Parental preconceptual α-cypermethrin exposure alters embryonic brain transcriptomics in mice: Implications for autism spectrum disorder and stress vulnerability.

Researchers exposed mice to a common household and agricultural insecticide before they had babies, then studied the brain development of their offspring. They found that exposure to this pesticide before conception changed how genes work in the developing baby brains. The changes were similar to patterns seen in autism and stress-related conditions. Both mother and father exposure affected the babies, but mother's exposure had stronger effects.

This suggests that pesticide exposure before pregnancy might increase the risk of developmental differences in children.

This mouse study examined how parental exposure to α-cypermethrin, a common pyrethroid insecticide, before conception affects offspring brain development. Adult mice were exposed to low or high doses for four weeks before mating, and researchers analyzed gene expression in embryonic brain tissue. Results showed dose-dependent changes in brain gene expression, with the greatest effects when both parents were exposed. Key findings included upregulation of genes associated with autism spectrum disorder and stress vulnerability, disrupted neuronal and synaptic processes, and altered mitochondrial function.

Maternal exposure particularly affected translation processes and activated EIF4E, a gene linked to autism. The study suggests preconception pesticide exposure may contribute to neurodevelopmental vulnerabilities in offspring.

Findings suggest preconception environmental exposures, particularly maternal pesticide exposure, may influence neurodevelopmental risk. Healthcare providers should consider discussing pesticide exposure reduction with couples planning pregnancy. However, human studies are needed to confirm these findings and establish clinical relevance for autism prevention strategies.

This is an animal study using mice, so results may not directly translate to humans. Sample size was not reported. The study examined only embryonic brain tissue, not behavioral outcomes or long-term effects. Causality between gene expression changes and actual neurodevelopmental outcomes cannot be established.

Pyrethroid insecticides are widely used in agriculture and households, and their exposure can affect neurodevelopment. Few studies have evaluated how preconception parental exposure could also affect this process. To address this knowledge gap, adult C57Bl6/J mice were gavaged daily with α-cypermethrin at a human relevant low (0.3 mg/kg) or high (10 mg/kg) dose in corn oil for four weeks prior to conception. Offspring embryonic day 16 dorsal forebrain was extracted for transcriptomic analysis.

In offspring forebrains of exposed compared to unexposed parents, there was increasing number of differentially expressed genes (DEGs) from paternal (least) to maternal to both parent exposure (most). A dose dependent effect was observed in offspring forebrain for paternal and maternal preconceptual exposures. Maternal and both parent exposures led to upregulated genes in offspring brain for biological processes involved in translation with predicted activation of EIF4E, a gene associated with autism. In contrast, paternal exposure upregulated cell cycle related DNA damage signaling processes.

After any parent exposure, there was upregulation of biological processes involved in mitochondria function and oxidative stress and a downregulation of neuronal and synaptic processes with predicted inhibition of BDNF signaling. Weighted gene correlation network analysis identified modules associated with different parent exposures that were over-represented with DEGs and had similar functional signatures as DEG-related pathways. Importantly, DEGs in offspring forebrain after any parent exposure were over-represented with genes related to autism spectrum disorder (ASD) and stress vulnerability. The study highlights the potential contribution of preconception parental pyrethroid exposure to aberrant brain functioning.