Cigarette smoke extract exposure induces differential morphological and transcriptional responses in the ovary and testes of mice.
5 affiliations
- 1School of Life Sciences, The University of Nottingham, Nottingham, United Kingdom.
- 2School of Medicine, The University of Nottingham, Nottingham, United Kingdom.
- 3School of Veterinary Medicine and Science, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.
- 4Nottingham Arabidopsis Stock Centre (NASC), School of Biosciences, University of Nottingham, Loughborough, United Kingdom.
- 5Division of Clinical Medicine, School of Medicine and Population Health, Beech Hill Road, University of Sheffield, Sheffield, United Kingdom.
Abstract
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.
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BibTeX
@article{azizbayli2026cigarette,
title = {{Cigarette smoke extract exposure induces differential morphological and transcriptional responses in the ovary and testes of mice.}},
author = {Yasmin Azizbayli and Laura G Bartlett and Amanda Tatler and Victoria James and Marcos Castellanos-Uribe and Iqbal Khan and Nazia Nazar and Sean T May and Adam J Watkins and Lucy C Fairclough},
journal = {Frontiers in toxicology},
year = {2026},
month = oct,
doi = {10.3389/ftox.2026.1943043},
url = {https://europepmc.org/article/MED/42948826},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cigarette smoke extract exposure induces differential morphological and transcriptional responses in the ovary and testes of mice.
AU - Yasmin Azizbayli
AU - Laura G Bartlett
AU - Amanda Tatler
AU - Victoria James
AU - Marcos Castellanos-Uribe
AU - Iqbal Khan
AU - Nazia Nazar
AU - Sean T May
AU - Adam J Watkins
AU - Lucy C Fairclough
PY - 2026
DA - 2026/10/14
JO - Frontiers in toxicology
DO - 10.3389/ftox.2026.1943043
UR - https://europepmc.org/article/MED/42948826
AB - 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.
SN - 2673-3080
ER -