Identification of early transcriptome signatures in placenta exposed to insulin and obesity.
Identification of early transcriptome signatures in placenta exposed to insulin and obesity.
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DOI：
10.1016/j.ajog.2015.02.026
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发表时间：
2015-05
影响因子：
9.8
通讯作者：
Hauguel-de Mouzon S
中科院分区：
文献类型：
--
作者：
Lassance L;Haghiac M;Leahy P;Basu S;Minium J;Zhou J;Reider M;Catalano PM;Hauguel-de Mouzon S
本研究的目的是探讨胰岛素对人类胎盘转录组和生物学过程的影响在早期妊娠。在自愿终止妊娠（7-12周）时，从17名瘦型（体重指数，20.9 ± 1.5 kg/m2）和18名肥胖型（体重指数，33.5 ± 2.6 kg/m2）妇女中获得母体血浆和胎盘绒毛组织。立即分离滋养层细胞，用胰岛素或溶媒进行体外处理。在与人类基因1.1 ST杂交后，使用基因组微阵列分析和真实的时间逆转录聚合酶链反应分析全局基因表达模式。在胰岛素治疗与未治疗的瘦女性滋养层中，定性分离了整体滋养层转录组。在瘦型妇女的滋养细胞中检测到的胰岛素敏感基因数量为2875（P <0.001）。母亲肥胖使胰岛素敏感基因的数量减少了30倍。胰岛素显着损害了几个基因网络调节细胞周期和胆固醇稳态，但没有修改相关的葡萄糖转运途径。肥胖与高胰岛素和胰岛素抵抗相关，但不是单独的母体高胰岛素血症，损害了妊娠早期胎盘的整体基因谱，突出线粒体功能障碍和能量代谢降低。我们首次报道人类滋养层细胞在妊娠早期对胰岛素调节高度敏感。与胰岛素抵抗相关的母体肥胖使胎盘转录组对胰岛素不敏感，对胎盘结构和功能具有潜在的不良后果。
The purpose of this study was to investigate the effects of insulin on human placental transcriptome and biological processes in first-trimester pregnancy. Maternal plasma and placenta villous tissue were obtained at the time of voluntary termination of pregnancy (7–12 weeks) from 17 lean (body mass index, 20.9 ± 1.5 kg/m2) and 18 obese (body mass index, 33.5 ± 2.6 kg/m2) women. Trophoblast cells were immediately isolated for in vitro treatment with insulin or vehicle. Patterns of global gene expression were analyzed using genome microarray profiling after hybridization to Human Gene 1.1 ST and real time reverse transcription–polymerase chain reaction. The global trophoblast transcriptome was qualitatively separated in insulin-treated vs untreated trophoblasts of lean women. The number of insulin-sensitive genes detected in the trophoblasts of lean women was 2875 (P < .001). Maternal obesity reduced the number of insulin-sensitive genes recovered by 30-fold. Insulin significantly impaired several gene networks regulating cell cycle and cholesterol homeostasis but did not modify pathways related to glucose transport. Obesity associated with high insulin and insulin resistance, but not maternal hyperinsulinemia alone, impaired the global gene profiling of early gestation placenta, highlighting mitochondrial dysfunction and decreased energy metabolism. We report for the first time that human trophoblast cells are highly sensitive to insulin regulation in early gestation. Maternal obesity associated with insulin resistance programs the placental transcriptome toward refractoriness to insulin with potential adverse consequences for placental structure and function.