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One exposure. Twenty generations later, the damage is still unfolding · U.S. Right to Know articles

A single exposure to a toxic agricultural fungicide during pregnancy can echo through 20 generations — with inherited disease risks from kidney disease to infertility not fading, but worsening over time, according to groundbreaking research published Tuesday.The <a href="https://www.pnas.org/doi/10.1073/pnas.2523071123">study</a>, which appeared in the Proceedings of the National Academy of Sciences, tracked rats whose ancestors were exposed in the womb to <a href="https://pubchem.ncbi.nlm.nih.gov/compound/vinclozolin">vinclozolin</a>, a fungicide once widely sprayed on turf grass and fruits and vegetables such as strawberries, raspberries, lettuce, and grapes, including wine grapes. Researchers found that chemical changes that control how genes are switched on or off in developing embryos and throughout life — known as <a href="https://my.clevelandclinic.org/health/articles/epigenetics">epigenetics</a>, or "epimutations" — were still altered in sperm 23 generations later.Later generations showed more severe disease, declining fertility and lethal birth complications than earlier ones. In some generations, mothers and entire litters died during childbirth. Just as striking, researchers also found a small number of rare DNA mutations.“The current study suggests after twenty generations that epigenetics can promote genetic alterations as well,” the authors wrote, adding that the dominant pattern was epigenetic change.The findings suggest that epigenetic changes linked to an ancestral chemical exposure and <a href="https://usrtk.org/category/endocrine-disruptors/">endocrine disruptor</a> can persist for many generations and accumulate over time. Twenty rat generations span a few years. In humans, that could translate to centuries.Past research has found changes in human eggs and sperm that correspond with mammal studies, and the increased incidence of human disease tracks with the transgenerational results found in animal studies.These new results could help explain some rising rates of chronic disease that have paralleled the rising use of pesticides and industrial chemicals, the researchers say. More than three-quarters of Americans live with at least one chronic disease such as heart disease, cancer or arthritis, and more than half have two diseases, according to the U.S. Centers for Disease Control.“The generational stability of transgenerational effects observed in this study has implications for human health, particularly regarding environmental toxicant exposures, reproductive health disorders, and disease susceptibility,” the authors wrote. “These results have importance in overall health and evolutionary biology, and the potential for environmental exposures to have long-term impacts on any organism’s population.”Key findings show:<li>Effects lasted 20 generations. Chemical changes that control how genes are switched on or off were still altered in rat sperm 23 generations after the original exposure. The number of these DNA “tags” increased over time, showing they were stably passed down and accumulated.</li><li>Disease worsened in later generations. Later generations developed higher rates of kidney, prostate, ovarian and testicular disease. In females, disease was more frequent and often more life-threatening.</li><li>Severe birth complications emerged. Even 16 generations later, females experienced prolonged or stalled labor. By the 22nd generation, reproductive success dropped sharply.</li><li>Sperm health steadily declined. Male descendants showed increasing numbers of dying sperm cells across generations. In later generations, sperm cell death rose sharply and coincided with high rates of birth complications.</li><li>The maternal line was hit hardest. Rats descended through the maternal lineage had far more altered DNA regions and more severe reproductive problems than those in the paternal lineage.</li><li>Changes were largely epigenetic, not genetic. Only a small number of permanent DNA mutations were detected. Most inherited effects involved shifts in gene regulation rather than changes to the DNA code itself.</li><li>Organ disease increased. Tissue examinations, including AI-assisted analysis, found abnormalities across multiple organs, including kidney disease and prostate problems. Large ovarian cysts and reduced mature follicles were more common in later generations.</li><li>Dramatic physical differences appeared. Even siblings raised in the same cage on the same diet showed significant differences. In one case, one brother was lean while the other was severely obese.</li>The findings underscore past research that found changes in human reproductive cells mirroring findings in animal studies, and rising disease rates in people following the same multigenerational patterns.“This study really does say that this is not going to go away,” said co-author <a href="https://skinner.wsu.edu/principal-investigator-michael-k-skinner/">Dr. Michael Skinner</a>, a professor in the School of Biological Sciences and founding director of the Center for Reproductive Biology at Washington State University. “We need to do something about it."<h2 class="wp-block-heading" id="h-a-chemical-with-a-troubled-history">A chemical with a troubled history</h2>Manufactured by the chemical company BASF, Vinclozolin was first registered in the United States in 1981 for use on crops under brand names such as Ronilan and Vorlan. In the 1990s, however, concerns grew as studies suggested the chemical could pose health risks. Vinclozolin blocks androgen receptors, the molecular switches that respond to male hormones such as testosterone. That can interfere with normal male hormone signaling and disrupt the development and function of the male reproductive system.<a href="https://oehha.ca.gov/sites/default/files/media/downloads/proposition-65/presentation/vinclozolincic121206.pdf">Animal studies</a> have linked vinclozolin to liver tumors, prostate abnormalities, adrenal and thyroid tumors, <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC9570110/#sec5-ijms-23-11296">kidney disease</a>, and uterine cancer. In November 2025, the International Agency for Research on Cancer classified it as “<a href="https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00702-8/fulltext">possibly carcinogenic to humans</a>.” The EPA phased out U.S.-grown food uses in the early 2000s, and the chemical is banned in the European Union, among other places.Laboratory and animal research has shown vinclozolin can cause lasting alterations in how genes are regulated that may be passed down to future generations. The new study underscores how the most consequential effects may not end with the exposed individual, instead lasting far longer than suspected.“These findings provide additional evidence of vinclozolin’s transgenerational effects, showing that ancestral exposure can trigger epigenetic modifications that contribute to disease development across multiple generations,” the authors wrote.<h2 class="wp-block-heading" id="h-following-exposure-across-generations">Following exposure across generations</h2>Researchers exposed pregnant rats — the F0 generation — to vinclozolin during a critical window of fetal reproductive development. Control rats received a neutral solution. Skinner said he scaled the dosage of the toxin conservatively, at a level below what the average person might consume in their diet.When a pregnant female is exposed, it affects three generations: the mother, the fetus and the fetus’s developing sperm or egg cells. The third generation (F3) is the first that was never directly exposed and is considered the first truly “transgenerational” generation.The team bred the rats for 23 generations, carefully outcrossing each generation with unrelated animals from a genetically diverse Sprague Dawley colony to prevent inbreeding. The colony has an inbreeding rate of about 0.15%, similar to humans.Researchers also contacted the supplier to confirm that maternal deaths and severe reproductive complications are rare in their general colonies. The supplier reported no unusual trends, suggesting the problems seen in the vinclozolin lineage were rare and not background strain effects.At one year of age, rats were evaluated for disease. Researchers collected sperm and examined tissues from the prostate, testes, ovaries, male and female kidneys and surrounding fat.<h2 class="wp-block-heading" id="h-measuring-epigenetic-change">Measuring epigenetic change</h2>Scientists used a laboratory method to identify “differentially methylated regions,” or DMRs, areas where gene-regulating marks differed from controls. By the 23rd generation:<li>The maternal lineage had 470 significant altered regions compared with controls.</li><li>The paternal lineage had 64.</li><li>Many changes involved roughly 50% increases or decreases in methylation, reflecting substantial changes in gene regulation.</li><li>Alterations were distributed across the genome, including near genes involved in metabolism, signaling and organ function.</li><li>Many of the same altered regions were seen 10 generations earlier. About 24% overlapped in the maternal line and nearly 44% in the paternal line, indicating the changes were stable and persisted.</li>Skinner first identified the epigenetic inheritance of disease in 2005 and has published dozens of papers since, including a foundational <a href="https://skinner.wsu.edu/documents/2017/03/2006-anway-leathers-skinner-endocrinology.pdf/">2006 </a>and <a href="https://pubmed.ncbi.nlm.nih.gov/17956218/">2007</a> studies on vinclozolin. Past studies have shown that inherited disease risk can exceed the harm caused by direct toxin exposure.“Essentially, when a gestating female is exposed, the fetus is exposed,” he said. “And then the germline inside the fetus is also exposed. From that exposure, the offspring will have potential effects of the exposure, and the grand offspring, and it keeps going. Once it's programmed in the germline [sperm and eggs], it's as stable as a genetic mutation.”Earlier research in 2007 found that female rats avoided males whose great-grandfathers had been exposed to certain chemicals, suggesting that inherited epigenetic changes can shape not only biology but behavior as well.<h2 class="wp-block-heading" id="h-disease-intensified-across-generations">Disease intensified across generations</h2>Researchers reported profound health consequences. Across generations, male descendants showed elevated sperm cell death, measured by a lab test that detects dying cells.Sperm cell death rose gradually, plateaued briefly around generations 15–17, then climbed sharply in generations 18–20. By the 20th generation, males descended through the maternal line averaged more than 400 dying sperm cells. Paternal-line males averaged nearly 380, far above controls.Around the same time, reproductive outcomes also deteriorated. Beginning around the 19th generation, female rats began dying during labor. Litters were lost to prolonged or stalled birth. By the 22nd generation, reproductive success had sharply declined.“By the 16th, 17th, 18th generations, disease became very prominent and we started to see abnormalities during the birth process,” Skinner said. “Either the mother would die, or all the pups would die, so it was a really lethal sort of pathology.”Many affected females were overweight or had obesity, which can interfere with uterine contractions. Declining sperm quality may also have reduced successful fertilization and healthy implantation, the study notes. Artificial intelligence-assisted tissue analysis, combined with manual review, revealed higher rates of kidney disease, ovarian cysts, fewer mature follicles and prostate abnormalities.“In some cases, more progressive and chronic diseases were seen in the F23 generation rats,” the authors wrote.<h2 class="wp-block-heading" id="h-implications-for-preventing-future-disease">Implications for preventing future disease</h2>The study also underscores a regulatory blind spot, since traditional toxicology focuses on direct toxicity and genetic mutations. Epigenetic inheritance suggests low-dose exposures could leave molecular imprints that amplify across generations but also pave the way for prevention strategies, the researchers say.For instance, epigenetic biomarkers have been identified for different disease susceptibilities, including pregnancy-related disorders such as preeclampsia. Because they may provide a stable signal of inherited biological change, they could help identify risk long before symptoms, the authors say.“Although the environmentally induced epigenetic transgenerational disease cannot be prevented and will impact our future generations health, the use of epigenetic biomarkers for disease susceptibility can be used early in life to allow preventative medicine approaches to be used to delay or prevent later life disease burden,” they wrote.ReferenceKorolenko AA, Nilsson EE, De Santos S, Skinner MK. <a href="https://www.pnas.org/doi/10.1073/pnas.2523071123">Stability of epigenetic transgenerational inheritance of adult-onset disease and parturition abnormalities</a>. Proceedings of the National Academy of Sciences. 2026;123(8). doi:10.1073/pnas.2523071123