicular development progressed to the same extent as in in vivo ovaries of comparable age, confirming the validity of our culture system. However, in the presence of AMH, cultured ovaries contained 40% fewer growing follicles compared with control ovaries. A similar reduction was found after 4 d of culture. Consistent with these findings, we noted lower inhibin alpha-subunit expression in AMH-treated ovaries compared with untreated ovaries. In contrast, expression of AMH ligand type II receptor and the expression of oocyte markers growth and differentiation factor 9 and zona pellucida protein 3 were not influenced by AMH. Based on the results, we suggest that AMH inhibits initiation of primordial follicle growth and therefore functions as an inhibitory growth factor in the ovary during these early stages of folliculogenesis.
authors.affiliation: Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands. durlinger@endov.fgg.eur.nl
authors.forename: Alexandra L L
authors.initials: AL
authors.lastname: Durlinger
authors.forename: Maria J G
authors.initials: MJ
authors.lastname: Gruijters
authors.forename: Piet
authors.initials: P
authors.lastname: Kramer
authors.forename: Bas
authors.initials: B
authors.lastname: Karels
authors.forename: Holly A
authors.initials: HA
authors.lastname: Ingraham
authors.forename: Mark W
authors.initials: MW
authors.lastname: Nachtigal
authors.forename: Jan Th J
authors.initials: JT
authors.lastname: Uilenbroek
authors.forename: J Anton
authors.initials: JA
authors.lastname: Grootegoed
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054304:Anti-Mullerian Hormone; D055430:Bone Morphogenetic Protein 15; D002478:Cells, Cultured; D004527:Egg Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins; D055429:Growth Differentiation Factor 9; D006131:Growth Inhibitors / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023282:Nuclease Protection Assays; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000187:drug effects* / Q000502:physiology*; D010053:Ovary / Q000166:cytology* / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013735:Testicular Hormones / Q000494:pharmacology*; D000072216:Zona Pellucida Glycoproteins
chemical_list: C525901:BMP15 protein, human; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; D004527:Egg Proteins; C525897:GDF9 protein, human; C525898:Gdf9 protein, mouse; D006023:Glycoproteins; D055429:Growth Differentiation Factor 9; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013735:Testicular Hormones; C082833:ZP4 protein, human; D000072216:Zona Pellucida Glycoproteins; D054304:Anti-Mullerian Hormone