GIG-EA 7404, Université de Versailles-St Quentin, Université Paris-Saclay, Unité de Formation et de Recherche des Sciences de la Santé Simone Veil, 2 avenue de la Source de la Bièvre, F-78180, Montigny-le-Bretonneux, France.
Service de Biologie Médicale, Centre Hospitalier de Poissy-Saint-Germain-en-Laye, Poissy, France.
Clin Epigenetics. 2019 Feb 7;11(1):20. doi: 10.1186/s13148-019-0612-6.
It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. Furthermore, it was recently reported that maternal obesity has a significant impact on placental development. Leptin and adiponectin are present at the fetal-maternal interface and are involved in the development of a functional placenta. However, less is known about leptin and adiponectin's involvement in the placental alterations described in obese women. Hence, the objective of the present study was to characterize the placental expression and DNA methylation of these two adipokine systems (ligands and receptors) in obese women.
Biopsies were collected from the fetal and maternal sides of third-trimester placenta in obese and non-obese (control) women. In both groups, leptin levels were higher on the fetal side than the maternal side, suggesting that this cytokine has a pivotal role in fetal growth. Secondly, maternal obesity (in the absence of gestational diabetes) was associated with (i) elevated DNA methylation of the leptin promoter on fetal side only, (ii) hypomethylation of the adiponectin promoter on the maternal side only, (iii) significantly low levels of leptin receptor protein (albeit in the absence of differences in mRNA levels and promoter DNA methylation), (iv) significantly low levels of adiponectin receptor 1 mRNA expression on the maternal side only, and (v) elevated DNA methylation of the adiponectin receptor 2 promoter on the maternal side only.
Our present results showed that maternal obesity is associated with the downregulation of both leptin/adiponectin systems in term placenta, and thus a loss of the beneficial effects of these two adipokines on placental development. Maternal obesity was also associated with epigenetic changes in leptin and adiponectin systems; this highlighted the molecular mechanisms involved in the placenta's adaptation to a harmful maternal environment.
肥胖与两种主要脂肪因子瘦素和脂联素之间比例的失调有关，这一点已得到充分证实。此外，最近有报道称，母体肥胖对胎盘发育有重大影响。瘦素和脂联素存在于胎儿-母体界面，参与功能性胎盘的发育。然而，关于肥胖女性中描述的胎盘改变中瘦素和脂联素的参与，人们知之甚少。因此，本研究的目的是描述肥胖女性中这两种脂肪因子系统（配体和受体）的胎盘表达和 DNA 甲基化。
在肥胖和非肥胖（对照）妇女的胎盘第三孕期胎儿和母体侧采集活检。在两组中，瘦素水平在胎儿侧均高于母体侧，这表明该细胞因子在胎儿生长中具有关键作用。其次，母体肥胖（无妊娠糖尿病）与以下情况相关：（i）仅在胎儿侧，瘦素启动子的 DNA 甲基化增加；（ii）仅在母体侧，脂联素启动子的低甲基化；（iii）瘦素受体蛋白水平显著降低（尽管在 mRNA 水平和启动子 DNA 甲基化方面没有差异）；（iv）仅在母体侧，脂联素受体 1 mRNA 表达水平显著降低；（v）仅在母体侧，脂联素受体 2 启动子的 DNA 甲基化增加。
本研究结果表明，母体肥胖与足月胎盘中的瘦素/脂联素系统下调有关，从而导致这两种脂肪因子对胎盘发育的有益作用丧失。母体肥胖还与瘦素和脂联素系统的表观遗传变化有关；这突出了涉及胎盘适应有害母体环境的分子机制。
