Single-cell investigation of lead toxicity from neurodevelopment to neurodegeneration: Current review and future opportunities.

Human exposure to the metal lead (Pb) is prevalent and associated with adverse neurodevelopmental and neurodegenerative outcomes. Pb disrupts normal brain function by inducing oxidative stress and neuroinflammation, altering cellular metabolism, and displacing essential metals. Prior studies on the molecular impacts of Pb have examined bulk tissues, which collapse information across all cell types, or in targeted cells, which are limited to cell autonomous effects.

piOxi database: a web resource of germline and somatic tissue piRNAs identified by chemical oxidation.

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs that are highly expressed and extensively studied from the germline. piRNAs associate with PIWI proteins to maintain DNA methylation for transposon silencing and transcriptional gene regulation for genomic stability. Mature germline piRNAs have distinct characteristics including a 24- to 32-nucleotide length and a 2'-O-methylation signature at the 3' end.

Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver Identifies Tissue- and Sex-Specific Changes with Implications for Genomic Imprinting.

Background: Maternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications.

Objective: We examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2-ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver.

Developmental exposures to common environmental contaminants, DEHP and lead, alter adult brain and blood hydroxymethylation in mice.

The developing epigenome changes rapidly, potentially making it more sensitive to toxicant exposures. DNA modifications, including methylation and hydroxymethylation, are important parts of the epigenome that may be affected by environmental exposures. However, most studies do not differentiate between these two DNA modifications, possibly masking significant effects.

PIWI-Interacting RNA (piRNA) and Epigenetic Editing in Environmental Health Sciences.

PURPOSE OF REVIEW: The epigenome modulates gene expression in response to environmental stimuli. Modifications to the epigenome are potentially reversible, making them a promising therapeutic approach to mitigate environmental exposure effects on human health. This review details currently available genome and epigenome editing technologies and highlights ncRNA, including piRNA, as potential tools for targeted epigenome editing.

Toxicoepigenetics and Environmental Health: Challenges and Opportunities.

The rapidly growing field of toxicoepigenetics seeks to understand how toxicant exposures interact with the epigenome to influence disease risk. Toxicoepigenetics is a promising field of environmental health research, as integrating epigenetics into the field of toxicology will enable a more thorough evaluation of toxicant-induced disease mechanisms as well as the elucidation of the role of the epigenome as a biomarker of exposure and disease and possible mediator of exposure effects. Likewise, toxicoepigenetics will enhance our knowledge of how environmental exposures, lifestyle factors, and diet interact to influence health.