Consequences of irradiation on adult spermatogenesis: Between infertility and hereditary risk

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• 作者：Henri-Baptiste Marjault ; Isabelle Allemand ; ^{isabelle.allemand@cea.fr}
• 关键词：ABCG2 ; ATP binding cassette subfamily G member 2 ; alt-EJ ; alternative end joining ; ATM ; ataxia telangiectasia mutated ; ATR ; ataxia telangiectasia and Rad3 related ; Aundiff ; undifferentiated spermatogonia ; DDR ; DNA damage response ; BAX ; BCL2-associated X protein ; DNA-PK ; protein kinase DNA activated catalytic polypeptide ; DSBs ; DNA double-strand breaks ; IR ; ionizing radiation ; GSCs ; germinal stem cells ; HSCs ; hematopoietic stem cells ; NHEJ ; non-homologous end joining ; MDC1 ; mediator of DNA damage
• 刊名：Mutation Research/Reviews in Mutation Research
• 出版年：2016
• 出版时间：October-December 2016
• 年：2016
• 卷：770
• 期：part_PB
• 页码：340-348
• 全文大小：965 K
• 卷排序：770

文摘

DNA damage response in adult spermatogenic cells should limit the propagation of mutations to the offspring, without being detrimental to fertility. In differentiating spermatogenic cells, the genomic instability is limited in time, whereas in spermatogonial stem cells it can be maintained all along life. Spermatogonial stem cells are long-lived cells that support normal germ cell differentiation and must be preserved throughout life. However after irradiation spermatogenesis recovery can be impaired as a consequence of the radiation-induced decline in spermatogonial stem cell. In this review, we summarize the differential sensitivities to DNA damage of spermatogenic cell populations, and the DNA repair mechanisms activated in these cells that paradoxically might favour the maintenance of cells with impaired genomic integrity. We describe how the testis tissue collapses in response to irradiation and we discuss the molecular pathways involved in the control of DNA damage response and homeostasis in spermatogonial stem cells.