Male reproductive toxicity involved in spermatogenesis induced by perfluorooctane sulfonate and perfluorooctanoic acid in Caenorhabditis elegans

As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have gained increasing research attention over recent years because of their potential risk to humans and the environment. In this paper, we investigated the reproductive toxicity of these pollutants using aC. elegansmodel to evaluate spermatogenesis throughout the entire developmental cycle ofhim-5 mutantby exposing to 0.001, 0.01, and 0.1 mmol/L PFOS or PFOA for 48 h. Experimental results suggested that PFOS and PFOA exposure led to reductions in brood size, germ cell number, spermatid size, and motility, and increases in rate of malformation spermatids. Analysis of variance (ANOVA) showed that exposure to PFOS resulted in higher levels of damage than PFOA in germ cells only in 0.001 mmol/L exposure group. RT-qPCR was used to further investigate the expression of genes associated with different stages of spermatogenesis, such as mitosis and meiosis, fibrous body-membranous organelles (FB-MOs), and sperm activation. The expression levels ofwee-1.3,spe-4,spe-6, andspe-17genes were increased, while those ofpuf-8,spe-10,fer-1,swm-1,try-5, andspe-15genes were decreased. Our results suggesting that PFOS or PFOA may cause spermatogenesis damage by disrupting the mitotic proliferation, meiotic entry, formation of the MOs, fusion of the MOs and plasma membrane (PM), and pseudopods. Loss-of-function studies usingpuf-8andspe-10mutants revealedspe-10gene was specifically involved in PFOS- or PFOA-induced reproductive toxicity via regulating one or more critical palmitoylation events, whilepuf-8gene was not direct target of PFOS and PFOA, and PFOS and PFOA may act on the upstream gene ofpuf-8, thus affecting reproductive ability. Taken together, these results demonstrate the potential adverse impact of PFOS and PFOA exposure on spermatogenesis and provide valuable data for PFC risk assessment.