Heat stress affects fetal brain and intestinal function associated with the alterations of placental barrier in late pregnant mouse

High ambient temperature-induced heat stress (HS) during pregnancy may affect the placental function and fetal development. Late gestation is a critical period of the developing fetal brain and intestine. The study aimed to investigate the effects of HS during late pregnancy on the function of placenta, fetal brain and intestine in a mouse model. We found that the number of stillborn fetal mice were increased due to maternal HS. Transcriptome analysis revealed that the expression of genes enriched in nutrients transport and metabolism of HS group were up-regulated in the placenta, but down-regulated in the fetal duodenum and jejunum. Interestingly, the concentration of triglyceride (TG) in the HS group was raised in the placenta, but reduced both in the fetal duodenum and jejunum compared with the thermal-neutral (TN) group. Additionally, maternal HS also reduced total cholesterol (TC) contents in the fetal duodenum. The mRNA expression and protein levels of placental fatty acid binding protein 2 and 4 (fabp2 and fabp4) were not affected by maternal HS, but the mRNA expression and protein levels of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase-2 (Dgat2) were decreased in the fetal intestine. Furthermore, maternal HS reduced the mRNA expression and protein levels of the placental 11beta-hydroxysteroid dehydrogenase type 2 (Hsd11b2) and 5-hydroxytryptamine receptor 1D (Htr1d). The concentrations of corticosterone and the expression of heat shock protein 90 beta family member 1 (hsp90b1), hypoxia up-regulated 1 (hyou1) and corticotropin releasing hormone receptor 1 (crhr1) enriched in response to glucocorticoids in the fetal brain were increased by maternal HS. Taken together, our findings demonstrated that maternal HS disrupted the placental glucocorticoid barrier and serotonin system associated with the raised corticosterone levels in the fetal brain, which might contribute to the decreased capacity of nutrients transport and metabolism in the fetal intestine.