DNA methylation changes in whole blood is associated with exposure to the environmental contaminants, mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF

Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Human Reproduction (Impact Factor: 4.57). 02/2012; 27(5):1401-10. DOI: 10.1093/humrep/des038
Source: PubMed


Changes in DNA methylation may play an important role in the deleterious reproductive effects reported in association with exposure to environmental pollutants. In this pilot study, we identify candidate methylation changes associated with exposure to pollutants in women undergoing in vitro fertilization (IVF).
Blood and urine were collected from women on the day of oocyte retrieval. Whole blood was analyzed for mercury and lead, and urine for cadmium using inductively coupled plasma mass spectrometry. Unconjugated bisphenol A (BPA) was analyzed in serum using high-performance liquid chromatography with Coularray detection. Participants were dichotomized as higher or lower exposure groups by median concentrations. Using the Illumina GoldenGate Methylation Cancer Panel I, DNA methylation in whole blood from 43 women was assessed at 1505 CpG sites for association with exposure levels of each pollutant. Candidate CpG sites were identified using a Diff Score >|13| (P< 0.05) and an absolute difference >10% which were confirmed using bisulfite pyrosequencing.
Methylation of the GSTM1/5 promoter was increased for women with higher mercury exposure (P= 0.04); however, no correlation was observed (r= 0.17, P= 0.27). Reduced methylation was detected in the COL1A2 promoter in women with higher exposure to lead (P= 0.004), and an inverse correlation was observed (r = - 0.45, P= 0.03). Lower methylation of a promoter CpG site at the TSP50 gene was detected in women with higher BPA exposure (P= 0.005), and again an inverse correlation was identified (r = - 0.51, P= 0.001).
Altered DNA methylation at various CpG sites was associated with exposure to mercury, lead or BPA, providing candidates to be investigated using a larger study sample, as the results may reflect an independently associated predictor (e.g. socioeconomic status, diet, genetic variants, altered blood cell composition). Further studies accommodating variations in these factors will be needed to confirm these associations and identify their underlying causes.

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Available from: Michael S Bloom, Oct 10, 2015
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    • "Characterization of universal EDCs-induced epigenetic alterations, such as hyper-or hypo-DNA methylation changes in select candidate genes, may allow for development of diagnostic tests for humans and wildlife species. It is now apparent from a variety of rodent and fish studies that BPA and EE2 exposure leads to DNA methylation and gene expression changes that might account for reproductive and developmental abnormalities (Anderson et al., 2012; Bromer et al., 2010; Chao et al., 2012; Dolinoy et al., 2007; Doshi et al., 2012; Fernandez et al., 2012; Greathouse et al., 2012; Hanna et al., 2012; Ho et al., 2006; Jang et al., 2012; Prins et al., 2008; Tang et al., 2012; Weng et al., 2010; Yaoi et al., 2008; Zhang et al., 2012). Circulating miRNAs (including other ncRNAs) may be essential in epigenetic inheritance in mammals (Sharma, 2014). "
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    • "Furthermore, once engaged in the neural differentiation pathway , a majority of DMCs showed Pb-associated hypomethylation . This " hypomethylation " effect is in accordance with previous human epidemiological studies showing an inverse relationship between bone/BLLs and methylation of LINE-1 (Pilsner et al., 2009; Wright et al., 2008) or collagen type1 al- pha2 (Hanna et al., 2012). Unexpectedly, we did not observe this " hypomethylation " effect in NPCs derived from hESCs chronically exposed to Pb throughout the entire neural differentiation protocol. "
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    • "However, stronger association between BPA and semen quality parameters was observed among those with higher LINE-1 methylation. This may be partly because of the less disturbance from other confounding chemicals in this group, as lowered methylation has been found to be associated with exposure to environmental hazardous chemicals (Bollati et al., 2007; Hanna et al., 2012; Hossain et al., 2012; Tajuddin et al., 2013). It is possible that abnormal DNA methylation of individual genes may still be involved in BPA-related impact on sperm quality. "
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