Researchers analyzed over 200 studies involving thousands of lab mice to understand what damages male fertility and why. They looked at nine different things that can harm sperm production, including chemicals like BPA, medications like chemotherapy drugs, and lifestyle factors like high-fat diets and heat exposure. The study found that three things cause the most damage: chemotherapy drugs, a diabetes medication, and microplastics. All of these harmful substances work through a similar mechanism in the body—they create something called oxidative stress, which damages cells. Understanding these common pathways could help scientists develop better treatments to protect or restore male fertility.

The Quick Take

  • What they studied: What different chemicals, medications, and lifestyle factors damage male fertility and how they cause that damage at the cellular level
  • Who participated: Analysis of 201 scientific studies involving 3,412 laboratory mice exposed to various harmful substances over a 15-year period (2009-2024)
  • Key finding: Three substances caused the most severe damage to sperm: chemotherapy drugs, a diabetes medication (streptozotocin), and microplastics. All three reduced sperm count to about 30-40% of normal levels and reduced sperm movement to about 30% of normal. The common cause of damage across all nine substances studied was oxidative stress—a type of cellular damage from harmful molecules.
  • What it means for you: If you’re concerned about male fertility, this research suggests avoiding exposure to known harmful chemicals and medications when possible, maintaining a healthy weight, and avoiding excessive heat exposure. However, these findings are from animal studies and may not directly apply to humans. Anyone with fertility concerns should consult a doctor rather than self-treating based on this research.

The Research Details

This was a network meta-analysis, which means researchers gathered data from 201 existing studies and combined the results to compare nine different substances that harm male fertility. The studies they analyzed all used laboratory mice as test subjects. Researchers looked at how each substance affected four main measures of fertility: sperm count, sperm movement (motility), sperm shape (morphology), and testis weight. They also measured hormone levels, particularly testosterone.

The researchers then used advanced computer analysis to identify the molecular pathways—essentially the cellular mechanisms—that these different substances use to cause damage. They focused particularly on something called oxidative stress, which is when harmful molecules called free radicals build up in cells and cause damage.

This approach allowed them to compare very different types of harmful substances (environmental chemicals, medications, and lifestyle factors) on equal footing and identify what they have in common at the cellular level.

This research approach is important because male infertility affects about half of all infertility cases worldwide, yet we don’t fully understand all the ways different substances can cause it. By combining data from many studies, researchers can identify patterns that might not be obvious from any single study. Understanding the common cellular mechanisms—in this case, oxidative stress—could help scientists develop treatments that work against multiple causes of infertility rather than just treating one specific substance’s effects.

This study is a comprehensive analysis of existing research rather than a new experiment, which means its strength depends on the quality of the studies it analyzed. The researchers looked at 201 studies, which is a large number and suggests thorough research. However, all the studies used laboratory mice, not humans, so the results may not directly apply to people. The findings are most useful for identifying patterns and suggesting directions for future human research. The study was published in a peer-reviewed journal focused on reproductive toxicology, indicating it was reviewed by experts in the field.

What the Results Show

The analysis revealed that different substances cause varying degrees of damage to male fertility. The three most damaging were: (1) Cyclophosphamide, a chemotherapy drug used to treat cancer, which reduced sperm count to about 30 million per milliliter (compared to normal levels); (2) Streptozotocin, a medication used in diabetes research, which had similar effects; and (3) Microplastics, tiny plastic particles found in the environment, which caused the most severe reduction in sperm count.

Across all nine substances studied, sperm count decreased by an average of 1.46 times (meaning it dropped to about 68% of normal), sperm movement decreased by 1.21 times, and testosterone levels decreased by 1.16 times. These changes were consistent across different substances, suggesting a common underlying mechanism.

The network pharmacology analysis—a technique that maps how different substances interact with genes and proteins—identified three key genes that were affected by all the harmful substances: NFE2L2, SOD1, and HMOX1. These genes are all involved in protecting cells from oxidative stress. This finding suggests that oxidative stress is the main way these different substances damage male fertility.

The research also showed that scientific interest in studying certain fertility hazards has changed over time. Studies on microplastics, high-fat diets, and lead exposure have increased significantly since 2009, reflecting growing concern about these modern environmental and lifestyle factors.

Beyond sperm count and movement, the study found that testis weight (the size of the reproductive glands) decreased in mice exposed to these harmful substances. Testosterone levels also dropped, which is important because testosterone is essential for sperm production and male sexual function. The study identified that environmental toxicants (BPA, lead, microplastics), medications (chemotherapy and diabetes drugs), and lifestyle factors (high-fat diet and heat) all work through similar cellular pathways, even though they’re very different types of exposures.

This is described as the first integrated analysis that combines toxicological effects with molecular mechanisms across multiple types of fertility hazards. Previous research has typically focused on individual substances or categories (like just environmental chemicals or just medications). By bringing all this research together and identifying the common mechanism of oxidative stress, this study provides a more complete picture of male fertility damage than previous reviews.

The main limitation is that all the data comes from studies using laboratory mice, not humans. While mice are commonly used in medical research because their biology is similar to humans in many ways, results don’t always translate directly to people. Additionally, the study relies on data from existing published studies, which means it can only analyze what other researchers have already measured and reported. Some important measures of fertility or mechanisms of damage might not have been studied in rodents. The study also doesn’t account for how multiple exposures together might affect fertility—it only looks at individual substances. Finally, the quality and methods of the 201 studies analyzed likely varied, which could affect the overall conclusions.

The Bottom Line

Based on this research, people concerned about male fertility should: (1) Avoid unnecessary exposure to known environmental toxicants like BPA (found in some plastics) and lead; (2) Maintain a healthy weight and avoid high-fat diets; (3) Avoid excessive heat exposure to the genital area; (4) If taking medications that might affect fertility, discuss this with a doctor rather than stopping medications on your own. However, these recommendations are based on animal studies and should be considered preliminary. Anyone with fertility concerns should consult a healthcare provider for personalized advice.

Men who are trying to conceive or planning to have children should be most interested in this research. Men with occupational exposure to chemicals, those taking medications like chemotherapy, and men concerned about environmental factors should also pay attention. Women whose partners might be exposed to these substances could also benefit from understanding these risks. However, this research is primarily relevant for prevention and understanding mechanisms rather than treating existing infertility, so men already experiencing fertility problems should work with a fertility specialist rather than relying solely on this information.

If someone makes lifestyle changes based on this research (like improving diet or reducing heat exposure), improvements in sperm production would likely take at least 2-3 months to appear, since that’s how long it takes the body to produce new sperm. For environmental exposures, avoiding the harmful substance would need to happen before conception is attempted. This research doesn’t provide information about how quickly fertility might recover after stopping exposure to harmful substances.

Want to Apply This Research?

  • Users concerned about fertility could track potential exposures: log daily heat exposure to genital area (wearing tight clothing, hot baths, laptop use), dietary patterns (especially high-fat foods), and any medications or supplements being taken. This creates a personal exposure profile to discuss with a healthcare provider.
  • Implement a ‘fertility-friendly lifestyle’ tracking feature where users can set and monitor goals like: maintaining a healthy weight, reducing processed foods, avoiding excessive heat exposure, and limiting time near known environmental toxicants. The app could send reminders about these protective behaviors.
  • For long-term tracking, users could monitor general health markers that relate to fertility: body weight, diet quality, exercise frequency, and stress levels. While the app can’t measure sperm directly, these lifestyle factors are modifiable and relevant to the research findings. Users should be encouraged to work with healthcare providers for actual fertility testing.

This research is based on studies in laboratory mice and has not been directly tested in humans. The findings suggest potential mechanisms of fertility damage but should not be used for self-diagnosis or self-treatment. If you have concerns about male fertility or are trying to conceive, consult with a qualified healthcare provider or fertility specialist. Do not stop taking prescribed medications based on this research without medical guidance. This information is for educational purposes only and is not a substitute for professional medical advice.