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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
Nutrients, Volume 15, No. 19, Article 4105, Year 2023
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Description
Prenatal alcohol exposure (PAE) is associated with alterations in maternal and infant iron homeostasis that are consistent with changes seen in the setting of inflammation. We hypothesized that PAE leads to alterations in the placental expression of genes related to iron metabolism and inflammation that play functional roles in the teratogenic effects of alcohol on iron homeostasis. A total of 126 heavy-drinking women (≥1 oz (30 mL) absolute alcohol/day (~1.67 standard drinks/day) or women reporting binge drinking (≥2 drinks/occasion)) and 80 control women (<0.5 oz AA per day, no binging) in Cape Town, South Africa were interviewed prenatally regarding demographics, and alcohol, smoking, and drug use around conception and during pregnancy. Prenatal/maternal and infant hemoglobin and ferritin were measured. Whole-transcriptome RNA sequencing analysis was performed on flash-frozen transplacental tissue samples. Gene sets related to iron metabolism (n = 398) and inflammation (n = 467) were constructed by searching the Molecular Signatures Database for related ontology terms. Principal component analysis (PCA) yielded 59 factors for each theme. In multivariable regression models, PAE was related to 2 iron metabolism PCA factors (PCs) and 5 inflammation PCs, among which 2 iron metabolism and 4 inflammation factors were related to at least 1 key maternal or infant iron outcome. In causal inference analyses based on marginal structural models and the product method, the alterations in the expression profile of genes with functions in immune cell regulation, cytokine activity, angiogenesis, hematopoiesis, and ubiquitous cell processes appeared to partially mediate the relation of prenatal drinking frequency (days/week) around conception to a lower maternal hemoglobin-to-log(ferritin) ratio (proportion mediation = 51.35%). These findings suggest that placental inflammation may be partly responsible for the differences in alcohol-related iron homeostasis patterns between pregnant and non-pregnant adults. © 2023 by the authors.
Authors & Co-Authors
Deyssenroth, Maya A.
United States, New York
Columbia University
Jacobson, Sandra W.
United States, Detroit
Wayne State University School of Medicine
South Africa, Cape Town
University of Cape Town
Jacobson, Joseph L.
United States, Detroit
Wayne State University School of Medicine
South Africa, Cape Town
University of Cape Town
Molteno, Christopher D.
South Africa, Cape Town
University of Cape Town
Dodge, Neil C.
United States, Detroit
Wayne State University School of Medicine
Wainwright, Helen Cecilia
South Africa, Johannesburg
National Health Laboratory Service
Meintjes, Ernesta M.
South Africa, Cape Town
University of Cape Town
Lesseur, Corina
United States, New York
Icahn School of Medicine at Mount Sinai
Li, Qian
United States, New York
Icahn School of Medicine at Mount Sinai
Hao, Ke
United States, New York
Icahn School of Medicine at Mount Sinai
Carter, Robert Colin
United States, New York
Vagelos College of Physicians and Surgeons
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 1
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.3390/nu15194105
ISSN:
20726643
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Sexual And Reproductive Health
Substance Abuse
Study Locations
South Africa
Participants Gender
Female