Protection of murine spermatogenesis against ionizing radiation-induced testicular injury by a green tea polyphenol.
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.
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi'an, People's Republic of China.
Jin
J
Ding
School of Preclinical Medicine, Fourth Military Medical University, Xi'an, People's Republic of China.
Hui
H
Wang
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
Zhen-Biao
ZB
Wu
Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi'an, People's Republic of China.
Jie
J
Zhao
Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Shun
S
Zhang
Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi'an, People's Republic of China liweipepeyato@163.com.
Wei
W
Li
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011832:Radiation Injuries / Q000517:prevention & control*; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects* / Q000528:radiation effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects
D011837:Radiation-Protective Agents; D002392:Catechin; C045651:epigallocatechin gallate
apoptosis; epigallocatechin-3-gallate (EGCG); ionizing radiation (IR); oxidative stress; spermatogenesis