Higher PDCD4 expression is associated with obesity, insulin resistance, lipid metabolism disorders, and granulosa cell apoptosis in polycystic ovary syndrome

Abstract

Objective: To investigate the expression and clinical significance of programmed cell death 4 (PDCD4), a novel metabolism-associated gene, during polycystic ovary syndrome (PCOS) pathogenesis.

Design: Case-control study.

Setting: University hospital.

Patient(s): A total of 77 PCOS patients and 67 healthy women as matched controls.

Intervention(s): PDCD4 expression in peripheral blood mononuclear cells analyzed by quantitative real-time polymerase chain reaction, and apoptosis of granulosa cells (GCs) detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and small-interfering RNA.

Main outcome measure(s): PDCD4 expression, body mass index (BMI), insulin 0, insulin 120, glucose 120, homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β-cell function (HOMA-β), triglycerides, high-density lipoprotein (HDL), and GC apoptosis.

Result(s): The PCOS patients had higher PDCD4 expression, but BMI was similar as matched with the obese group, which positively correlated with BMI, insulin 0, insulin 120, glucose 120, HOMA-IR, HOMA-β, triglycerides and negatively correlated with HDL (P<.05). After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance. Compared with the healthy controls, the apoptosis percentage of GCs was higher in the PCOS group and was decreased by knocking down PDCD4. Furthermore, expression of proapotosis factor Bax and the Bax/Bcl-2 ratio were lower, whereas the expression of antiapoptosis factor Bcl-2 was increased. In a multivariate logistic regression analysis, the level of PDCD4 expression independently related to the odds of PCOS risk after controlling for estradiol and insulin 120 (odds ratio 1.318).

Conclusion(s): Our study suggests for the first time that higher PDCD4 expression might play an important role in PCOS pathogenesis by affecting obesity, insulin resistance, lipid metabolism disorders, and GC apoptosis.

Keywords: Apoptosis; PDCD4 expression; granulosa cells; insulin resistance; lipid metabolism; obesity; polycystic ovary syndrome.