title: Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue.
abstract: OBJECTIVE
  Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure.
  
  
  METHODS
  During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations.
  
  
  RESULTS
  Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage.
  
  
  CONCLUSIONS
  SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.
authors.affiliation: Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Grewenig
authors.affiliation: Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schuler
authors.affiliation: Department of Radiation Oncology, Saarland University, Homburg/Saar, Germany. Electronic address: claudia.ruebe@uks.eu.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Rübe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D008297:Male; D051379:Mice; D011829:Radiation Dosage; D012671:Seminiferous Tubules / Q000166:cytology; D013091:Spermatogenesis / Q000528:radiation effects*; D013093:Spermatogonia / Q000166:cytology* / Q000528:radiation effects*; D013234:Stem Cells / Q000528:radiation effects*; D013737:Testis; D013997:Time Factors