Lingling Ding1, Fei Gao2, Meng Zhang2, Wenjiang Yan2, Rong Tang1, Cheng Zhang2, Zi-Jiang Chen3. 1. Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, People's Republic of China; Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, People's Republic of China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, People's Republic of China. 2. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, People's Republic of China. 3. Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, People's Republic of China; Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, People's Republic of China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, People's Republic of China; Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, People's Republic of China. Electronic address: chenzijiang@hotmail.com.
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.
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 PCOSpatients 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 PCOSpatients 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 obesewomen 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, lipidmetabolism disorders, and GC apoptosis.
Authors: Vivian K Kawai; Rebecca T Levinson; Abiodun Adefurin; Daniel Kurnik; Sarah P Collier; Douglas Conway; Charles Michael Stein Journal: Pharmacogenomics Date: 2017-10-04 Impact factor: 2.533