Comparing the Predictivity of Human Placental Gene, microRNA, and CpG Methylation Signatures in Relation to Perinatal Outcomes

Jeliyah Clark, Vennela Avula, Caroline Ring, Lauren A Eaves, Thomas Howard, Hudson P Santos, Lisa Smeester, Jacqueline T Bangma, Thomas Michael O’Shea, Rebecca C Fry, Julia E Rager

Toxicol Sci. 2021 Sep 28;183(2):269-284. doi: 10.1093/toxsci/kfab089. PMID: 34255065; PMCID: PMC8478332.

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This study evaluated mRNA and microRNA (miRNA) expression and cytosine-guanine dinucleotide (CpG) methylation signatures in human placental tissues in relation to birth weight, placenta weight, placental damage, and placental inflammation. The following hypotheses were tested: (1) different molecular signatures will demonstrate varying levels of predictivity towards perinatal outcomes, and (2) these signatures will show disruptions from an example exposure (ie, cadmium) known to elicit perinatal toxicity. Epigenomic signatures (ie, miRNA and CpG methylation) consistently demonstrated the highest levels of predictivity; top-ranking predictors included miRNAs involved in injury and inflammation. These top-ranking miRNA predictors were analyzed in a separate pregnancy cohort and related to cadmium. Key predictive miRNAs demonstrated altered expression in association with cadmium exposure, including miR-210, known to impact placental cell growth, blood vessel development, and fetal weight.