Insights into a novel pathway of paraben-induced endotoxin affecting human sperm quality: Parabens’ dual effects of antibacterial and estrogenic activity

Background: The decline of human sperm quality has caused great concern. Whether exposure to parabens and the intestinal endotoxin (IE) they induce are related to sperm quality is a challenging scientific question. Results We measured seminal methyl-(MeP), ethyl-(EtP), propyl-(PrP), and butyl-(BuP) parabens, their metabolites PHBA and 3,4-DHB, semen parameters, and blood IE (lipopolysaccharide, LPS) of 315 healthy men. Bivariate correlation and multiple linear regression were used to evaluate their interrelationships. For the first time, we found that MeP, EtP, PrP, BuP, PHBA, and 3,4-DHB in semen were negatively correlated with sperm parameters (r = − 0.184 to − 0.438), with EtP showing the strongest correlation. LPS was detected in all plasma samples (0.021–0.195 EU/mL) and negatively correlated with sperm concentration and total sperm count with R 2  = 0.295 and R 2  = 0.236, respectively, when LPS was higher than 0.104 EU/mL. LPS was positively correlated with EtP and BuP. Conclusion We concluded that seminal parabens affected sperm quality possibly due to estrogenic activity. Parabens likely promote intestinal endotoxemia and affect sperm quality in healthy people by altering the composition of gut microbiota through antimicrobial activity. The finding that parabens exert dual toxicological effects on sperm quality provides novel insights for future research.