Single-cell RNA sequencing reveals altered placental microenvironment due to maternal high-fat diet

Abstract

Background

The prevalence of childhood metabolic diseases has markedly increased in recent decades whereas the effects of maternal nutrients affecting the placental microenvironment are not clearly addressed.

Methods

In the present study, female C57BL/6J mice were fed with a high-fat diet (HFD) or control diet (CON) for 5 weeks prior to mating and then during pregnancy. Single-cell RNA sequencing (scRNA-seq) was used to dissect the placental cell atlas at embryonic day(E) 18.5.

Results

Maternal HFD led to a reduction in the composition of placental labyrinth zone (LZ) trophoblast cells and endothelial cells, together with a diminished LZ area and narrowed fetal vessels, related to a decreased placental efficiency. Pro-inflammatory placental NK1 cells and M1-like macrophages were more apparent in the placenta from HFD dams with inflammation features. Increased glycogen deposition and glycogen trophoblast cells were also detectable in the HFD placenta, likely associated with the altered metabolism of placental NK cells and macrophages.

Conclusions

Maternal HFD before and during pregnancy leads to an altered placental microenvironment with more inflammatory features and abnormal metabolic properties, which provides a better understanding on the mechanisms of intergenerational inheritance.