07
Apr
Multigenerational Abnormalities Linked to Prostate Cancer Associated with Neonicotinoid Insecticide
(Beyond Pesticides, April 7, 2026) In the International Journal of Molecular Sciences, a study of gestational (during pregnancy) exposure to the neonicotinoid insecticide thiacloprid shows epigenetic effects (alterations in genes without altering underlying DNA) within prostate tissues. To analyze the role of gene expression in subsequent generations after initial thiacloprid exposure, the authors exposed pregnant outbred Swiss mice to the insecticide in order to assess the offspring for multiple generations. As a result, the researchers from the Université de Rennes in France state, “Our study revealed that exposure to thiacloprid induces [cell] proliferation and is associated with epigenetic alterations in the sperm of genes important for prostate development.†Increased cell proliferation in the prostate can cause the development of conditions such as benign prostatic hyperplasia (BPH) and prostatic intraepithelial neoplasia (PIN), and lead to prostate cancer.
The study also finds elevated levels of specific biomarkers within the prostates of both the first and third generations, including phosphorylated histone H3, a marker crucial for cell division. Hox gene expression in both generations was also impacted, which plays a role in prostate development, based on the altered DNA methylation (abnormal changes) in the sperm of the analyzed mice.
“In this study, we aimed to reveal the effects of thiacloprid on prostate morphology and to gain insight into the epigenetic mechanisms involved in the regulation of genes important for prostate functioning and development using a mouse model,†the authors say. They continue, “Although the mouse prostate is anatomically and histologically different from the human prostate, there is extensive evidence that the genetic lesions in human prostate cancer can lead to neoplasia in the murine prostate, suggesting that there is a common conserved mechanism of prostate pathology development.â€
Study Importance
A wide body of science, that continues to grow, connects the intensive use of neonicotinoids to adverse health effects in a multitude of organisms. Most notably, dramatic declines in bees and other pollinators are linked to neonicotinoids and neonicotinoid-treated seeds. (See What the Science Shows on Biodiversity for more information on the effect of pesticides on pollinators and other beneficial organisms.)
As the current study authors point out, neonicotinoids in Europe were banned in 2018 but continue to be detected in the environment and contaminate organisms. For instance, studies find that thiacloprid is detected in aquatic invertebrates in the Danube River, as well as in honey samples, years after the ban. (See research here, here, and here.) Birds in Europe, such as the house sparrow Passer domesticus, have detectable neonicotinoid residues in their feathers. Residues in farmland birds, including gray partridges and Montagu’s harrier chicks, also show the persistence of neonicotinoids in nature.
Additional studies find thiacloprid in mammals. One study finds levels of thiacloprid in the urine of domesticated dogs and cats, while another shows residues in the hair of small mammals. A human biomonitoring study finds urinary neonicotinoids and their metabolites correlated with oxidative stress biomarkers. This widespread and persistent presence of neonicotinoids in organisms, particularly where their use has been banned, shows the long-lasting effects that need to be taken into consideration prior to permitting the release of hazardous or potentially harmful chemicals into the environment.
Methodology and Results
In this study, multiple generations of Swiss mice are assessed for potential changes in gene expression within the prostate with exposure to thiacloprid. The control mice and the pregnant mice with neonicotinoid exposure represent the F0 generation, while their immediate offspring are F1. The researchers further describe, “Both control and exposed F1 generation males were crossed with non-related, untreated females to obtain the F2 generation. Both control and exposed male progeny of F2 were crossed with non-related, untreated females to obtain the F3 generation.â€
For the F0 mice that were exposed to thiacloprid, this occurred over 10 days during the embryonic period based on the lowest-observed-adverse-effect level (LOAEL), the lowest concentration of a substance in which adverse alterations of morphology or function occur. As the authors point out, “The chosen dose was approximately four times lower than the LOAEL established by the EPA [Environmental Protection Agency] for thiacloprid for mice†and “~5 times lower than the human equivalent LOAEL dose established by the EPA.†The entire experiment, from the F0 generation to the F3 generation, was performed twice.
The results of the study show some epigenetic effects in both the F1 and F3 generations, while other effects are only noted in the F1 generation despite the persistence of epigenetic markers. The researchers explain, saying: “[I]t is likely that gestational exposure to thiacloprid induces some alterations in the F1 generation, causing an increase in proliferation, based on analysis of markers. However, the effects were not detected in F3, suggesting that most of the effects induced in F1 were not transgenerational but intergenerational.â€
Other effects show variation between the generations. “We also noted that alterations in our studies in F1 and F3 epigenetic marks had opposite effects,†the authors state. They continue: “We cannot simply explain this phenomenon; we suggest that some unknown mechanisms compensate for the previously induced epigenetic alterations in F3 males. Similar opposite effects were observed in our previous study in prostates exposed to chlordecone. We suggest that compensatory effects could be promoted during fertilization.†This variation requires further research to elucidate the mechanisms at play, but continues to expand the current knowledge regarding the effects of neonicotinoids through solely laboratory-based transgenerational exposure and without any direct exposure as would be encountered in the environment.
Gestational exposure to thiacloprid increases epithelial hyperplasia in the anterior prostate in the F1 generation, as well as elevates the expression of mitosis. As the researchers share, additional study results include:
- “We detected increased levels of the mitosis marker PHH3 in the prostate of F1 and F3, and the expression of the oncogenesis (cancer-causing) marker Ki-67 was significantly increased in directly exposed F1 but not in F3 males.
- The expression of genes encoding transcription factors, hormones, and chromatin factors was altered in both the F1 and F3 anterior prostates.
- We observed that gene expression and histone H3K4me3 occupancy at promoters of Hox and several transcriptional factors were consistently changed in similar directions in exposed mice.
- Compared with changes in gene expression, alterations in DNA methylation at the promoters of prostate development genes were observed in F1 and F3, mainly in opposite directions.
- The H3K4me3 global level increased in both generations, which could be due to an increased level of mitosis resulting from a significantly increased level of PHH3, a marker of mitosis, in F1 and F3.
- The DNA methylation of several genes essential for prostate development was altered. Notably, the analysis of markers (Ki-67, PHH3, and HDAC1) showed the effects in F1 but not in F3. However, there are some alterations in Hox genes (gene expression, histone H3K4me3 occupancy, sperm DNA methylation level) and in some other factors, such as HDAC1, suggesting that certain alterations could be persistent and possibly impact the prostate at a later age in F3 animals.â€
Previous Research
In a prior study, the study authors show that gestational exposure to thiacloprid induces transgenerational alterations in the male reproductive system. That research led to the current study to identify specific impacts of thiacloprid exposure on the prostate. One study links thiacloprid exposure to a reduction in testosterone in the blood serum of F3 males. Additional scientific literature (see here and here)also connects thiacloprid exposure to toxicity within the thyroid glands of mice, where it “induces alterations in thyroid gland morphology and interferes with the production of thyroid hormones.†(See Daily News coverage on thiacloprid here.)
Other research connects other neonicotinoids to prostate effects. “Specifically, it has been determined that the neonicotinoid imidacloprid (IMI) is toxic to human prostate epithelial cells and induces apoptosis [cell death] and oxidative stress,†the researchers note. (See here.) Another study shows that “IMI exposure affected the weight of the prostates and led to a decrease in testosterone levels.†(See Daily News coverage on neonicotinoids and prostate effects here and here.)
Recent research published in Critical Reviews in Toxicology (CRT) and Proceedings of the National Academy of Sciences (PNAS), as shared in a Daily News piece entitled Studies Find Genetic and Epigenetic Effects from Pesticide Exposure, Threatening Future Generations, documents the genetic and epigenetic effects to pesticide-exposed groups through early-life exposure and from transgenerational inheritance (passed down through generations). These studies highlight the complex nature of mechanisms of toxicity, as well as the various pesticide exposure routes that begin even prior to conception. Through a systematic review and meta-analysis of studies on “DNA damage, cytogenetic damage, DNA methylation, or gene expression outcomes associated with prenatal and early childhood pesticide exposure,†the CRT authors link genotoxic mechanisms and epigenetic alterations to adverse health outcomes while the PNAS study shows pesticide-induced epigenetic alterations in mammals across 20 generations that “suggest the maternal and paternal lineages can both induce and inherit epigenetic alterations that influence disease (e.g., kidney, testis, ovary, prostate) incidence, reproductive health (e.g., parturition, infertility), and overall fitness generationally.â€
The Organic Solution
As an alternative to neonicotinoid insecticides like thiacloprid, Beyond Pesticides advocates for the precautionary approach of organic agricultural and land management practices. Buying, growing, and supporting organic can help eliminate the extensive use of pesticides in the environment, which protects all organisms within it. To learn more about the numerous health and environmental benefits of organic systems, see here and here.
Make The Safer Choice by learning how to avoid hazardous home, garden, community, and food use pesticides. ManageSafeâ„¢ also helps to identify the organic management practices and compatible control options for pests in the home and garden. For more information on alternatives, see the factsheet Managing Pests Safely Without Neonicotinoids: For Homes, Schools, and Other Indoor/Outdoor Areas, created through the BEE Protective project.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source:
Dali, O. et al. (2026) Intergenerational Effects of Neonicotinoid Thiacloprid in Murine Prostate Tissue Are Associated with Epigenetic Alterations in Homeobox Hox Genes, International Journal of Molecular Sciences. Available at: https://www.mdpi.com/1422-0067/27/7/2921.
