Perinatal exposure to the environmental pollutant butyl benzyl phthalate (BBP) induces sex-specific alterations in the neuro-immune-endocrine network in adult rats.

The plasticizer butyl benzyl phthalate (BBP), a ubiquitous endocrine disruptor, is commonly used in PVC products and can leach into the environment, leading to human exposure. BBP has been detected in the placenta, amniotic fluid, and breast milk, indicating potential exposure during gestation and lactation. BBP is an endocrine disruptor compound (EDC) with estrogenic and anti-androgenic activity, which, at high or acute doses, may interfere with the development of hormone-dependent systems, including components of the neuro-immune-endocrine network (NIE) and sexual dimorphism. This study aimed to investigate the effects of perinatal BBP exposure on various components of the NIE network in adult male and female rats. Pregnant rats were administered drinking water with or without BBP (50 μg/L) from gestational day 5 until weaning. Offspring were assessed at 9 weeks of age by examining sex hormone levels in serum, immune cell populations in the spleen, neurotransmitters in the hippocampus, and cytokines in serum, hippocampus, and spleen. Results showed that BBP exposure led to lower weaning weights in both sexes, with persistent effects in males. Splenic T and T-helper lymphocyte populations increased in both sexes. In the hippocampus, females exhibited elevated proinflammatory cytokines, while males showed decreased serotonin levels, indicating sex-specific alterations in hormone, cytokine, and neurotransmitter levels in adult offspring.