For the first time in primates, it has been shown that maternal unhealthy diet and obesity can affect the fetus's immune system

Researchers reported Nov.
3 in the journal Stem Cell Reports that maternal consumption of a Western-style diet changed the transcriptional pattern
of fetal blood stem cells.

Oleg Vallamov of the National Primate Research Center in Oregon said: "This finding is the first to prove in primates that maternal unhealthy diet and obesity can damage the immune system
of the developing fetus.
" "The main implication of this study is that maternal obesity may affect the development
of fetal bone marrow and the fetal immune system.
"

Preconception obesity is associated with an increased risk of offspring infection and abnormal inflammatory responses, but the underlying mechanisms remain largely unclear
.
In particular, the effects of Western diets on fetal hematopoiesis (i.
e.
, the formation of blood cell components) in animal models similar to human development are poorly
understood.

In the later stages of development, fetal bone marrow becomes the main site
for the differentiation of immune cells macrophages and b lymphocytes through hematopoietic stem and progenitor cells (HSPCs).
In the new study, Valamov and his collaborators analyzed the transcriptional pattern
of fetal bone marrow fever SPCs at single-cell resolution in fetal monkeys on either a maternal high-fat Western-style diet or a low-fat control diet.

"Our motivation is to study how maternal obesity during pregnancy in non-human primates affects the fetal immune system, which represents the most relevant animal model
for studying human development," Valamov said.

The results showed that the Western-style diet induced a hyperinflammatory response of HSPCs and fetal macrophages, and inhibited the expression
of B cell development genes.
In addition, an unhealthy diet led to poor
transfer of embryonic HSPCs in immunodeficient mice.

"Maternal obesity greatly affects the ability of fetal blood stem cells to produce B lymphocytes, which are immune cells that produce antibodies to deal with infection and make fetal blood stem cells more susceptible to inflammation
," Valamov said.

Limitations of the study included small sample sizes, which may have limited the ability to detect the
weaker effects of maternal diet on fetal outcomes.
In addition, the researchers did not explore the effects of maternal obesity on postpartum development, focusing only on prenatal development
.
Further research is needed to test whether maternal obesity disrupts offspring's response
to infection and inflammation.

"This study lays the foundation for understanding the link between maternal obesity, prenatal nutrition and diseases involving immune offspring of children's HSPC compartments, and highlights the need to better understand the sensitivity
of the developing hematopoietic system to metabolic disorders throughout life," Varlamov said.

The study was supported
by the National Institutes of Health.

Journal Reference:

1. Suhas Sureshchandra, Chi N.
   Chan, Jacob J.
   Robino, Lindsay K.
   Parmelee, Michael J.
   Nash, Stephanie R.
   Wesolowski, Eric M.
   Pietras, Jacob E.
   Friedman, Diana Takahashi, Weining Shen, Xiwen Jiang, Jon D.
   Hennebold, Devorah Goldman, William Packwood, Jonathan R.
   Lindner, Charles T.
   Roberts, Benjamin J.
   Burwitz, Ilhem Messaoudi, Oleg Varlamov.
   Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques.
   Stem Cell Reports, 2022; DOI: 10.
   1016/j.
   stemcr.
   2022.
   10.
   003).