Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta.
Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta.
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DOI：
10.3390/genes13010130
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发表时间：
2022-01-12
期刊：
影响因子：
3.5
通讯作者：
Salbaum JM
中科院分区：
文献类型：
--
作者：
Kappen C;Kruger C;Salbaum JM
怀孕期间的不良暴露已被证明有助于后代对慢性疾病的易感性。妊娠期糖尿病与妊娠并发症、结构性出生缺陷和生命后期心脏代谢健康损害的风险较高相关。我们先前在小鼠模型中显示，糖尿病妊娠的胎盘较小，结合区和迷路的尺寸减小。此外，细胞迁移受损，导致迷路内海绵滋养细胞异位积聚。本研究的目的是确定潜在的生长缺陷和滋养细胞迁移异常的机制。基于47个候选基因的基因表达测定，我们能够将糖尿病胎盘生长减少归因于胰岛素生长因子和5-羟色胺信号通路的改变，并为前列腺素信号转导缺陷作为异常滋养层迁移的可能原因提供证据。此外，我们的研究结果加强了这样一种观点，即母体糖尿病对妊娠中期时间点的基因表达有特别明显的影响。这些发现的一个含义是，潜在的机制发育编程的行为在怀孕早期，胎盘形态发生期间，和之前的概念从histiotrophic营养切换到hemotrophic营养。
Adverse exposures during pregnancy have been shown to contribute to susceptibility for chronic diseases in offspring. Maternal diabetes during pregnancy is associated with higher risk of pregnancy complications, structural birth defects, and cardiometabolic health impairments later in life. We showed previously in a mouse model that the placenta is smaller in diabetic pregnancies, with reduced size of the junctional zone and labyrinth. In addition, cell migration is impaired, resulting in ectopic accumulation of spongiotrophoblasts within the labyrinth. The present study had the goal to identify the mechanisms underlying the growth defects and trophoblast migration abnormalities. Based upon gene expression assays of 47 candidate genes, we were able to attribute the reduced growth of diabetic placenta to alterations in the Insulin growth factor and Serotonin signaling pathways, and provide evidence for Prostaglandin signaling deficiencies as the possible cause for abnormal trophoblast migration. Furthermore, our results reinforce the notion that the exposure to maternal diabetes has particularly pronounced effects on gene expression at midgestation time points. An implication of these findings is that mechanisms underlying developmental programming act early in pregnancy, during placenta morphogenesis, and before the conceptus switches from histiotrophic to hemotrophic nutrition.
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