Early-life PFOA exposure-induced male reproductive adverse effects are associated with the activation of the NF-κB signaling pathway: The mitigative role of inulin.

Perfluorooctanoic acid (PFOA) is widely distributed in various environmental media and has adverse health effects. The underlying mechanisms of the effects of PFOA on the developmental toxicity of the male reproductive system are poorly understood. In this study, 8-week-old C57BL/6 J female mice were given Milli-Q water, PFOA (1 mg/kg/day), PFOA and inulin (5 g/kg/day) or inulin by gavage from the first day of pregnancy until weaning to evaluate the effects of PFOA on the reproductive function of male offspring. Early-life PFOA exposure resulted in decreased sperm quality and testosterone levels, impaired testicular structure, suggesting adverse reproductive effects. According to the transcriptomics analysis, the NF-κB pathway was enriched by KEGG enrichment analysis in the testes of the PFOA group. Consistently, the decreased protein expression ratio of p-p65 to p65 (p-p65/p65) suggested disturbance of the NF-κB signaling pathway. Inulin alleviated testicular structure injury resulting from early-life PFOA exposure, increased sperm quality and testosterone, and decreased the protein expression of the p-p65/p65 ratio. Taken together, our results suggested that early-life PFOA exposure might disrupt the integrity of the blood‒testicular barrier in the testis by activating the NF-κB signaling pathway, resulting in adverse male reproductive effects, which were alleviated by inulin intervention.