Oncotarget

Research Papers:

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

Qianying Liu, Zhixin Lei, Menghong Dai, Xu Wang and Zonghui Yuan _

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Oncotarget. 2017; 8:87512-87528. https://doi.org/10.18632/oncotarget.20916

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Abstract

Qianying Liu1, Zhixin Lei2, Menghong Dai2, Xu Wang1 and Zonghui Yuan1,2,3

1National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, China

2MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, China

3Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China

Correspondence to:

Zonghui Yuan, email: yuan5802@mail.hzau.edu.cn

Xu Wang, email: wangxu@mail.hzau.edu.cn

Keywords: mequindox, reproductive toxicity, blood-testis barrier, Sertoli cells, Y chromosome microdeletion

Received: August 02, 2017    Accepted: August 28, 2017    Published: September 15, 2017

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.


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