Cigarette Smoke Rewrites Gene Activity in Ovaries and Testes, Mouse Study Reveals

A new study from researchers at the Universities of Nottingham and Sheffield has revealed, at the level of individual genes, how exposure to cigarette smoke may interfere with reproductive health in both sexes. The research, published in the journal Frontiers, used a mouse model to examine how the ovaries and testes respond to different levels of cigarette-smoke exposure, and it uncovered a striking asymmetry: while the female ovary preserved its physical structure but altered its gene activity, the male testis showed measurable structural changes alongside shifts in the genes that govern sperm production. The findings offer some of the most detailed mechanistic insight yet into why smoking has long been associated with reduced fertility in men and women.

The scale of the problem the study addresses is considerable. According to the World Health Organization, approximately one in six people worldwide experience infertility at some point during their reproductive years, making it one of the most common health burdens of adulthood. Although epidemiological studies have repeatedly linked smoking to poorer reproductive outcomes, the precise biological pathways connecting smoke exposure to impaired ovarian function and sperm development have remained incompletely understood. The new work was designed to close that gap by looking directly at reproductive tissue after controlled exposure, rather than relying solely on associations drawn from human population data.

In the study, mice were exposed to different levels of cigarette smoke, and the researchers then examined the ovaries and testes for two kinds of change. The first was morphological: alterations to the physical structure of the reproductive organs and the specialised compartments within them. The second was transcriptional: changes in the activity of genes involved in the normal functioning of those tissues. This dual approach matters because an organ can look outwardly normal while its molecular machinery is quietly drifting away from healthy operation, a distinction that could prove important for understanding subfertility that develops gradually in smokers.

The female results were, in some ways, the more surprising of the two. The number and structure of ovarian follicles, the tiny structures in which eggs mature, showed relatively little change following smoke exposure, even at higher exposure levels. On its face, that might suggest the ovary had escaped harm. But when the researchers measured gene activity, they found clear and widespread alterations. Genes involved in cell division and metabolism became less active, while genes associated with protein production became more active. Crucially, the overall pattern of gene activity bore similarities to biological processes previously associated with ovarian ageing and reduced ovarian function, suggesting that smoke exposure may push ovarian tissue toward molecular states resembling accelerated decline.

The male findings told a different story. At higher levels of smoke exposure, the researchers observed changes to structures within the testes, including enlargement of the seminiferous tubules, the coiled compartments where sperm are produced. Alongside these structural changes came shifts in the activity of genes involved in sperm production, immune responses and cell signalling. Some genes associated with sperm production became more active, while others involved in immune function became less active. Together, the results indicate that cigarette smoke may alter biological processes that are essential for normal testicular function and healthy sperm development, and that the testis responds to smoke in a visibly different way than the ovary does.

Professor Lucy Fairclough, from the School of Life Sciences at the University of Nottingham and co-author of the study, said the work had identified potential biological mechanisms that could help explain the link between smoking and reproductive health in both men and women. She noted that in females the team identified changes in gene activity associated with processes previously linked to ovarian ageing and reduced ovarian function, while in males they found changes in genes involved in sperm production and testicular function. She emphasised that further research will be needed to establish how these biological changes relate to fertility in humans, a caution that reflects the inherent limits of translating findings from mice to people.

Dr Adam Watkins, from the University of Sheffield, highlighted the contrast between the two organs. While it is well established that smoking is harmful to reproductive health, he said, the exact mechanisms have not been fully understood, and the mouse model allowed the team to explore how the ovaries and testes respond following exposure to cigarette smoke. He observed that the ovary and testis respond differently: the structure of the ovary was unaltered, whereas the testis showed measurable changes in its morphology. Within the ovary, the team identified changes in genes that regulate cell proliferation and the synthesis of proteins, while in the testis, genes regulating sperm production were altered. He stressed that although the study only assessed the effects of cigarette smoke on the ovaries and testes, it provides new mechanistic insight into how parental smoking may shape reproductive health.

The technical significance of the study lies in its demonstration that the two gonads mount fundamentally different responses to the same insult. The ovary appears to buffer its architecture while its transcriptional programme shifts, with suppressed cell-cycle and metabolic genes potentially reflecting a slowdown of the proliferative activity that follicles require, and upregulated protein-synthesis genes hinting at a stress or remodelling response. The testis, by contrast, shows both structural remodelling of the seminiferous tubules and altered expression of genes tied to spermatogenesis and immune regulation. Because the testis is an immunologically specialised environment, the observed dampening of immune-function genes could have consequences for the carefully balanced conditions sperm need to mature, though the study stops short of drawing that causal conclusion.

For the public health conversation, the findings add mechanistic weight to existing advice that people who wish to conceive should avoid smoking. Rather than merely reinforcing a statistical association, the study points to concrete biological processes, follicular gene regulation in the ovary and tubule structure and spermatogenesis-related gene activity in the testis, that smoke exposure can perturb. The researchers say the results add to the existing evidence on the potential impact of smoking on reproductive health and underscore the need to better understand the underlying mechanisms, work that could eventually inform how clinicians counsel prospective parents and how the risks of second-hand smoke are assessed in fertility contexts.

The study, titled Cigarette smoke extract exposure induces differential morphological and transcriptional responses in the ovary and testes of mice, was published in Frontiers on 14 October 2026 as a peer-reviewed experimental study using animal subjects. Its central message is likely to resonate well beyond the laboratory: the reproductive systems of both sexes are molecularly sensitive to cigarette smoke, and they respond in ways that are measurable, distinct and potentially consequential for fertility. As the authors note, connecting these biological changes to fertility outcomes in humans is the essential next step, but the study provides a clear and testable map of where to look.

Subject of Research: Effects of cigarette smoke exposure on ovarian and testicular gene activity and structure in mice

Article Title: Smoking may affect fertility in both men and women, new study finds

Article References: Smoking may affect fertility in both men and women, new study finds. (n.d.). Original publication

Image Credits: AI Generated

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Keywords: smoking, fertility, infertility, ovary, testis, gene expression, sperm production, ovarian ageing, reproductive health, mouse model, cigarette smoke, seminiferous tubules