Abstract Short-chain chlorinated paraffins (SCCPs) are prevalent persistent organic pollutants (POPs) that were officially listed under the Stockholm Convention in 2017. Due to their widespread environmental distribution, human exposure to SCCPs is inevitable, particularly in occupational settings where elevated concentrations pose significant health risks, including hepatic toxicity, endocrine disruption, and occupational diseases. Although early SCCPs exposure has been linked to parental toxicity and related diseases, potential cross-generational neurotoxic effects remain unexplored. This study investigated whether prenatal exposure to different doses of SCCPs induces Alzheimer’s disease (ad)-like neuropathology in adult mouse offspring and provides the first evidence of cross-generational neurotoxicity. Compared with the control group, adult offspring exposed to SCCPs exhibited significant alterations in body weight, and the brain organ coefficient of female offspring in the medium-dose group was significantly increased. Histopathological examinations revealed substantial neuronal loss, disruption of Nissl body structure, nuclear dissolution, and enhanced formation of neurofibrillary tangles (NFTs) in the brains of SCCP-exposed offspring. Additionally, phosphorylation levels of Tau protein at Ser396 and Ser199 were significantly elevated, accompanied by increased expression of amyloid beta (Aβ), which is consistent with hallmark pathological features of ad. These effects were more pronounced in male offspring, indicating sex-dependent susceptibility. Mechanistically, SCCP-induced neurotoxicity may involve upregulation of Tau kinases CDK5 and GSK-3β and downregulation of the Tau phosphatase PP2A, promoting Tau hyperphosphorylation. Overall, prenatal SCCPs exposure induces persistent ad-like neuropathological changes in adult offspring, suggesting that early-life SCCPs exposure may increase the risk of neurodegenerative diseases later in life.
Wang et al. (Mon,) studied this question.