BDE-209 toxicity: From spermiogenesis to sexual maturity in F1 male mice

Abstract

Most studies of enviromental toxic chemicals focused on the meiosis stage during spermatogenesis, however, the research on the spermiogenesis damage phenotype of BDE-209 is limited. This study aimed to evaluate the processes by which BDE-209 regulates the formation of acrosomes and mitochondrial sheath (MS), key structures during spermiogenesis and fertilization. ICR mice were divided into control, low, medium, and high-dose BDE-209 groups and treated for 42 days. A comprehensive method combining ultrastructural analysis, transcriptomics, molecular biology, and fertility experiments was adopted. In mice exposed to BDE-209, testicular dysplasia, altered sex hormone concentrations, decreased semen quality, and head and tail deformities occurred. Chromatin condensation failure was present in BDE-209-exposed spermatozoa with decreased mRNA and protein levels of PRM1 and TNP1. BDE-209 disrupts the acrosome biogenesis process by disrupting the Golgi structure and the apical ectoplasmic specialization (ES) structure. BDE-209 exposure caused multiple damage to the MS and down-regulated the mRNA levels of Akap3, Akap4, Cfap44, Ccdc40, Dhah1, etc. These injuries resulted in subfertility in BDE-209 male mice, and the male offspring also exhibited gonadal dysplasia, sex hormonal changes, and decreased semen quality. Conclusively, BDE-209 exposure induced spermiogenesis defects and subfertility. F0 and F1 males showed a similar injury phenotype. This study advanced the understanding of the damage phenotype of spermiogenesis and complemented the reproductive toxicity of F1 male mice. These findings might be important for the study of related molecular mechanisms and the mitigation of BDE-209 exposure on offspring development.

Keywords

• Deca-bromodiphenyl ether (BDE-209)
• Spermiogenesis disorders
• Golgi apparatus
• Mitochondrion
• Cell junction
• Genetic toxicity