Maternal cadmium, iron and zinc levels, DNA methylation and birth weight
Vidal, Adriana C.; Semenova, Viktoriya; Darrah, Thomas; Vengosh, Avner; Huang, Zhiqing; King, Katherine; Nye, Monica D.; Fry, Rebecca; Skaar, David; Maguire, Rachel; Murtha, Amy; Schildkraut, Joellen; Murphy, Susan; Hoyo, Cathrine
Background Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited. Methods We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight. Results Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05). Conclusions Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required.
Vidal, Adriana C., & Semenova, Viktoriya, & Darrah, Thomas, & Vengosh, Avner, & Huang, Zhiqing, & King, Katherine, & Nye, Monica D., & Fry, Rebecca, & Skaar, David, & Maguire, Rachel, & Murtha, Amy, & Schildkraut, Joellen, & Murphy, Susan, & Hoyo, Cathrine. (July 2015). Maternal cadmium, iron and zinc levels, DNA methylation and birth weight. BMC Pharmacology & Toxicology, 16(), 1- 9. Retrieved from http://hdl.handle.net/10342/5835
Vidal, Adriana C., and Semenova, Viktoriya, and Darrah, Thomas, and Vengosh, Avner, and Huang, Zhiqing, and King, Katherine, and Nye, Monica D., and Fry, Rebecca, and Skaar, David, and Maguire, Rachel, and Murtha, Amy, and Schildkraut, Joellen, and Murphy, Susan, and Hoyo, Cathrine. "Maternal cadmium, iron and zinc levels, DNA methylation and birth weight". BMC Pharmacology & Toxicology. 16:. (1-9), July 2015. December 18, 2018. http://hdl.handle.net/10342/5835.
Vidal, Adriana C. and Semenova, Viktoriya and Darrah, Thomas and Vengosh, Avner and Huang, Zhiqing and King, Katherine and Nye, Monica D. and Fry, Rebecca and Skaar, David and Maguire, Rachel and Murtha, Amy and Schildkraut, Joellen and Murphy, Susan and Hoyo, Cathrine, "Maternal cadmium, iron and zinc levels, DNA methylation and birth weight," BMC Pharmacology & Toxicology 16, no. (July 2015), http://hdl.handle.net/10342/5835 (accessed December 18, 2018).
Vidal, Adriana C., Semenova, Viktoriya, Darrah, Thomas, Vengosh, Avner, Huang, Zhiqing, King, Katherine, Nye, Monica D., Fry, Rebecca, Skaar, David, Maguire, Rachel, Murtha, Amy, Schildkraut, Joellen, Murphy, Susan, Hoyo, Cathrine. Maternal cadmium, iron and zinc levels, DNA methylation and birth weight. BMC Pharmacology & Toxicology. July 2015; 16(): 1-9. http://hdl.handle.net/10342/5835. Accessed December 18, 2018.