Cuproptosis is involved in small intestinal toxicity in the paraffins during pregnancy

Short-chain chlorinated paraffins (SCCPs) is generally regarded as an emerging persistent organic pollutant. So far, small intestine injury in the progeny of adult mice exposed to SCCPs during pregnancy has not yet been the subject of any research. To investigate potential intestinal injury in the progeny of adult mice exposed to SCCPs during pregnancy. There were no noticeable variations in litter size, sex ratio, or the birth weight of male and female mice. However, SCCPs gestational exposure significantly reduced the adult body weight of female and male mice. In addition, we discovered that SCCPs exposure resulted in histological alterations in the small intestines of both female and male newborns. Furthermore, the small intestines of SCCPs-treated female and male mice showed a significantly elevated superoxide dismutase (SOD) activity and reduced glutathione (GSH) activity compared to control group. Moreover, SCCPs exposure led to downregulation of FDX1 protein level and upregulation the protein levels of DLAT and SLC31A1, indicating initiation of coppers. Interestingly, the alterations in FDX1, DLAT, and LIAS mRNA expression levels varied between female and male progeny. Even while none of the phenotypes showed the typical dose-dependent effects, the findings suggest that female offspring are more susceptible to small intestine toxicity than male offspring. According to our findings, SCCPs exposure during pregnancy might develop sex-specific small intestine toxicity, which may lead to reactive oxygen species activation and following coppers. In summary, this study demonstrated that exposure to SCCPs during pregnancy had deleterious effects on the offspring's small intestine.