Placental molecular mechanisms as pathways linking prenatal exposure to ambient air pollution to preeclampsia and fetal growth
(2023) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- Background: Preeclampsia (PE) is a “multifactorial syndrome” in which ambient air pollution may contribute to the etiology of PE. However, the underlying mechanism of this association is not clearly elucidated. This dissertation aims at understanding the placental molecular mechanism underlying the relationship of prenatal exposure to ambient air pollution with preeclampsia and fetal growth by characterizing and evaluating the mediator role of placental aging using mitochondrial DNA content, telomere length, DNA methylation and gene expression analyses.
Methods: Scania in Sweden and Barcelona in Spain are the two main study areas. Maternal Air Pollution in Southern Sweden (MAPSS) is a population-based cohort consisting of 43,688... (More) - Background: Preeclampsia (PE) is a “multifactorial syndrome” in which ambient air pollution may contribute to the etiology of PE. However, the underlying mechanism of this association is not clearly elucidated. This dissertation aims at understanding the placental molecular mechanism underlying the relationship of prenatal exposure to ambient air pollution with preeclampsia and fetal growth by characterizing and evaluating the mediator role of placental aging using mitochondrial DNA content, telomere length, DNA methylation and gene expression analyses.
Methods: Scania in Sweden and Barcelona in Spain are the two main study areas. Maternal Air Pollution in Southern Sweden (MAPSS) is a population-based cohort consisting of 43,688 singleton pregnancies recorded from 2000 to 2009 in Scania, Sweden. For placental molecular studies, we selected a sub- cohort of 361 mother-child pairs from the Barcelona Life Study Cohort (BiSC), a prospective cohort consisting of 1080 mother-child pairs recruited between 2018 and 2021 as well as 137 participants from unique biobank designed to study PE at Lund University. Each individual-level air pollutant concentrations were estimated either by a high-resolution dispersion model or by a passive sampling methods. Placental mtDNAcn and TL were measured using qPCR. Placental DNAm and gene expression were analyzed with EPIC array and RNA-seq, respectively. Linear, logistic regression and linear mixed effects models were used on SPSS and R statistical programs.
Results: In a setting with fair air quality in Scania, the increased risk of PE and SGA were associated with both linear exposure trend and quartile-specific exposure of ambient particles and NOx. In a setting with moderate air quality in Barcelona, early pregnancy exposure to ambient NO2 measured by home- outdoor and personal sensors were associated with lower birth weight and increased odds of having SGA neonate. Although the mediatory role of placental mtDNAcn and telomere length were not confirmed, prenatal exposure to ambient NOx and NO2 affect the placental aging process differently depending on the exposure concentration and exposure period during pregnancy. We observed reduced mtDNAcn and shorter TL in placenta in relation to exposure during first trimester, whereas increased mtDNAcn in relation to NO2 exposure during third trimester. Prenatal exposure to ambient NOx during first trimester affected differential placental DNA methylation in PE and NOx combined groups, resulting in placental age deceleration and showing sexual dimorphism.
Conclusion: Placental senescence and aging may be the underlying molecular mechanism linking the association between prenatal exposure to ambient air pollution and pregnancy complications including preeclampsia and small-for-gestational age foetuses and neonates. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/6f47df1a-e1e0-45ce-b89c-2741bdf7ae54
- author
- Mandakh, Yumjirmaa LU
- supervisor
-
- Ebba Malmqvist LU
- Stefan Hansson LU
- Christina Isaxon LU
- Anna Oudin LU
- opponent
-
- Associate Professor Pedersen, Marie, Section of Epidemiology, Department of Public Health, University of Copenhagen
- organization
- publishing date
- 2023
- type
- Thesis
- publication status
- published
- subject
- keywords
- Preeclampsia, Ambient air pollution, placenta, Small-for-gestational age, mitochondrial DNA content, telomere length, global DNA methylation, gene expression, epigenetic age
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2023:9
- pages
- 56 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Segerfalksalen, BMC A10, Sölvegatan 17 i Lund. Join by Zoom: https://lu-se.zoom.us/j/65924961317?pwd=T2JCR0tQU0dQRWVGclNodWxSRWR0UT09 Meeting ID: 659 2496 1317
- defense date
- 2023-01-27 08:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-348-6
- language
- English
- LU publication?
- yes
- id
- 6f47df1a-e1e0-45ce-b89c-2741bdf7ae54
- date added to LUP
- 2023-01-03 22:27:30
- date last changed
- 2023-01-10 12:25:24
@phdthesis{6f47df1a-e1e0-45ce-b89c-2741bdf7ae54,
abstract = {{Background: Preeclampsia (PE) is a “multifactorial syndrome” in which ambient air pollution may contribute to the etiology of PE. However, the underlying mechanism of this association is not clearly elucidated. This dissertation aims at understanding the placental molecular mechanism underlying the relationship of prenatal exposure to ambient air pollution with preeclampsia and fetal growth by characterizing and evaluating the mediator role of placental aging using mitochondrial DNA content, telomere length, DNA methylation and gene expression analyses.<br/>Methods: Scania in Sweden and Barcelona in Spain are the two main study areas. Maternal Air Pollution in Southern Sweden (MAPSS) is a population-based cohort consisting of 43,688 singleton pregnancies recorded from 2000 to 2009 in Scania, Sweden. For placental molecular studies, we selected a sub- cohort of 361 mother-child pairs from the Barcelona Life Study Cohort (BiSC), a prospective cohort consisting of 1080 mother-child pairs recruited between 2018 and 2021 as well as 137 participants from unique biobank designed to study PE at Lund University. Each individual-level air pollutant concentrations were estimated either by a high-resolution dispersion model or by a passive sampling methods. Placental mtDNAcn and TL were measured using qPCR. Placental DNAm and gene expression were analyzed with EPIC array and RNA-seq, respectively. Linear, logistic regression and linear mixed effects models were used on SPSS and R statistical programs.<br/>Results: In a setting with fair air quality in Scania, the increased risk of PE and SGA were associated with both linear exposure trend and quartile-specific exposure of ambient particles and NOx. In a setting with moderate air quality in Barcelona, early pregnancy exposure to ambient NO2 measured by home- outdoor and personal sensors were associated with lower birth weight and increased odds of having SGA neonate. Although the mediatory role of placental mtDNAcn and telomere length were not confirmed, prenatal exposure to ambient NOx and NO2 affect the placental aging process differently depending on the exposure concentration and exposure period during pregnancy. We observed reduced mtDNAcn and shorter TL in placenta in relation to exposure during first trimester, whereas increased mtDNAcn in relation to NO2 exposure during third trimester. Prenatal exposure to ambient NOx during first trimester affected differential placental DNA methylation in PE and NOx combined groups, resulting in placental age deceleration and showing sexual dimorphism.<br/>Conclusion: Placental senescence and aging may be the underlying molecular mechanism linking the association between prenatal exposure to ambient air pollution and pregnancy complications including preeclampsia and small-for-gestational age foetuses and neonates.}},
author = {{Mandakh, Yumjirmaa}},
isbn = {{978-91-8021-348-6}},
issn = {{1652-8220}},
keywords = {{Preeclampsia; Ambient air pollution; placenta; Small-for-gestational age; mitochondrial DNA content; telomere length; global DNA methylation; gene expression; epigenetic age}},
language = {{eng}},
number = {{2023:9}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Placental molecular mechanisms as pathways linking prenatal exposure to ambient air pollution to preeclampsia and fetal growth}},
url = {{https://lup.lub.lu.se/search/files/133330347/Thesis_Yumjiirmaa_e_nailing.pdf}},
year = {{2023}},
}