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.