BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice

Guogang Xu, Kristine S. Vogel, C. Alex McMahan, Damon C. Herbert, Christi A. Walter

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wildtype mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis.

Original languageEnglish (US)
Pages (from-to)979-987
Number of pages9
JournalBiology of reproduction
Volume83
Issue number6
DOIs
StatePublished - Dec 1 2010

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Keywords

  • Apoptosis
  • Gamete biology
  • Ionizing radiation
  • Mutant frequency
  • Spermatogenesis

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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