The single and combined effects of decabromodiphenyl ethane and mixed microplastics on male mice reproductive toxicity†.

The expansive surface area of microplastics (MPs) allows them to retain pollutants; however, the combined toxicity of mixed MPs and organic contaminants remains poorly studied. The semen quality of men worldwide was observed to exhibit downward trends. This study investigates the reproductive toxicity and underlying mechanisms of male mice exposed to MPs and a novel brominated flame retardant, decabromodiphenyl ethane (DBDPE), individually or combined. Male mice were treated by oral gavage with corn oil, 5 or 50 mg/kg DBDPE, 10 mg/kg MPs [a mixture of PE (polyethylene) and PVC (polyvinyl chloride)], and DBDPE + MPs (50 mg/kg DBDPE mixed with 10 mg/kg MPs) for 7 weeks. Our results suggested that DBDPE alone decreased the sex hormone levels and sperm count, whereas MPs alone had no significant effect. DBDPE and/or MPs impaired testicular morphology, sperm malformation rate, oxidative stress levels, and apoptosis. Our results of transcriptomics from GC-2 cells indicated that DBDPE and MPs lead to changes in oxidative stress, apoptosis, inflammation, proliferation, and differentiation. Furthermore, DBDPE and/or MP exposure inhibited the Kelch-like ECH-associated protein 1- NF-E2-related factor 2 (Keap1-Nrf2) signaling pathway. Moreover, the combined treatment of MPs and DBDPE exerted an antagonistic effect on the reproductive system of mice. This study provides valuable insights into the mechanisms of joint action in reproductive toxicity in mammals due to the combined exposure to MPs and DBDPE.