RAD51 plays a crucial role in halting cell death program induced by ionizing radiation in bovine oocytes

Loro L. Kujjo, Reg Ronningen, Pablo Ross, Ricardo J G Pereira, Ramon Rodriguez, Zeki Beyhan, Marcelo D. Goissis, Thomas Baumann, Wataru Kagawa, Cagri Camsari, George W. Smith, Hitoshi Kurumizaka, Shigeyuki Yokoyama, Jose B. Cibelli, Gloria I. Perez

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Abstract

Reproductive health of humans and animals exposed to daily irradiants from solar/cosmic particles remains largely understudied. We evaluated the sensitivities of bovine and mouse oocytes to bombardment by krypton-78 (1 Gy) or ultraviolet B (UV-B; 100 microjoules). Mouse oocytes responded to irradiation by undergoing massive activation of caspases, rapid loss of energy without cytochrome-c release, and subsequent necrotic death. In contrast, bovine oocytes became positive for annexin-V, exhibited cytochrome-c release, and displayed mild activation of caspases and downstream DNAses but with the absence of a complete cell death program; therefore, cytoplasmic fragmentation was never observed. However, massive cytoplasmic fragmentation and increased DNA damage were induced experimentally by both inhibiting RAD51 and increasing caspase 3 activity before irradiation. Microinjection of recombinant human RAD51 prior to irradiation markedly decreased both cytoplasmic fragmentation and DNA damage in both bovine and mouse oocytes. RAD51 response to damaged DNA occurred faster in bovine oocytes than in mouse oocytes. Therefore, we conclude that upon exposure to irradiation, bovine oocytes create a physiologically indeterminate state of partial cell death, attributed to rapid induction of DNA repair and low activation of caspases. The persistence of these damaged cells may represent an adaptive mechanism with potential implications for livestock productivity and long-term health risks associated with human activity in space.

Original languageEnglish
Article number76
JournalBiology of Reproduction
Volume86
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1
Externally publishedYes

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Keywords

  • Apoptosis
  • Bovine
  • Female germ cells
  • Ionizing radiation
  • Mouse
  • Oocytes
  • RAD51
  • Solar/cosmic radiation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kujjo, L. L., Ronningen, R., Ross, P., Pereira, R. J. G., Rodriguez, R., Beyhan, Z., Goissis, M. D., Baumann, T., Kagawa, W., Camsari, C., Smith, G. W., Kurumizaka, H., Yokoyama, S., Cibelli, J. B., & Perez, G. I. (2012). RAD51 plays a crucial role in halting cell death program induced by ionizing radiation in bovine oocytes. Biology of Reproduction, 86(3), [76]. https://doi.org/10.1095/biolreprod.111.092064