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Placental expression of microRNAs in infants born small for gestational age
Örebro University, School of Medical Sciences. Department of Obstetrics and Gynecology.ORCID iD: 0000-0003-4496-519X
Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.ORCID iD: 0000-0003-1785-8540
Örebro University, School of Medical Sciences. Department of Laboratory Medicine.ORCID iD: 0000-0003-2317-5738
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics.ORCID iD: 0000-0002-5292-4913
2019 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 81, p. 46-53Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 81, p. 46-53
Keywords [en]
Foetal growth, Inflammation, Placenta, RNA-Sequencing, Small for gestational age, microRNA
National Category
Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
URN: urn:nbn:se:oru:diva-74556DOI: 10.1016/j.placenta.2019.05.001ISI: 000468874700007PubMedID: 31138431Scopus ID: 2-s2.0-85065481896OAI: oai:DiVA.org:oru-74556DiVA, id: diva2:1320579
Note

Funding Agency:

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

Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2025-04-09Bibliographically approved
In thesis
1. Aspects of placental inflammatory response and birth weight, with specific focus on SARS-CoV-2 infection during pregnancy
Open this publication in new window or tab >>Aspects of placental inflammatory response and birth weight, with specific focus on SARS-CoV-2 infection during pregnancy
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2025. p. 107
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 319
Keywords
Birth weight, COPE-study, COVID-19, foetal growth, inflammatory response, microRNA, placenta, pregnancy, proteomics, SARS-CoV-2, small for gestational age
National Category
General Practice Gynaecology, Obstetrics and Reproductive Medicine Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-119081 (URN)9789175296456 (ISBN)9789175296463 (ISBN)
Public defence
2025-05-02, Örebro universitet, Campus USÖ, Tidefeltsalen, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2025-02-04 Created: 2025-02-04 Last updated: 2025-04-29Bibliographically approved

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Östling, HannaKruse, RobertHelenius, GiselaLodefalk, Maria

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