Cellular nucleic acid-binding protein is vital to testis development and spermatogenesis in mice

Zheng, Bo; Yu, Jun; Guo, Yueshuai; Gao, Tingting; Shen, Cong; Zhang, Xi; Li, Hong; Huang, Xiaoyan

doi:10.1530/rep-17-0666

Cited by 27 publications

(15 citation statements)

References 36 publications

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“…Cells were harvested, fixed in 4% (w/v) paraformaldehyde (PFA), blocked with 2% bovine serum albumin (BSA) (w/v) (Sigma) for 45 min at RT, and incubated with primary antibodies (Supplementary Table 1) overnight at 4 • C according to a previously reported protocol (Zheng et al, 2018;Zhao et al, 2019). Next, the cells were rinsed with PBS and incubated with Alexa Fluor-conjugated secondary antibodies (Thermo Scientific) for 45 min.…”

Section: Immunofluorescencementioning

confidence: 99%

BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway

et al. 2021

Front. Cell Dev. Biol.

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Testosterone biosynthesis progressively decreases in aging males primarily as a result of functional changes to Leydig cells. Despite this, the mechanisms underlying steroidogenesis remain largely unclear. Using gene knock-out approaches, we and others have recently identified Bmi1 as an anti-aging gene. Herein, we investigate the role of BMI1 in steroidogenesis using mouse MLTC-1 and primary Leydig cells. We show that BMI1 can positively regulate testosterone production. Mechanistically, in addition to its known role in antioxidant activity, we also report that p38 mitogen-activated protein kinase (MAPK) signaling is activated, and testosterone levels reduced, in BMI1-deficient cells; however, the silencing of the p38 MAPK pathway restores testosterone production. Furthermore, we reveal that BMI1 directly binds to the promoter region of Map3k3, an upstream activator of p38, thereby modulating its chromatin status and repressing its expression. Consequently, this results in the inhibition of the p38 MAPK pathway and the promotion of steroidogenesis. Our study uncovered a novel epigenetic mechanism in steroidogenesis involving BMI1-mediated gene silencing and provides potential therapeutic targets for the treatment of hypogonadism.

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Section: Immunofluorescencementioning

confidence: 99%

BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway

et al. 2021

Front. Cell Dev. Biol.

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“…In this process, spermatogonial stem cells (SSCs) are triggered to produce spermatogonia, which will transform to spermatocytes, spermatids, and finally mature spermatozoa 2,3 . The migration of germ cells (GCs) and the release of spermatozoa require timely cell junctions disassemble and reassemble between Sertoli cells-Sertoli cells (SCs-SCs) and SCs-GCs 4,5 . Such adherens junctions (AJs) are named as ectoplasmic specializations (ES) in the testis, and are divided into the basal ES at the SCs-SCs interface and the apical ES at the SCs-spermatids interface 6 .…”

Section: Introductionmentioning

confidence: 99%

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

2019

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The functions of Sertoli cells in spermatogenesis have attracted much more attention recently. Normal spermatogenesis depends on Sertoli cells, mainly due to their influence on nutrient supply, maintenance of cell junctions, and support for germ cells’ mitosis and meiosis. Accumulating evidence in the past decade has highlighted the dominant functions of the MAPK, AMPK, and TGF-β/Smad signaling pathways during spermatogenesis. Among these pathways, the MAPK signaling pathway regulates dynamics of tight junctions and adherens junctions, proliferation and meiosis of germ cells, proliferation and lactate production of Sertoli cells; the AMPK and the TGF-β/Smad signaling pathways both affect dynamics of tight junctions and adherens junctions, as well as the proliferation of Sertoli cells. The AMPK signaling pathway also regulates lactate supply. These signaling pathways combine to form a complex regulatory network for spermatogenesis. In testicular tumors or infertile patients, the activities of these signaling pathways in Sertoli cells are abnormal. Clarifying the mechanisms of signaling pathways in Sertoli cells on spermatogenesis provides new insights into the physiological functions of Sertoli cells in male reproduction, and also serves as a pre-requisite to identify potential therapeutic targets in abnormal spermatogenesis including testicular tumor and male infertility.

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“…We found that MTMR7 was exclusively located in SSCs. Pioneering study by Sato et al first obtained functional sperm in cultured neonatal mouse testis [18], we as well as other researchers have widely used this culture method as a platform to gain mechanistic understanding of spermatogenesis [31][32][33][34]. As for SSC culture, it is also a reliable model to explore the development of SSCs and intricate mechanisms of spermatogenesis [19,35,36].…”

Section: Discussionmentioning

confidence: 99%

Myotubularin related protein 7 is essential for the spermatogonial stem cell homeostasis via PI3K/AKT signaling

et al. 2019

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Myotubularin related protein 7 (MTMR7), a key member of the MTMR family, depicts phosphatase activity and is involved in myogenesis and tumor growth. We have previously identified MTMR7 in the proteomic profile of mouse spermatogonial stem cell (SSC) maturation and differentiation, implying that MTMR7 is associated with neonatal testicular development. In this study, to further explore the distribution and function of MTMR7 in mouse testis, we studied the effect of Mtmr7 knockdown on neonatal testicular development by testicular and SSC culture methods. Our results revealed that MTMR7 is exclusively located in early germ cells. Deficiency of MTMR7 by morpholino in neonatal testis caused excessive SSC proliferation, which was attributable to the aberrant PI3K/AKT signaling activation. Altogether, our study demonstrates that MTMR7 maintains SSC homeostasis by inhibiting PI3K/AKT signaling activation.

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Cellular nucleic acid-binding protein is vital to testis development and spermatogenesis in mice

Cited by 27 publications

References 36 publications

BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway

BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

Myotubularin related protein 7 is essential for the spermatogonial stem cell homeostasis via PI3K/AKT signaling

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