Bisphenol S Induced Transgenerational Lipid Accumulation by Triggering Intestine-to-Germline Histone H3K4me3 Modification in Caenorhabditis elegans

Despite the widespread prevalence of BPS in human populations, its potential impacts on offspring and the underlying mechanisms remain poorly understood. In this study, we found that parental exposure to BPS at environmental doses induced lipid accumulation in Caenorhabditis elegans from one-generational parent (P0) to two-generational offspring (F2), even in the absence of BPS exposure in offspring. Mechanistically, BPS-induced transgenerational lipid accumulation was due to the activation of lipogenic genes (fat-5 and fat-7, encoding delta-9 desaturases) and the associated transcriptional regulators (sbp-1 and mdt-15). Knockdown of methyltransferase wdr-5.1 reversed BPS-induced transgenerational inheritance via inhibiting histone H3K4 trimethylation (H3K4me3). Interestingly, germline-specific wdr-5.1/H3K4me3, rather than intestinal, was identified as being responsible for transgenerational inheritance. Our study provides the first evidence elucidating the mechanisms through which environmentally relevant BPS exposure induces lipid accumulation and transmits this effect across generations.