Fetal brain health is indicated by placental cells

Neuroscience News

Summary: Fetal placental macrophages can serve as indicators of fetal brain microglia health, which are crucial for brain development.
Key Facts: Fetal placental macrophages can indicate the health of fetal brain microglia.
It’s not possible to monitor how microglia are developing within the fetal brain, but new research indicates that the health of fetal macrophages in the placenta can act as an indicator of the health of fetal brain microglia.
“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.
Single-cell RNA sequencing of mouse fetal placental macrophages (or Hofbauer cells) revealed similar gene expression signatures as fetal brain microglia during normal conditions and also in response to maternal diet-induced obesity.
Specifically, male placental macrophages and fetal brain microglia had a greater number of genes dysregulated by maternal obesity and more neuroinflammatory signaling than female cells.
“Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity” by Andrea Edlow et al.
We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs.

POSITIVE

Summary: Fetal placental macrophages, which are essential for brain development, can act as markers of the health of fetal brain microglia. The development of the fetus’s brain may be adversely affected by immune activation in pregnant women, such as that caused by infections or obesity.

Using mouse models, the research discovered that maternal obesity has a greater impact on male fetuses than female fetuses. This study creates opportunities for neurodevelopmental disorders early detection and treatment.

Important Information:.

Fetal brain microglia’s state can be determined by fetal placental macrophages.

Pregnancy-related immune activation impairs the development of the fetus’s brain.

The effects of maternal obesity affect male fetuses more than those of females.

The Mass General is the source.

Pregnancy-related immune activation can even result in neurodevelopmental disorders in the fetus by negatively impacting the development of macrophage immune cells, or fetal brain microglia.

The development of fetal brain microglia cannot be observed, but recent studies suggest that the health of fetal macrophages in the placenta may serve as a proxy for the health of fetal brain microglia.

The study, which is published in Cell Reports, was headed by researchers from Massachusetts General Hospital, one of the original institutions of the Mass General Brigham healthcare system.

We possess the potential to identify children who are most vulnerable to in utero immune-activating exposures if we can utilize fetal placental macrophages as a biomarker or substitute cell type for fetal brain microglial programming.

Senior author Andrea Edlow, MD, MSc, an associate professor of obstetrics, gynecology, and reproductive biology as well as a specialist in maternal-fetal medicine at Massachusetts General Hospital, said, “Identifying these children early creates the potential to intervene during key developmental windows to ameliorate the impact of those pregnancy exposures.”. Additionally, Dr. Edlow is an MGH Research Scholar.

During pregnancy, metabolic inflammation caused by obesity and diabetes, environmental toxins, stress on the mother, and bacterial and viral infections are a few examples of exposures that activate the immune system. In a mouse model of obesity brought on by a mother’s diet, Edlow and her colleagues evaluated placental macrophages.

Mice fetal placental macrophages, also known as Hofbauer cells, were subjected to single-cell RNA sequencing, which demonstrated gene expression signatures akin to those of fetal brain microglia both under normal circumstances and in response to obesity-induced maternal diet.

The way that maternal obesity affects the placenta and the fetal brain is interestingly dependent on the sex of the fetus. More genes dysregulated by maternal obesity and more neuroinflammatory signaling were present in male placental macrophages and fetal brain microglia than in female cells.

The researchers discovered conserved gene expression patterns in human and mouse placental macrophages when they compared their mouse data with publicly available human datasets. This finding raises the possibility that the therapeutic implications of the researchers’ mouse research may extend to human patients.

“This work is a promising beginning for using fetal placental macrophages as a biomarker for fetal brain microglial programming in a range of maternal exposures, and it may serve as a foundation for the development of customized fetal neurodevelopment models using readily accessible placental cells at birth,” added Edlow.

Funding: This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Robert and Donna Landreth Family Foundation, and the Charles Lafitte Foundation.

Regarding the news of this neurodevelopmental study.

Written by McKenzie Ridings.

Mass General is the source.

Reach out to McKenzie Ridings, Mass General.

Photo credit: Neuroscience News is acknowledged for this image.

Original Study: Disclosed under open access.

“Transcriptional profiles and responses to maternal diet-induced obesity are shared by Hofbauer cells and fetal brain microglia,” according to Andrea Edlow and colleagues. reports from cells.

Abstraction.

The transcriptional profiles and responses to maternal diet-induced obesity are similar in fetal brain microglia and Hofbauer cells.

Key points.

Microglia and Hofbauer cells, which are fetal placental macrophages, originate from the same place—the yolk sac.

Maternal obesity is revealed by scRNA-seq to have common transcriptional programs in these two cell types.

The effects of maternal obesity on microglia and Hofbauer cells differ depending on the sex.

Microglia’s response to maternal exposures may be measured by Hofbauer cells.

In conclusion.

Negative neurodevelopmental outcomes in offspring are linked to maternal immune activation; many of these effects are mediated by in utero microglial programming.

Because microglia are inaccessible during development, finding noninvasive biomarkers that correspond to the microglial programming of the fetal brain may enable screening and intervention.

We utilized single-cell RNA-seq to show shared transcriptional programs and lineage tracing to illustrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity.

The similarities and differences in placental resident macrophage signatures between humans and mice were found through comparison with human datasets.

Single-cell RNA-seq revealed sex differences in the common changes in fetal microglial and Hofbauer cell gene expression caused by maternal obesity.

We suggest that readily available at birth Hofbauer cells offer information about the programs of fetal brain microglia and could help identify children at risk for neurodevelopmental disorders at an early age.

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