Placental Macrophages Offer Insight into Fetal Brain Health

Immune activation during pregnancy can negatively impact the development of fetal brain microglia—immune cells crucial for brain health—potentially leading to neurodevelopmental disorders in newborns. However, monitoring microglia development within the fetal brain is not feasible. New research from Massachusetts General Hospital suggests that the health of fetal macrophages in the placenta can serve as an indicator of fetal brain microglia health.

"If we can use fetal placental macrophages as a surrogate cell type or biomarker for fetal brain microglial programming, we have the opportunity to identify those children at greatest risk from in utero immune-activating exposures," said Andrea Edlow, senior author on the study published in Cell Reports. Immune-activating exposures during pregnancy include infections, obesity, diabetes, environmental toxins, and maternal stress.

Edlow and her team assessed placental macrophages in a mouse model of maternal diet-induced obesity using single-cell RNA sequencing. The study revealed similar gene expression signatures between fetal placental macrophages (Hofbauer cells) and fetal brain microglia under normal conditions and in response to maternal obesity. Interestingly, the sex of the fetus impacted how maternal obesity affected the placenta and fetal brain, with male cells exhibiting more dysregulated genes and neuroinflammatory signaling. 

When the researchers compared their mouse data with published human datasets, they found conserved gene expression patterns in placental macrophages, suggesting their findings may have clinical implications for humans.

"This work is a promising start for using fetal placental macrophages as a biomarker for fetal brain microglial programming in a variety of maternal exposures, and it could form the basis for creating personalized fetal models of neurodevelopment using cells from the placenta that are easily accessible at birth," said Edlow.