Algae Toxin in Urine Linked to Poorer Sperm Quality in Landmark Men’s Health Study

A toxin produced by the blue-green algae that bloom in lakes and reservoirs around the world has now been measured, with unprecedented sensitivity, in the urine of hundreds of adult men — and the results point to a troubling connection with male fertility. In a study published in the Journal of Exposure Science & Environmental Epidemiology, a team led by researchers at Zhengzhou University in China reports that microcystin-LR, one of the most common and potent cyanobacterial toxins, was detectable in the urine of roughly seven in ten men recruited from a reproductive medicine center, and that men with higher urinary concentrations tended to have lower semen volume, reduced sperm concentration, and lower total sperm counts. The work, published on 14 October 2026, pairs a major analytical advance with one of the largest human investigations to date of this toxin’s relationship to reproductive health.

Microcystin-LR is a cyclic peptide toxin released by cyanobacteria — microscopic organisms often called blue-green algae — when they form dense blooms in warm, nutrient-rich waters. These blooms are becoming more frequent and more widespread as climate change warms surface waters and agricultural runoff delivers the nitrogen and phosphorus that feed them. The toxin is notorious for its hepatotoxicity: it potently inhibits protein phosphatases inside cells, and acute exposures through contaminated drinking water have caused illness in both humans and animals. What has been far harder to establish is what chronic, low-level exposure does to people who are not acutely sick — including whether it quietly undermines the male reproductive system, as laboratory studies in rodents and experiments on human sperm cells have long suggested.

The central obstacle has been measurement. Microcystin-LR circulates at extremely low concentrations in the human body, and the analytical methods available to epidemiologists were simply not sensitive enough to capture it reliably in urine, the matrix of choice for large-scale biomonitoring because samples are easy to collect noninvasively. Earlier approaches, including enzyme-linked immunosorbent assays and some liquid chromatography tandem mass spectrometry protocols, either lacked the necessary detection limits or suffered from interference in the complex chemical environment of urine, which is loaded with salts, metabolites, and endogenous compounds that can mask trace analytes. Without a dependable way to quantify the toxin in a general population, epidemiological evidence linking environmental exposure to health outcomes remained thin.

The research team, led by Yu Fu and Hao Wu as co-first authors under the supervision of Huizhen Zhang and Xingde Du, set out to close that gap. They developed and validated a method built on ultra-performance liquid chromatography coupled with tandem mass spectrometry, or UPLC-MS/MS, a technique that separates molecules in a liquid sample with high resolution and then identifies and quantifies them by their mass-to-charge ratios and characteristic fragmentation patterns. A critical component of the workflow was sample preparation: the team systematically optimized solid-phase extraction, testing different extraction columns and refining the conditions used with hydrophilic-lipophilic balanced, or HLB, sorbent material to pull microcystin-LR out of urine and concentrate it while leaving behind the matrix components that would otherwise interfere with detection.

The result was a method with a limit of detection of 0.001 micrograms per liter — a nanogram per liter — which the authors report is lower than the detection limits achieved in previously published studies. That sensitivity matters enormously in practice. When the threshold of detection falls, the fraction of samples in which a contaminant can be quantified rises, and researchers gain the ability to distinguish genuinely unexposed individuals from those carrying trace amounts of the toxin. In this study, microcystin-LR was detected in 447 of 633 urine samples, with a median concentration of 0.03 micrograms per liter. In other words, roughly seventy percent of the men in the study carried measurable levels of the algal toxin in their bodies, a finding that speaks to how pervasive environmental exposure to cyanobacterial toxins may be even among people who are not aware of any contact with contaminated water.

With the validated method in hand, the investigators applied it to a cross-sectional study of 633 men recruited from the Reproductive Medicine Center of Henan Provincial People’s Hospital in Zhengzhou. Each participant provided a urine sample and a semen sample, and semen quality was assessed according to the standardized procedures of the World Health Organization laboratory manual, covering parameters such as semen volume, sperm concentration, total sperm count, and sperm morphology, including abnormalities of the sperm tail. The researchers then examined how urinary microcystin-LR concentrations related to these parameters using multivariable linear regression models adjusted for urine creatinine — which corrects for differences in urine dilution — as well as age, body mass index, alcohol consumption, and smoking status, the standard confounders in studies of male fertility.

The associations were consistent and statistically significant. Higher urinary microcystin-LR concentrations were associated with decreased semen volume, decreased sperm concentration, and decreased total sperm count, and with increased rates of sperm tail abnormalities, with all trend tests across exposure categories reaching statistical significance. When the men were divided into quartiles of exposure, those in the highest quartile showed significantly reduced semen volume, sperm concentration, and total sperm count compared with men in the lowest quartile, while men in the third and fourth quartiles had significantly increased rates of sperm tail abnormalities. The tail findings are particularly noteworthy mechanistically: sperm tail structure and motility depend on tightly regulated energy metabolism and calcium signaling, and prior laboratory work by some of the same collaborators has implicated a calcium-dependent signaling pathway in microcystin-induced damage to human sperm.

These human findings align with a substantial body of experimental evidence. Studies in male mice have shown that chronic low-dose exposure to microcystin-LR degrades sperm quality and testicular function, and research in testicular cells has documented oxidative stress, DNA damage responses, inflammatory signaling, and apoptosis following toxin exposure. A previous cross-sectional study in Jiangsu and Anhui provinces reported associations between microcystin levels measured directly in semen and reproductive quality. The new study adds a crucial piece: it uses urine, a far more practical matrix for population-scale surveillance, and it does so with a detection limit sensitive enough to capture the low-level exposures that most people actually experience. The authors suggest that urinary microcystin-LR could serve as a biomarker for human exposure assessment and reproductive risk evaluation going forward.

As with any cross-sectional study, caution is warranted in interpreting the findings as proof of causation. The measurements of exposure and semen quality were taken at the same time, so the analysis cannot fully rule out reverse causation or the influence of unmeasured factors, and the participants were recruited at a reproductive hospital, which may not represent the general male population. Urinary concentrations reflect recent exposure, whereas sperm production is a process spanning roughly three months, so a single urine sample may not capture the exposure window most relevant to the semen parameters measured. Longitudinal studies with repeated urine collections would help clarify whether the observed associations reflect a genuine toxic effect over time. Even so, the strength and consistency of the dose-response patterns, together with the converging animal and cellular evidence, make the case for concern considerably stronger than it was before.

The broader implications extend well beyond the laboratory. Harmful cyanobacterial blooms are an escalating global problem, contaminating drinking water supplies, recreational waters, and irrigated crops, and microcystins are notoriously difficult to remove completely with conventional water treatment. If chronic low-level exposure to microcystin-LR does impair male fertility, then the estimated burden of bloom-related disease may be substantially underestimated, and water quality standards may need reexamination with reproductive endpoints in mind. The analytical method described in this study gives regulators and epidemiologists a tool they have lacked: a way to measure the toxin in urine at the vanishingly low concentrations at which ordinary people encounter it. As blooms intensify with warming waters, that capability may prove essential for tracking who is exposed, how much, and with what consequences for human health.

Subject of Research: Urinary biomonitoring of the cyanobacterial toxin microcystin-LR and its association with semen quality in adult men

Article Title: Development and application of a sensitive method for urinary biomonitoring of microcystin-LR: association with semen quality in adult men

Article References: Fu, Y., Wu, H., Liu, X., Yang, J., Wan, F., Meng, R., Chen, Y., Liang, X., Chen, X., Losiewicz, M. D., Ge, K., Guo, H., Du, X., & Zhang, H. (2026). Development and application of a sensitive method for urinary biomonitoring of microcystin-LR: association with semen quality in adult men. Journal of Exposure Science & Environmental Epidemiology. https://doi.org/10.1038/s41370-026-00990-4

Image Credits: AI Generated

DOI: 10.1038/s41370-026-00990-4

Keywords: microcystin-LR, cyanobacterial toxins, urinary biomonitoring, UPLC-MS/MS, semen quality, male fertility, male reproductive health, harmful algal blooms, exposure assessment, environmental epidemiology, sperm concentration, water quality