Uric acid (UA) is the end metabolic product of purine metabolism. Early on, UA was considered to be a metabolite with a certain antioxidant capacity. As research has progressed, other properties of UA have been explored, and its association with many diseases has been found. The association between UA and kidney disease and cardiovascular disease is well established; however, there is still a paucity of reviews on the association between UA and the female reproductive system. An increasing number of epidemiological studies have shown elevated serum UA levels in patients with polycystic ovary syndrome (PCOS), endometriosis, etc. Additionally, serum UA can be used as a predictor of pregnancy complications and adverse foetal outcomes. An increasing number of animal experiments and clinical studies have revealed possible mechanisms related to the involvement of UA in certain female reproductive disorders: oxidative stress, chronic inflammation, mitochondrial dysfunction, etc. This article reviews the current mainstream mechanisms regarding the pathogenesis of UA and the role of UA in certain specific female reproductive disorders (direct involvement in the development of certain diseases or enhancement of other risk factors) in the hope of contributing to clinical prevention, diagnosis, treatment and improvement in prognosis.

Polycystic ovary syndrome (PCOS) is one of the most common diseases with the coexistence of reproductive malfunction and metabolic disorders. Previous studies have found increased branched chain amino acid (BCAA) levels in women with PCOS. However, it remains unclear whether BCAA metabolism is causally associated with the risk of PCOS. The changes of BCAA levels in the plasma and follicular fluids of PCOS women were detected. Mendelian randomization (MR) approaches were used to explore the potential causal association between BCAA levels and the risk of PCOS. The function of the gene coding the protein phosphatase Mg²⁺/Mn²⁺-dependent 1K (PPM1K) was further explored by using Ppm1k-deficient mouse model and PPM1K down-regulated human ovarian granulosa cells. BCAA levels were significantly elevated in both plasma and follicular fluids of PCOS women. Based on MR, a potential direct, causal role for BCAA metabolism was revealed in the pathogenesis of PCOS, and PPM1K was detected as a vital driver. Ppm1k-deficient female mice had increased BCAA levels and exhibited PCOS-like traits, including hyperandrogenemia and abnormal follicle development. A reduction in dietary BCAA intake significantly improved the endocrine and ovarian dysfunction of Ppm1k^-/- female mice. Knockdown of PPM1K promoted the conversion of glycolysis to pentose phosphate pathway and inhibited mitochondrial oxidative phosphorylation in human granulosa cells. Ppm1k deficiency-impaired BCAA catabolism causes the occurrence and development of PCOS. PPM1K suppression disturbed energy metabolism homeostasis in the follicular microenvironment, which provided an underlying mechanism of abnormal follicle development. This study was supported by the National Key Research and Development Program of China (2021YFC2700402, 2019YFA0802503), the National Natural Science Foundation of China (81871139, 82001503, 92057107), the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001), Key Clinical Projects of Peking University Third Hospital (BYSY2022043), the China Postdoctoral Science Foundation (2021T140600), and the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01).

Background: Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. Main text: Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. Conclusion: More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

Objective: To evaluate the association between neck circumference (NC) and hyperuricemia in women with polycystic ovary syndrome (PCOS).Methods: This is a cross-sectional study that recruited 601 women with PCOS from January 2018 to January 2021. PCOS was diagnosed according to the Rotterdam definition. Hyperuricemia was defined as serum uric acid level of at least 357 μmol/L.Results: PCOS females with hyperuricemia had significantly greater values of NC, body mass index (BMI), waist circumference (WC) and hip circumference (HC). NC was positively associated with serum uric acid levels, with a standardized regression coefficient of 0.34 after adjusting for confounding factors. Furthermore, logistic regression analysis showed that NC was significantly associated with an increased risk of hyperuricemia, with an adjusted odds ratio of 1.36. The associations between NC and serum uric acid levels were more considerable in those with medium/high BMI (BMI ≥ 21.63 kg/m²), all ranges of WC or medium/high HC (HC ≥ 90 cm). The optimal cut-off point of NC in predicting hyperuricemia was 32.0 cm (Youden index = 0.48), with the sensitivity and negative predictive value of 84.81% and 92.08%, respectively.Conclusions: NC was positively correlated with serum uric acid levels and the prevalence of hyperuricemia in women with PCOS. Therefore, we suggest NC as a simple, novel, and reliable anthropometric measure to be used in the routine clinical assessment of women with PCOS to screen those at high risk of hyperuricemia.