Metastasis tumor antigen 1 (MTA1) might contribute to maintain the cellular integrity of germ cells by coordination with p53 through EGF-pathway stimulation during spermatogenesis

DNA quality control is expected to be highly regulated in tetraploid spermatocytes, since chromosome crossover, which involves DNA strand break, transfer, and renaturation, is an active event at this stage of germ cell development. p53-mediated apoptosis is an effector of cellular proofreading that acts to maintain the cellular integrity of germ cells during spermatogenesis and the highest levels of testicular p53 are found in tetraploid spermatocytes. MTA1 has been previously implicated in cellular transformation through its ability to regulate the epithelial-to-mesenchymal transition and to enhance metastasis. MTA1 is a component of the Mi-2/nucleosome remodeling and deacetylating (NURD) complex that contains both histone deacetylase and nucleosome remodeling activity, and its expression and deacetylase activity could be remarkably upregulated by the stimulation of epidermal growth factor (EGF). Recent studies revealed that MTA1 inhibits p53-induced apoptosis in both cancer cells and testicular function. All these observations lent support to the hypotheses that up-regulation of MTA1 by EGF might repress testicular expression of p53 and lead to low abundance of p53 expression during adult spermatogenesis. This repression as well as p53-mediated apoptosis may play important roles in the regulation of homeostasis of germ cell proliferation and death. Further investigation in this field is urgently requested.