Journal Article

AMH specifically targets neuronal AMHR2 to modulate the progression of polycystic ovary syndrome

Wu, Kaiming, Sun, Chang, Din, Ning, Guo, Jinqian, Wang, Ying, Sun, Miao, Li, Jing, Pan, Zimeng, Kuang, Hongying

2026

Overview

Background Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder among women of childbearing age, characterized by elevated serum anti-Müllerian hormone (AMH) levels as a key biomarker. This study primarily investigates the tissue-specific expression of AMHR2 (the receptor for AMH) and its mechanistic role in PCOS pathogenesis. Methods In this study, we employed a two-phase experimental approach to investigate the tissue-specific roles of AMHR2 in PCOS pathogenesis. First, we established extra-ovarian (Ex-AMHR2) and intra-ovarian (In-AMHR2) AMHR2 expression models through reciprocal ovarian transplantation between wild-type (WT) and conventional AMHR2 knockout (AMHR2 −/− ) female mice. Second, we systematically compared tissue-specific effects using conditional knockout models targeting either neuronal (Neur-AMHR2 −/− ) or ovarian (Ovary-AMHR2 −/− ) AMHR2 expression. All experimental groups received standardized AMH intervention (0.12 mg/kg, i.p., twice weekly for 4 weeks). Comprehensive evaluations included: (1) reproductive cyclicity monitoring and ovarian index calculation; (2) ELISA quantification of serum AMH, LH, FSH, T, E1, and E2 levels with derived hormonal ratios; (3) histopathological assessment of ovarian morphology via H&E staining with follicular enumeration; and (4) molecular analyses of oocyte quality markers (GDF9, BMP15) at both protein (Western blot) and mRNA (qPCR) levels. This integrated experimental paradigm enabled multi-dimensional characterization of compartmentalized AMHR2 signaling in PCOS development. Results By comparing mice with intraovarian and extraovarian expression of AMHR2, we discovered that the Ex-AMHR2 + AMH group exhibited significantly higher serum AMH levels than the In-AMHR2 + AMH group, along with hormonal profiles more consistent with PCOS pathology. Histological (H&E staining) analysis revealed severe follicular atresia, disorganized granulosa cell layers, and impaired luteal development in the Ex-AMHR2 + AMH group, further corroborated by reduced protein and mRNA expression of oocyte quality markers (GDF9, BMP15). Subsequent tissue-specific studies on AMHR2 reveal that the Neur-AMHR2 −/− +AMH group demonstrated restored estrous cyclicity, improved serum levels of AMH and related hormones, compared with Ovary-AMHR2 −/− +AMH group, indicating attenuated PCOS symptoms. Consistently, H&E staining and GDF9/BMP15 expression (protein & mRNA) confirmed enhanced oocyte quality in Neur-AMHR2 −/− mice, reinforcing the central role of neuronal AMHR2 in mediating AMH-induced ovarian dysfunction. Conclusion Neuronal AMHR2 serves as the specific binding site for AMH, and the neuronal AMH/AMHR2 signaling pathway contributes to PCOS pathogenesis by disrupting HPO axis hormone secretion and interfering with cyclic follicular development. Clinical trial number Not applicable.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Androgens / Anti-Müllerian hormone / Anti-Müllerian hormone type 2 receptor / CRISPR / Dehydration / Diabetes / Endocrine disorders / Endocrinology / Enumeration / Estrus cycle / Euthanasia / Females / Follicle-stimulating hormone / Gene expression / Genomes / Luteinizing hormone / Medicine / Medicine & Public Health / Metabolic Diseases / Metabolism / Ovaries / Pathogenesis / Polycystic ovary syndrome / rology / Serum levels / Signal transduction / Sutures / Traditional Chinese medicine / Womens health