Endocrine Abstracts

JOINT1564

Background: The incidence of polycystic ovarian syndrome (PCOS) has been rising in India, affecting one in five women. While the aetiology of PCOS is multifactorial, growing evidence suggests that metabolic dysfunction and environmental contaminants, particularly phthalate exposure, may play a role. This study investigates the association between plasma phthalate metabolite concentrations and metabolic dysfunction in PCOS patients. Additionally, it explores the role of phthalates in modulating gene expression related to glucose and lipid metabolism, potentially linking phthalate exposure to metabolic dysfunction.

Methodology: Age-matched PCOS patients (n = 177) and healthy controls were recruited in the study after obtaining ethical clearance (IECPG-294/07. 06. 2023). PCOS patients were diagnosed according to the evidence-based Rotterdam diagnostic criteria (2023), and female individuals with no history of irregular menses, thyroid-related issues and metabolic dysfunction were recruited as healthy controls. Their plasma, serum and buffy coat samples were collected. Participants were screened for basic biochemical parameters, including fasting plasma glucose and lipid profile. The PCOS group was further stratified into high (hiTyG) and low (loTyG) triglyceride-glucose index (TyG) subgroups, using a cut-off value of 8. 5 based on studies conducted in Asian population. Plasma phthalate metabolite levels were quantified using LC-MS/MS, and gene expression analysis was conducted using qPCR.

Results: The PCOS group exhibited significantly higher fasting triglyceride levels (P<0. 001), with nearly 65% of them showing an elevated TyG index (P < 0. 01) indicative of metabolic dysfunction. The PCOS-hiTyG group had significantly higher phthalate metabolite concentrations compared to controls (P < 0. 01). Moreover, a strong correlation was observed between elevated plasma phthalate metabolite levels and increased TyG index (r_Pearson=0. 7610, P < 0. 05), with altered expression of key metabolic genes, including pparV°, cd36, glut4, and pten. These gene alterations negatively correlated with both the TyG index and phthalate metabolite levels (P < 0. 05), suggesting that phthalates may actively contribute to metabolic dysfunction in PCOS.

Conclusion: This study establishes a novel, significant link between phthalate exposure and genetic alterations in PCOS, highlighting phthalates as potential exacerbators of metabolic dysfunction. These findings underscore the need to monitor phthalate exposure in vulnerable populations and further investigate environmental contributors to endocrine disorders. Additionally, the study emphasizes the importance of early metabolic dysfunction screening in PCOS patients, advocating for the inclusion of indices such as the TyG index in early diagnosis.

Funding: This study is funded by Council of Scientific and Industrial Research (CSIR), Govt. Of India, F. No. 09/006(0525)/2020-EMR-I.