Acute gonadal toxicity induced by Bothrops atrox venom in mice

Bothrops atrox is responsible for most snakebite incidents in the Amazon region. Its venom is recognized for causing significant tissue damage and systemic effects. However, its effect on reproductive organs remains poorly explored. This study aimed to investigate the acute effects of B. atrox venom on testes and ovaries of adult mice. Male and female mice were exposed to B. atrox venom (½ LD₅₀) via four administration routes subcutaneous (SC), intramuscular (IM), intravenous (IV), and intraperitoneal (IP), followed by comprehensive assessment of gonadal histology, sperm function, oxidative stress biomarkers, antioxidant enzyme activities, and mRNA expression of inflammatory and apoptotic markers. Following B. atrox venom exposure, ovarian histological architecture remained preserved across all routes, whereas testicular tissue exhibited route-dependent injury ranging from moderate luminal apoptosis after SC and IV administration to severe epithelial disorganization and Sertoli cell vacuolization after IM and IP administration. Sperm motility and viability declined significantly after IP injection, accompanied by increased morphological abnormalities. Oxidative stress markers (Reactive oxygen species, nitric oxide, hydrogen peroxide, lipid hydroperoxides, and malondialdehyde) rose in both sexes, with higher levels in males and maximal induction via the IP route. Antioxidant enzymes (Superoxide dismutase, catalase, and glutathione peroxidase) decreased in testes but increased in ovaries, indicating divergent redox responses. IL-6 and TNF-α mRNA were strongly upregulated by IP exposure in both sexes, revealing a pronounced inflammatory reaction. Bax expression confirmed increased apoptotic signaling, particularly following IP administration. These findings demonstrate that acute B. atrox envenoming can compromise male gonadal integrity while sparing ovarian structure with preservation of antioxidant enzyme activity, highlighting an overlooked dimension of viperid venom pathophysiology.