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硫化氢作为预防生精失败和睾丸功能障碍的潜在靶点。

Hydrogen Sulfide As a Potential Target in Preventing Spermatogenic Failure and Testicular Dysfunction.

机构信息

1 State Key Laboratory of Reproductive Medicine, Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Department of Pharmacology, School of Pharmacy, Nanjing Medical University , Nanjing, People's Republic of China .

2 Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University , Nanjing, People's Republic of China .

出版信息

Antioxid Redox Signal. 2018 Jun 1;28(16):1447-1462. doi: 10.1089/ars.2016.6968. Epub 2017 Oct 16.

DOI:10.1089/ars.2016.6968
PMID:28537489
Abstract

AIMS

Testis and sperm are particularly susceptible to inflammation and oxidative stress. Although hydrogen sulfide (HS) has been considered an important biological signaling molecule in inflammatory and oxidative stress processes, its role in the male reproductive system was poorly understood. The aim of this study was to investigate the role of HS in the regulation of male reproductive system.

RESULTS

We found that both subfertile and infertile patients, especially asthenospermic patients, exhibited decreased concentration of HS in their seminal plasma and diminished expression of HS-generating enzyme (cystathionine β-synthase [CBS]) in sperm. Supplying exogenous HS to semen improved sperm motility of these asthenospermic patients. Furthermore, decreased sperm motility was observed in animal models with a defective in HS generation such as lipopolysaccharide-treated mice, diabetic mice, and CBS-deficient mice. Our research showed that stress-induced reductions of endogenous HS production and CBS expression are correlated with impaired spermatogenesis and a defective blood-testis barrier. Supplying exogenous HS or overexpressing CBS could relieve the spermatogenic failure. This occurred primarily through the combination of anti-inflammatory and antioxidative effects.

INNOVATION

These results provide the first indication that HS is important for maintaining male fertility and protecting testicular function.

CONCLUSION

HS plays an important role in spermatogenic failure and testicular dysfunction mainly by its anti-inflammatory and antioxidative effects. Antioxid. Redox Signal. 28, 1447-1462.

摘要

目的

睾丸和精子特别容易受到炎症和氧化应激的影响。尽管硫化氢 (HS) 已被认为是炎症和氧化应激过程中的一种重要生物信号分子,但它在男性生殖系统中的作用还知之甚少。本研究旨在探讨 HS 在男性生殖系统调节中的作用。

结果

我们发现,无论是生育能力低下还是不育患者,尤其是弱精子症患者,其精液中 HS 浓度降低,精子中 HS 生成酶(半胱氨酸 β-合成酶 [CBS])的表达减少。向精液中补充外源性 HS 可改善这些弱精子症患者的精子活力。此外,在 HS 生成缺陷的动物模型中,如脂多糖处理的小鼠、糖尿病小鼠和 CBS 缺陷小鼠中,观察到精子运动能力下降。我们的研究表明,应激诱导的内源性 HS 产生减少和 CBS 表达降低与精子发生受损和血睾屏障缺陷有关。补充外源性 HS 或过表达 CBS 可以缓解精子发生衰竭。这主要是通过抗炎和抗氧化作用的结合来实现的。

创新点

这些结果首次表明 HS 对于维持男性生育力和保护睾丸功能很重要。

结论

HS 通过其抗炎和抗氧化作用在精子发生衰竭和睾丸功能障碍中发挥重要作用。抗氧化还原信号 28, 1447-1462。

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