Maternal immunometabolism adaptation in pregnancy

REES, APRIL

doi:10.23889/SUthesis.59676

E-Thesis 824 views 245 downloads

Maternal immunometabolism adaptation in pregnancy / APRIL REES

Swansea University Author: APRIL REES

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Copyright: The author, April Rees, 2022.
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DOI (Published version): 10.23889/SUthesis.59676

Abstract

Pregnant women undergo a series of metabolic and immunologic changes to ensure provision of nutrients to, and prevent rejection of, the fetus. To ensure continuous supply of glucose to the fetus, the mother increases glucose production, glucose intolerance and insulin resistance. To meet her own ene...

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Published:	Swansea 2022
Institution:	Swansea University
Degree level:	Doctoral
Degree name:	Ph.D
Supervisor:	Thornton, Catherine A. ; Cronin, James G. ; Jones, Nick
URI:	https://cronfa.swan.ac.uk/Record/cronfa59676
Tags:	Add Tag immunology 1 immunometabolism 1 monocytes 1 pregnancy 1 sars-cov-2 1

first_indexed	2022-03-21T10:48:34Z
last_indexed	2022-03-22T04:30:48Z
id	cronfa59676
recordtype	RisThesis
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spelling	2022-03-21T11:06:38.6164054 v2 59676 2022-03-21 Maternal immunometabolism adaptation in pregnancy d1b2ab7a5290f86f6f196f7ebf83e76f APRIL REES APRIL REES true false 2022-03-21 Pregnant women undergo a series of metabolic and immunologic changes to ensure provision of nutrients to, and prevent rejection of, the fetus. To ensure continuous supply of glucose to the fetus, the mother increases glucose production, glucose intolerance and insulin resistance. To meet her own energy demands, the mother transitions from lipid storage to lipolysis. To prevent rejection of the fetal semi-allograft, the mother’s immune system must be regulated, whilst maintaining protection against pathogens. Hypothesis: Well-recognised metabolic changes in pregnancy could impact maternal immune function. The aims of this project are to landscape the lipidomic profile using novel mass spectrometry techniques, and to determine whether monocytes undergo metabolic adaptation, if this occurs at 28 weeks of gestation, and if maternal obesity sabotages immunological adaptations. In addition, aims included investigation into the mechanisms which may protect the mother and fetus against SARS-CoV-2. Key findings unveiled significant phenotypic adaptations in the monocyte subsets during pregnancy, which are sabotaged by obesity. As the effect of maternal obesity is poorly understood, other immunological adaptations were investigated which revealed a shift to a Th1 and Th17 response which might contribute to the detrimental effects of obesity on pregnancy. At term, the monocytes illustrate a strong metabolic adaptation where their oxidative phosphorylation capabilities are reduced, confirmed by alterations in their mitochondria, with a downstream effect on their functionality with reduced production of lipid mediators and cytokines. While risk of infection with SARS-CoV-2 is low to pregnant women and the fetus, there is increased risk of preterm birth and admission into ICU. The fetus is relatively protected against infection, with cases of vertical transmission being rare. This thesis illustrates an elevated presence of soluble SARS-CoV-2 related molecules in breast milk and amniotic fluid which are postulated to act as decoy traps for the virus, which protects the neonate. In conclusion, this thesis has revealed novel findings into the immunometabolism adaptation to pregnancy. E-Thesis Swansea 21 3 2022 2022-03-21 10.23889/SUthesis.59676 ORCiD identifier: https://orcid.org/0000-0002-4408-634X COLLEGE NANME COLLEGE CODE Swansea University Thornton, Catherine A. ; Cronin, James G. ; Jones, Nick Doctoral Ph.D 2022-03-21T11:06:38.6164054 2022-03-21T10:44:20.2075502 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine APRIL REES 1 59676__22632__fda36b88e2904100a6c02869ecc05fd7.pdf Rees_April_PhD_Thesis_Final_Redacted_Signature.pdf 2022-03-21T10:59:34.8366977 Output 44901568 application/pdf E-Thesis – open access true Copyright: The author, April Rees, 2022. true eng
title	Maternal immunometabolism adaptation in pregnancy
spellingShingle	Maternal immunometabolism adaptation in pregnancy APRIL REES
title_short	Maternal immunometabolism adaptation in pregnancy
title_full	Maternal immunometabolism adaptation in pregnancy
title_fullStr	Maternal immunometabolism adaptation in pregnancy
title_full_unstemmed	Maternal immunometabolism adaptation in pregnancy
title_sort	Maternal immunometabolism adaptation in pregnancy
author_id_str_mv	d1b2ab7a5290f86f6f196f7ebf83e76f
author_id_fullname_str_mv	d1b2ab7a5290f86f6f196f7ebf83e76f_***_APRIL REES
author	APRIL REES
author2	APRIL REES
format	E-Thesis
publishDate	2022
institution	Swansea University
doi_str_mv	10.23889/SUthesis.59676
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	Pregnant women undergo a series of metabolic and immunologic changes to ensure provision of nutrients to, and prevent rejection of, the fetus. To ensure continuous supply of glucose to the fetus, the mother increases glucose production, glucose intolerance and insulin resistance. To meet her own energy demands, the mother transitions from lipid storage to lipolysis. To prevent rejection of the fetal semi-allograft, the mother’s immune system must be regulated, whilst maintaining protection against pathogens. Hypothesis: Well-recognised metabolic changes in pregnancy could impact maternal immune function. The aims of this project are to landscape the lipidomic profile using novel mass spectrometry techniques, and to determine whether monocytes undergo metabolic adaptation, if this occurs at 28 weeks of gestation, and if maternal obesity sabotages immunological adaptations. In addition, aims included investigation into the mechanisms which may protect the mother and fetus against SARS-CoV-2. Key findings unveiled significant phenotypic adaptations in the monocyte subsets during pregnancy, which are sabotaged by obesity. As the effect of maternal obesity is poorly understood, other immunological adaptations were investigated which revealed a shift to a Th1 and Th17 response which might contribute to the detrimental effects of obesity on pregnancy. At term, the monocytes illustrate a strong metabolic adaptation where their oxidative phosphorylation capabilities are reduced, confirmed by alterations in their mitochondria, with a downstream effect on their functionality with reduced production of lipid mediators and cytokines. While risk of infection with SARS-CoV-2 is low to pregnant women and the fetus, there is increased risk of preterm birth and admission into ICU. The fetus is relatively protected against infection, with cases of vertical transmission being rare. This thesis illustrates an elevated presence of soluble SARS-CoV-2 related molecules in breast milk and amniotic fluid which are postulated to act as decoy traps for the virus, which protects the neonate. In conclusion, this thesis has revealed novel findings into the immunometabolism adaptation to pregnancy.
published_date	2022-03-21T04:17:10Z
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score	11.03559

Maternal immunometabolism adaptation in pregnancy / APRIL REES

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