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Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis

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...

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Autores principales: Masehi-Lano, Jacqueline J., Deyssenroth, Maya, Jacobson, Sandra W., Jacobson, Joseph L., Molteno, Christopher D., Dodge, Neil C., Wainwright, Helen C., Meintjes, Ernesta M., Lesseur, Corina, Cheng, Haoxiang, Li, Qian, Hao, Ke, Chen, Jia, Carter, R. Colin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574168/
https://www.ncbi.nlm.nih.gov/pubmed/37836388
http://dx.doi.org/10.3390/nu15194105
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author Masehi-Lano, Jacqueline J.
Deyssenroth, Maya
Jacobson, Sandra W.
Jacobson, Joseph L.
Molteno, Christopher D.
Dodge, Neil C.
Wainwright, Helen C.
Meintjes, Ernesta M.
Lesseur, Corina
Cheng, Haoxiang
Li, Qian
Hao, Ke
Chen, Jia
Carter, R. Colin
author_facet Masehi-Lano, Jacqueline J.
Deyssenroth, Maya
Jacobson, Sandra W.
Jacobson, Joseph L.
Molteno, Christopher D.
Dodge, Neil C.
Wainwright, Helen C.
Meintjes, Ernesta M.
Lesseur, Corina
Cheng, Haoxiang
Li, Qian
Hao, Ke
Chen, Jia
Carter, R. Colin
author_sort Masehi-Lano, Jacqueline J.
collection PubMed
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.
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spelling pubmed-105741682023-10-14 Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis Masehi-Lano, Jacqueline J. Deyssenroth, Maya Jacobson, Sandra W. Jacobson, Joseph L. Molteno, Christopher D. Dodge, Neil C. Wainwright, Helen C. Meintjes, Ernesta M. Lesseur, Corina Cheng, Haoxiang Li, Qian Hao, Ke Chen, Jia Carter, R. Colin Nutrients Article 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. MDPI 2023-09-22 /pmc/articles/PMC10574168/ /pubmed/37836388 http://dx.doi.org/10.3390/nu15194105 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Masehi-Lano, Jacqueline J.
Deyssenroth, Maya
Jacobson, Sandra W.
Jacobson, Joseph L.
Molteno, Christopher D.
Dodge, Neil C.
Wainwright, Helen C.
Meintjes, Ernesta M.
Lesseur, Corina
Cheng, Haoxiang
Li, Qian
Hao, Ke
Chen, Jia
Carter, R. Colin
Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
title Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
title_full Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
title_fullStr Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
title_full_unstemmed Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
title_short Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis
title_sort alterations in placental inflammation-related gene expression partially mediate the effects of prenatal alcohol consumption on maternal iron homeostasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574168/
https://www.ncbi.nlm.nih.gov/pubmed/37836388
http://dx.doi.org/10.3390/nu15194105
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