Short-Chain Chlorinated Paraffins May Induce Ovarian Damage in Mice via AIM2- and NLRP12-PANoptosome

Humans may intake 0.02 mg/kg/day of short-chain chlorinated paraffins (SCCPs), and no study is available on mammalian ovarian damage caused by low-level SCCPs. In this study, four groups of 5-week-old female Institute of Cancer Research (ICR) mice were orally administered 0, 0.01, 0.1, and 1.0 mg/kg/day SCCPs for 21 consecutive days, and serum and ovaries were collected 20 h after the last SCCPs-administration. SCCPs at ≥0.1 mg/kg/day were found to reduce follicle counts at each stage, induce dose-dependent oxidative stress in mice, and lower serum E2 and ovarian anti-Müllerian hormone levels. The data indicated that cellular PANoptosis increased in the ovaries of all SCCP-treated mice. Furthermore, AIM2- and NLRP12-PANoptosome gene and protein levels were considerably elevated. Female germline stem cells (FGSCs) in the cortical portion of the ovary exhibited substantial damage in all SCCP groups, additionally, the expression of FGSC marker genes and major marker proteins was diminished in the ovaries. Oral administration of SCCPs with 0.01, 0.1, and 1.0 mg/kg/day to mice resulted in PANoptosis of the ovaries. Therefore, it was suggested that the oral administration of ≥0.1 mg/kg/day of SCCPs suppressed ovarian function, which may be attributed to the fact that SCCPs induced the generation of AIM2- and NLRP12-PANoptosome in ovary cells.