Prenatal Manganese Exposure, Placental Imprinting and Fetal Growth
In October, principal investigator Jia Chen, ScD was awarded $25,000 to investigate prenatal manganese exposure, placental imprinting, and fetal growth. Manganese (Mn) is both an essential nutrient and a toxicant, with environmental exposure via air, water, and soil, particularly in areas where Mn is either mined, transported, or added to gasoline as methylcyclopentadienyl manganese tricarbonyl (MMT), an anti-knocking agent. Prenatal exposure to both high and low levels of manganese have been shown to impair fetal growth and neurodevelopment.
Recent evidence has implicated alterations in epigenetic programming as a potential mechanism in these effects, and alterations in the expression profiles of imprinted genes in the placenta may be of particular importance, given the critical roles of these genes in fetal growth and neurodevelopment.
Dr. Chen is joined by a multidisciplinary team of co-investigators that include CEHC faculty Robert Wright, MD, MPH, Professor of Pediatrics at Boston Children’s Hospital R. Colin Carter, MD, Child Development Researchers at Wayne State University School of Medicine Sandra Jacobson, PhD and Joseph Jacobson, PhD, Assistant Professor at The University of Texas Health Science Center Pei Wang, PhD, and Christopher Molteno, MD. The cohort for this study was recruited in Cape Town, South Africa, where Mn exposure levels are particularly high due to Mn mining and the addition of MMT to gasoline.
“We hypothesize that prenatal Mn exposure modulates imprinted gene expression that leads to deficits in fetal growth. We will test this hypothesis in banked placenta samples obtained from 68 mother-infant pairs in a prospective longitudinal cohort study examining the effects of prenatal alcohol exposure on growth and development, including both drinkers and abstaining controls.”
“A major strength of our approach is the measurement of Mn content directly in the target tissue, the placenta, as blood concentrations of Mn may not correlate with degree of environmental exposure. ”
– Jia Chen, ScD
Placental Mn content (mg/g dried placental tissue) is being measured using ICP-MS, and placental expression of imprinted genes are being assayed using a validated, multiplexed imprintome assay by nanoString. The placenta is an ideal target tissue for this study because it is fetally-derived, and imprinted genes are highly expressed in the placenta.
Furthermore, prospectively obtained data regarding prenatal alcohol exposure provides a unique opportunity to explore potential interactions between Mn and alcohol, which have similar effects on fetal growth and neurobehavior.