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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
RNA-seq analysis reveals prenatal alcohol exposure is associated with placental inflammatory cells and gene expression
Gene, Volume 894, Article 147951, Year 2024
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Description
Background: Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders worldwide. The placenta is the crucial interface between mother and fetus. Prenatal alcohol exposure (PAE) has been shown to alter placental structure and expression of genes in bulk placental tissue samples, but prior studies have not examined effects on placental cell-type composition or taken cell-type into consideration in transcriptome analyses. Methods: We leveraged an existent placenta single-cell RNA-seq dataset to perform cell-type deconvolution of bulk placental RNA-seq data from 35 heavy drinking pregnant women and 33 controls in a prospective birth cohort in Cape Town, South Africa. We used bivariate analyses and multivariable adjusted linear regression models to assess the relation of PAE on inferred placental cell-type proportions. We also examined differential expression of inflammatory response genes and PAE, using multivariable adjusted linear models. Results: Deconvolution analyses showed heterogeneous placenta cell-type composition in which stromal (27 %), endothelial (26 %) and cytotrophoblasts (18 %) were the predominant cell-types. PAE around conception was associated with a higher proportion of Hofbauer cells (B = 0.51, p = 0.035) in linear models adjusted for maternal age, infant sex, and gestational age. Among the 652 inflammatory genes examined, 35 were differential expressed in alcohol exposed placentas (FDR p < 0.05). Conclusions: Our findings suggest that heavy alcohol exposure during pregnancy can influence the proportion of fetal placental villi macrophages (Hofbauer cells) and increased expression of inflammatory genes. Future studies are needed to further characterize these effects and to assess the potential functional roles of placental inflammation in FASD. © 2023
Authors & Co-Authors
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
Deyssenroth, Maya A.
United States, New York
Columbia University
Molteno, Christopher D.
South Africa, Cape Town
University of Cape Town
Meintjes, Ernesta M.
South Africa, Cape Town
University of Cape Town
Jacobson, Sandra W.
South Africa, Cape Town
University of Cape Town
United States, Detroit
Wayne State University School of Medicine
Jacobson, Joseph L.
South Africa, Cape Town
University of Cape Town
United States, Detroit
Wayne State University School of Medicine
Wainwright, Helen Cecilia
South Africa, Johannesburg
National Health Laboratory Service
Hao, Ke
United States, New York
Icahn School of Medicine at Mount Sinai
Carter, Robert Colin
South Africa, Cape Town
University of Cape Town
United States, New York
Vagelos College of Physicians and Surgeons
Statistics
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1016/j.gene.2023.147951
ISSN:
03781119
Research Areas
Genetics And Genomics
Maternal And Child Health
Sexual And Reproductive Health
Substance Abuse
Study Design
Cohort Study
Study Locations
South Africa
Participants Gender
Female