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Oncotarget. 2017 Aug 16;8(51):88630-88644. doi: 10.18632/oncotarget.20289. eCollection 2017 Oct 24.

Olaquindox disrupts tight junction integrity and cytoskeleton architecture in mouse Sertoli cells.

Wu D1,2, Huang CJ1,2, Jiao XF1,2, Ding ZM1,2, Zhang JY1,2, Chen F1,2, Wang YS1,2, Li X1,2, Huo LJ1,2.

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Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
Department of Hubei Province Engineering Research Center in Buffalo Breeding and Products, Wuhan 430070, Hubei, China.


Sertoli cells, by creating an immune-privileged and nutrition supporting environment, maintain mammalian spermatogenesis and thereby holds the heart of male fertility. Olaquindox, an effective feed additive in livestock industry, could potentially expose human into the risk of biological hazards due to its genotoxicity and cytotoxicity, highlighting the significance of determining its bio-safety regarding human reproduction. Herein, we deciphered the detrimental effects of olaquindox on male fertility by mechanistically unraveling how olaquindox intervenes blood-testis barrier in mouse. Olaquindox (400 μg/ml) exposure significantly compromised tight junction permeability function, decreased or dislocated the junction proteins (e.g., ZO-1, occludin and N-cadherin) and attenuated mTORC2 signaling pathway in primary Sertoli cells. Furthermore, olaquindox disrupted F-actin architecture through interfering with the expression of actin branching protein complex (CDC42-N-WASP-Arp3) and actin bunding protein palladin. Olaquindox also triggered severely DNA damage and apoptosis while inhibiting autophagic flux in Sertoli cell presumably due to the exacerbated generation of reactive oxygen species (ROS). Pre-treatment with antioxidant N-acetylcysteine effectively ameliorated olaquindox-induced exhaustion of ZO-1 and N-Cadherin proteins, DNA damage and apoptosis. More significantly, olaquindox disrupted the epigenetic status in Sertoli cells with hypermethylation and concomitantly hypoacetylation of H3K9 and H3K27. Overall, our study determines olaquindox targets Sertoli cells to affect BTB function through tight junction proteins and F-actin orgnization, which might disrupt the process of spermatogenesis.


Sertoli cell; blood-testis barrier; cytoskeleton; olaquindox; tight junction

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interests.

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