Bisphenol S perturbs Sertoli cell junctions in male rats via alterations in cytoskeletal organization mediated by an imbalance between mTORC1 and mTORC2.

Huan Wu, Yuexin Wei, Yu Zhou, Chunlan Long, Yifan Hong, Yan Fu, Tianxin Zhao, Junke Wang, Yuhao Wu, Shengde Wu, Lianju Shen, Guanghui Wei

The Science of the total environment 2021 Mar 25

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Bisphenol S (BPS) is now used as an alternative of bisphenol A (BPA), but has been implicated in male reproductive dysfunction-including diminished sperm number and quality and altered hormonal concentrations. However, the mechanisms of action subserving these effects remains unclear. In the present study, BPS at doses of 50 mg/kg bw and 100 mg/kg bw caused defects in the integrity of the blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), and we also delineated an underlying molecular mechanism of action. BPS induced F-actin and α-tubulin disorganization in seminiferous tubules, which in turn led to the truncation of actin filaments and microtubules. Additionally, BPS was found to perturb the expression of the actin-binding proteins Arp3 and Eps8, which are critical for the organization of the actin filaments. mTORC1 and mTORC2 manifest opposing roles in Sertoli cell junctional function, and we demonstrated that mTORC1/rpS6/Akt/MMP9 signaling was increased and that mTORC2/rictor activity was also attenuated. In summary, we showed that BPS-induced disruption of the BTB and apical ES perturbed normal spermatogenic function that was mediated by mTORC1 and mTORC2. The imbalance in mTORC1 and mTORC2, in turn, altered the expression of actin-binding proteins, resulting in the impairment of F-actin and MT organization, and inhibited the expression of junctional proteins at the BTB and apical ES. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Huan Wu, Yuexin Wei, Yu Zhou, Chunlan Long, Yifan Hong, Yan Fu, Tianxin Zhao, Junke Wang, Yuhao Wu, Shengde Wu, Lianju Shen, Guanghui Wei. Bisphenol S perturbs Sertoli cell junctions in male rats via alterations in cytoskeletal organization mediated by an imbalance between mTORC1 and mTORC2. The Science of the total environment. 2021 Mar 25;762:144059