MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice
Autor: | Hisashi Oishi, Shosei Yoshida, Ahmed A. H. Abdellatif, Toshiaki Usui, Yu Kitadate, Walaa A Basha, Satoru Takahashi, Masafumi Muratani, Risa Okada, Kazunori Hasegawa, Atsuo Ogura, Hany A. El-Shemy, Hossam H. Shawki, Keiji Mochida |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Physiology Cellular differentiation Gene Expression lcsh:Medicine Biochemistry Epithelium Spermatocytes Animal Cells Reproductive Physiology Testis Medicine and Health Sciences Testosterone Testes Cell Cycle and Cell Division lcsh:Science Cells Cultured Mice Knockout Multidisciplinary Chromosome Biology Leydig Cells Cell Differentiation Seminiferous Tubules Sertoli cell Cell biology Meiosis medicine.anatomical_structure MAFB Cell Processes Proto-Oncogene Proteins c-maf Female Cellular Types Anatomy Genital Anatomy Germ cell Research Article Cell type endocrine system MafB Transcription Factor Biology 03 medical and health sciences DNA-binding proteins medicine Genetics Animals Gene Regulation RNA Messenger Transcription Factor MafB Spermatogenesis Sertoli Cells lcsh:R Reproductive System Biology and Life Sciences Proteins Epithelial Cells Cell Biology Embryonic stem cell Sperm Spermatogonia Regulatory Proteins Mice Inbred C57BL 030104 developmental biology Fertility Biological Tissue Germ Cells lcsh:Q Transcriptome Developmental Biology Transcription Factors |
Zdroj: | PLoS ONE, Vol 13, Iss 1, p e0190800 (2018) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafbfl/fl CAG-CreER™ (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells. |
Databáze: | OpenAIRE |
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