Background <p>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.</p> Methods <p>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&#xa0;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&amp;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.</p> Results <p>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&amp;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&amp;E staining and GDF9/BMP15 expression (protein &amp; mRNA) confirmed enhanced oocyte quality in Neur-AMHR2^−/− mice, reinforcing the central role of neuronal AMHR2 in mediating AMH-induced ovarian dysfunction.</p> Conclusion <p>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.</p> Clinical trial number <p>Not applicable.</p>