p53-mediated germ cell quality control in spermatogenesis.

Spontaneous germ cell death is a common cellular process in the mammalian testis, although the function of this process during spermatogenesis is unclear. An investigation was undertaken to determine whether p53 serves as a mechanism in germ cell quality control by causing spontaneous germ cell death. Using an annexin V assay, lower levels of spontaneous apoptosis were found in the testes of p53-/- mice compared to p53+/+ mice. Propidium iodine staining revealed that the greatest reduction in apoptosis and the largest increase in cell numbers occurred in the tetraploid germ cell population of p53-/- mice. Microscopic examination of sperm morphology showed an increased percentage of abnormal forms in p53-/- mice. Furthermore, p53-/- mice sired fewer offspring than p53+/+ mice did when both groups were mated with p53+/+ females. These results suggest that p53 mediates spontaneous testicular germ cell apoptosis and failure to remove defective germ cells by this mechanism results in increased percentages of abnormal sperm and reduced fertility. p53-mediated apoptosis may be an effector of cellular proofreading that acts to maintain the cellular integrity of germ cells during spermatogenesis.