Postnatal exposure to low-dose tetrabromobisphenol A increases the susceptibility of mammal testes to chemical-induced spermatogenic stress in adulthood

There is increasing data showing that some environmental chemicals can increase susceptibility to follow-up stress or injuries, possibly thereby contributing to certain clinical and subclinical diseases. Previous studies re-ported that tetrabromobisphenol A (TBBPA), one of the most used brominated flame retardants, exerted little male reproductive toxicity in terms of conventional endpoints but affected testis development and thereby caused testicular alterations at the molecular and cellular levels. Here, we aimed to reveal whether develop-mental exposure to TBBPA can increase testicular susceptibility to follow-up stress in adulthood. For this pur-pose, newborn mice were exposed to 50 or 500 mu g/kg/d TBBPA for 56 days to confirm adverse effects on testes, followed by a single intraperitoneal injection of 3 mg/kg busulfan (BSF) to induce spermatogenic stress. Four weeks after BSF injection, TBBPA-treated mice exhibited severe pathological alterations, including reduced testis weight, damaged testicular histological structure, declined sperm count, apoptosis of spermatogenic cells, while no remarkable damage was observed in mice without historical exposure to TBBPA. These results demonstrate that historical exposure to TBBPA, either 50 or 500 mu g/kg/d, increased the susceptibility of mouse testes to BSF-induced spermatogenic stress, resulting in severe adverse reproductive outcomes. Further analysis indicates that TBBPA-caused microtubule and microfilament damage, along with spermatogonia and spermatocyte reduction, could contributed to the increased susceptibility of testes, suggesting that these non-conventional reproductive lesions caused by chemicals should not be ignored. This is the first study to investigate the reproductive hazard of chemicals from the perspective of testicular susceptibility to stress, thereby opening a new avenue to identify environmental chemicals possibly contributing to male infertility and subfertility.

Automated summary

There is increasing evidence that certain environmental chemicals can make individuals more vulnerable to stress or injuries, contributing to clinical and subclinical diseases. Tetrabromobisphenol A (TBBPA), a commonly used flame retardant, has been found to impact testis development at the molecular and cellular levels. This study aimed to investigate whether developmental exposure to TBBPA could increase testicular susceptibility to stress in adulthood. The results show that historical exposure to TBBPA increased the susceptibility of mouse testes to spermatogenic stress, leading to severe reproductive problems.