Prenatal pyrethroid exposure, placental gene network modules, and neonatal neurobehavior

Area of Science:

• Environmental Health
• Developmental Neuroscience
• Molecular Biology

Background:

• Prenatal pesticide exposure is a potential risk factor for adverse child neurodevelopment.
• Placental function is crucial for fetal development and may be a target for pesticide-induced neurotoxicity.

Purpose of the Study:

• To investigate the association between prenatal pyrethroid pesticide exposure, placental gene expression, and newborn neurobehavior.
• To identify specific placental gene networks and critical exposure periods linking pyrethroids to neurodevelopmental outcomes.

Main Methods:

• A cohort of 248 pregnant farmworkers in Thailand was studied.
• Urinary pyrethroid metabolites, placental transcriptome sequencing, and NICU Network Neurobehavioral Scales (NNNS) were analyzed.
• Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules associated with exposure and neurobehavior.

Main Results:

• Pyrethroid metabolites were linked to nine placental gene network modules, and thirteen modules correlated with NNNS scores, with eight overlapping modules.
• Specific modules, including interferon alpha response and Myc targets, were associated with neonatal stress, attention, arousal, and movement quality.
• Early pregnancy exposure was linked to the protein secretion module, while late pregnancy exposure affected oxidative phosphorylation (OXPHOS) and DNA repair modules.

Conclusions:

• Prenatal pyrethroid exposure may affect neonatal neurobehavior via placental gene expression changes in metabolic and response pathways.
• The timing of pyrethroid exposure during pregnancy is critical, influencing distinct placental functions.
• Findings support targeted risk assessment and interventions to mitigate neurodevelopmental risks from pesticide exposure.