Yu Jun, Xu Jinfu, Li Hong, Wu Pengfei, Zhu Shiyao, Huang Xiaoyan, Shen Cong, Zheng Bo, Li Wenqing
Institute of Reproductive Medicine, Medical School of Nantong University, Nantong University, Nantong 226001, China.
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China.
Ecotoxicol Environ Saf. 2023 Apr 15;255:114827. doi: 10.1016/j.ecoenv.2023.114827. Epub 2023 Mar 23.
Despite the rapidly growing interest in nanoparticle-mediated controllable male contraception and recovery of male fertility, novel applications of nanoparticles in these processes are limited by a knowledge gap regarding their transport and distribution in the testes. Here, we investigated the fate of gold nanoparticles in the mouse testes using two injection methods, namely, interstitial testicular injection (IT-AuNPs, AuNPs exposure in the interstitial compartment of the testes) and rete testis injection (RT-AuNPs, AuNPs exposure in the adluminal compartment of the seminiferous tubules). In this study, we used 100 nm spherical AuNPs and microinjected with 5 μL AuNPs (30 mg/mL) for the experiments. For IT-AuNP injection, we found that AuNPs could not penetrate through the Sertoli cell-mediated blood-testis barrier (BTB) of the seminiferous tubules, and no male reproductive toxicity was observed. For RT-AuNP injection, AuNPs could be retrogradely transported from the adluminal compartment to the interstitial compartment of the testes via Sertoli cell-mediated endocytosis/exocytosis, resulting in damage and the release of inflammatory cytokines in the mouse testis. Our results highlight a retrograde nanoparticle transport function of Sertoli cells, thereby providing a mechanistic overview of the development and use of nanobiotechnology in male reproduction. SYNOPSIS: This study provides new insights into male reproductive immunotoxicity for AuNPs exposure and elucidates a mechanism via Sertoli cell-mediated endocytosis/exocytosis.
尽管纳米颗粒介导的可控男性避孕和男性生育能力恢复越来越受到关注，但纳米颗粒在这些过程中的新应用受到其在睾丸中运输和分布知识空白的限制。在这里，我们使用两种注射方法研究了金纳米颗粒在小鼠睾丸中的命运，即睾丸间质注射（IT-AuNPs，纳米颗粒暴露于睾丸间质区）和睾丸网注射（RT-AuNPs，纳米颗粒暴露于生精小管的管腔面）。在本研究中，我们使用了100nm球形金纳米颗粒，并以5μL金纳米颗粒（30mg/mL）进行显微注射实验。对于IT-AuNP注射，我们发现金纳米颗粒无法穿透生精小管中支持细胞介导的血睾屏障（BTB），并且未观察到雄性生殖毒性。对于RT-AuNP注射，金纳米颗粒可通过支持细胞介导的内吞/外排作用从管腔面逆行运输到睾丸间质区，导致小鼠睾丸损伤并释放炎性细胞因子。我们的结果突出了支持细胞的纳米颗粒逆行运输功能，从而为纳米生物技术在男性生殖中的发展和应用提供了一个机制概述。摘要：本研究为金纳米颗粒暴露的男性生殖免疫毒性提供了新见解，并阐明了一种通过支持细胞介导的内吞/外排作用的机制。
