11
Mar
Study Finds Spermiotoxicity and Impacts on Male Mammal Fertility with Ipconazole Fungicide Exposure
(Beyond Pesticides, March 11, 2025) A study in Toxics analyzes ipconazole, a triazole fungicide often used as a coating on treated seeds and as a foliar treatment on the leaves of plants. “Triazole pesticides are widely used throughout the world, but their abuse causes toxic effects in non-targeted organisms,†the researchers state. In the current study, unintended reproductive effects are noted in male sheep (ram) and pigs (also known as porcine or swine). This research focuses on the impact of ipconazole exposure on spermatozoa (sperm) in two mammal species and finds spermiotoxicity through significantly reduced sperm viability, as well as alterations in enzyme and gene expression related to fertility.Â
“To our knowledge, this is the first study to evaluate the cytotoxic effect of the triazole ipconazole on mammalian spermatozoa,†the authors share. This analysis utilizes semen samples from the Reproductive Biotechnology Laboratory of the Major National University of San Marcos in Lima, Peru, the university where six of the nine researchers are Faculty of Veterinary Medicine. Â
“The sperm were exposed to ipconazole concentrations of 1, 5, 10, 50 and 100 µM, and to a control without ipconazole,†they say. Similar concentrations have been used in previous cytotoxicity studies with ipconazole. One, a 2023 Toxics study, finds reduced cell viability, oxidative stress, and cell death, specifically in SH-SY5Y neuroblastoma cells, that suggests ipconazole exposure as a factor for neurotoxicity and neurodegeneration.Â
The study evaluated a range of cell functions to determine adverse health outcomes. The latest Toxics study utilized sperm viability, reactive oxygen species (ROS) production (critical to the central nervous system), superoxide dismutase (SOD) activity (an enzyme critical to the regulation of oxygen), and catalase activity assays, as well as an analysis of gene expression through qPCR (which stands for quantitative polymerase chain reaction and is a technology used for measuring DNA).Â
As a result of the experiment, the authors report: “Ipconazole led to a significant decrease in cell viability and a significant increase in ROS generation, as well as several changes in catalase and SOD activity. It also altered the molecular expression of structural and oxidative stress biomarkers in spermatozoa of both species.â€Â The alterations in the molecular mRNA expression of structural biomarkers include PRM1, ODF2, AKAP4, THEG, SPACA3, and CLGN, which are related to fertility in males.Â
“Ipconazole-induced oxidative stress has been demonstrated experimentally in vitro and in vivo,†the researchers note. They continue: “Data from this study suggests that ipconazole is able to alter the oxidative state by inducing ROS production and reducing or increasing the activity of the antioxidant enzymes SOD and catalase in porcine and ram spermatozoa. Overall, the oxidative effect (ROS generation) of ipconazole was higher in porcine spermatozoa than in ram spermatozoa, even reaching up to 3 times higher ROS levels compared to the control group.â€Â
The authors also relay that there was an overexpression of BAX (cell death) and ROMO1 (oxidative stress) mRNA, which shows the ability of ipconazole to cause epigenetic changes in mammals. Overall, these results indicate that “the fungicide triazole is involved in cellular, enzymatic and molecular alteration of porcine and ram spermatozoa, and is possibly a factor in the development of infertility in male mammals,†they conclude.Â
Previous research finds triazole pesticides cause various health effects in terrestrial and aquatic nontarget organisms including humans and wildlife. Other pesticide classes are also documented as impacting sperm and fertility. Relevant results highlighted in the current study include:Â
- “Agrochemicals such as pesticides can alter seminal parameters, with total sperm count, motility and morphology being the most frequently worsened.†(See study here.)Â
- “There is a strong association between decreased sperm concentration and the presence of pyrethroid, organophosphate [OP], BPA and phthalate pesticide metabolites in urine… Synthetic pyrethroids, OPs and phthalates have also been found to cause sperm aneuploidy and an altered X:Y ratio.†(See studies here, here, here, here, and here.)Â
- Difenoconazole, when administered to rats, reduced sperm numbers in all treated groups.Â
- “[C]ontinuous exposure to penconazole reduces testosterone levels, causes spermatogenic alterations, and impairs Sertoli and Leydig cell morphology.†(See study here.)Â
- Triazole compounds impact chick testicular functions “by reducing cell viability, steroidogenesis and lactate production. Furthermore, the exposure of spermatozoa to triazoles causes a decrease in sperm motility, and an increase in sperm abnormalities and ROS production.â€Â
- “[T]ebuconazole caused a decrease in the number of germ cells and increased oxidative stress-related genes in fetal mouse testis.†(See study here.)Â
- Exposing sperm cells to pesticides “induces the expression of oxidative stress and cell death such as BAX.†(See studies here, here, and here.)Â
- “[T]he additive mixture of tebuconazole and econazole induced ROS-dependent cytotoxicity in TM4 Sertoli cells.â€Â
There is a level of complexity here that is not adequately addressed in regulatory processes within the United States (U.S.). While ipconazole is not registered for use in the European Union as of 2023 due to concerns about its impact on the environment and risks to agricultural workers, there are still permitted uses in seed treatments and for ornamental plants and turf in the U.S. Additionally, many other triazole fungicides are registered for use despite evidence of endocrine disruption. Triazole pesticides, as a class of fungicides, exhibit common mechanisms of toxicity often disregarded in risk assessments.Â
The wide body of science presented in this study, as well as previous coverage from Beyond Pesticides on the impacts of pesticides on sperm, infertility, and other sexual and reproductive dysfunction, showcases the myriads of health threats that the U.S. Environmental Protection Agency (EPA) does not consider in their chemical registration processes. (See more on EPA failures and regulatory deficiencies here.)Â Â
To mitigate these threats from harmful chemicals, alternative land management options need to be considered. There is the existence of an alternative—an organic production system—that does not harm human health, other species, or ecosystems and, in addition, helps to mitigate climate change. In all its regulatory decisions, EPA must switch to using organic production as a yardstick, denying any application for a toxic chemical in which organic production delivers a successful replacement.Â
Organic agriculture provides health and environmental benefits, as well as protects and enhances biodiversity. (See recent coverage on the health benefits of organic diets here and here.) Learn more about choosing organic food through Eating with a Conscience, and consider buying organic products (on a budget!) or growing your own organic food.Â
Beyond Pesticides’ mission is rooted in protecting healthy air, water, land, and food for ourselves and future generations by eliminating petrochemical pesticides and synthetic fertilizers. We are working for holistic change in food production and land management—from farms to homes, gardens, parks, playing fields, and schools. Join as a member today or give now to help support our work in 2025.Â
All unattributed positions and opinions in this piece are those of Beyond Pesticides. Â
Source:Â
Falero, C. et al. (2025) Oxidative and Molecular–Structural Alterations of Spermatozoa in Swine and Ram Exposed to the Triazole Ipconazole, Toxics. Available at: https://www.mdpi.com/2305-6304/13/3/176.Â
