DNA/RNA is altered by Prenatal Mercury Exposure
In the FDA’s 186-page report on the Epidemiological Evidence on the Adverse Health Effects Reported in Relation to Mercury from Dental Amalgam: A systematic literature (2010 – Present) released in September 2019, there were several omissions. One of them was the lack of any reporting on the effects of mercury on DNA and RNA. It is well-known that alterations in DNA/RNA can lead to genetic disorders, developmental problems and increase risk of cancer and other disease. Since 2019, much more research has been conducted in the arena. Here we present a summary of the results of a meta-analysis of the available research of the effects of mercury on prenatal exposure, as well as summaries from some individual relevant studies.
Lozano, Manuel, Paul Yousefi, Karin Broberg, Raquel Soler-Blasco, Chihiro Miyashita, Giancarlo Pesce, Woo Jin Kim, et al. “DNA Methylation Changes Associated with Prenatal Mercury Exposure: A Meta-Analysis of Prospective Cohort Studies from PACE Consortium.” Environmental Research 204, no. Pt B (March 2022): 112093. https://doi.org/10.1016/j.envres.2021.112093.
This meta-analysis, published in 2022 examines DNA methylation changes associated with prenatal mercury exposure. Mercury influences DNA methylation, a crucial epigenetic mechanism that regulates gene expression. Findings from prospective cohort studies, provide evidence of significant changes in DNA methylation patterns associated with prenatal mercury exposure. Specific CpG sites exhibit alterations in their methylation status due to mercury exposure, underscoring the compound’s potential to affect gene regulation profoundly and persistently throughout development.
A primary finding from this meta-analysis is the alteration of methylation at sites associated with the Paraoxonase 1 gene (PON1) in infants exposed to mercury in utero. Research indicates that changes in methylation at these sites were initially observed in cord blood and demonstrated varying levels of persistence, suggesting that mercury exposure can have long-term implications for DNA methylation profiles. The methylation marks associated with PON1 were found to persist into early childhood.
In addition to specific genes like PON1, the broader implications of these DNA methylation changes suggest potential disruptions in metabolic and oxidative stress pathways linked to mercury exposure. The alterations in DNA methylation patterns may lead to changes in gene expression that predispose individuals to various health outcomes, including neurodevelopmental issues and other chronic conditions. This highlights the importance of understanding the epigenetic effects of environmental toxicants like mercury, especially during sensitive developmental windows such as prenatal exposure
Overall, current evidence points to mercury as a significant environmental risk factor that can induce epigenetic changes through DNA methylation alterations, thus influencing gene expression and potentially leading to adverse health outcomes throughout the life course.
Bakulski, Kelly M., HwaJin Lee, Jason I. Feinberg, Ellen M. Wells, Shannon Brown, Julie B. Herbstman, Frank R. Witter, et al. “Prenatal Mercury Concentration Is Associated with Changes in DNA Methylation at TCEANC2 in Newborns.” International Journal of Epidemiology 44, no. 4 (August 2015): 1249–62. https://doi.org/10.1093/ije/dyv032.
This study investigates the relationship between prenatal exposure to mercury and its subsequent impact on DNA methylation, particularly focusing on the TCEANC2 gene in newborns. The findings emphasize that exposure to mercury, even at low concentrations during prenatal development, correlates with significant changes in DNA methylation patterns that could have lasting effects on gene regulation and potentially influence health outcomes later in life.
The researchers observed that higher concentrations of mercury in maternal blood were associated with increased DNA methylation at specific CpG sites within the TCEANC2 promoter region. This region is notable for its involvement in various biological processes, and methylation changes could alter gene expression. The study suggests that such alterations may have implications for neurodevelopment, as previous research has indicated that changes in DNA methylation are linked to adverse neurobehavioral outcomes, including lower cognitive scores and behavioral issues in children.
Additionally, TCEANC2 may play a significant role in cellular processes, including responses to environmental stressors. The study posits that the epigenetic changes observed in newborns could serve as biomarkers for evaluating the impact of prenatal environmental exposures, such as mercury, on developmental outcomes. Thus, the findings highlight the potential of DNA methylation as a mechanism through which toxicants like mercury exert their effects during critical periods of development.
In conclusion, this research underscores the importance of monitoring and mitigating prenatal mercury exposure to safeguard epigenetic health and developmental outcomes in offspring. Given the implications of altered DNA methylation patterns on gene expression and developmental processes, understanding these relationships is crucial in public health discussions around prenatal environmental exposures.
Cardenas, Andres, Devin C. Koestler, E. Andres Houseman, Brian P. Jackson, Molly L. Kile, Margaret R. Karagas, and Carmen J. Marsit. “Differential DNA Methylation in Umbilical Cord Blood of Infants Exposed to Mercury and Arsenic in Utero.” Epigenetics 10, no. 6 (2015): 508–15. https://doi.org/10.1080/15592294.2015.1046026.
This study investigates the effects of prenatal exposure to mercury (Hg) and arsenic (As) on DNA methylation patterns in umbilical cord blood. The research focused on understanding how these environmental toxicants might influence epigenetic modifications that can affect fetal development and potentially lead to adverse health outcomes in children.
Several specific genomic loci were identified where differential DNA methylation occurs in response to exposure to mercury and arsenic. The researchers discovered that two notable loci located in the CpG islands of the Gamma-Glutamyltransferase 7 gene (GGT7) exhibited hypermethylation. The GGT7 gene plays a crucial role in the metabolism of glutathione, a tripeptide that protects cells against oxidative stress and neurotoxicity, particularly from methylmercury. This hypermethylation may indicate a functional impairment in the expression of GGT7, potentially compromising the infant’s ability to detoxify harmful compounds such as methylmercury, which could enhance susceptibility to neurodevelopmental disorders.
Additionally, the differential methylation patterns were associated with the interaction between mercury and arsenic, suggesting that co-exposure to these two toxicants may amplify their effects on epigenetic modifications. The findings raise concerns about the cumulative impact of environmental toxins during critical stages of development and highlight the need for further investigation into the long-term health consequences of prenatal exposure to mercury and arsenic.
In summary, this study provides compelling evidence of the impact of prenatal exposure to mercury and arsenic on DNA methylation in newborns, particularly affecting genes involved in detoxification processes. The observed hypermethylation of specific loci suggests a potential mechanism through which these toxicants may contribute to neurodevelopmental risks.
Sanders, Alison P., Heather H. Burris, Allan C. Just, Valeria Motta, Chitra Amarasiriwardena, Katherine Svensson, Emily Oken, et al. “Altered miRNA Expression in the Cervix during Pregnancy Associated with Lead and Mercury Exposure.” Epigenomics 7, no. 6 (2015): 885–96. https://doi.org/10.2217/epi.15.54.
This study investigates the impact of prenatal exposure to lead and mercury on microRNA (miRNA) expression in the cervix, focusing on the potential implications for pregnancy outcomes such as preterm birth. The research draws upon data collected from pregnant women, analyzing associations between exposure to these heavy metals and alterations in miRNA profiles.
A key finding is that specific miRNAs were significantly altered in women who had higher blood lead levels, elevated bone lead concentrations, or increased levels of mercury in toenail samples. The researchers provide substantial evidence that lead exposure is linked to increased expression levels of certain miRNAs, such as miR-155 and miR-21, both of which are known to play roles in inflammatory responses and cellular stress pathways. This is particularly relevant as increased inflammation has been implicated in the risk of preterm birth and other pregnancy complications (Sanders et al., 2015).
Additionally, the study highlights that mercury exposure may similarly affect miRNA expression patterns, although the relationship appears less pronounced than that observed with lead. The changes in miRNA profiles suggest potential pathways through which heavy metal exposure could disrupt normal cervical function, possibly leading to adverse pregnancy outcomes. The findings underscore the need for further research to clarify the biological mechanisms involved and the potential for these miRNAs to serve as biomarkers for risk assessment in pregnant populations exposed to environmental pollutants.
In conclusion, the study emphasizes the association between prenatal exposure to lead and mercury and altered miRNA expression in the cervix, providing insights into how these environmental exposures may contribute to negative pregnancy outcomes, specifically preterm birth.
