Chronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts.

TitleChronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts.
Publication TypeJournal Article
Year of Publication2022
AuthorsMan L, Guahmich NLustgarten, Kallinos E, Caiazza B, Khan M, Liu Z-Y, Patel R, Torres C, Pepin D, Yang HS, Bodine R, Zaninovic N, Schattman G, Rosenwaks Z, James D
JournalSci Adv
Volume8
Issue10
Paginationeabi7315
Date Published2022 03 11
ISSN2375-2548
KeywordsAnimals, Anti-Mullerian Hormone, Endothelial Cells, Female, Heterografts, Humans, Luteinization, Mice, Ovarian Follicle
Abstract

Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and provides a diagnostic measure of reproductive reserve in women; however, the impact of AMH on folliculogenesis is poorly understood. We cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and downstream single-cell RNA sequencing of granulosa and theca/stroma cell fractions. A total of 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals (>10 weeks). In the context of exogenous AMH, follicles exhibited a decreased ratio of primordial to growing follicles and antral follicles of increased diameter. Transcriptomic analysis and immunolabeling revealed a marked increase in factors typically noted at more advanced stages of follicle maturation, with granulosa and theca/stroma cells also displaying molecular hallmarks of luteinization. These results suggest that superphysiologic AMH alone may contribute to ovulatory dysfunction by accelerating maturation and/or luteinization of antral-stage follicles.

DOI10.1126/sciadv.abi7315
Alternate JournalSci Adv
PubMed ID35263130
PubMed Central IDPMC8906729
Grant ListR21 HD103956 / HD / NICHD NIH HHS / United States