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Aspects of placental inflammatory response and birth weight, with specific focus on SARS-CoV-2 infection during pregnancy
Örebro universitet, Institutionen för medicinska vetenskaper.ORCID-id: 0000-0003-4496-519x
2025 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Placental function and foetal growth can be influenced by environmental factors or maternal medical conditions. The aim of this thesis was to characterise biological pathways in the placenta of importance for normal and impaired foetal growth, and to investigate whether maternal SARS-CoV-2 infection affects placental protein expression or is clinically associated with aberrant newborn birth weight. In study I, placental microRNA and protein expression profiles were characterised in pregnancies with normal newborn birth weights. Study II explored microRNA expression in placentas from pregnancies complicated by small-for-gestational-age (SGA) newborns. In study III, the impact of maternal SARS-CoV-2 infection on placental levels of inflammatory and cardiovascular proteins was investigated. In study IV, potential associations between maternal SARS-CoV-2 infection with aberrant birth weight, was investigated using Swedish registers. Inflammatory response, lipid metabolism, and neurodevelopment were highlighted as key biological processes in the healthy term placenta, suggesting that these pathways may be particularly susceptible to environmental insults and maternal disease. In SGA placentas, eight microRNAs were found to be differentially expressed and connected with inflammation and the insulin/IGF system. These findings indicate that subclinical inflammation, through disturbances in the insulin/IGF system, may be involved in unexplained SGA births. For pregnancies complicated by maternal SARS-CoV-2 infection, no persistent changes were seen in placental levels of inflammatory or cardiovascular proteins in term birth. Further, in the general pregnant population, maternal SARS-CoV-2 infection was not associated with an increased risk of SGA or abnormal birth weight at term, regardless of infection timing or severity.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro University , 2025. , s. 107
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 319
Nyckelord [en]
Birth weight, COPE-study, COVID-19, foetal growth, inflammatory response, microRNA, placenta, pregnancy, proteomics, SARS-CoV-2, small for gestational age
Nationell ämneskategori
Allmänmedicin Gynekologi, obstetrik och reproduktionsmedicin Infektionsmedicin
Identifikatorer
URN: urn:nbn:se:oru:diva-119081ISBN: 9789175296456 (tryckt)ISBN: 9789175296463 (digital)OAI: oai:DiVA.org:oru-119081DiVA, id: diva2:1934499
Disputation
2025-05-02, Örebro universitet, Campus USÖ, Tidefeltsalen, Södra Grev Rosengatan 32, Örebro, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2025-02-04 Skapad: 2025-02-04 Senast uppdaterad: 2025-04-29Bibliografiskt granskad
Delarbeten
1. Global microRNA and protein expression in human term placenta
Öppna denna publikation i ny flik eller fönster >>Global microRNA and protein expression in human term placenta
2022 (Engelska)Ingår i: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 9, artikel-id 952827Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Introduction: Description of the global expression of microRNAs (miRNAs) and proteins in healthy human term placentas may increase our knowledge of molecular biological pathways that are important for normal fetal growth and development in term pregnancy. The aim of this study was to explore the global expression of miRNAs and proteins, and to point out functions of importance in healthy term placentas.

Materials and methods: Placental samples (n = 19) were identified in a local biobank. All samples were from uncomplicated term pregnancies with vaginal births and healthy, normal weight newborns. Next-generation sequencing and nano-scale liquid chromatographic tandem mass spectrometry were used to analyse miRNA and protein expression, respectively.

Results: A total of 895 mature miRNAs and 6,523 proteins were detected in the placentas, of which 123 miRNAs and 346 proteins were highly abundant. The miRNAs were in high degree mapped to chromosomes 19, 14, and X. Analysis of the highly abundant miRNAs and proteins showed several significantly predicted functions in common, including immune and inflammatory response, lipid metabolism and development of the nervous system.

Discussion: The predicted function inflammatory response may reflect normal vaginal delivery, while lipid metabolism and neurodevelopment may be important processes for the term fetus. The data presented in this study, with complete miRNA and protein findings, will enhance the knowledge base for future research in the field of placental function and pathology.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2022
Nyckelord
RNA-sequencing, fetal growth, inflammatory response, microRNA, placenta, proteomics, term pregnancy
Nationell ämneskategori
Biokemi Molekylärbiologi
Identifikatorer
urn:nbn:se:oru:diva-102145 (URN)10.3389/fmed.2022.952827 (DOI)000878519300001 ()36330066 (PubMedID)2-s2.0-85140952815 (Scopus ID)
Forskningsfinansiär
Region Örebro län, OLL-935801 OLL-939071 OLL-878121 OLL-550861 OLL-577401 OLL-640561 OLL-812631 OLL-840481
Tillgänglig från: 2022-11-10 Skapad: 2022-11-10 Senast uppdaterad: 2025-04-29Bibliografiskt granskad
2. Placental expression of microRNAs in infants born small for gestational age
Öppna denna publikation i ny flik eller fönster >>Placental expression of microRNAs in infants born small for gestational age
2019 (Engelska)Ingår i: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 81, s. 46-53Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

INTRODUCTION: The molecular mechanisms behind poor foetal growth are not fully known. The aim of this study was to explore global microRNA expression in placentas of infants born small for gestational age (SGA) compared to infants with a normal birth weight (NBW).

METHODS: Placental biopsies from term infants were identified in a biobank and divided into four groups: infants born SGA with (n = 13) or without (n = 9) exposure to low maternal gestational weight gain (GWG) and infants born with NBWs with (n = 20) or without (n = 26) exposure to low GWG. All women and infants were healthy, and no woman smoked during pregnancy. Only vaginal deliveries were included. Next-generation sequencing was performed with single read sequencing of >9 million reads per sample. Differential microRNA expression was analysed using ANOVA for unequal variances (Welch) with multiple testing corrections through the Benjamini-Hochberg method. A fold change >2 and a corrected p value < 0.05 were considered significant. Adjustments for possible confounding factors were made using a linear regression model.

RESULTS: A total of 1870 known, mature human microRNAs were detected in the sample. MiR-3679-5p and miR-193b-3p were significantly upregulated, and miR-379-3p, miR-335-3p, miR-4532, miR-519e-3p, miR-3065-5p, and miR-105-5p were significantly downregulated after adjustment for potential confounding factors in SGA infants with normal GWG compared to infants with NBWs and normal GWG.

DISCUSSION: Infants born unexplained SGA show differential microRNA expression in their placenta. Important pathways for the differentially expressed microRNAs include inflammation and the insulin-IGF system.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019
Nyckelord
Foetal growth, Inflammation, Placenta, RNA-Sequencing, Small for gestational age, microRNA
Nationell ämneskategori
Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
urn:nbn:se:oru:diva-74556 (URN)10.1016/j.placenta.2019.05.001 (DOI)000468874700007 ()31138431 (PubMedID)2-s2.0-85065481896 (Scopus ID)
Anmärkning

Funding Agency:

Research Committee of Region Örebro County and ALF funding Region Örebro County

Tillgänglig från: 2019-06-05 Skapad: 2019-06-05 Senast uppdaterad: 2025-04-09Bibliografiskt granskad
3. Inflammatory and cardiovascular markers in placenta following SARS-CoV-2 infection during pregnancy: A Swedish prospective cohort study
Öppna denna publikation i ny flik eller fönster >>Inflammatory and cardiovascular markers in placenta following SARS-CoV-2 infection during pregnancy: A Swedish prospective cohort study
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2024 (Engelska)Ingår i: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 158, s. 78-88Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

INTRODUCTION: Maternal SARS-CoV-2 infection can affect pregnancy outcome, but the placental response to and the effect of timing of infection is not well studied. The aim of this study was to investigate the placental levels of inflammatory and cardiovascular markers in pregnancies complicated by SARS-CoV-2 infection compared to non-infected pregnancies, and to investigate whether there was an association between time point of infection during pregnancy and placental inflammatory and cardiovascular protein levels.

METHODS: Placental samples from a prospectively recruited pregnancy cohort of SARS-CoV-2-infected (n = 53) and non-infected (n = 50) women were analysed for 177 inflammatory and cardiovascular proteins, using an antibody-based proximity extension assay. In the SARS-CoV-2-infected group, half of the women were infected before 20 weeks of gestation, and five women were hospitalised for severe SARS-CoV-2 infection. Single-protein analyses were performed with linear mixed effects models, followed by Benjamini-Hochberg correction for multiple testing. Multi-protein analyses were performed using principal component analysis and machine learning algorithms.

RESULTS: The perinatal outcomes and the placental levels of inflammatory or cardiovascular proteins in women with SARS-CoV-2 infection were similar to those in non-infected women. There were no differences in inflammatory or cardiovascular protein levels between early and late pregnancy SARS-CoV-2 infection, nor any linear correlations between protein levels and gestational age at time of infection.

DISCUSSION: Women with SARS-CoV-2 infection during pregnancy without clinical signs of placental insufficiency have no changes in inflammatory or cardiovascular protein patterns in placenta at time of birth regardless of the timing of the infection.

Ort, förlag, år, upplaga, sidor
Elsevier, 2024
Nyckelord
COPE-Study, COVID-19, Inflammatory and cardiovascular protein, Placenta, Pregnancy, SARS-CoV-2
Nationell ämneskategori
Infektionsmedicin Gynekologi, obstetrik och reproduktionsmedicin
Identifikatorer
urn:nbn:se:oru:diva-116698 (URN)10.1016/j.placenta.2024.09.017 (DOI)001335262600001 ()39393251 (PubMedID)2-s2.0-85205970467 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2018–00470NyckelfondenRegion Örebro län, OLL-886131Region Örebro län, OLL-972366Region Örebro län, OLL-964888Region Örebro län, OLL-942175Region Örebro län, OLL-939073Jane och Dan Olssons Stiftelse, VS 2021–02
Anmärkning

Funding:

Initiation of the COPE study was financed by Swedish Research Council grants (Backman 2018–00470) in accordance with the decision, in spring 2020, to conduct COVID-19 research. The study was financed by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (YC ALFGBG-75710, YC ALFGBG-77860, VS ALFGBG-970689, HÖ OLL-93581, HÖ OLL-939073, MZ YF00054). The study was supported by grants from Nyckelfonden and the Research Committee, Region Örebro County (RK: OLL-886131, HB: OLL-972366, OLL-964888, OLL-942175, OLL-939073) and by grants from Wallenberg Centre for Molecular and Translational Medicine (LB), the Jane and Dan Olsson Foundation (VS 2021–02), Stiftelsen Erik & Lily Philipsons minnesfond (VS dnr 98) and Simons Foundation Autism Research Initiative, SFARI, (#863675, VS).

Tillgänglig från: 2024-10-14 Skapad: 2024-10-14 Senast uppdaterad: 2025-04-09Bibliografiskt granskad
4. The association of severity and timing of SARS-CoV-2 infection during pregnancy with birth weight: a Swedish register-based cohort study
Öppna denna publikation i ny flik eller fönster >>The association of severity and timing of SARS-CoV-2 infection during pregnancy with birth weight: a Swedish register-based cohort study
Visa övriga...
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Allmänmedicin
Identifikatorer
urn:nbn:se:oru:diva-120451 (URN)
Tillgänglig från: 2025-04-09 Skapad: 2025-04-09 Senast uppdaterad: 2025-04-29Bibliografiskt granskad

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