Perinatal exposure to perfluoroalkyl substances impairs maternal care and induces depressive-like behavior in mice

Abstract Postpartum mental health disorders are a critical yet understudied aspect of maternal health. Exposure to environmental toxicants such as per- and poly-fluoroalkyl substances (PFAS) has been associated with adverse health outcomes, including reproductive and neurobehavioral dysfunction, whereas their specific effects on maternal behavior and mental health remain poorly characterized. This study investigated the effects of perinatal exposure to environmentally relevant concentrations of a PFAS mixture comprising 10 individual PFAS (PFHxA, PFPeA, PFHpA, PFBA, perfluorooctanoic acid [PFOA], PFOS, PFHxS, PFDA, and PFNA), as well as the alternative PFAS compound, perfluorobutane sulfonate (PFBS), on maternal caregiving behaviors and mental health. Female mice were exposed to the PFAS mixture (758.6 ng/l) or PFBS (7.9 ng/l) in reverse osmosis filtered water at levels detected in North Carolina drinking water, beginning before conception and continuing until the first day of birth. Maternal behaviors, including pup-directed care and nest construction, were assessed along with depressive- and anxiety-like behaviors using standardized behavioral tests. Fluoxetine was administered to a subset of animals to pharmacologically validate depressive-like outcomes. Both PFAS mixture and PFBS-exposed dams exhibited impaired maternal caregiving, including diminished nurturing behavior and poor nest building. Litters of PFBS-exposed dams emitted fewer ultrasonic vocalizations, suggesting altered maternal–offspring interaction. Dams exposed to the PFAS mixture also exhibited depressive-like behaviors that were reversed by fluoxetine treatment, whereas anxiety-like behavior was unaffected. These findings demonstrate that perinatal PFAS exposure disrupts maternal behavior and induces depressive-like phenotypes, reflecting the neurobehavioral risks of exposure during the perinatal period. This study emphasizes the potential for environmental contaminants to contribute to maternal mental health disorders and supports the need for further research on the effect of PFAS exposure in human populations.