Data for: Developmental origins of Parkinson’s disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain

Epidemiological studies show that exposure to the organochlorine pesticide
dieldrin is associated with increased risk of Parkinson’s disease (PD).
Animal studies support a link between developmental dieldrin exposure and
increased neuronal susceptibility in the α-synuclein preformed fibril
(α-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous
study, we showed that developmental dieldrin exposure was associated with
sex-specific changes in DNA modifications within genes related to
dopaminergic neuron development and maintenance at 12 weeks of age. Here,
we used capture hybridization-sequencing with custom baits to interrogate
DNA modifications across the entire genetic loci of the previously
identified genes at multiple time points – birth, 6 weeks, 12 weeks, and
36 weeks old. We identified largely sex-specific dieldrin-induced changes
in DNA modifications at each time point that annotated to pathways
important for neurodevelopment, potentially related to critical steps in
early neurodevelopment, dopaminergic neuron differentiation,
synaptogenesis, synaptic plasticity, and glial-neuron interactions.
Despite large numbers of age-specific DNA modifications, longitudinal
analysis identified a small number of DMCs with dieldrin-induced
deflection of epigenetic aging. The sex-specificity of these results adds
to evidence that sex-specific responses to PD-related exposures may
underly sex-specific differences in disease. Overall, these data support
the idea that developmental dieldrin exposure leads to changes in
epigenetic patterns that persist after the exposure period and disrupt
critical neurodevelopmental pathways, thereby impacting risk of late life
diseases, including PD.