Human sperm Toll-like receptor 4 (TLR4) mediates acrosome reaction, oxidative stress markers, and sperm parameters in response to bacterial lipopolysaccharide in infertile men

Sahnoun, Sana; Sellami, Afifa; Chakroun, N.; Mseddi, Malek; Attia, Hammadi; Rebaï, Tarek; Lassoued, Saloua

doi:10.1007/s10815-017-0957-8

Cited by 25 publications

(23 citation statements)

References 53 publications

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“…On the other hand, the caput epididymal inflammation, as reflected by the increased expression of IL-1β, CXCL-10, MCP-1 and NF-κBp65, could be a likely ‘culprit’ responsible for the reduced sperm counts and motility in the HFD-FMT mice. Multiple studies have demonstrated that epididymal inflammation condition negatively affects sperm quality 38 39 47–52. Global elevation of NF-κB p65 expression has been shown to exert anti-inflammatory and antiobesity effects by increasing energy expenditure 53.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have well established the causal relationship between the endotoxaemia/epididymal inflammation and low sperm motility/spermatogenic dysfunction in both animal models and humans 38 39 47–52. Intraperitoneal administration of lipopolysaccharides (LPS) could elevate the expression of pro-inflammatory cytokines, such as IL-1β, IL-6 and CXCLi2 in the epididymis and testis of roosters48 and increase the level of IL-18 in mouse testes 49.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, LPS injection could also elevate seminal plasma IL-1β, TNF-α, IL-6 levels and lead to low sperm motility in rats 50. Importantly, incubation of human spermatozoa with LPS could cause reduction in sperm motility 51. Metabolic endotoxaemia in human obesity is strongly linked with impaired sperm DNA integrity 52.…”

Section: Discussionmentioning

confidence: 99%

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Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Ding

Zhang²,

Zhang

et al. 2020

Gut

211

158

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ObjectiveHigh-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility.DesignFaecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin.ResultsTransplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice.ConclusionWe revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes.Trial registration numberNCT03634644.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Ding

Zhang²,

Zhang

et al. 2020

Gut

211

158

View full text Add to dashboard Cite

show abstract

“…Its result is statistically significant ( p < 0.001), with MD values of 1.42 µmol/L and heterogeneity coefficient of 99.75% [ 57 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. MDA values have been shown to be significantly higher in men with varicocele or infective diseases in the urogenital tract, which correlates with decreased sperm motility [ 76 ] and higher percentages of necrotic and apoptotic sperm, and heat stress [ 77 ]. This phenomenon can be explained by reduced heat shock proteins and B-cell lymphoma 2 (BCL2) expression, increased BCL2-associated X protein (BAX) expression and higher polymorphism of genes encoding S-glutathione transferase or nitric oxide synthase.…”

Section: Discussionmentioning

confidence: 99%

Sperm Antioxidant Biomarkers and Their Correlation with Clinical Condition and Lifestyle with Regard to Male Reproductive Potential

Krzyściak

Papież

Bąk³

et al. 2020

JCM

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Measurement of sperm oxidative-antioxidant indicators is widely used in the assessment and detection of biochemical causes of male infertility. The main purpose of this study was to identify biomarkers that assist in diagnostics and monitoring of male reproductive potential. We performed the assessment of oxidative-antioxidant malondialdehyde (MDA), glutathione (GSH), and total redox antioxidant potential (TRAP) indicators in seminal plasma, seminogram, clinical condition, and lifestyle of people with reproductive problems. The combined assessment of GSH and TRAP as potential biomarkers of male infertility in semen plasma was characterized by the highest total sensitivity and specificity. Furthermore, we provide evidence that male reproductive potential is significantly correlated with basic sperm parameters, sperm cell membrane integrity, their morphology, lifestyle, eating habits, occupation, and mental health. Our results provide evidence on the importance of oxidative stress and defense against free radicals in diagnosing and monitoring men with infertility that are consistent with previously conducted research. We provide an alternative approach on the possibility of interpreting the combination of the biomarkers that can bring benefits to a multi-threaded approach to the diagnosis and treatment of male infertility.

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“…However, it remains to be determined whether spermatozoa bearing FASLG contribute to immunoprivileged status within the seminiferous tubule (Li, Wang, & Han, ; Zhao et al, ). Though the role of TLR10 in the developmental process of spermatogenesis (Saeidi et al, ) has been reported, the immune regulatory functions of TLR in testis and spermatozoa quality have yet to be detailed (Li et al, ; Sahnoun et al, ; Girling and Hedger, ). TLR initiates the innate immune response through cytokines including tumor necrosis factor α (TNFA), interleukin 1 (IL1), IL6, and its regulation is essential for the protection of germ cell from immune attack (Zhao et al, ) and pathogenic molecules (Bhushan et al, ; Sahnoun et al, ).…”

Section: Testicular Immune Mechanismmentioning

confidence: 99%

Immune regulatory molecules as modifiers of semen and fertility: A review

Archana

Selvaraju

Binsila

et al. 2019

Molecular Reproduction Devel

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Declining fertility rates in both human and animals is a cause for concern. While many of the infertility cases are due to known causes, idiopathic infertility is reported in 30% of the infertile couples. In such cases, 18% of the infertile males carry antisperm antibodies (ASAs). Such data are lacking in livestock, wherein 20–30% of the animals are being culled due to low fertility. In males, the blood–testis barrier (BTB) and biomolecules in the semen provide an immuno‐tolerant microenvironment for spermatozoa as they traverse the immunologic milieu of both the male and female reproductive tracts. For example, insults from environmental contaminants, infections and inflammatory conditions are likely to impact the immune privilege state of the testis and fertility. The female mucosal immune system can recognize allogenic spermatozoa‐specific proteins affecting sperm kinematics and sperm‐zona binding leading to immune infertility. Elucidating the functions and pathways of the immune regulatory molecules associated with fertilization are prerequisites for understanding their impact on fertility. An insight into biomolecules associated with spermatozoal immune tolerance may generate inputs to develop diagnostic tools and modulate fertility. High‐throughput sequencing technologies coupled with bioinformatics analyses provides a path forward to define the array of molecules influencing pregnancy outcome. This review discusses the seminal immune regulatory molecules from their origin in the testis until they traverse the uterine environment enabling fertilization and embryonic development. Well‐designed experiments and the identification of biomarkers may provide a pathway to understand the finer details of reproductive immunology that will afford personalized therapies.

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Human sperm Toll-like receptor 4 (TLR4) mediates acrosome reaction, oxidative stress markers, and sperm parameters in response to bacterial lipopolysaccharide in infertile men

Abstract: These findings indicate that human spermatozoa express TLR4 and respond to LPS stimulation with alterations in viability, motility, and the acrosome reaction implicating reactive oxygen species (ROS) production in sperm samples from infertile patients.

Cited by 25 publications

References 53 publications

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Sperm Antioxidant Biomarkers and Their Correlation with Clinical Condition and Lifestyle with Regard to Male Reproductive Potential

Immune regulatory molecules as modifiers of semen and fertility: A review

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