Efeito do uso prolongado do glifosato e 2,4-D sobre parâmetros reprodutivos de camundongos C57BL/6J obesos

Abstract

The consumption of Western diet (WD) - enriched in fats and sugars - is associated with overweight, obesity and male reproductive disorders. In addition to WD intake, crops and dairy products display residues of herbicides, including glyphosate and acid 2,4-diclorofenoxiacético (2,4-D) that are widely applied worldwide. The concomitant exposure to WD and herbicides - mimicking contemporary scenarios - is not fully investigated. Thus, we evaluated the effects of glyphosate and 2,4-D, alone or in mixture, on WD-induced alterations in the male reproductive system. Male C57BL6 mice were submitted to WD (chow hyperlipidic and hypercaloric, and high sugar solution with D-fructose and D-glucose). Concomitantly to WD, the animals received glyphosate (0.05, 5 or 50 mg/kg/day), 2,4-D (0.02, 2 or 20 mg/kg/day) or their mixture (0, 05+0.02; 5+2 or 50+20 mg/kg/day) by force feeding (5×/week). Doses were based on Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) values. Herbicide exposure did not alter the WD-induced obesity, hypercholesterolemia and glucose intolerance. WD induced abnormalities in sperm morphology, reduced the proliferation of spermatogonia, the number, area and volume of Leydig cells in the testis, in addition to increasing the occurrence of histological abnormalities in the epididymis. Remarkably, only herbicide mixtures promoted such WD-induced effects: the mixture at the lower doses (0.05+0.02) reduced spermatogonia proliferation. The herbicide mixture at intermediate (5+2) and higher (50+20) doses increased the frequency spermatozoa with straight head abnormality, and reduced the area and volume of Leydig cells. Finally, the mixture of higher doses (50+20) increased the frequency of epididymal abnormalities (absence of sperm, cytoplasmic vacuoles, and clear cell hypertrophy). Our findings indicate that the mixture of glyphosate and 2,4-D herbicides, mimicking environmentally relevant scenarios, promotes WD-induced changes in the male reproductive system.