Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis

• Published in: Biology of reproduction Vol. 105; no. 4; pp. 958 - 975
• Main Authors: Li, Shu-Yun, Gu, Xiaowei, Heinrich, Anna, Hurley, Emily G, Capel, Blanche, DeFalco, Tony
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 01-10-2021; Oxford University Press
• Subjects: Animals; Cell differentiation; Developmental biology; Embryo, Mammalian - embryology; Embryos; Endothelial cells; Fetuses; Germ cells; gonad; Interstitial cells; Macrophages; Maf; Mafb; MafB Transcription Factor - genetics; MafB Transcription Factor - metabolism; Male; Mice; monocyte; Monocytes; Morphogenesis; Myeloid Cells - metabolism; Neomycin; Organogenesis; Organogenesis - genetics; Proto-Oncogene Proteins c-maf - genetics; Proto-Oncogene Proteins c-maf - metabolism; RESEARCH ARTICLE; Sertoli cells; Sex determination; Supernumerary; Testes; Testis - embryology; vascular remodeling; Vascularization; monocyte; morphogenesis; vascular remodeling; gonad; Maf; Mafb
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioab098

Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here, we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb; Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation. Summary sentence Deletion of Mafb and Maf genes leads to supernumerary monocytes in fetal mouse gonads, resulting in vascular, morphogenetic, and differentiation defects during testicular organogenesis.