Nanoplastic PS and cadmium co-exposure accelerates ferroptosis mediated by HIF-1α-related signaling in spermatogonium

Microplastics (MPs) in the real environment media often adsorbed toxic substances such as heavy metals and this co-exposure may exert various negative effects on human reproduction. In particular, the adsorption capacity of nanoplastics (NPs) is stronger. However, there are few studies focused on the combined toxicity of NPs and heavy metal co-exposure to germ cells. In this study, mouse spermatogonium GC-1 cells were applied as in vitro model to observe the effects of PS-NPs (0.1 μm, 200 mg/L) and cadmium (Cd) chloride (5 μM) on mouse spermatogonia and the underlying mechanism. The results showed that GC-1 cells turned significantly abnormal in morphology, and cell number and survival rate reduced in the co-exposed group. These injuries were restored after the intervention of ferroptosis inhibitor (Fer-1, 1 μM), HIF-1α specific inhibitor (YC-1, 10 μM) and miR-199a-5p mimic (50 nM). Double luciferase gene reporting experiment showed that there existed binding sites of miR-199a-5p to HIF-1α mRNA. Collectively, we found that PS-NPs + Cd co-exposure induced GC-1 cell ferroptosis, which might be mediated by miR-199a-5p/HIF-1α signaling axis. Hopefully, these findings will shed new light on how PS-NPs may impair male reproductive function in real scenario.