Merhi Zaher, Polotsky Alex J, Bradford Andrew P, Buyuk Erkan, Chosich Justin, Phang Tzu, Jindal Sangita, Santoro Nanette
Division of Reproductive Biology, Department of Obstetrics and Gynecology, NYU Langone Medical Center, New York, NY, USA Division of Reproductive Endocrinology and Infertility, University of Vermont College of medicine, Burlington, VT, USA
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado, Denver, CO, USA.
Reprod Sci. 2015 Oct;22(10):1220-8. doi: 10.1177/1933719115572484. Epub 2015 Feb 11.
To determine whether obesity alters genes important in cellular growth and inflammation in human cumulus granulosa cells (GCs).
Eight reproductive-aged women who underwent controlled ovarian hyperstimulation followed by oocyte retrieval for in vitro fertilization were enrolled. Cumulus GC RNA was extracted and processed for microarray analysis on Affymetrix Human Genome U133 Plus 2.0 chips. Gene expression data were validated on GCs from additional biologically similar samples using quantitative real-time polymerase chain reaction (RT-PCR). Comparison in gene expression was made between women with body mass index (BMI) <25 kg/m(2) (group 1; n = 4) and those with BMI ≥25 kg/m(2) (group 2; n = 4).
Groups 1 and 2 had significantly different BMI (21.4 ± 1.4 vs 30.4 ± 2.7 kg/m(2), respectively; P = .02) but did not differ in age (30.5 ± 1.7 vs 32.7 ± 0.3 years, respectively; P = .3). Comparative analysis of gene expression profiles by supervised clustering between group 1 versus group 2 resulted in the selection of 7 differentially expressed genes: fibroblast growth factor 12 (FGF-12), protein phosphatase 1-like (PPM1L), zinc finger protein multitype 2 (ZFPM2), forkhead box M1 (FOXM1), cell division cycle 20 (CDC20), interleukin 1 receptor-like 1 (IL1RL1), and growth arrest-specific protein 7 (GAS7). FOXM1, CDC20, and GAS7 were downregulated while FGF-12 and PPM1L were upregulated in group 2 when compared to group 1. Validation with RT-PCR confirmed the microarray data except for ZFPM2 and IL1RL. As BMI increased, expression of FOXM1 significantly decreased (r = -.60, P = .048).
Adiposity is associated with changes in the expression of genes important in cellular growth, cell cycle progression, and inflammation. The upregulation of the metabolic regulator gene PPM1L suggests that adiposity induces an abnormal metabolic follicular environment, potentially altering folliculogenesis and oocyte quality.
确定肥胖是否会改变人卵丘颗粒细胞（GCs）中对细胞生长和炎症起重要作用的基因。
招募了8名接受控制性卵巢过度刺激后进行卵母细胞采集用于体外受精的育龄妇女。提取卵丘颗粒细胞RNA，并在Affymetrix人类基因组U133 Plus 2.0芯片上进行微阵列分析。使用定量实时聚合酶链反应（RT-PCR）在其他生物学相似样本的颗粒细胞上验证基因表达数据。对体重指数（BMI）<25 kg/m²（第1组；n = 4）和BMI≥25 kg/m²（第2组；n = 4）的女性的基因表达进行比较。
第1组和第2组的BMI有显著差异（分别为21.4±1.4和30.4±2.7 kg/m²；P = 0.02），但年龄无差异（分别为30.5±1.7和32.7±0.3岁；P = 0.3）。通过监督聚类对第1组和第2组之间的基因表达谱进行比较分析，筛选出7个差异表达基因：成纤维细胞生长因子12（FGF-12）、类蛋白磷酸酶1（PPM1L）、多类型锌指蛋白2（ZFPM2）、叉头框M1（FOXM1）、细胞分裂周期20（CDC20）、白细胞介素1受体样蛋白1（IL1RL1）和生长停滞特异性蛋白7（GAS7）。与第1组相比，第2组中FOXM1、CDC20和GAS7下调，而FGF-12和PPM1L上调。RT-PCR验证除ZFPM2和IL1RL外均证实了微阵列数据。随着BMI增加，FOXM1的表达显著降低（r = -0.60，P = 0.048）。
肥胖与细胞生长、细胞周期进程和炎症中重要基因的表达变化有关。代谢调节基因PPM1L的上调表明肥胖会诱导异常的卵泡代谢环境，可能改变卵泡发生和卵母细胞质量。
