Effects of Postnatal Exposure to Tetrabromobisphenol A on Testis Development in Mice and Early Key Events

Whether or not tetrabromobisphenol A (TBBPA) has reproductive developmental toxicity remains controversial. Here, we evaluated the effects of postnatal TBBPA exposure of dams (before weaning) and pups through drinking water (15, 150, 1500 ng/mL) on testis development in mice. On postnatal day (PND) 56, we found that TBBPA exerted little effects on testis weight, anogenital distance, sperm parameters, and the serum testosterone level, but resulted in dose-dependent reductions in the seminiferous tubule area coupled with decreased Sertoli cells and spermatogonia and the number of stage VII-VIII seminiferous tubules, and cytoskeleton damage in Sertoli cells, along with down-regulated expression of marker genes for Sertoli cells, spermatogonia and spermatocyte. Further study revealed that the reduced tubule area coupled decreased Sertoli cell and germ cell numbers and marker gene expression also occurred in TBBPA-treated testes on PND 7, along with reduced cell proliferation and disordered arrangement of Sertoli cell nuclei. On PND 15, most of these testicular alterations were still observed in TBBPA-treated males, and cytoskeleton damage in Sertoli cells became observable. All observations convincingly demonstrate that postnatal exposure to TBBPA disturbed testis development in early life and ultimately caused adverse outcomes in adult testes, and that cell proliferation inhibition, the reduction in the seminiferous tubule area coupled decreased Sertoli cell and germ cell numbers and marker gene expression, and cytoskeleton damage in Sertoli cells, are early events contributing to adverse outcomes in adult testes. Our study improves the understanding of reproductive developmental toxicity of TBBPA, highlighting its risk for human health.