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Altered gene expression linked to germline dysfunction following exposure to environmentally relevant level of DEET

ABSTRACT: N,N-Diethyl-meta-toluamide (DEET) is a synthetic insect repellent invented in 1946 by the US Department of Agriculture for use by military personnel and now used worldwide as evidenced by its detection at various levels in human urine, serum, semen, and cord serum (1–5). While the neurological effects of DEET have been widely investigated (6–8), its effects on the germline and reproductive health are less understood. Here we used the nematode Caenorhabditis elegans, a genetically and cytologically tractable model system that shares a high degree of conservation of its genes and biochemical pathways with humans and is highly predictive of mammalian reprotoxicity, to study how DEET affects the germline (9–12). We found that exposure to environmentally relevant levels of DEET causes activation of p53/CEP-1-dependent germ cell apoptosis and alters recombination by inducing elevated levels of meiotic DNA double-strand breaks (DSBs) and crossovers (COs) resulting in chromosome abnormalities and missegregation. RNA sequencing (RNA-seq) analysis links DEET induced alterations in the expression of genes related to oxidation and reduction (redox) processes and chromatin structure to reduced mitochondrial function, altered DSB repair progression, and impaired early embryonic cell division. Our work shows that exposure to environmentally relevant levels of DEET interferes with gene expression, leading to increased oxidative stress and altered chromatin structure resulting in detectable germline effects that can pose a risk to reproductive health.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE242682 | GEO | 2024/02/07

REPOSITORIES: GEO

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