The male germline-specific protein MAPS is indispensable for pachynema progression and fertility
| Autor: | Gaopeng Li, Raymond H.W. Li, Chunsheng Han, Dandan Cao, Kui Liu, Jiahuan Zheng, William S.B. Yeung, Zexiong Lin, Haiwei Feng, Louise T. Chow, M. Li, Dongteng Liu, Dongliang Li, Ernest Hung Yu Ng, Hengbin Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cell division DNA Repair Somatic cell Spermatocyte Biology Germline Mice Meiosis meiosis prophase I Spermatocytes Gene expression MAPS medicine male germline-specific protein Animals Spermatogenesis Gene Infertility Male Mice Knockout Multidisciplinary Sex Chromosomes Nuclear Proteins Biological Sciences Protein ubiquitination pachynema progression Cell biology Mice Inbred C57BL Chromosome Pairing medicine.anatomical_structure Female Pachytene Stage Developmental Biology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance During meiosis prophase I in mammals, a series of events occur, such as homologous recombination, DSB repair, crossover formation, XY body formation, and meiotic sex chromosome inactivation (MSCI). We report here that a male pachynema-specific (MAPS) protein is essential for prophase I progression in mouse spermatocytes. Maps knockout causes the demise of pachytene spermatocytes throughout early to mid- and late pachynema, resulting in male but not female infertility. Moreover, protein ubiquitination was dramatically increased in Maps−/− pachytene spermatocytes, likely contributing to the dysregulated global gene expression, including failed MSCI. In summary, MAPS is an indispensable protein for male fertility. Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail 1700102P08Rik, one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking Maps (Maps−/−) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal Maps−/− spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult Maps−/− spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult Maps−/− pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in Maps−/− pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general. |
| Databáze: | OpenAIRE |
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