Gamma-ray irradiation promotes premature meiosis of spontaneously differentiating testis–ova in the testis of p53-deficient medaka (Oryzias latipes)

Abstract

In this study, the roles of p53 in impaired spermatogenic male germ cells of p53-deficient medaka were investigated by analyzing histological changes, and gene expressions of 42Sp50, Oct 4 and vitellogenin (VTG2) by RT-PCR or in situ hybridization in the testes. We found that a small number of oocyte-like cells (testis–ova) differentiated spontaneously in the cysts of type A and early type B spermatogonia in the p53-deficient testes, in contrast to the wild-type (wt) testes in which testis–ova were never found. Furthermore, ionizing radiation (IR) irradiation increased the number of testis–ova in p53-deficient testes, increased testis–ova size and proceeded up to the zygotene or pachytene stages of premature meiosis within 14 days after irradiation. However, 28 days after irradiation, almost all the testis–ova were eliminated presumably by p53-independent apoptosis, and spermatogenesis was restored completely. In the wt testis, IR never induced testis–ova differentiation. This is the first study to demonstrate the pivotal role of the p53 gene in the elimination of spontaneous testis–ova in testes, and that p53 is not indispensable for the restoration of spermatogenesis in the impaired testes in which cell cycle regulation is disturbed by IR irradiation.

Tumor suppressor WWOX binds to ΔNp63α and sensitizes cancer cells to chemotherapy

“…This family of proteins play very important roles in cell differentiation stemness and plasticity, 30, 31, 32, 33 in immune response regulation, 34 in tumorigenesis and tumor suppression, 33, 35, 36, 37, 38 in development and reproduction, 39, 40 DNA damage, 41 and apoptosis and cell-cycle regulation. 33, 42, 43 In addition to regulating each other's function, 37, 44, 45 the functional outcome of these proteins are regulated by different mechanisms, including miRNAs, post-translational modifications, and protein–protein interactions.…”

Molecular dynamics of the full-length p53 monomer

“…[127][128][129] The more ancient members of the family include p73, involved in cancer, 130 neurodevelopment, 131,132 and aging, 133 and p63, involved in epidermal development, 119,[134][135][136] cancer, [137][138][139][140][141] reproduction, 142 and heart development. 143 Understanding the structural restrain of its structure is pivotal to understand the function of p53 [144][145][146] as well as its potential therapeutic exploitation. 147,148 The regulation of p53 protein half-life is crucial to his function 149,150 and, consequently, for cancer progression.…”

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