Impact of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) exposure on reproductive development in adolescent offspring.

Polybrominated diphenyl ethers (PBDEs) are known to disrupt neuroendocrine functions and impaired perinatal growth and reproductive health. However, the long-term reproductive toxicity of PBDEs following perinatal exposure remains poorly understood. This study investigated the effects of perinatal exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on reproductive development in adolescent offspring. Female C57BL/6 J mice were exposed to BDE-47 at doses of 0 (control), 10, and 50 mg/kg during the perinatal period (gestational day 13.5 to postnatal day 7). Subsequently, gonadal tissues and serum were collected from adolescent offspring mice for analysis. Histological examination of gonadal tissue sections using hematoxylin and eosin (H&E) staining revealed structural alterations. ELISA was employed to evaluate the reproductive endocrine hormone levels (E2, LH, FSH, AMH and T) in the serum of dams and offspring. Subsequently, multiplex immunohistochemical (mIHC) staining was employed to observe the protein expression in the testicular stroma of adolescent male pups. In maternal mice, perinatal exposure to BDE-47 led to an increased number of primary and secondary oocytes, accompanied by a decreased number of corpora luteum in the ovaries. Additionally, an increase in endometrial thickness and elevated serum E2 levels was observed in the 10 mg/kg BDE-47 group. In adolescent female offspring, an increase in secondary oocytes and corpora lutea in ovaries were found, along with increased serum E2 levels at both doses, while AMH levels decreased in 10 mg/kg BDE-47 group. In male offspring, testicular structural loosening, detachment of some spermatogenic cells, and cytoplasmic vacuolation were noted. The epididymal epithelial cells were shorter compared to the control group, with vacuolar structures and reduced sperm content. Testosterone secretion was decreased correspondingly with increasing dose. Consistent with the hormonal changes, a decrease in Cyp11a1-positive cells and StAR and Cyp11a1dual-positive cells was observed in the testicular stroma of adolescent male pups exposed to 50 mg/kg BDE-47, suggesting dysfunction of steroidogenic enzymes. In conclusion, perinatal exposure to BDE-47 disrupts the structure of gonadal tissues in both maternal and offspring mice, affects hormonal levels, and impairs the normal synthesis of steroid hormones, thereby exerting reproductive toxicity effects. These findings highlight the potential long-term reproductive health risks associated with perinatal exposure to BDE-47 and underscore the need for further research to elucidate the underlying mechanisms and develop preventive strategies.