Variation in placental microRNA expression associates with maternal family history of cardiovascular disease

• Type of Material: Article
• Authors: Jesse M Tehrani, Emory University; Elizabeth M Kennedy, Emory University; Fu-Ying Tian, Emory University; Todd M Everson, Emory University; Maya Deyssenroth, Columbia University; Amber Burt, Emory University; Karen Hermetz, Emory University; Ke Hao, Icahn School of Medicine at Mount Sinai; Jia Chen, Icahn School of Medicine at Mount Sinai; Devin C Koestler, University of Kansas; Carmen J Marsit, Emory University
• Language: English
• Date: 2022-07-11
• Publisher: CAMBRIDGE UNIV PRESS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Author(s), 2022
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1017/S2040174422000319
• Title of Journal or Parent Work: JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
• Volume: 14
• Issue: 1
• Start Page: 132
• End Page: 139
• Grant/Funding Information: This work was supported by the National Institutes of Health (NIH-NIGMS T32GM008490, NIH-NIEHS R24ES028507, NIH-NIEHS R01ES025145, NIH-NIEHS P30 ES019776; NIH-NIGMS P20GM104416).
• Keywords: MIRNA BIOGENESIS; WEIGHT; GENES; RNA sequencing; Science & Technology; Life Sciences & Biomedicine; cardiovascular disease; OBESITY; microRNA; ROLES; PREGNANCY; DATABASE; FETAL-GROWTH RESTRICTION; RISK; placenta; BETA; Public, Environmental & Occupational Health
• Research Categories: Engineering, Environmental; Biology, Biostatistics; Health Sciences, Public Health; Biology, Genetics

Abstract

In the United States, cardiovascular disease is the leading cause of death and the rate of maternal mortality remains among the highest of any industrialized nation. Maternal cardiometabolic health throughout gestation and postpartum is representative of placental health and physiology. Both proper placental functionality and placental microRNA expression are essential to successful pregnancy outcomes, and both are highly sensitive to genetic and environmental sources of variation. Placental pathologies, such as preeclampsia, are associated with maternal cardiovascular health but may also contribute to the developmental programming of chronic disease in offspring. However, the role of more subtle alterations to placental function and microRNA expression in this developmental programming remains poorly understood. We performed small RNA sequencing to investigate microRNA in placentae from the Rhode Island Child Health Study (n = 230). MicroRNA counts were modeled on maternal family history of cardiovascular disease using negative binomial generalized linear models. MicroRNAs were considered to be differentially expressed at a false discovery rate (FDR) less than 0.10. Parallel mRNA sequencing data and bioinformatic target prediction software were then used to identify potential mRNA targets of differentially expressed microRNAs. Nine differentially expressed microRNAs were identified (FDR < 0.1). Bioinformatic target prediction revealed 66 potential mRNA targets of these microRNAs, many of which are implicated in TGFβ signaling pathway but also in pathways involving cellular metabolism and immunomodulation. A robust association exists between familial cardiovascular disease and placental microRNA expression which may be implicated in both placental insufficiencies and the developmental programming of chronic disease.