More than half of polycystic ovary syndrome (PCOS) are overweight or obese. Environmental endocrine-disrupting chemicals (EDCs) are one of the important pathogenic factors in PCOS women. Methyl dihydrojasmonate (MDJ) is a food flavor additive, which can enter the body through several paths. However, the impact of MDJ on obese PCOS patients is still unknown. Hence, the study aims to determine whether MDJ may induce hallmarks of PCOS as new EDCs. The blood samples (33 obese PCOS patients and 30 controls) were collected for metabonomic sequencing. Sequencing results that serum MDJ level was significantly increased in obese PCOS patients, and was closely associated with the clinical phenotype of PCOS. C57BL/6J female mice fed high-fat diets were randomly divided into four groups. The PCOS model was established by subcutaneous injection of dehydroepiandrosterone for 21 days. Different concentrations of MDJ group were gavage of MDJ (60, and 120 mg/kg/d), and the control group was gavage of corn oil, once daily from pregnancy to offspring 16 weeks old. After 16 weeks, different concentrations of MDJ treatment resulted in an irregular estrus cycle and disturbed ovarian development in female mice. Serum TT and insulin resistance levels were increased in the MDJ group. At the cellular level, different concentrations of MDJ (50, and 100 μg/L) intervention mouse-primary-granulosa-cells (mpGCs) and measured supernatant TT levels after 48h. In the mouse ovarian tissue and mpGCs, we found that the expression of key genes for steroid synthesis (Star, Cyp17a1, Hsd3b1, Lhcgr) was increased significantly, while the expression of Cyp19a1 decreased after different concentrations of MDJ treatments. In preliminary experiments, we found that long-term exposure to MDJ during pregnancy and growth can induce PCOS phenotype in C57BL/6J female mice. Ongoing studies will determine how MDJ induces the hallmarks of PCOS and related mechanisms, which may help reveal the pathogenesis of PCOS.

Disclosure

M.Cai: None. D.Dilimulati: None. Y.Zhang: None. X.Shao: None. S.Qu: None. M.Zhang: None.

Funding

National Key R&D Program of China (2018YFC1314100); National Natural Science Foundation of China (81601269)

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