High-fat diet in pregnant monkeys impairs fetal blood stem cells

Maternal consumption of a Western-like diet alters the transcriptional landscape of fetal blood stem cells in rhesus macaques, researchers report Nov.rd in the review Stem Cell Reports.

“This finding is the first demonstration in primates that poor maternal nutrition and obesity disrupt the immune system of the developing fetus,” says Oleg Varlamov of the National Primate Research Center in Oregon. “The main implication of this study is that maternal obesity may influence the development of fetal bone marrow and fetal immune system.”

Obesity before pregnancy is associated with an increased risk of infection and aberrant inflammatory responses in offspring, but the underlying mechanisms remain largely unknown. In particular, very little is known about the effect of a Western-style diet on fetal hematopoiesis – the formation of blood cell components – in animal models that resemble human development.

During late development, the fetal bone marrow becomes the primary site where immune cells called macrophages and B lymphocytes are produced via the differentiation of hematopoietic stem and progenitor cells (HSPCs). In the new study, Varlamov and collaborators analyzed the transcriptional landscape of fetal bone marrow HSPCs at single-cell resolution in fetal macaques exposed to either a maternal high-fat Western-style diet or a low-fat control diet.

“We were motivated to investigate the impact of maternal obesity on the fetal immune system during pregnancy in non-human primates, which represents the most relevant animal model for studying human development,” says Varlamov.

The results demonstrated that a Western-style diet induced a hyperinflammatory response in HSPCs and fetal macrophages and suppressed the expression of B-cell developmental genes. Additionally, the unhealthy diet led to poor engraftment. of fetal HSPC in immunodeficient mice.

“Maternal obesity had a dramatic impact on the ability of fetal blood stem cells to produce B lymphocytes – immune cells that make antibodies in response to infection – and made fetal blood stem cells more inflamed” , explains Varlamov.

Limitations of the study included small sample size, which may limit the ability to detect weaker effects of maternal diet on fetal outcomes. Additionally, researchers did not explore the effects of maternal obesity on postnatal development and focused only on prenatal development. Further studies are also needed to test whether maternal obesity impairs offspring responses to infection and inflammation.

“This study paves the way for understanding the link between maternal obesity, prenatal nutrition and diseases involving the immune progeny of the HSPC compartment in children and highlights the need to better understand the sensitivity of the developing hematopoietic system to metabolic dysregulation over the lifespan,” says Varlamov.

This study was supported by the National Institutes of Health.

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