Due to high sensitivity to environmental exposures, Caenorhabditis elegans is helpful for toxicity evaluation and toxicological study of pollutants. Using this animal model, we investigated the reproductive toxicity of 20&#
x202f;nm polystyrene nanoparticle (PS-NP) in the range of &#
x3bc;g/L and the following pharmacological intervention of paeoniflorin. After exposure from L1-larvae to young adults, 10-100&#
x202f;&#
x3bc;g/L PS-NP could cause the reduction in reproductive capacity reflected by the endpoints of brood size and number of fertilized eggs in uterus. Meanwhile, the enhancements in germline apoptosis analyzed by AO staining and germline DNA damage as shown by alteration in HUS-1::GFP signals were detected in 10-100&#
x202f;&#
x3bc;g/L PS-NP exposed nematodes, suggesting the role of DNA damage-induced germline apoptosis in mediating PS-NP toxicity on reproductive capacity. Following the exposure to 100&#
x202f;&#
x3bc;g/L PS-NP, posttreatment with 25-100&#
x202f;mg/L paeoniflorin increased the reproductive capacity and inhibited both germline apoptosis and DNA damage. In addition, in 100&#
x202f;&#
x3bc;g/L PS-NP exposed nematodes, treatment with 100&#
x202f;mg/L paeoniflorin modulated the expressions of genes governing germline apoptosis as indicated by the decrease in
ced-3,
ced-4, an
egl-1 expressions and the increase in
ced-9 expression. After exposure to 100&#
x202f;&#
x3bc;g/L PS-NP, treatment with 100&#
x202f;mg/L paeoniflorin also decreased expressions of genes (
cep-1,
clk-2,
hus-1, and
mrt-2) governing germline DNA damage. Molecular docking analysis further demonstrated the binding potential of paeoniflorin with three DNA damage checkpoints (CLK-2, HUS-1, and MRT-2). Therefore, our data suggested the toxicity of PS-NP in the range of &#
x3bc;g/L on reproductive capacity after exposure from L1-larvae to young adults, which was associated with the enhancement in DNA damage-induced germline apoptosis. More importantly the PS-NP-induced reproductive toxicity on nematodes could be inhibited by the following paeoniflorin treatment.