J114 prevents short-chain chlorinated paraffin-induced damage to female germline stem cells by inhibiting AIM2-and NLRP12-PANoptosome

The concentration of short-chain chlorinated paraffins (SCCPs) in human breast milk and blood ranges from 1.4 to 1400 μg/L. In this study, after treating female germ stem cells (FGSCs) with SCCPs at concentrations of 0, 1.4, 14, 140, and 1400 μg/L for 24, 48, and 72 h separately, it was found that ≥14 μg/L SCCPs inhibited the proliferation of FGSCs and induced oxidative stress in FGSCs. After 48 h, SCCPs at a concentration of ≥14 μg/L not only reduced the FGSC biomarkers, but also increased the member levels of AIM2-and NLRP12-PANoptosome. NLRP3 and AIM2 are key proteins in AIM2-and NLRP12- PANoptosome, respectively, and J114 (NLRP3/AIM2-IN-3) can effectively inhibit them. And 0.025, 0.1, and 0.4 μM J114 were used to intervene in the FGSCs damage induced by 1400 μg/L SCCPs for 24, 48, and 72 h, respectively. After 24 h, ≥0.1 μM J114 significantly enhanced the proliferation of FGSCs and inhibited their oxidative stress. After treatment with 0.1 and 0.4 μM J114 for 48 h, the FGSC biomarkers were elevated, and the AIM2-and NLRP12-PANoptosomes were significantly suppressed. This suggests that SCCPs at low-level can inhibit FGSC proliferation and induce PANapoptosis, because SCCPs induce the formation of AIM2-and NLRP12-PANoptosome. Meanwhile, ≥0.1 μM J114 can alleviate/inhibit the toxic effects of SCCPs on FGSCs by inhibiting the production of AIM2-and NLRP12-PANoptosome.