Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Sci Total Environ. 2021 Mar 25;762:144059. doi: 10.1016/j.scitotenv.2020.144059. Epub 2020 Dec 14.
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.
双酚 S（BPS）现在被用作双酚 A（BPA）的替代品，但已被牵连到男性生殖功能障碍中，包括精子数量和质量下降以及激素浓度改变。然而，这些作用的作用机制仍不清楚。在本研究中，BPS 的剂量为 50mg/kg bw 和 100mg/kg bw 时，会导致血睾屏障（BTB）和顶端质膜特化（ES）的完整性受损，我们还描绘了其潜在的作用机制。BPS 诱导生精小管中的 F-肌动蛋白和α-微管蛋白解聚，进而导致肌动蛋白丝和微管的截断。此外，发现 BPS 扰乱了肌动蛋白结合蛋白 Arp3 和 Eps8 的表达，这对于肌动蛋白丝的组织至关重要。mTORC1 和 mTORC2 在支持细胞连接功能方面表现出相反的作用，我们证明 mTORC1/rpS6/Akt/MMP9 信号通路增加，而 mTORC2/rictor 活性也减弱。总之，我们表明，BPS 诱导的 BTB 和顶端 ES 破坏会干扰正常的精子发生功能，这是由 mTORC1 和 mTORC2 介导的。mTORC1 和 mTORC2 的失衡反过来又改变了肌动蛋白结合蛋白的表达，导致 F-肌动蛋白和 MT 组织受损，并抑制了 BTB 和顶端 ES 处连接蛋白的表达。
