Mechanistic\nInsight into the Reproductive Toxicity\nof Trifloxystrobin in Male <i>Sprague–Dawley</i> Rats

Previous\nstudies have demonstrated the reproductive toxicity of\ntrifluorostrobin (TRI) in male organisms. However, the underlying\nmechanisms of TRI responsible for testicular damage and hormonal disruption\nremain elusive. This study elucidated the male reproductive toxicity\nof TRI at the molecular level under environmentally relevant concentrations\nand its associations with gut microbiota dysbiosis. The rats were\nadministered TRI (1.5, 15, and 75 mg/kg of body weight/day) continuously\nvia gavage for 90 days. Exposure to 15 mg/kg (below the no-observed\nadverse effect level (NOAEL) of 30 mg/kg) and 75 mg/kg TRI damaged\ntesticular tissue, reduced sperm count, and lowered serum hormone\nand total cholesterol levels. Transcriptomics analysis combined with\nmolecular docking simulations and cell proliferation assays showed\nthat exposure to TRI led to testicular damage by inhibiting the expression\nof cholesterol receptor genes, which, in turn, disrupted steroid hormone\nbiosynthesis. Furthermore, exposure to TRI resulted in a marked decline\nin the relative abundance of the probiotic bacteria. Consistently,\nsignificant reductions in the relative abundance of short-chain fatty\nacids (SCFAs), retinoic acids, and steroid hormones in the gut were\nobserved. Additionally, a significant correlation was observed between\nthe relative abundance of <i>Parabacteroides</i> and serum\ntestosterone levels, a vital biomarker for reproductive toxicity monitoring.\nThese findings shed light on the mode of action of TRI-induced male\nreproductive toxicity and highlight the link between testicular injury\nand gut microbiota.