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 a C. elegans model to evaluate spermatogenesis throughout the entire developmental cycle of him-5 mutant by 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 of wee-1.3, spe-4, spe-6, and spe-17 genes were increased, while those of puf-8, spe-10, fer-1, swm-1, try-5, and spe-15 genes 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 using puf-8 and spe-10 mutants revealed spe-10 gene was specifically involved in PFOS- or PFOA-induced reproductive toxicity via regulating one or more critical palmitoylation events, while puf-8 gene was not direct target of PFOS and PFOA, and PFOS and PFOA may act on the upstream gene of puf-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. Grapical abstract.

Di (2-ethylhexyl) phthalate-induced reproductive toxicity involved in dna damage-dependent oocyte apoptosis and oxidative stress in Caenorhabditis elegans.

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer with a high environmental exposure level. As a persistent organic pollutant, DEHP causes reproductive and developmental toxicity in mammals. In this paper, the reproductive toxicity of DEHP was discussed using the model organism Caenorhabditis elegans to determine the sensitivity indices for evaluating the ecotoxicological effects of DEHP. L4 C. elegans larvae to evaluate the LC50 of DEHP and the changes in brood size and generation time, we found that the LC50 of DEHP to C. elegans exceeded 100 mg/L. And 10 mg/L DEHP exposure significantly reduced the brood sizes but not the generation time. Results of oocyte and distal-tip cell (DTC) counting suggested that the number of oocytes were decreased and apoptotic cells that from the unilateral gonad arm were increased in the 1 mg/L and 10 mg/L DEHP exposed groups. In contrast, there was no significant difference in the fluorescence intensity of DTC. Fluorescence analysis of HUS-1 showed that HUS-1 protein was overexpressed after DEHP exposure. The H2O2 level and DNA damage were measured by Bradford protein assay and AP staining respectively. The results showed that there was no significant difference in H2O2 level after DEHP exposure, in contrast, DNA damage was increased significantly. Moreover, 10 mg/L concentration DEHP exposure significantly increased the expression levels of apoptosis-related genes cep-1, egl-1, ced-4, and ced-3 and decreased the expression levels of ced-9. It suggested that cep-1, egl-1, ced-4, and ced-3 genes promote apoptosis and the ced-9 gene inhibits apoptosis. Meanwhile, 10 mg/L concentration DEHP exposure decreased the expression of oxidative stress-related genes mev-1 and gas-1. The mev-1 and gas-1 are mainly involved in the inhibition of oxidative stress in nematodes. In short, the decreased oocyte numbers and increased apoptosis oocyte numbers in C. elegans when exposed to DEHP, which may involve in the DNA damage induced by oxidative stress.