• PMID: 29324782
• Gene Name: MAFB
• Condition: Problems in fetal testis morphogenesis and spermatogenesis maintenance
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Problems in fetal testis morphogenesis and spermatogenesis maintenance

MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice

Shawki HH, Oishi H, Usui T, Kitadate Y, Basha WA, Abdellatif AM, Hasegawa K, Okada R, Mochida K, El-Shemy HA, Muratani M, Ogura A, Yoshida S, Takahashi S.

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-CreERâ„¢ (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. FAU - Shawki, Hossam H AU - Shawki HH AUID- ORCID: 0000-0002-1962-9701 AD - Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. AD - Department of Animal Genetic Resources, National Gene Bank, Giza, Egypt. FAU - Oishi, Hisashi AU - Oishi H AD - Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. AD - Department of Comparative and Experimental Medicine, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan. FAU - Usui, Toshiaki AU - Usui T AD - Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. FAU - Kitadate, Yu AU - Kitadate Y AD - Division of Germ Cell Biology, National Institute for Basic Biology, Okazaki, Japan. FAU - Basha, Walaa A AU - Basha WA AD - Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. FAU - Abdellatif, Ahmed M AU - Abdellatif AM AD - Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. FAU - Hasegawa, Kazunori AU - Hasegawa K AD - Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Okada, Risa AU - Okada R AD - Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan. FAU - Mochida, Keiji AU - Mochida K AD - BioResource Center, RIKEN, Tsukuba, Japan. FAU - El-Shemy, Hany A AU - El-Shemy HA AD - Cairo University Research Park, Cairo University, Giza, Egypt. FAU - Muratani, Masafumi AU - Muratani M AD - Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. FAU - Ogura, Atsuo AU - Ogura A AD - BioResource Center, RIKEN, Tsukuba, Japan. FAU - Yoshida, Shosei AU - Yoshida S AD - Division of Germ Cell Biology, National Institute for Basic Biology, Okazaki, Japan.