How tobacco and cannabis affect male fertility and genetic integrity

By Vijay Kumar MalesuReviewed by Lily Ramsey, LLMMar 6 2025

A new study reveals that both tobacco and cannabis use negatively affect sperm quality and DNA integrity—but cannabis may cause even greater damage. Could this be a hidden reproductive crisis?

Study: Effects of marijuana and tobacco on male fertility and their relationship to genetic variation of mitochondrial cytochrome C oxidase genes. Image Credit: ELENA GOR/Shutterstock.com

In a recent study published in the Scientific Reports, a group of researchers investigated the effects of tobacco and cannabis smoking on sperm quality, Deoxyribonucleic acid (DNA) integrity, and their association with genetic variations in mitochondrial Cytochrome C Oxidase 1 (MT-CO1), MT-CO2, and MT-CO3 genes.

Background

Could a single lifestyle choice impact future generations? Infertility affects approximately 14% of couples worldwide, with male factors contributing to nearly 50% of cases. Yet, despite this alarming statistic, recreational cannabis use is rising, and tobacco use remains a public health challenge.

Sperm health is a key factor in successful reproduction, yet millions of men unknowingly compromise their fertility through smoking. Tobacco smoke contains over 7,000 chemicals, many of which are known carcinogens and mutagens that directly affect sperm DNA.

On the other hand, tetrahydrocannabinol (THC), the active compound in cannabis, binds to receptors in sperm cells, altering motility, viability, and morphology. Studies show that frequent cannabis use may even change the epigenetic landscape of sperm, potentially impacting future generations.

As cannabis becomes increasingly legal worldwide, it is crucial to understand its implications on reproductive health. Further research is needed to clarify the genetic and epigenetic effects of these substances.

About the study

Semen samples were collected from 113 men and categorized into non-smokers (NS, n=37), tobacco smokers (TS, n=39), and cannabis smokers (CS, n=37).

Participants with alcohol dependency, chronic diseases, or genetic abnormalities were excluded. Semen parameters, including volume, sperm concentration, morphology, and motility, were analyzed following the World Health Organization (WHO) guidelines.

DNA integrity was assessed using Acridine Orange (AO) and Chromomycin A3 (CMA3) staining. Sperm samples underwent density gradient centrifugation to remove somatic cells before DNA extraction. Mitochondrial DNA (mtDNA) was isolated, amplified, and analyzed for variations in MT-CO1, MT-CO2, and MT-CO3 genes.

Polymerase chain reaction (PCR) primers were designed based on National Center for Biotechnology Information (NCBI) reference sequences, and sequencing was performed using the Sanger method.

Fluorescence microscopy was used to assess sperm chromatin packaging and DNA fragmentation. CMA3 staining was employed to determine the level of sperm protamination. Statistical analyses, including one-way Analysis of Variance (ANOVA) and chi-square tests, were conducted to compare parameters among groups. Data were represented as mean ± standard error of the mean (SEM), with a p-value of <0.05 considered statistically significant.

The findings were analyzed in the context of global health trends to assess the broader implications of tobacco and cannabis use on reproductive health and potential interventions that could reduce the damage caused by these substances.

Study results

Semen analysis revealed a significant decline in normal sperm morphology in both TS (5.02 ± 4.8%) and CS (2.26 ± 2.3%) groups compared to NS (7.46 ± 5.9%) (p<0.001). Cannabis smokers exhibited significantly lower morphology scores than tobacco smokers (p=0.002).

Sperm progressive motility was lower in the CS group (10.18 ± 10.6%) compared to TS (13.12 ± 10.6%) and NS (14.27 ± 11.3%), though this reduction was not statistically significant (p=0.223).

However, non-progressive motility was significantly lower in CS (20.63 ± 12.6%) than in TS (27.82 ± 16.6%) and NS (34.40 ± 14.3%) (p<0.001). Immotile sperm percentage was highest in CS (68.66 ± 21.9%), followed by TS (58.92 ± 24.4%) and NS (51.73 ± 18.8%) (p<0.001).

Sperm concentration and semen volume showed no significant differences between groups (p=0.199 and p=0.091, respectively). AO staining revealed a significantly higher proportion of sperm with DNA fragmentation in CS (28.53 ± 15.8%) compared to NS (10.1 ± 14.2%) and TS (6.4 ± 10.2%) (p<0.001). CMA3 staining indicated increased protamine deficiency in CS (37.13 ± 20.1%) compared to TS (25.3 ± 14.9%) and NS (15.0 ± 15.4%) (p<0.001).

Further analysis showed that while tobacco and cannabis use negatively impacted sperm quality, cannabis appeared to have a more detrimental effect on DNA integrity. The high AO+ and CMA3+ scores in cannabis smokers suggest an increased risk of infertility due to DNA fragmentation and improper chromatin packaging, factors that influence embryo viability and pregnancy success rates.

Analysis of mtDNA sequences revealed 23 single nucleotide polymorphisms (SNPs) in MT-CO1, 15 in MT-CO2, and 30 in MT-CO3. However, no significant differences in SNP distributions were observed among groups (MT-CO1, p=0.10; MT-CO2, p=0.23; MT-CO3, p=0.07).

This suggests that smoking does not induce detectable genetic mutations in these mitochondrial genes but may contribute to epigenetic alterations affecting sperm function.

Conclusions

Tobacco and cannabis use negatively impact sperm quality and DNA integrity, with cannabis smokers experiencing the most severe impairments. These findings are not just statistics, they affect real families struggling with infertility.

Reduced sperm health can lead to difficulties conceiving, higher miscarriage rates, and long-term health risks for offspring. As cannabis use continues to rise globally, the public must recognize its potential reproductive dangers.

On a broader scale, the increasing legalization and social acceptance of cannabis may contribute to a hidden reproductive crisis. Policymakers, healthcare professionals, and individuals should prioritize awareness and preventive measures.

Public health campaigns should highlight the risks of smoking on fertility, particularly among young men who may be unaware of the long-term consequences.