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

Olaquindox disrupts tight junction integrity and cytoskeleton architecture in mouse Sertoli cells. Oncotarget. 2017 Oct 24;8(51):88630-88644 Authors: Wu D, Huang CJ, Jiao XF, Ding ZM, Zhang JY, Chen F, Wang YS, Li X, Huo LJ Abstract 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-treat...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research