Toxic metabolites, Sertoli cells and Y chromosome related genes are potentially linked to the reproductive toxicity induced by mequindox

Abstract

Mequindox (MEQ) is a relatively new synthetic antibacterial agent widely applied in China since the 1980s. However, its reproductive toxicity has not been adequately performed. In the present study, four groups of male Kunming mice (10 mice/group) were fed diets containing MEQ (0, 25, 55 and 110 mg/kg in the diet) for up to 18 months. The results show that M4 could pass through the blood-testis barrier (BTB), and demonstrate that Sertoli cells (SCs) are the main toxic target for MEQ to induce spermatogenesis deficiency. Furthermore, adrenal toxicity, adverse effects on the hypothalamic-pituitary-testicular axis (HPTA) and Leydig cells, as well as the expression of genes related to steroid biosynthesis and cholesterol transport, were responsible for the alterations in sex hormones in the serum of male mice after exposure to MEQ. Additionally, the changed levels of Y chromosome microdeletion related genes, such as DDX3Y, HSF2, Sly and Ssty2 in the testis might be a mechanism for the inhibition of spermatogenesis induced by MEQ. The present study illustrates for the first time the toxic metabolites of MEQ in testis of mice, and suggests that SCs, sex hormones and Y chromosome microdeletion genes are involved in reproductive toxicity mediated by MEQ in vivo.