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Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex

The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health an...

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Autores principales: Kedziora, Sarah M., Obermayer, Benedikt, Sugulle, Meryam, Herse, Florian, Kräker, Kristin, Haase, Nadine, Langmia, Immaculate M., Müller, Dominik N., Staff, Anne Cathrine, Beule, Dieter, Dechend, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740420/
https://www.ncbi.nlm.nih.gov/pubmed/36499721
http://dx.doi.org/10.3390/ijms232315388
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author Kedziora, Sarah M.
Obermayer, Benedikt
Sugulle, Meryam
Herse, Florian
Kräker, Kristin
Haase, Nadine
Langmia, Immaculate M.
Müller, Dominik N.
Staff, Anne Cathrine
Beule, Dieter
Dechend, Ralf
author_facet Kedziora, Sarah M.
Obermayer, Benedikt
Sugulle, Meryam
Herse, Florian
Kräker, Kristin
Haase, Nadine
Langmia, Immaculate M.
Müller, Dominik N.
Staff, Anne Cathrine
Beule, Dieter
Dechend, Ralf
author_sort Kedziora, Sarah M.
collection PubMed
description The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio–temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples (n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ.
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spelling pubmed-97404202022-12-11 Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex Kedziora, Sarah M. Obermayer, Benedikt Sugulle, Meryam Herse, Florian Kräker, Kristin Haase, Nadine Langmia, Immaculate M. Müller, Dominik N. Staff, Anne Cathrine Beule, Dieter Dechend, Ralf Int J Mol Sci Article The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio–temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples (n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ. MDPI 2022-12-06 /pmc/articles/PMC9740420/ /pubmed/36499721 http://dx.doi.org/10.3390/ijms232315388 Text en © 2022 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
Kedziora, Sarah M.
Obermayer, Benedikt
Sugulle, Meryam
Herse, Florian
Kräker, Kristin
Haase, Nadine
Langmia, Immaculate M.
Müller, Dominik N.
Staff, Anne Cathrine
Beule, Dieter
Dechend, Ralf
Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex
title Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex
title_full Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex
title_fullStr Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex
title_full_unstemmed Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex
title_short Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex
title_sort placental transcriptome profiling in subtypes of diabetic pregnancies is strongly confounded by fetal sex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740420/
https://www.ncbi.nlm.nih.gov/pubmed/36499721
http://dx.doi.org/10.3390/ijms232315388
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