Protection of Murine Spermatogenesis Against Ionizing Radiation-Induced Testicular Injury by a Green Tea Polyphenol
Protection of Murine Spermatogenesis Against Ionizing Radiation-Induced Testicular Injury by a Green Tea Polyphenol
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DOI：
10.1095/biolreprod.114.122333
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Li, Wei
中科院分区：
文献类型：
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作者：
Ding, Jin;Wang, Hui;Li, Wei
表没食子儿茶素没食子酸酯(EGCG)是绿茶中的一种生物活性多酚，在不同的刺激下具有抗细胞凋亡和防止组织损伤的作用。在这里，我们研究了EGCG治疗在电离辐射(IR)(剂量为2Gy时)后同时促进精子发生的效果。照射前3d给小鼠腹腔注射EGCG50 mg/kg或赋形剂对照组，间歇给药24d。补充外源性EGCG可防止短期生殖细胞丢失，并减轻IR引起的睾丸氧化应激。从机制上讲，EGCG对IR应激的生存效应至少部分是通过丝裂原活化蛋白激酶/bcl2家族/caspase3途径来调节的。一贯地，在IR后第21天，组织学分析显示照射后睾丸的小管损伤、生殖细胞脱屑和尾部参数受损，间歇性EGCG治疗可以显著改善这些情况。此外，长期应用EGCG可改善IR引起的血-睾丸屏障通透性，抑制睾丸类固醇激素的生成，从而促进生精功能的恢复。总体而言，EGCG似乎通过多种机制有效地防止生殖细胞受到辐射诱导的细胞死亡。使用这种具有生物活性的多酚应该是一种有吸引力的策略，以保护接受常规放射治疗的男性的生育能力，并值得进一步研究。
Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol in green tea, exerts antiapoptotic activity and prevents tissue damage against different stimuli. Herein, we investigated the effects of EGCG treatment to simultaneously improve spermatogenesis following ionizing radiation (IR) (at a dose of 2 Gy). Mice were intraperitoneally injected with 50 mg/kg EGCG or vehicle control 3 days prior to the irradiation, and the treatment lasted intermittently for 24 days. Supplement with exogenous EGCG protected against short-term germ cell loss and attenuated IR-elicited testicular oxidative stress. Mechanistically, prosurvival effects of EGCG treatment upon IR stress were regulated, at least in part, via the mitogen-activated protein kinase/BCL2 family/caspase 3 pathway. Consistently, at post-IR Day 21, histological analyses revealed tubule damage, desquamation of germ cells, and impairment of caudal parameters in irradiated testis, which could be significantly improved by intermittent EGCG treatment. In addition, long-term EGCG application ameliorated the IR-induced blood-testicular barrier permeability and suppressed testicular steroidogenesis, thus exerting a stimulatory effect on the spermatogenic recovery. Collectively, EGCG appeared to efficiently prevent germ cells from radiation-induced cell death via multiple mechanisms. Employment of this bioactive polyphenol should be an attractive strategy to preserve fertility in males exposed to conventional radiation therapy and warrants further investigation.