Expression and significance of ependymin-related protein 1 and neuregulin 4 in the serum of patients with polycystic ovary syndrome.

OBJECTIVE: This study investigates the expression of ependymin-related protein 1 (EPDR1) and neuregulin 4 (NRG4) in the serum of patients with polycystic ovary syndrome (PCOS) and their relationship with glucose and lipid metabolism in order to explore the pathogenesis of PCOS and provide new theoretical basis for its treatment.

METHODS: A total of 282 PCOS patients were selected as the experimental group, and 60 healthy women were selected as the control group. The levels of EPDR1 and NRG4 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), progesterone (P), and prolactin (PRL) were also measured. All subjects underwent tests for triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) as well as insulin release test (IRT) and oral glucose tolerance test (OGTT). The PCOS group was further divided into obese and non-obese subgroups based on body mass index (BMI) and into insulin resistance (PCOS-IR) and non-insulin resistance (PCOS-non-IR) subgroups based on HOMA-IR values. Further stratification was performed based on BMI and HOMA-IR to divide the PCOS group into PCOS obese IR, PCOS obese non-IR, PCOS non-IR non-obese, and PCOS-IR non-obese subgroups to clarify the relationship between NRG4, EPDR1, and PCOS.

RESULTS: The BMI, waist-to-hip ratio (WHR), LH, LH/FSH, T, HOMA-IR, TC, TG, and LDL-C levels in the PCOS group were significantly higher than those in the control group, while HDL-C, EPDR1 and NRG4 levels were significantly lower than those in the control group (P < 0.05). The HOMA-IR, BMI, WHR, TC, TG, and LDL-C levels in the PCOS obese subgroup were significantly higher than those in the non-obese subgroup, while HDL-C, NRG4, and EPDR1 levels were significantly lower than those in the non-obese subgroup (P < 0.05). The BMI, WHR, TC, TG, and LDL-C levels in the PCOS-IR subgroup were significantly higher than those in the PCOS-non-IR subgroup, while NRG4 and EPDR1 levels were significantly lower than those in the PCOS-non-IR subgroup (P < 0.05). Multiple linear regression analysis showed that NRG4 was negatively correlated with BMI, IR, T, LH/FSH, TC, and EPDR1 (P < 0.05); EPDR1 was negatively correlated with BMI, LH/FSH, and TC (P < 0.05). In the PCOS group, NRG4 was negatively correlated with BMI, IR, LDL-C, and EPDR1 (P < 0.05); EPDR1 was negatively correlated with BMI, IR, LH/FSH, TC, and LDL-C and positively correlated with HDL-C (P < 0.05).

CONCLUSION: Serum levels of EPDR1 and NRG4 were significantly decreased in PCOS patients and showed significant correlations with key metabolic and endocrine parameters (BMI, T, HOMA-IR, LH/FSH ratio, and lipid profiles). These findings highlight their potential value as diagnostic biomarkers for PCOS, reflecting the associated metabolic disturbances.