Lipopolysaccharide inhibits the self-renewal of spermatogonial stem cells in vitro via downregulation of GDNF expression in Sertoli cells

Zhang, Xiaoli; Shi, K.; Li, Yang; Zhang, Haiyu; Hao, Jing

doi:10.1016/j.reprotox.2014.01.009

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…Tight junction proteins ZO-1, Claudin-11, and connexin-43 are important structural components of Sertoli cells essential to BTB function. [107][108][109] Deregulation of these genes is observed in a number of diseases. Environmental toxins can impair the viability and function of Sertoli cells, inducing BTB disruption.…”

mentioning

confidence: 99%

“…GDNF, secreted by these cells, is essential for self-renewal, proliferation, and differentiation of SSCs. 107,108 The cells exposed to AgNPs showed reduced Gdnf mRNA expression, indicating that AgNPs exposure may downregulate GDNF synthesis and secretion ( Figure 10B). Overall, these results suggest that AgNPs exposure could affect the development of germ cells in the testes, and ultimately cause reproductive toxicity.…”

mentioning

confidence: 99%

“…Braydich-Stolle et al 71 have revealed that 10 µg/mL of AgNPs inhibited SSC proliferation in vitro. Zhang et al 108 have shown that lipopolysaccharide inhibits the expression of GDNF in Sertoli cells and prevents SSC self-renewal via downregulation of GDNF-targeted genes. Collectively, our results suggest that AgNPs have a significant negative impact on spermatogenesis and expression of tight junction proteins involved in the regulation of germ cell cycle progression, cell proliferation, and cell motility.…”

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confidence: 99%

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

Zhang¹,

Choi²,

Han³

et al. 2015

IJN

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“…Nuclear factor-κB (NF-κB) is subsequently activated to transcribe downstream inflammatory factors (Gioannini and Weiss 2007). Several studies have revealed that LPS has male reproductive toxicity (Kajihara et al 2006;Brecchia et al 2010;Metukuri et al 2010;Winnall et al 2011;Aly et al 2012;Zhang et al 2014). Intraperitoneal administration of 0.1 mg/kg/day LPS to ICR mice for 7 days reduced the epididymal sperm count and motility via apoptosis of spermatogonia (Kajihara et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The same dose of LPS administrated to rabbits over 56 days resulted in infertility and disturbed sperm membrane integrity (Brecchia et al 2010). In vitro experiments on cultured Sertoli cells showed that 10 µg/ml LPS significantly decreased the expression of self-renewal-related genes for spermatogonial stem cells (Zhang et al 2014). To date, such studies have mainly focused on the toxicities of LPS for testicular function and spermatogenesis but the effect of LPS on mature sperm in vitro is poorly known.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide Compromises Human Sperm Function by Reducing Intracellular cAMP

Zhang

et al. 2016

Tohoku J. Exp. Med.

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A worldwide decline in the quality of human semen is currently occurring. In mammals, sperm are produced from diploid stem-cell spermatogonia by spermatogenesis in testes and become mature in epididymis. Nevertheless, these biological processes can be affected by Gram-negative bacterial infection mediated by lipopolysaccharide (LPS), the major endotoxin of Gram-negative bacteria. It is well known that LPS can disturb spermatogenesis and affect sperm maturation and quality in vivo. However, the effect of LPS on the ejaculated mature sperm in vitro remains unclear. Thus, this study aimed to assess the in vitro toxicity of LPS on human sperm function and to elucidate the underlying mechanism. Human sperm were incubated with LPS (0.1-100 μg/ml) for 1-12 h in vitro and, subsequently, sperm viability, motility and capacitation, and the acrosome reaction were examined. LPS dose-dependently inhibited total and progressive motility and the ability to move through a viscous medium of the sperm but did not affect sperm viability, capacitation, and the acrosome reaction. To explore the underlying mechanism of LPS's actions, we examined the effects of LPS on the intracellular concentrations of cyclic adenosine monophosphate (cAMP) and calcium ([Ca 2+ ] i ) and protein-tyrosine phosphorylation of human sperm, which are key regulators of human sperm function. LPS decreased intracellular cAMP dose-dependently but had no effect on [Ca 2+ ] i and protein-tyrosine phosphorylation of human sperm. These findings suggest that LPS inhibits human sperm motility by decreasing intracellular cAMP.

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The inflammatory mediators TNFα and nitric oxide arrest spermatogonia GC-1 cell cycle

Ferreiro

Amarilla

Glienke

et al. 2019

Reproductive Biology

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Lipopolysaccharide inhibits the self-renewal of spermatogonial stem cells in vitro via downregulation of GDNF expression in Sertoli cells

Cited by 8 publications

References 31 publications

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

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

Lipopolysaccharide Compromises Human Sperm Function by Reducing Intracellular cAMP

The inflammatory mediators TNFα and nitric oxide arrest spermatogonia GC-1 cell cycle

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