Fetus

About: Fetus is a research topic. Over the lifetime, 21567 publications have been published within this topic receiving 646380 citations. The topic is also known as: foetus & fœtus.

Activation of the maternal immune system induces endocrine changes in the placenta via IL-6.

Abstract: Activation of the maternal immune system in rodent models sets in motion a cascade of molecular pathways that ultimately result in autism- and schizophrenia-related behaviors in offspring. The finding that interleukin-6 (IL-6) is a crucial mediator of these effects led us to examine the mechanism by which this cytokine influences fetal development in vivo. Here we focus on the placenta as the site of direct interaction between mother and fetus and as a principal modulator of fetal development. We find that maternal immune activation (MIA) with a viral mimic, synthetic double-stranded RNA (poly(I:C)), increases IL-6 mRNA as well as maternally-derived IL-6 protein in the placenta. Placentas from MIA mothers exhibit increases in CD69+ decidual macrophages, granulocytes and uterine NK cells, indicating elevated early immune activation. Maternally-derived IL-6 mediates activation of the JAK/STAT3 pathway specifically in the spongiotrophoblast layer of the placenta, which results in expression of acute phase genes. Importantly, this parallels an IL-6-dependent disruption of the growth hormone-insulin-like growth factor (GH-IGF) axis that is characterized by decreased GH, IGFI and IGFBP3 levels. In addition, we observe an IL-6-dependent induction in pro-lactin-like protein-K (PLP-K) expression as well as MIA-related alterations in other placental endocrine factors. Together, these IL-6-mediated effects of MIA on the placenta represent an indirect mechanism by which MIA can alter fetal development.

Function of IRE1 alpha in the placenta is essential for placental development and embryonic viability

Abstract: Inositol requiring enzyme-1 (IRE1), a protein located on the endoplasmic reticulum (ER) membrane, is highly conserved from yeast to humans. This protein is activated during ER stress and induces cellular adaptive responses to the stress. In mice, IRE1α inactivation results in widespread developmental defects, leading to embryonic death after 12.5 days of gestation. However, the cause of this embryonic lethality is not fully understood. Here, by using in vivo imaging analysis and conventional knockout mice, respectively, we showed that IRE1α was activated predominantly in the placenta and that loss of IRE1α led to reduction in vascular endothelial growth factor-A and severe dysfunction of the labyrinth in the placenta, a highly developed tissue of blood vessels. We also used a conditional knockout strategy to demonstrate that IRE1α-deficient embryos supplied with functionally normal placentas can be born alive. Fetal liver hypoplasia thought to be responsible for the embryonic lethality of IRE1α-null mice was virtually absent in rescued IRE1α-null pups. These findings reveal that IRE1α plays an essential function in extraembryonic tissues and highlight the relationship of physiological ER stress and angiogenesis in the placenta during pregnancy in mammals.