Cigarette smoke extract exposure induces differential morphological and transcriptional responses in the ovary and testes of mice

Introduction: Cigarette smoking is a major public health concern and is associated with impaired reproductive function in both females and males. While smoking related fertility defects have been reported, the molecular mechanisms underlying smoke-induced reproductive toxicity, particularly in gonadal tissues, remain poorly defined.

Methods: An in vivo mouse model of cigarette smoke extract exposure was utilized. Cigarette smoke was drawn through RPMI medium and diluted to create a light-dose (1%, representing a light smoker), or heavy-dose (3%, representing a heavy smoker) cigarette smoke extract. Sixteen eight-week-old male and female C57BL/6J mice were sedated with isoflurane and administered either the 1%, 3% or control (RPMI medium alone) intranasally three times per week for 12 weeks. After 12 weeks, ovarian and testicular tissues were collected for either histological analysis of tissue morphology (n = 4 mice per male/female gonad) or for transcriptomic analysis by microarray (n = 4 mice per male/female gonad). No detrimental impact of our cigarette smoke extracts on animal welfare was observed.

Results: While there was no measurable change in ovarian histology between groups, significant downregulation of transcription factors and genes regulating cell division in response to the 1% and 3% extract was observed. In addition, increased expression of multiple ribosomal proteins in both the 1% and 3% exposure females was also observed. In males, a significant increase in mean seminiferous tubule cross-section area in 3% males was observed.

Discussion: Transcriptomic analysis identified differential expression of genes associated with immune responses, spermatogenesis and male fertility across the groups. Our data highlight the significant impacts of cigarette smoking on reproductive health in males and females. Our data also highlights the differential responses of ovarian and testicular tissue to the effects of smoking, suggesting parental specific influences of smoking on reproductive health, fertility and potentially offspring wellbeing.