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Placental genomic and epigenomic signatures associated with infant birth weight highlight mechanisms involved in collagen and growth factor signaling.

ABSTRACT: Birth weight (BW) represents an important clinical and toxicological measure, indicative of the overall health of the newborn as well as potential risk for later-in-life outcomes. BW can be influenced by endogenous and exogenous factors and is known to be heavily impacted in utero by the health and function of the placenta. An aspect that remains understudied is the influence of genomic and epigenomic programming within the placenta on infant BW. To address this gap, we set out to test the hypothesis that genes involved in critical placental cell signaling are associated with infant BW, and are likely regulated, in part, through epigenetic mechanisms based on microRNA (miRNA) mediation. This study leveraged a robust dataset based on 390 infants born at low gestational age (ranged 23-27 weeks) to evaluate genome-wide expression profiles of both mRNAs and miRNAs in placenta tissues and relate these to infant BW. A total of 254 mRNAs and 268 miRNAs were identified as associated with BW, the majority of which showed consistent associations across placentas derived from both males and females. BW-associated mRNAs were found to be enriched for important biological pathways, including glycoprotein VI (the major receptor for collagen), human growth, and hepatocyte growth factor signaling, a portion of which were predicted to be regulated by BW-associated miRNAs. These miRNA-regulated pathways highlight key mechanisms potentially linking endogenous/exogenous factors to changes in birth outcomes that may be deleterious to infant and later-in-life health.

SUBMITTER: Payton A

PROVIDER: S-EPMC7855285 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Gestational weight gain is a determinant of infant birth weight, but it is unclear whether its timing in pregnancy may hold implications in this regard. Previous studies have yielded conflicting findings on the association of maternal weight gain in early pregnancy with birth weight. However, as these studies have typically recruited women during the first trimester, they are inherently limited by a reliance on self-reported pregravid weight. Objective:To evaluate the associations of directly measured maternal pregravid weight and the timing of subsequent weight gain across pregnancy with infant birth weight. Design, Setting, and Participants:In this prospective, preconception, observational cohort study, 1164 newly married women in Liuyang, China, underwent pregravid evaluation at a median of 19.9 weeks before a singleton pregnancy during which they underwent serial weight measurements. The study was conducted from February 1, 2009, to November 4, 2015. Data analysis was performed between September 1, 2016, and May 6, 2017. Exposure:Maternal weight gain was calculated for the following 10 gestational intervals: from pregravid to less than 14, 14 to 18, 19 to 23, 24 to 28, 29 to 30, 31 to 32, 33 to 34, 35 to 36, 37 to 38, and 39 to 40 weeks. Main Outcomes and Measures:Associations of pregravid weight and weight gain within each of the 10 gestational intervals with the outcome of infant birth weight. Results:The mean (SD) age of the 1164 women included in the study was 25.3 (3.1) years. Pregravid weight was consistently associated with infant birth weight. However, among the 10 gestational intervals, only weight gain from pregravid to 14 weeks and from 14 to 18 weeks was associated with birth weight. Birth weight increased by 13.6 g/kg (95% CI, 3.2-24.1 g/kg) of maternal weight gain from pregravid to 14 weeks and by 26.1 g/kg (95% CI, 3.8-48.4 g/kg) of maternal weight gain from 14 to 18 weeks. Conclusion and Relevance:Maternal weight only in the first half of gestation is a determinant of infant birth weight. Before pregnancy and early gestation may be a critical window for intervention to affect subsequent birth weight.

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Placental genomic and epigenomic signatures associated with infant birth weight highlight mechanisms involved in collagen and growth factor signaling.

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