Abstract
BackgroundNovel research has suggested that altered miRNA expression in the placenta is associated with adverse pregnancy outcomes and with potentially harmful xenobiotic exposures. We hypothesized that aberrant expression of miRNA in the placenta is associated with fetal growth, a measurable phenotype resulting from a number of intrauterine factors, and one which is significantly predictive of later life outcomes.Methodology/Principal FindingsWe analyzed 107 primary, term, human placentas for expression of 6 miRNA reported to be expressed in the placenta and to regulate cell growth and development pathways: miR-16, miR-21, miR-93, miR-135b, miR-146a, and miR-182. The expression of miR-16 and miR-21 was markedly reduced in infants with the lowest birthweights (p<0.05). Logistic regression models suggested that low expression of miR-16 in the placenta predicts an over 4-fold increased odds of small for gestational age (SGA) status (p = 0.009, 95% CI = 1.42, 12.05). Moreover, having both low miR-16 and low miR-21 expression in the placenta predicts a greater increase in odds for SGA than having just low miR-16 or miR-21 expression (p<0.02), suggesting an additive effect of both of these miRNA.Conclusions/SignificanceOur study is one of the first to investigate placental miRNA expression profiles associated with birthweight and SGA status. Future research on miRNA whose expression is associated with in utero exposures and markers of fetal growth is essential for better understanding the epigenetic mechanisms underlying the developmental origins of health and disease.
Highlights
Fetal development represents a critical period during which perturbations to the intrauterine environment through various factors in the extrauterine environment can have major ramifications on the proper growth and development of the fetus and on risk for disease later in life [1]
Female Male Mode of delivery*, n (%) Caesarian section Vaginal delivery Maternal age, years, mean Maternal ethnicity**, n (% ) Non-white White Maternal cigarette smoking during pregnancy*** No Yes Relative weight gained during pregnancy, % of prepregnancy weight, mean**** Maternal insurance Public Private
Observing that expression in the lowest quartiles of miR-16 and miR-21 was associated with reduced birthweight percentile, we examined the association between low expression (#median vs. .median) of the miRNA and infants considered small for gestational age (SGA), using logistic regression to control for potential confounders
Summary
Fetal development represents a critical period during which perturbations to the intrauterine environment through various factors in the extrauterine environment can have major ramifications on the proper growth and development of the fetus and on risk for disease later in life [1]. Barker and Hales [1] hypothesized that fetuses receive a poor or rich maternal forecast depending, in part, on the intrauterine and extrauterine conditions during pregnancy, but that this maternal forecast may not always accurately predict the post-birth environment and that such mismatches give rise to disease risk later in life. This has played out in a number of epidemiologic studies linking low birthweight with morbidity and mortality in early infancy [2] as well as with an increased risk for certain diseases later in life, coronary heart disease, diabetes mellitus type 2, and hypercholesterolemia [2]. We hypothesized that aberrant expression of miRNA in the placenta is associated with fetal growth, a measurable phenotype resulting from a number of intrauterine factors, and one which is significantly predictive of later life outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
