🧬 BDNF Extraction Viewer

To investigate the therapeutic potential of ANA-12 in restoring testicular health by modulating local neurochemical balance in adult rats of passive smoking, secondhand smoking or environmental tobacco smoke/nicotine exposure. Preclinical rodent models mimicking a real-life human smoking scenario. Post-acclimatization, adult male rats of 250-300 g body weight were randomized into passive smoking, oral nicotine, ANA-12 pre-treatment, and healthy unexposed controls. Rats were exposed to passive smoking through a whole-body inhalation chamber and oral nicotine through gavage with/without intraperitoneal administration of ANA-12 at differential dosages prior to passive smoking/nicotine exposure for a period of 4- and 12-week studies. Testes histopathology, DNA damage potency, and fertility indices alongside redox homeostasis and expressions of local neurotransmitter dopamine and its receptors D1 and D2, and neurotrophic factor, brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase beta (Trk-β) in testes, comet assay in whole blood, and serum cotinine levels. Compared with the healthy unexposed controls, passive smoking and oral nicotine exposure dose- and time-dependently disrupt developing spermatogonia, spermatocytes, and spermatids of the seminiferous tubules and basement membrane; reduce sperm count with concomitant higher deoxyribonucleic acid (DNA) damage; and upregulate BDNF/Trk-β and dopamine/D1 expressions, as well as oxidative stress with subsequent antioxidant depletion in testes. In contrast, regardless of the duration of exposure, ANA-12 pre-treatment significantly restores germ cells of the seminiferous epithelium, improves spermatogenesis, downregulates aberrant local neurochemical systems, and maintains redox homeostasis in the testicular milieu. These results are in accordance with the whole blood DNA damage and serum cotinine levels, a biomarker of nicotine exposure. The results offer a novel insight into therapeutic interventions for passive or secondhand smoking- or environmental tobacco smoke-induced male reproductive impairment via regulation of BDNF-dopaminergic signaling and antioxidant balance in testes by ANA-12, leading to improved fertility potential and overall testicular health, which could establish the modulation of the brain-testes axis, implicated in nicotine addiction. This study holds translational potential of ANA-12 for the management of smoking- or nicotine-related male infertility of individuals unable or unwilling to quit smoking.