• Cigarette smoke exposure affects the reproductive organs of men and women differently, showing how smoking may harm fertility in both sexes, new research has revealed

• The study, led by researchers from the Universities of Sheffield and Nottingham, examined how different levels of cigarette smoke affected the structure and gene activity in mouse ovaries and testes

• The findings identified changes in biological processes involved in ovarian function and sperm production, helping to explain how smoking affects fertility in humans

Exposure to cigarette smoke could affect reproductive health, as new research identifies changes in biological processes involved in ovarian function and sperm production.

According to the World Health Organization, approximately one in six people globally experience infertility at some point in their lives. While smoking is a well established risk factor for poor fertility, how it affects the ovaries and testes at a molecular level is still misunderstood.

A new study, led by researchers from the Universities of Sheffield and Nottingham examined how different levels of cigarette smoke exposure affect the reproductive organs of male and female mice.

Male and female mice were exposed to cigarette smoke extract at a lower or higher dose for 12 weeks. Researchers then examined the structure of the ovaries and testes and measured gene activity in each. The findings offer valuable insight into the biological processes that may help explain how smoking affects reproductive health in humans.

In females, the number and structure of ovarian follicles, where eggs develop, showed relatively little change following exposure, even at higher levels. However, smoke exposure reduced the activity of genes responsible for cell division and metabolism, while increasing the activity of genes that control protein production. These shifts mirror biological changes typically seen in accelerated ovarian ageing and declining fertility in women.

In males, higher levels of smoke exposure led to physical changes inside the testes, including the enlargement of the seminiferous tubules where sperm develop. Genes regulating sperm production become over active, while genes that protect against infection and inflammation became less active. These results suggest that cigarette smoke directly disrupts essential biological processes essential for healthy testicular function and sperm development.

Co author of the study, Dr Adam Watkins, Senior Lecturer in Reproductive Medicine from the University of Sheffield School of Medicine and Population Health, said: “While it’s well-established that smoking is harmful to people's reproductive health, exactly how it does this is not fully understood. What this research interestingly showed is how differently the two organs responded to cigarette smoke.

“In the ovary, the overall structure of the tissue was unaltered, but the genes told a different story, we saw changes in those that regulate cell proliferation and protein synthesis. In the testis, the changes were visible in the tissue itself, with measurable differences in morphology, alongside altered expression of genes that regulate sperm production. These results suggest that the quality of the sperm and eggs produced might be compromised by smoking’’.

"While our study only looked at the effects of cigarette smoke on the ovaries and testes, it gives us valuable new insight into the potential mechanisms by which smoking affects reproductive health. We can now build on these findings to establish how these biological changes relate to fertility in humans.”

Professor Lucy Fairclough, from the School of Life Sciences at the University of Nottingham and co-author of the study, said: “Our study has identified potential biological mechanisms that could help explain the link between smoking and reproductive health in both men and women.

“In females, we identified changes in gene activity associated with biological processes that have previously been linked to ovarian ageing and reduced ovarian function. In males, we found changes in genes involved in sperm production and testicular function.

“These findings are important because they help us understand how exposure to cigarette smoke could affect reproductive health. Further research will be needed to establish how these biological changes relate to fertility in humans.”

The next steps for this research are to establish if parental smoking reduces the ability of the mice to become pregnant, and whether the health of their offspring is affected.

The research was shaped by individual expertise, while benefiting from collaboration across teams and partners.