Cigarette smoke extract shifted fertility-related genes in both ovaries and testes of mice

Mice that breathed in cigarette smoke extract three times a week for 12 weeks showed altered gene activity in both the ovaries and the testes, according to a paper published on Oct. 14 in Frontiers in Toxicology. The work was led by researchers at the Universities of Nottingham and Sheffield, and it is an animal experiment rather than a human study.

In the female mice the tissue looked ordinary under the microscope while the genes told a different story. In the males, the higher dose physically enlarged the tubules where sperm develop. The authors treat the results as a map of where to look next, not as proof of harm to human fertility.

What changed in the ovaries and testes

The experiment, described in the Frontiers in Toxicology paper, compared three groups of C57BL/6J mice: a control group given culture medium alone, a group given a 1% cigarette smoke extract meant to mimic a light smoker, and a group given a 3% extract meant to mimic a heavy smoker. The exposure was intranasal, began when the animals were eight weeks old, and ran for 12 weeks.

In the ovary, follicle counts and structure did not differ between groups, even at the higher dose. Gene expression did. Genes tied to cell division and to transcription factors were less active at both doses, while genes for ribosomal proteins, the machinery of protein production, were more active. The university release distributed through EurekAlert says this pattern resembles changes previously linked to ovarian ageing and reduced ovarian function.

In the testes, the 3% dose enlarged the seminiferous tubules, the structures where sperm are made, and the 1% and 3% groups showed different distributions of tubule sizes. Some genes involved in sperm production became more active, while some immune-function genes became less active, and genes for cell signalling were also altered. The paper counts 1,641 differentially expressed genes at the heavier dose and 788 at the lighter one, each measured against controls.

The paper’s own title, which refers to differential morphological and transcriptional responses in the ovary and testes, captures the contrast. Under the microscope the female tissue held steady while the male tissue did not; at the level of gene activity, both organs responded. For a reader trying to weigh the study, that split matters: it means a normal-looking ovary in this experiment was not evidence of an unaffected ovary, and the reverse caution applies to the testes, where the enlarged tubules appeared only at the 3% dose.

How far a four-mice-per-group result can be pushed

The caveats are substantial, and the paper states them itself. The methods section describes 12 animals, four per group, while the abstract gives a different total of 16, a discrepancy a reader would want resolved in the full text. There was no power calculation, and no individual gene passed the false-discovery-rate correction; the gene lists rest on relaxed thresholds of a fold change of at least 1.1 and a p-value under 0.05. The authors describe the findings as hypothesis-generating rather than confirmatory.

Nor did the team measure the outcomes that define fertility. Hormone levels, egg quality, ovulation, sperm counts and actual breeding success were not assessed, and the gene and tissue changes were not independently validated in a second round of experiments. The conversion from a mouse dose to a human smoking habit used a simplified calculation that ignores differences in lung anatomy and metabolism between the two species, so the labels light smoker and heavy smoker are approximations.

Professor Lucy Fairclough of Nottingham’s School of Life Sciences, a co-author, said further research will be needed to establish how these biological changes relate to fertility in humans. Dr Adam Watkins of the University of Sheffield noted that the study assessed only the ovaries and testes, and added that it does provide new mechanistic insight into how parental smoking shapes reproductive health.

The infertility backdrop

The release frames the work against the World Health Organization’s estimate that about one in six people globally experience infertility at some point in their reproductive years. The WHO’s April 2023 report put the lifetime figure at 17.5% of adults, drawn from 133 studies published between 1990 and 2021, with little difference between high-income countries at 17.8% and low- and middle-income countries at 16.5%.

That prevalence is the reason a toxicology result in a small mouse cohort draws attention at all. Smoking is a modifiable exposure, and the experiment’s distinctive feature is that it examined female and male reproductive organs together, using the same extract, the same dose design and the same schedule, which makes the two tissue responses directly comparable. The ovary changed at the level of genes; the testis changed in both gene activity and physical structure.

What would turn this into evidence about people is the work the authors call for: larger animal groups with corrected statistics, direct fertility endpoints such as hormone levels and sperm counts, and eventually human data. The paper’s identifier, 10.3389/ftox.2026.1943043, leads to the full text, and related science releases sit in EurekAlert’s medicine news section.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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