Abstract
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.
Highlights
Diabetes during pregnancy is a known risk factor for congenital defects and pregnancy complications, such as spontaneous abortions and preeclampsia [1,2,3,4]
In a mouse model of type I diabetes, we previously showed that fetal growth is reduced, noticeable after gestational day 15.5, and that the growth reduction was more pronounced when the dam was fed a diet with higher fat and lower protein content compared to chow [11]
We showed that maternal diabetes affects metabolically normal pregnancies [13]
Summary
Diabetes during pregnancy is a known risk factor for congenital defects and pregnancy complications, such as spontaneous abortions and preeclampsia [1,2,3,4]. Even with normal diet, the contribution of spongiotrophoblast cells to the junctional zone of the placenta was decreased in diabetic pregnancies, and cells expressing the spongiotrophoblast marker Trophoblast-specific protein alpha (TpbpA) ectopically accumulated in the labyrinth [13].
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