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.

出生体重 (BW) 是一项重要的临床和毒理学指标，表明新生儿的整体健康状况以及晚年结局的潜在风险。BW 可能受到内源性和外源性因素的影响，并且已知在子宫内受到严重影响取决于胎盘的健康和功能。尚未研究的一个方面是胎盘内基因组和表观基因组编程对婴儿体重的影响。为了解决这一差距，我们着手检验参与关键胎盘细胞信号传导的基因与婴儿 BW 相关的假设，并且可能部分通过基于 microRNA (miRNA) 介导的表观遗传机制进行调节。本研究利用基于 390 名低胎龄（23-27 周）出生的婴儿的稳健数据集来评估胎盘组织中 mRNA 和 miRNA 的全基因组表达谱，并将其与婴儿体重相关联。共有 254 种 mRNA 和 268 种 miRNA 被鉴定为与 BW 相关，其中大多数在来自男性和女性的胎盘中显示出一致的关联。BW 相关 mRNA 被发现富含重要的生物学途径，包括糖蛋白 VI（胶原蛋白的主要受体）、人类生长和肝细胞生长因子信号传导，其中一部分预计受 BW 相关 miRNA 调节。这些 miRNA 调节的途径突出了可能将内源性/外源性因素与可能对婴儿和晚年健康有害的出生结果变化联系起来的关键机制。