The expansion of intensive agricultural systems leads to increasing degradation of natural habitats, caused, among other factors, by the widespread use of herbicides such as glyphosate (Gly), whichis widely used despite growing evidence of its potential adverse effects. Among the vertebrates most exposed to ecotoxicological risk are reptiles, whose populations are particularly sensitive to habitat loss and endocrine disruption. In this context, this study combines in vivo and in vitro approaches to assess the impact of glyphosate on the male reproductive system.

In the in vivo model, adult males of Podarcis siculus lizards were exposed orally, every other day for three weeks, to two concentrations of Gly (0.05 and 0.5 μg/kg bw). The analyses conducted revealed marked alterations in testicular morphology, a reduction in spermatogenesis and changes in the cell junctions. In addition, the expression and localisation of oestrogen receptors (ERα and ERβ) in germ cells were significantly altered, with a dose-dependent increase in expression. Gly, at the concentrations tested, did not cause appreciable changes in steroidogenesis parameters. Overall, these results indicate that the herbicide can compromise the reproductive morphophysiology of male lizards, potentially reducing their reproductive fitness.

At the same time, in the in vitro model based on human prostate epithelial cells PNT1A, Gly induced cytotoxicity and rapid activation of oestrogen receptors via nuclear translocation. Functional analyses of mitochondrial metabolism showed reduced ATP production, respiratory reserve capacity and proton leak, suggesting the onset of mitochondrial dysfunction. Furthermore, the data suggest the activation of apoptotic pathways in response to treatment.

Overall, the evidence gathered confirms Gly as a potential endocrine disruptor, capable of altering reproductive function in both animal models and human cells, highlighting the urgent need for more controlled use of the herbicide.