Ding Lingling, Gao Fei, Zhang Meng, Yan Wenjiang, Tang Rong, Zhang Cheng, Chen Zi-Jiang
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.
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.
Fertil Steril. 2016 May;105(5):1330-1337.e3. doi: 10.1016/j.fertnstert.2016.01.020. Epub 2016 Feb 8.
To investigate the expression and clinical significance of programmed cell death 4 (PDCD4), a novel metabolism-associated gene, during polycystic ovary syndrome (PCOS) pathogenesis.
Case-control study.
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.
研究新型代谢相关基因程序性细胞死亡4（PDCD4）在多囊卵巢综合征（PCOS）发病机制中的表达及临床意义。
病例对照研究。
大学医院。
共77例PCOS患者和67例健康女性作为匹配对照。
采用定量实时聚合酶链反应分析外周血单个核细胞中PDCD4的表达，通过流式细胞术、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）和小干扰RNA检测颗粒细胞（GCs）的凋亡。
PDCD4表达、体重指数（BMI）、空腹胰岛素、120分钟胰岛素、120分钟血糖、胰岛素抵抗稳态模型评估（HOMA-IR）、β细胞功能稳态模型评估（HOMA-β）、甘油三酯、高密度脂蛋白（HDL）以及GC凋亡。
PCOS患者的PDCD4表达较高，但BMI与肥胖组匹配时相似，且与BMI、空腹胰岛素、120分钟胰岛素、120分钟血糖、HOMA-IR、HOMA-β、甘油三酯呈正相关，与HDL呈负相关（P<0.05）。二甲双胍治疗后，有胰岛素抵抗的肥胖PCOS女性的PDCD4表达明显下调。与健康对照相比，PCOS组GCs的凋亡百分比更高，敲低PDCD4后凋亡减少。此外，促凋亡因子Bax的表达及Bax/Bcl-2比值降低，而抗凋亡因子Bcl-2的表达增加。在多因素逻辑回归分析中，控制雌二醇和120分钟胰岛素后，PDCD4表达水平与PCOS风险几率独立相关（比值比1.318）。
我们的研究首次表明，较高的PDCD4表达可能通过影响肥胖、胰岛素抵抗、脂质代谢紊乱和GC凋亡在PCOS发病机制中起重要作用。
