Smoking May Alter Male, Female Reproductive Organs In Different Ways

Cigarette Smoke Altered Mouse Ovaries and Testicles in Different Ways

Smoking may affect the ovaries and the testicles in two very different ways, and only one of them shows up under a microscope. In a new mouse study, males given the heaviest dose of cigarette smoke extract had visibly enlarged sperm-making tubes. Exposed females had ovaries that looked normal. Their genes told a different story, with shifts no microscope could catch.

Published in Frontiers in Toxicology, the work from researchers at the University of Nottingham and the University of Sheffield hints at smoke reaching male and female reproductive tissue through different biological routes, though the experiment was small and early.

Cigarette smoking is already linked to reduced reproductive function in both women and men, and a World Health Organization estimate cited in the paper put tobacco users at about 1.25 billion adults in 2022. Still, how smoke actually harms the ovaries and testicles remains poorly understood. That gap is what this team set out to probe.

Smoking and Fertility Tests in Mice Showed Gene Changes in Ovaries That Looked Normal

To mimic smoking, researchers pulled smoke from Marlboro Red cigarettes through a liquid and diluted it into two strengths. The weaker mixture stood in for a light smoker of five cigarettes a day, the stronger one for a heavy smoker of 15 a day, and a third group got the plain liquid. The conversion was a rough estimate based on body weight, and the authors acknowledged that it ignores differences in metabolism and lung structure between mice and people.

Eight-week-old male and female mice were briefly sedated and given their mixture through the nose three times a week for 12 weeks. A common approach keeps whole animals in smoke-filled chambers, where mice can swallow residue while grooming their fur, which can muddy results. Dosing a liquid extract through the nose avoids that problem, and no harm to the animals’ welfare was observed. After 12 weeks, the team examined ovaries and testicles under a microscope and measured which genes were more or less active, like turning a dimmer switch up or down. Each type of analysis used just four animals per dose group, a small sample the authors flagged as a limit.

On the surface, the female mice looked fine. Toxic components of cigarette smoke are known to build up in the fluid around developing eggs, which makes the ovaries’ normal look surprising. Follicles, the tiny fluid-filled sacs that each hold a developing egg, appeared in similar numbers at every stage of development in light-dose, heavy-dose, and unexposed females.

Their genes were another matter. In both smoke groups, genes that help control cell division were turned down, while genes that build the cell’s protein-making machinery were turned up. Researchers noted that the combination resembles a pattern tied to premature ovarian insufficiency, a condition in which the egg supply runs out early. Earlier research the authors cite links smoking to earlier menopause in women, which makes that resemblance worth watching. Lighter-dose females also showed more activity in genes tied to inflammation, cell death, and DNA damage.

Because hormones, ovulation, and egg quality weren’t measured, whether these mice were actually less fertile remains unknown.

Heavy Smoke Exposure Enlarged Sperm-Producing Tubes in Male Mice

Males showed a physical change. At the heaviest dose, the coiled tubes inside the testicles where sperm are made were larger on average than in unexposed males, and lightly exposed males had more oversized tubes than usual too. Larger tubes can come from extra cell growth or from fluid backing up behind a blockage, and the study couldn’t say which was at work. Smoking has not been tied to such blockages, though it has been linked to a total lack of sperm in semen, a condition behind roughly 10% to 15% of male infertility cases. Whether the enlargement affects sperm count or quality is unknown.

Gene activity in the testicles moved in its own direction. In heavily exposed males, genes tied to sperm development and to the nurse cells that support developing sperm were turned up, while some immune-related genes were turned down. The authors said the immune dip could point to trouble with those nurse cells, which also help keep the testicles’ immune activity in check, but stressed that more studies are needed to confirm it.

Male tissue also showed more overlap in its gene changes. Comparing the three male groups against one another, 200 genes differed in every pairing, versus only 20 in females.

Smoking and Fertility Harm May Follow Different Paths in Males and Females

Taken together, the results raise the possibility that male and female reproductive harm from smoking is not the same problem wearing two different faces. If that holds up, researchers may need to study the two separately. The authors say their mouse model could help scientists trace how environmental exposures such as smoking connect to declining fertility, and they call for more work on how these changes translate into outcomes for males, females, and their offspring.

A normal-looking ovary isn’t necessarily an unaffected one, and the next step is clear: measure hormones, eggs, and sperm directly.

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Disclaimer: This article is for informational purposes only and is not medical advice. The study involved mice, and its results may not apply to people. Anyone with questions about smoking, fertility, or reproductive health should consult a qualified healthcare professional.

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