文章摘要

电离辐射对睾丸生殖功能的影响

作者: 1杨娟, 2曾慧红, 1邵立健
1 南昌大学公共卫生学院,江西省预防医学重点实验室,南昌大学预防医学研究所,南昌 330006
2 南昌大学基础医学院,南昌 330006
通讯: 邵立健 Email: lshao@ncu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2022.09.033
基金: 国家自然科学基金(82073484;81960104);江西省自然科学基金(2020ACB206009)。

摘要

电离辐射不仅发生在辐射性恐怖事件或核事故中,也广泛存在于医疗和日常生活中。目前大量研究集中在电离辐射导致的骨髓和消化道损伤防护,但对其在雄性生殖功能损伤的有效防护研究甚少。睾丸的正常生殖功能是维持雄性终生生育能力的根本,其位置浅且对电离辐射敏感,探究睾丸生殖功能的辐射损伤机制有助于提出高效的辐射损伤防护策略。精原干细胞是实现睾丸生殖功能的基础,在支持细胞和间质细胞等组成的干细胞微环境中生长发育,其功能受到胶质细胞源性神经营养因子(glial cell-derived neurotrophic factor,GDNF)和早幼粒细胞白血病锌指蛋白(promyelocytic leukemia zinc finger,PLZF)等多种因子的调节。电离辐射可通过DNA损伤、氧自由基、不同形式的细胞死亡、激活哺乳动物雷帕霉素靶复合物1(mammalian rapamycin target complex 1,mTORC1)和p38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase,p38 MAPK)等信号通路对精原细胞及其微环境造成损伤。因此,抑制细胞凋亡、抗氧化损伤、抑制mTORC1和p38 MAPK信号通路激活为现有的常见睾丸辐射损伤的防护措施。多肽类药物和精原干细胞移植等在电离辐射导致雄性生殖功能损伤防护中有较好的潜力。电离辐射导致雄性生殖功能损伤机制研究的深入有利于探索多种潜在且高效的睾丸辐射损伤防护新思路。
关键词: 电离辐射;睾丸;精原细胞;DNA损伤;氧自由基

Effects of ionizing radiation on testicular reproductive function

Authors: 1YANG Juan, 2ZENG Huihong, 1SHAO Lijian
1 School of Public Health; Jiangxi Provincial Key Laboratory of Preventive Medicine; Institute of Preventive Medicine, Nanchang University, Nanchang 330006, China
2 School of Basic Medicine, Nanchang University, Nanchang 330006, China

CorrespondingAuthor: SHAO Lijian Email: lshao@ncu.edu.cn

DOI: 10.3978/j.issn.2095-6959.2022.09.033

Foundation: This work was supported by the National Natural Science Foundation (82073484; 81960104) and Natural Science Foundation of Jiangxi Province (2020ACB206009), China.

Abstract

Ionizing radiation not only occurs in radiation terrorist events or nuclear accidents, but also widely exists in clinical practice and daily life. Presently, many studies have focused on the protection of bone marrow and gastrointestinal damage caused by ionizing radiation while there are few studies on its effective protection in male reproductive function damage upon exposure. The normal reproductive function of testis is essential to maintain male lifelong fertility. The location of testis is shallow with high sensitivity to ionizing radiation. Exploring mechanisms of testicular reproductive function damage induced by irradiation are beneficial to develop new countermeasures against radiation injury in testis. Spermatogonial stem cells are the basis for efficient testicular reproductive function. Spermatogonial stem cells develop and grow in the stem cell microenvironment which is composed of Sertoli cells and interstitial cells. Their function is regulated by many factors such as glial cell-derived neurotrophic factor (GDNF) and promyelocytic leukemia zinc finger (PLZF) protein. Ionizing radiation can damage spermatogonia and their microenvironment through DNA damage, oxygen free radicals, different forms of cell death, activation of mammalian rapamycin target complex 1 (mTORC1) and p38 mitogen activated protein kinase (p38 MAPK). Therefore, inhibition of apoptosis, antioxidants, inhibition of mTORC1 and p38 MAPK signal pathways are the existing common protective measures against radiation-induced testicular injury. Polypeptide drugs and spermatogonial stem cell transplantation have good potential in the protection of male reproductive function under ionizing radiation condition. With the in-depth study of the mechanism of male reproductive function damage caused by ionizing radiation, it will be helpful to explore a variety of potential and efficient new ideas for the protection of radiation-induced testicular injury.

Keywords: ionizing radiation; testis; spermatogonia; DNA damage; reactive oxygen species

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