Plant Compounds Show Promise Against Pesticide-Linked Sperm Damage in Animal Studies

Pyrethroids, the insecticide class that accounts for more than 30 percent of worldwide insecticide consumption, have long been associated with damage to the male reproductive system. A new systematic review now brings together the experimental evidence on whether natural products can blunt that damage, and its overall message is cautiously encouraging: in laboratory animals, a wide range of antioxidant-rich plant extracts and purified phytochemicals appear to counteract many of the reproductive harms caused by pyrethroid exposure. The review, published in Frontiers in Pharmacology, followed PRISMA guidelines, searched four major databases from inception to July 2025, and was prospectively registered with PROSPERO.

The analysis included 33 experimental animal studies published between 2003 and 2025, involving adult male rats, mice, rabbits and guinea pigs. The animals were exposed to five pyrethroid compounds: cypermethrin, deltamethrin, fenpropathrin, fenvalerate and permethrin, with cypermethrin and deltamethrin the most frequently studied. Across the included work, pyrethroid exposure consistently reduced sperm count, motility, viability and normality, elevated markers of oxidative stress such as malondialdehyde and lipid peroxidation, and suppressed the activity of antioxidant enzymes including superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, alongside reduced glutathione levels.

The hormonal picture was more complicated. Several studies reported reductions in testosterone, luteinizing hormone and follicle-stimulating hormone after pyrethroid exposure, but others found increases or no statistically significant changes in individual gonadotropins. The review’s authors emphasize that this variability appeared across different pyrethroids, species, doses, exposure durations and experimental designs, so the evidence does not support a uniform direction of change for LH and FSH across all experimental models. Histological examinations, meanwhile, showed significant testicular tissue damage, including disrupted seminiferous tubule structure, reduced germinal epithelial height, lower Leydig cell counts and increased interstitial space.

Against this backdrop, the natural products tested in the included studies showed broadly protective effects. Sage (Salvia officinalis) extract, rosemary extract, onion juice, ginseng, Tribulus terrestris extract, green tea extract, Chlorella vulgaris, wheat germ oil, ginger, Ginkgo biloba extract, Curculigo orchioides, pomegranate peel extract, Sambucus nigra extract, date palm kernel extract, lycopene, beta-carotene, matrine and fenugreek aqueous extract all improved at least some reproductive parameters relative to pesticide-only groups. Purified compounds told a similar story: curcumin and quercetin increased sperm count, motility and normality, reproductive organ weights, testosterone, LH and FSH in rats co-exposed to cypermethrin and deltamethrin, with curcumin showing slightly greater activity than quercetin and the combination of the two offering greater protection than either alone.

The most consistent benefit appeared in oxidative stress markers. Across pesticide groups, natural products decreased pyrethroid-induced increases in MDA, lipid peroxidation, thiobarbituric acid-reactive substances and protein carbonyl content, while increasing antioxidant enzyme activities and reduced glutathione relative to the corresponding pesticide-only groups. Histopathological assessment showed that most natural products also significantly reduced testicular tissue damage, and several restored specific structural features: green tea extract increased Johnsen’s score, germinal epithelial height and seminiferous tubule diameter in deltamethrin-exposed mice, while Sambucus nigra and date palm kernel extracts each increased Leydig cell counts, tubule diameter and germ cell layer thickness in fenpropathrin-exposed rats.

Molecular findings, though drawn from a smaller subset of studies, hint at mechanisms. Curculigo orchioides and the curcumin-quercetin pair increased testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase activity, enzymes central to testosterone synthesis. Curcumin and chitosan-encapsulated curcumin nanoparticles increased testicular expression of StAR, CYP11A1, CYP17A1, CYP19A1, HSD17B3, Kiss-1, Kiss1r and GLP-1 in fenpropathrin-exposed rats, with the nanoparticle formulation outperforming free curcumin, an effect attributed to improved bioavailability. Lycopene decreased testicular caspase-8 and caspase-3 expression in fenvalerate-exposed animals, pomegranate peel extract shifted the balance of Bcl-2, p53 and caspase-3 expression, and matrine increased StAR expression while reducing DNA fragmentation in permethrin-exposed rats.

The protective record is not unblemished. Allium sativum, or garlic, produced no significant difference from the deltamethrin-only group in testis weight or in any of the measured oxidative stress markers. Date fruit extract failed to improve sperm motility, normality, viability, mass activity or pH relative to cypermethrin-only animals, and testosterone and FSH were further reduced, a paradox the review’s authors suggest may reflect a dual effect combining antioxidant protection with endocrine disruption, possibly linked to phytoestrogen content or dose-dependent biphasic responses. Moringa and sage leaf powder improved sperm parameters but further reduced seminal vesicle weight, and Panax ginseng and resveratrol did not change testis or epididymis weight even as other parameters improved.

The authors also flag a methodological concern that cuts to the heart of the field: several of the most frequently studied compounds, including curcumin, quercetin and resveratrol, are well-documented pan-assay interference compounds, or PAINS, which can generate non-specific or artefactual signals in colorimetric and enzyme-based assays through redox cycling, metal chelation and non-specific protein reactivity. Because most primary studies relied on exactly such assays, some reported protective effects might partly reflect assay interference rather than genuine biological activity. The mechanistic conclusions are further constrained by the fact that most primary studies measured only downstream, non-specific markers such as total antioxidant capacity, MDA or hormone concentrations, without directly probing pathway activation, so the proposed mechanisms should be read as hypothesis-generating rather than established causal pathways.

The risk-of-bias assessment reinforces that caution. Using SYRCLE’s Risk of Bias tool, the reviewers found that random sequence generation was explicitly reported in only 21 of 33 studies, while allocation concealment, baseline comparability, random housing, blinding of caregivers and random outcome assessment were unclear, meaning not reported, in all 33 studies. Blinding of the outcome assessor was reported in just one study. Incomplete outcome data and selective outcome reporting were low risk in 32 of 33 studies, but the overall profile means the internal validity of the primary evidence is largely unverifiable from the published methods sections.

The review’s authors are explicit that the evidence base spans only a single tier: in vivo animal experiments. No in vitro mechanistic or human clinical studies met the eligibility criteria, and how well these findings translate to human reproductive health remains undetermined. Heterogeneity in doses, formulations, treatment durations and animal models also precluded a quantitative meta-analysis. The authors call for standardized experimental protocols, broader coverage of the pyrethroids actually on the market, detailed investigation of molecular pathways, and eventually clinical studies to verify whether natural compounds can serve as adjunctive strategies against pyrethroid-induced reproductive toxicity. Until then, the promise of sage, curcumin, quercetin and their botanical kin remains exactly that: promising, preliminary, and confined to the laboratory.

Subject of Research: Natural products as mitigators of pyrethroid-induced male reproductive toxicity in experimental animals

Article Title: Natural products mitigate pyrethroid-induced male reproductive toxicity: a systematic review

Article References: Babaei, A., Moradi, S., Azari-Dolatabad, N., Fakhri, S., Farzaei, M. H., & Echeverría, J. (2026). Natural products mitigate pyrethroid-induced male reproductive toxicity: a systematic review. Frontiers in Pharmacology, 17, Article 1933092. https://doi.org/10.3389/fphar.2026.1933092

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1933092

Keywords: pyrethroids, natural products, male reproductive toxicity, systematic review, oxidative stress, sperm parameters, testosterone, curcumin, quercetin, animal studies, antioxidants, endocrine disruption