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Maternal obesity is associated with phenotypic alterations in fetal immune cells by single-cell mass cytometry
Elizabeth Ann L Enninga1, Jin Sung Jang2,3, Benjamin Hur4,5
1Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA.
Insights
Maternal obesity alters fetal immune cell development. Infants born to obese mothers show increased CD4+ T cells and decreased myeloid cells, indicating a link between maternal body mass index and infant immunity.
Area of Science:
- Immunology
- Perinatal Medicine
- Developmental Biology
Background:
- Maternal obesity during pregnancy poses risks to offspring health.
- The impact of maternal obesity on fetal immune system development at a cellular level is not well understood.
Purpose of the Study:
- To investigate the effects of maternal obesity on fetal immune cell populations and phenotypes.
- To characterize cellular-level immune alterations in newborns exposed to maternal metabolic dysregulation.
Main Methods:
- Single-cell mass cytometry (CyTOF) was used to analyze cord blood mononuclear cells (CBMCs) from infants of mothers with high BMI (>25kg/m²) versus normal BMI (18-25kg/m²).
- CBMCs were matched for confounding variables, and statistical analyses were adjusted for fetal sex.
- Data analysis was performed using viSNE and FlowSOM software.
Main Results:
- Significant alterations in immune cell populations were observed in newborns from mothers with high BMI.
- Specifically, there were increases in CD4+ T cells and decreases in myeloid cell populations.
- Elevated concentrations of IL-12p40 and MDC were found in the high BMI group.
Conclusions:
- Maternal obesity is associated with significant changes in fetal immunity.
- These findings highlight the need for long-term monitoring of immunologic outcomes and clinical risks in children born to mothers with high pre-pregnancy BMI.
Problem:
Prenatal exposure to metabolic dysregulation arising from maternal obesity can have negative health consequences in post-natal life. To date, the specific effects of maternal obesity on fetal immunity at a cellular level have not been well characterized.
Method Of Study:
Using cord blood mononuclear cells (CBMCs) and cord plasma (n = 9/group) isolated from infants born to women with a high body mass index (BMI>25kg/m2 ) compared to women with a normal BMI (18-25kg/m2 ), we evaluated differences in immune cell populations using single-cell mass cytometry (CyTOF). CBMCs were matched according to potentially confounding variables, such as maternal and gestational age, ethnicity, smoking status, and gravidity. Statistical results were adjusted for fetal sex. Data were analyzed by viSNE and FlowSOM softwares in Cytobank™ .
Results:
In newborn CBMCs from women with high BMI, we observed changes in frequency and phenotype of immune cell populations, including significant increases in CD4+ T cells and decreases in myeloid cell populations. IL-12p40 and MDC concentrations were significantly elevated in the high BMI group compared to control.
Conclusion:
This study demonstrates an association between maternal obesity and fetal immunity. Our results warrant following long-term immunologic outcomes and associated clinical risks in children born to women with a high pre-pregnancy BMI.
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