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Dartmouth Team Awarded $2.5M Grant to Study Placental microRNAs


NEW YORK (GenomeWeb) – With a four-year, $2.5 million grant from the National Institute of Environmental Health Sciences, a Dartmouth College team has kicked off a study examining the roles of placental microRNAs in neonatal outcomes, as well as the effects environmental exposures have on these non-coding RNAs.

As part of the effort, the researchers — led by Dartmouth's Carmen Marsit — will analyze more than 2,000 placental and matched blood samples obtained from mothers and infants in Rhode Island and New Hampshire, representing urban and rural populations with unique environmental exposure profiles.

Amid growing evidence that the placenta physiology is key to newborn health and disease, Marsit and others have been exploring the effects miRNAs have on neonatal outcomes. For instance, he and colleagues published data in 2011 linking the expression of two miRNAs — miR-16 and miR-21 — with fetal growth. Two years later, they reported that expression of these and other miRNAs were associated with infant neurobehavioral outcomes.

Others, meanwhile, have shown that placental-specific miRNAs can be found in maternal circulation and may have diagnostic potential.

In his early work, Marsit told GenomeWeb that he and his collaborators cherry picked candidate miRNAs that had already been shown in the literature to have important biological functions. With the NIEH funding, he is planning to cast a broader net and identify the full expression pattern of as many placental miRNAs as possible.

"Then we'll start asking if these microRNAs play some role in mediating how exposures during the in utero period lead to outcomes in children," such as growth, neurodevelopment, and immunity, he said. This will involve studying miRNA expression both in the placenta and in maternal blood.

Marsit expects to begin by using next-generation sequencing in a subset of maternal and neonatal samples to gain a comprehensive view of the miRNA transcriptome, then follow up with a more focused analysis on the full set of samples using Nanostring's nCounter platform.

The samples will come from two cohorts. The first comprises around 900 placental and blood samples previously obtained from mothers and newborns in Providence, Rhode Island, which Marsit said represents an urban cohort with "a wide range of exposures, as well as a range of neurobehavioral outcomes."

The second cohort comes from the ongoing New Hampshire Birth Cohort Study, a prospective longitudinal study that has currently enrolled about 1,500 women and newborns. Notably, this study is focused on women who use private wells as their drinking water source, which creates the potential for exposure to arsenic and other trace metals, he said.

In the New Hampshire study, participants have also provided toenail clippings that will be analyzed for trace metals, representing chronic long-term exposures.

Using these two cohorts "gives us nice comparison populations … that have different types of [environmental] exposures," Marsit added.

Ultimately, this work could lead to biomarkers of neonatal outcomes, as well as provide insights into the exact roles these miRNAs play in pregnancy and fetal development and point to interventions to counteract the effects of negative environmental exposures.

"It would be great to say, 'Just don't get exposed,' but that's not always possible," Marsit said. "So, it would be [beneficial] to be able to potentially prevent some of these problems."