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ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese

Obesity has become a global health challenge also affecting reproductive health. In pregnant women, obesity increases the risk of complications such as preterm birth, macrosomia, gestational diabetes, and preeclampsia. Moreover, obesity is associated with long-term adverse effects for the offspring,...

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Autores principales: Justesen, Signe, Bilde, Katrine, Olesen, Rasmus H., Pedersen, Lars H., Ernst, Erik, Larsen, Agnete
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063677/
https://www.ncbi.nlm.nih.gov/pubmed/36997557
http://dx.doi.org/10.1038/s41598-023-31598-5
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author Justesen, Signe
Bilde, Katrine
Olesen, Rasmus H.
Pedersen, Lars H.
Ernst, Erik
Larsen, Agnete
author_facet Justesen, Signe
Bilde, Katrine
Olesen, Rasmus H.
Pedersen, Lars H.
Ernst, Erik
Larsen, Agnete
author_sort Justesen, Signe
collection PubMed
description Obesity has become a global health challenge also affecting reproductive health. In pregnant women, obesity increases the risk of complications such as preterm birth, macrosomia, gestational diabetes, and preeclampsia. Moreover, obesity is associated with long-term adverse effects for the offspring, including increased risk of cardiovascular and metabolic diseases and neurodevelopmental difficulties. The underlying mechanisms are far from understood, but placental function is essential for pregnancy outcome. Transporter proteins P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are important for trans-placental transport of endogenous substances like lipids and cortisol, a key hormone in tissue maturation. They also hold a protective function protecting the fetus from xenobiotics (e.g. pharmaceuticals). Animal studies suggest that maternal nutritional status can affect expression of placental transporters, but little is known about the effect on the human placenta, especially in early pregnancy. Here, we investigated if overweight and obesity in pregnant women altered mRNA expression of ABCB1 encoding P-gp or ABCG2 encoding BCRP in first trimester human placenta. With informed consent, 75 first trimester placental samples were obtained from women voluntarily seeking surgical abortion (< gestational week 12) (approval no.: 20060063). Villous samples (average gestational age 9.35 weeks) were used for qPCR analysis. For a subset (n = 38), additional villi were snap-frozen for protein analysis. Maternal BMI was defined at the time of termination of pregnancy. Compared to women with BMI 18.5–24.9 kg/m(2) (n = 34), ABCB1 mRNA expression was significantly increased in placenta samples from women classified as overweight (BMI 25–29.9 kg/m(2), n = 18) (p = 0.040) and women classified as obese (BMI ≥ 30 kg/m(2), n = 23) (p = 0.003). Albeit P-gp expression did not show statistically significant difference between groups, the effect of increasing BMI was the same in male and female pregnancies. To investigate if the P-gp increase was compensated, we determined the expression of ABCG2 which was unaffected by maternal obesity (p = 0.291). Maternal BMI affects ABCB1 but not ABCG2 mRNA expression in first trimester human placenta. Further studies of early placental function are needed to understand how the expression of placental transport proteins is regulated by maternal factors such as nutritional status and determine the potential consequences for placental–fetal interaction.
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spelling pubmed-100636772023-04-01 ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese Justesen, Signe Bilde, Katrine Olesen, Rasmus H. Pedersen, Lars H. Ernst, Erik Larsen, Agnete Sci Rep Article Obesity has become a global health challenge also affecting reproductive health. In pregnant women, obesity increases the risk of complications such as preterm birth, macrosomia, gestational diabetes, and preeclampsia. Moreover, obesity is associated with long-term adverse effects for the offspring, including increased risk of cardiovascular and metabolic diseases and neurodevelopmental difficulties. The underlying mechanisms are far from understood, but placental function is essential for pregnancy outcome. Transporter proteins P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are important for trans-placental transport of endogenous substances like lipids and cortisol, a key hormone in tissue maturation. They also hold a protective function protecting the fetus from xenobiotics (e.g. pharmaceuticals). Animal studies suggest that maternal nutritional status can affect expression of placental transporters, but little is known about the effect on the human placenta, especially in early pregnancy. Here, we investigated if overweight and obesity in pregnant women altered mRNA expression of ABCB1 encoding P-gp or ABCG2 encoding BCRP in first trimester human placenta. With informed consent, 75 first trimester placental samples were obtained from women voluntarily seeking surgical abortion (< gestational week 12) (approval no.: 20060063). Villous samples (average gestational age 9.35 weeks) were used for qPCR analysis. For a subset (n = 38), additional villi were snap-frozen for protein analysis. Maternal BMI was defined at the time of termination of pregnancy. Compared to women with BMI 18.5–24.9 kg/m(2) (n = 34), ABCB1 mRNA expression was significantly increased in placenta samples from women classified as overweight (BMI 25–29.9 kg/m(2), n = 18) (p = 0.040) and women classified as obese (BMI ≥ 30 kg/m(2), n = 23) (p = 0.003). Albeit P-gp expression did not show statistically significant difference between groups, the effect of increasing BMI was the same in male and female pregnancies. To investigate if the P-gp increase was compensated, we determined the expression of ABCG2 which was unaffected by maternal obesity (p = 0.291). Maternal BMI affects ABCB1 but not ABCG2 mRNA expression in first trimester human placenta. Further studies of early placental function are needed to understand how the expression of placental transport proteins is regulated by maternal factors such as nutritional status and determine the potential consequences for placental–fetal interaction. Nature Publishing Group UK 2023-03-30 /pmc/articles/PMC10063677/ /pubmed/36997557 http://dx.doi.org/10.1038/s41598-023-31598-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Justesen, Signe
Bilde, Katrine
Olesen, Rasmus H.
Pedersen, Lars H.
Ernst, Erik
Larsen, Agnete
ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
title ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
title_full ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
title_fullStr ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
title_full_unstemmed ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
title_short ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
title_sort abcb1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063677/
https://www.ncbi.nlm.nih.gov/pubmed/36997557
http://dx.doi.org/10.1038/s41598-023-31598-5
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