Cigarette smoke exposure disrupts the blood-testis barrier and negatively impacts reproductive capacity in mice.

Maintaining normal testicular structure and function is closely related to the blood-testis barrier (BTB). Meanwhile, cigarette smoke extract (CSE) affects testicular function. However, whether CSE mediates BTB damage and the underlying mechanism(s) are unclear. This study investigates the effects of CSE on the BTB in mice by focusing on changes in hormone levels. CSE was prepared and administered intranasally at different concentrations to 6-8-week-old male Balb/c mice for five weeks. After cigarette smoke components successfully entered and accumulated in the mice, the seminiferous tubules of the testes were atrophied, spermatogenic cell arrangement became disordered, sperm quality declined, and spermatogenesis was impaired. Furthermore, CSE exposure disrupted the hypothalamic-pituitary-gonadal axis. CSE also damaged the ultrastructure of the BTB, leading to impaired integrity and increased permeability. The associated disruption of BTB function was caused by inhibiting key proteins, including occludin, Zonula occludens-1(ZO-1), N-cadherin, β-catenin, and connexin-43, correlated with hormonal changes. Collectively, these findings suggest that cigarette smoke exposure disrupts BTB structure and function by altering hormone levels and suppressing the expression of BTB-related proteins, affecting spermatogenesis and male reproductive capacity.