Characterization and differentiation of CD51+ Stem Leydig cells in adult mouse testes

Chen, Panpan; Guan, Xiaoju; Zhao, Xingxing; Chen, Fen-Fen; Yang, Jianying; Wang, Yiyan; Hu, Yue; Lian, Qingquan; Chen, Haolin

doi:10.1016/j.mce.2019.110449

Cited by 13 publications

(24 citation statements)

References 36 publications

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“…Total RNA was extracted with RNeasy ® Mini Kit (Qiagen, Germany) according to the manufacturer’s instructions. cDNA and QPCR analyses were performed as previously reported ( 49 ). We analyzed the mRNA levels of testicular cell marker genes of LCs ( Lhcgr , Star , Cyp11a1 , Cyp17a1 , Hsd3b1 , and Insl3 ), SLCs ( Gli1 , Cd90 , and Pdgfra ), immune cells ( Ptprc ), macrophages ( Adgre1 ), smooth muscle cells ( Acta2 ), germ cells ( Smc1b and Ddx4 ), vascular endothelial cells ( Vwf ), and Sertoli cells ( Sox9 ).…”

Section: Methodsmentioning

confidence: 99%

“…We analyzed the mRNA levels of testicular cell marker genes of LCs ( Lhcgr , Star , Cyp11a1 , Cyp17a1 , Hsd3b1 , and Insl3 ), SLCs ( Gli1 , Cd90 , and Pdgfra ), immune cells ( Ptprc ), macrophages ( Adgre1 ), smooth muscle cells ( Acta2 ), germ cells ( Smc1b and Ddx4 ), vascular endothelial cells ( Vwf ), and Sertoli cells ( Sox9 ). The mRNA levels of ribosomal protein S16 ( Rps16 ) were used as internal controls, and the Ct value of target genes was normalized to that of Rps16 as described ( 49 ).…”

Section: Methodsmentioning

confidence: 99%

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Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells In Vitro

Zhao

Wen

et al. 2021

Front. Endocrinol.

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BackgroundMidazolam is a neurological drug with diverse functions, including sedation, hypnosis, decreased anxiety, anterograde amnesia, brain-mediated muscle relaxation, and anticonvulsant activity. Since it is frequently used in children and adolescents for extended periods of time, there is a risk that it may affect their pubertal development. Here, we report a potential effect of the drug on the development of Leydig cells (LCs), the testosterone (T)-producing cells in the testis.MethodsStem LCs (SLCs), isolated from adult rat testes by a magnetic-activated cell sorting technique, were induced to differentiate into LCs in vitro for 3 weeks. Midazolam (0.1–30 μM) was added to the culture medium, and the effects on LC development were assayed.ResultsMidazolam has dose-dependent effects on SLC differentiation. At low concentrations (0.1–5 μM), the drug can mildly increase SLC differentiation (increased T production), while at higher concentrations (15–30 μM), it inhibits LC development (decreased T production). T increases at lower levels may be due to upregulations of scavenger receptor class b Member 1 (SCARB1) and cytochrome P450 17A1 (CYP17A1), while T reductions at higher levels of midazolam could be due to changes in multiple steroidogenic proteins. The uneven changes in steroidogenic pathway proteins, especially reductions in CYP17A1 at high midazolam levels, also result in an accumulation of progesterone. In addition to changes in T, increases in progesterone could have additional impacts on male reproduction. The loss in steroidogenic proteins at high midazolam levels may be mediated in part by the inactivation of protein kinase B/cAMP response element-binding protein (AKT/CREB) signaling pathway.ConclusionMidazolam has the potential to affect adult Leydig cell (ALC) development at concentrations comparable with the blood serum levels in human patients. Further studies are needed to test the effects on human cells.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells In Vitro

Zhao

Wen

et al. 2021

Front. Endocrinol.

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“…In addition to LC lineage, mouse- and human-derived SLCs have also been successfully differentiated into neurons, astrocytes, osteocytes, adipocytes, and chondrocytes in vitro . 27 28 29 30 31 32 …”

Section: Generation Of Testosterone-producing Leydig-like Cells ...mentioning

confidence: 99%

“…Mouse SLCs have been isolated from adult C57BL/6 mouse testes by sorting nestin + - or CD51 + -expressing cells. 27 28 29 30 The cells can be differentiated into Leydig-like cells using differentiation-inducing medium (M199 medium containing bovine serum albumin, ITS, LH and the smoothened agonist). Compared with rat cells, the mouse cells are easier and faster to differentiate in vitro under the same culture conditions.…”

Section: Generation Of Testosterone-producing Leydig-like Cells ...mentioning

confidence: 99%

Generation of Leydig-like cells: approaches, characterization, and challenges

et al. 2022

Asian J Androl

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Testosterone production by Leydig cells (LCs) plays a crucial role in male reproduction. The functional degeneration of LCs can cause testosterone deficiency, ultimately resulting in primary male hypogonadism. Transplantation of exogenous LCs with the ability to produce testosterone in response to the regulation of the hypothalamus–pituitary–gonad axis could be a promising alternative option to treat male primary hypogonadism. Recent studies have shown that it is possible to generate Leydig-like cells from stem cells by various approaches. In addition, somatic cells, such as embryonic or adult fibroblasts, have also been successfully reprogrammed into Leydig-like cells. In this review, we summarized the recent advances in the generation of Leydig-like cells, with an emphasis on comparing the effectiveness and safety of different protocols used and the cells generated. By further analyzing the characteristics of Leydig-like cells generated from fibroblasts based on small signaling molecules and regulatory factors, we found that although the cells may produce testosterone, they are significantly different from real LCs. For future in vivo applications, it is important that the steroidogenic cells generated be evaluated not only for their steroidogenic functions but also for their overall cell metabolic state by proteomics or transcriptomic tools.

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“…6 Fifty-six days after EDS, ALCs are fully regenerated and the ability to produce T has also been completely restored. 6 Although several growth factors such as platelet-derived growth factors 7 and desert hedgehog 8 and cytokines (interleukin-6 9 and oncostatin M 10 ) have been identified to regulate the regeneration of ALCs (see review 2), other factors may also determine the development of SLCs into the Leydig cell lineage.…”

Section: Introductionmentioning

confidence: 99%

Characterization and differentiation of CD51+ Stem Leydig cells in adult mouse testes

Cited by 13 publications

References 36 publications

Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells In Vitro

Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells In Vitro

Generation of Leydig-like cells: approaches, characterization, and challenges

Neurotrophin‐3 stimulates stem Leydig cell proliferation during regeneration in rats

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