Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Center of Reproductive Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Curr Drug Deliv. 2020;17(5):438-446. doi: 10.2174/1567201817666200514080811.
To investigate the application of Scrotal Heat Stress (SHS) and Pulsed Unfocused Ultrasound (PuFUS) to explore Blood-Testis Barrier (BTB) permeability in adult mice.
The BTB provides a stable microenvironment and a unique immune barrier for spermatogenesis. Meanwhile, it blocks macromolecular substances access, including therapeutic agents and antibodies, thereby it decreases the therapeutic or immunocontraception effects.
To determine the viability of these physical approaches in delivering macromolecular substances into seminiferous tubules.
MATERIALS & METHODS: Mice were subjected to receive single SHS intervention at 39°C, 41°C, or 43°C for 30 min. Whereas, mice received the PuFUS intervention at 1.75w/cm2, 1.25w/cm2, and 2.5w/cm2 for 2 min, 5 min, and 10 min, respectively. The Biotin and macromolecular substances (IgG, IgM, and exosomes) were separately injected into the testicular interstitium at different times following SHS or PuFUS interventions, to observe their penetration through BTB into seminiferous tubules.
As detected by Biotin tracer, the BTB opening started from day-2 following the SHS and lasted for more than three days, whereas the BTB opening started from 1.5h following PuFUS and lasted up to 24h. Apparent penetration of IgG, IgM, and exosomes into seminiferous tubules was observed after five days of the SHS at 43°C, but none at 39°C, or any conditions tested with PuFUS.
The current results indicate that SHS at 43°C comparatively has the potential for delivering macromolecular substances into seminiferous tubules, whereas the PuFUS could be a novel, quick, and mild approach to open the BTB. These strategies might be useful for targeted drug delivery into testicular seminiferous tubules. However, further studies are warranted to validate our findings.
探讨阴囊热应激（SHS）和脉冲非相干超声（PuFUS）在成年小鼠血睾屏障（BTB）通透性研究中的应用。
BTB 为精子发生提供了稳定的微环境和独特的免疫屏障。同时，它阻止大分子物质进入，包括治疗剂和抗体，从而降低治疗或免疫避孕的效果。
确定这些物理方法在将大分子物质递送到生精小管中的可行性。
将小鼠分别接受 39°C、41°C 或 43°C 单次 SHS 干预 30 分钟。而小鼠则分别接受 1.75w/cm2、1.25w/cm2 和 2.5w/cm2 的 PuFUS 干预 2 分钟、5 分钟和 10 分钟。在 SHS 或 PuFUS 干预后不同时间将生物素和大分子物质（IgG、IgM 和外泌体）分别注入睾丸间质，观察其穿透 BTB 进入生精小管。
通过生物素示踪剂检测到，SHS 后第 2 天开始出现 BTB 开放，持续超过 3 天，而 PuFUS 后 1.5 小时开始出现 BTB 开放，持续至 24 小时。在 SHS 于 43°C 下进行 5 天后，明显观察到 IgG、IgM 和外泌体穿透进入生精小管，但在 39°C 或任何 PuFUS 测试条件下均未观察到。
目前的结果表明，43°C 的 SHS 具有将大分子物质递送到生精小管的潜力，而 PuFUS 可能是一种新的、快速、温和的打开 BTB 的方法。这些策略可能有助于将靶向药物递送到睾丸生精小管中。然而，需要进一步的研究来验证我们的发现。
