Endocrine and metabolic profiling of PMOS rat models in relation to clinical obese and non-obese phenotypes

Polyendocrine metabolic ovarian syndrome (PMOS) is a highly heterogeneous disorder characterized by diverse phenotypes, including obesity and hyperandrogenism. However, the extent to which current animal models replicate these clinical features remains poorly defined. This study systematically compared the endocrine and metabolic fidelity of different PMOS models to provide a basis for model selection in targeted research. A clinical cohort of 110 BMI-stratified PMOS patients and 100 healthy controls was recruited for endocrine and metabolic profiling. Concurrently, three PMOS rat models were established using Letrozole (Let), letrozole plus high-fat diet (Let + HFD), or dehydroepiandrosterone (DHEA). Eight-week-old female rats were used to establish the Let and Let + HFD models and their corresponding control groups ( n = 8 per group), whereas 3-week-old female rats were used to establish the DHEA model and its corresponding control group ( n = 8 per group). The phenotypic fidelity of these models was systematically evaluated by comparing body weight, hormonal levels, ovarian morphological changes, and metabolic markers with clinical features of PMOS. Patients with PMOS exhibited typical endocrine and metabolic abnormalities, including hyperandrogenism, insulin resistance, and increased antral follicle count (AFC), with metabolic disturbances being more pronounced in the obese phenotype. All three animal models reproduced the key features of PMOS, including hyperandrogenism and ovarian follicular abnormalities, but displayed distinct phenotypic characteristics. The Let model predominantly reflected reproductive endocrine dysfunction, the Let + HFD model showed more severe metabolic impairment characterized by obesity and dyslipidemia, and the DHEA model was mainly characterized by hyperandrogenism accompanied by hyperuricemia. Different PMOS animal models reflect distinct endocrine and metabolic features rather than the full clinical heterogeneity of PMOS. Appropriate model selection should therefore be guided by the specific research objective.