The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis

Hai, Yanan; Hou, Jingmei; Liu, Yun; Liu, Yang; Yang, Hao; Li, Zheng; He, Zuping

doi:10.1016/j.semcdb.2014.04.007

Cited by 174 publications

(114 citation statements)

References 87 publications

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“…Moreover, significant decreases in sperm motility and androgen production were found in NP-treated adult rats (Duan et al 2016a). Normal spermatogenic progression is highly dependent on microenvironment provided by SCs, and conversely, SC dysfunction causes alterations of testis differentiation and adult spermatogenesis, potentially leading to temporary or permanent infertility (Dong et al 2015;Hai et al 2014). We were interested to investigate the mechanism how NP interferes with SC activity related to spermatogenesis, such as autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…SCs, one of the somatic cells of the testis, are critical regulators of spermatogenesis as their main functions are to control germ cell differentiation in the seminiferous tubules, to provide physical and nutritional support for the developing sperm and to form the blood-testis-barrier (Escott et al 2014;Hai et al 2014). It is now well established that the in vitro study of SC physiology is a useful model to disclose deleterious effects of toxicant exposure to male fertility and to probe the molecular mechanisms that regulate spermatogenesis (Li et al 2016;Reis et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

Duan

Quan

et al. 2017

Toxicology Letters

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The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the "nursemaid cells" for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100 mg/kg body weight/2 days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10 µM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1 mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6K/4EBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

Duan

Quan

et al. 2017

Toxicology Letters

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“…[1][2][3][4] To explore how autophagy affects sperm head morphology and motility in Sertoli cells, we detected which stage of spermatogenesis was influenced in the Sertoli cell-specific autophagy-deficient mice. ZBTB16/PLZF is a transcription factor involved in SSC self-renewal, 37 and its immunohistochemical analysis performed in AMH-atg7 ¡/¡ mice testes showed no significant differences compared with Atg7-Flox/Flox mice (Fig.…”

Section: The Apical Es Is Disrupted In Sertoli Cell-specific Autophagmentioning

confidence: 99%

“…Their functions include providing structural support and nourishment to developing germ cells, mediating the self-renewal and differentiation of spermatogonial stem cells (SSCs), phagocytosing degenerating germ cells, protecting the autoreactive immune response of germ cells, releasing spermatids at spermiation and hormonal regulation. 3,4 At all stages of spermatogenesis, Sertoli cells and germ cells have developed a set of communication devices that are involved in attachment, displacement, degeneration, and cellcell transfer of signaling molecules and cellular materials. 5 This Sertoli-germ cell communication is necessary for successful spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Autophagy is required for ectoplasmic specialization assembly in sertoli cells

et al. 2016

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The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads. In autophagy-deficient mouse testes, cytoskeleton structures were disordered and ES assembly was disrupted. The disorganization of the cytoskeleton structures might be caused by the accumulation of a negative cytoskeleton organization regulator, PDLIM1, and these defects could be partially rescued by Pdlim1 knockdown in autophagy-deficient Sertoli cells. Altogether, our works reveal that the degradation of PDLIM1 by autophagy in Sertoli cells is important for the proper assembly of the ES, and these findings define a novel role for autophagy in Sertoli cell-germ cell communication.

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“…116 The main function of Leydig cells in the testes is the synthesis and secretion of testosterone, important for germ cell production from SSCs, ie, spermatogenesis. Sertoli cells provide physical support for SSCs and also express proteins and other factors, such as GDNF, SCF, and BMP4, which regulate all aspects of germ cell development.…”

mentioning

confidence: 99%

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

Zhang¹,

Choi²,

Han³

et al. 2015

IJN

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Background Silver nanoparticles (AgNPs) possess unique physical, chemical, and biological properties. AgNPs have been increasingly used as anticancer, antiangiogenic, and antibacterial agents for the treatment of bacterial infections in open wounds as well as in ointments, bandages, and wound dressings. The present study aimed to investigate the effects of two different sizes of AgNPs (10 nm and 20 nm) in male somatic Leydig (TM3) and Sertoli (TM4) cells and spermatogonial stem cells (SSCs). Methods Here, we demonstrate a green and simple method for the synthesis of AgNPs using Bacillus cereus culture supernatants. The synthesized AgNPs were characterized using ultraviolet and visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy (TEM). The toxicity of the synthesized AgNPs was evaluated by the effects on cell viability, metabolic activity, oxidative stress, apoptosis, and expression of genes encoding steroidogenic and tight junction proteins. Results AgNPs inhibited the viability and proliferation of TM3 and TM4 cells in a dose- and size-dependent manner by damaging cell membranes and inducing the generation of reactive oxygen species, which in turn affected SSC growth on TM3 and TM4 as feeder cells. Small AgNPs (10 nm) were more cytotoxic than medium-sized nanoparticles (20 nm). TEM revealed the presence of AgNPs in the cell cytoplasm and nucleus, and detected mitochondrial damage and enhanced formation of autosomes and autolysosomes in the AgNP-treated cells. Flow cytometry analysis using Annexin V/propidium iodide staining showed massive cell death by apoptosis or necrosis. Real-time polymerase chain reaction and western blot analyses indicated that in TM3 and TM4 cells, AgNPs activated the p53, p38, and pErk1/2 signaling pathways and significantly downregulated the expression of genes related to testosterone synthesis (TM3) and tight junctions (TM4). Furthermore, the exposure of TM3 and TM4 cells to AgNPs inhibited proliferation and self-renewal of SSCs. Conclusion Our results suggest that AgNPs exhibit size-dependent nanoreprotoxicity in male somatic cells and SSCs, strongly suggesting that applications of AgNPs in commercial products must be carefully evaluated. Further studies of AgNPs-induced nanoreprotoxicity in animal models are required.

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The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis

Cited by 174 publications

References 87 publications

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

Autophagy is required for ectoplasmic specialization assembly in sertoli cells

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

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