||Miki Inoue, Yuichi Shima, Kanako Miyabayashi, Kaori Tokunaga, Tetsuya Sato, Takashi Baba, Yasuyuki Ohkawa, Haruhiko Akiyama, Mikita Suyama, Ken-Ichirou Morohashi, Isolation and characterization of Fetal Leydig progenitor cells of male mice, Endocrinology, 10.1210/en.2015-1773, 157, 3, 1222-1233, 2016.03, Fetal and adult Leydig cells develop in mammalian prenatal and postnatal testes, respectively. In mice, fetal Leydig cells (FLCs) emergeintheinterstitial spaceofthe testisatembryonic day 12.5 and thereafter increase in number, possibly through differentiation from progenitor cells. However, the progenitor cells have not yet been identified. Previously, we established transgenic mice in which FLCs are labeled strongly with enhanced green fluorescent protein (EGFP). Interestingly, fluorescence-activated cell sorting provided us with weakly EGFP-labeled cells as well as strongly EGFP-labeled FLCs. In vitro reconstruction of fetal testes demonstrated that weakly EGFP-labeled cells contain FLC progenitors. Transcriptome from the 2 cell populations revealed, as expected, marked differences in the expression of genes required for growth factor/receptor signaling and steroidogenesis. In addition, genes for energy metabolisms such as glycolytic pathways and the citrate cycle were activated in strongly EGFP-labeled cells, suggesting that metabolism is activated during FLC differentiation..
||Kanako Miyabayashi, Yuichi Shima, Miki Inoue, Tetsuya Sato, Takashi Baba, Yasuyuki Ohkawa, Mikita Suyama, Ken-Ichirou Morohashi, Alterations in Fetal Leydig Cell Gene Expression during Fetal and Adult Development, Sexual Development, 10.1159/000453323, 11, 2, 53-63, 2017.05, Fetal Leydig cells (FLCs) and adult Leydig cells (ALCs) develop in the mammalian prenatal and postnatal testes, respectively. In mice, FLCs emerge in the interstitial space of the testis as early as embryonic day 12.5 and thereafter increase in number during the fetal stage. We previously established a transgenic mouse line in which FLCs are labeled with EGFP and demonstrated that the EGFP-labeled FLCs were present even in adult testes. However, the characteristics of FLCs during postnatal stages remained unclear. In the present study, a comparison of the transcriptomes of FLCs from prenatal and postnatal testes and of ALCs from adult testes revealed that FLCs gradually alter their characteristics across developmental stages and come to roughly resemble ALCs. Many cholesterogenic genes simultaneously expressed a unique alternation pattern, while many oxidative phosphorylation and β-oxidation (both mitochondrial functions) genes showed a different unique pattern. These metabolic gene expression alterations might be triggered by milieu changes, such as nutrient and oxygen supply, from the prenatal to the postnatal period..
||Miki Inoue, Takashi Baba, Ken-ichirou Morohashi, Recent progress in understanding the mechanisms of Leydig cell differentiation, Molecular and Cellular Endocrinology, 10.1016/j.mce.2017.12.013, 468, 39-46, 2018.06, Leydig cells in fetal and adult testes play pivotal roles in eliciting male characteristics by producing androgen. Although numerous studies of Leydig cells have been performed, the mechanisms for differentiation of the two cell types (fetal Leydig and adult Leydig cells), their developmental and functional relationship, and their differential characteristics remain largely unclear. Based on recent technical progress in genome-wide analysis and in vitro investigation, novel and fascinating observations concerning the issues above have been obtained. Focusing on fetal and adult Leydig cells, this review summarizes the recent progress that has advanced our understanding of the cells..