Effect of silencing HIF-1α gene on testicle spermatogenesis function in varicocele rats

Zhao, Wei; Liu, Jianrong; Wang, Danfeng; Wang, Yimin; Zhang, Fang; Jin, Guo Fan; Yuan, Caixia; Wang, Xin; Qin, Qin

doi:10.1007/s00441-019-03064-0

Cited by 22 publications

(22 citation statements)

References 29 publications

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“…Subsequent studies showed that hypoxia-related lncRNA expression is significantly elevated in semen from varicocele patients ( Ata-Abadi et al, 2020 ). Mechanistically, oxidative and heat stress caused by hypoxia or hypoxia-ischemia and HIF-1α mediated germ cell apoptosis or sperm damage may be the main reasons ( Zhang et al, 2016 ; Goren et al, 2017 ; Zhu et al, 2017 ; Samanta et al, 2018 ; Zhao et al, 2019 ). (A summary of the studies in the last 5 years is shown in Table 2 ).…”

Section: Hypoxic Factors Causing Male Infertilitymentioning

confidence: 99%

“…In rat models, silencing the HIF-1α gene in varicocele testes using the CRISPR/Cas9 gene editing technique significantly reduced the rate of apoptosis of spermatogenic cells and improved spermatogenic function by downregulating the VEGF/PI3K/AKT signaling pathway (Wang D. et al, 2020). Another study revealed that silencing HIF-1α significantly downregulated the expression of Bax and cleaved caspase-3 in the testes of varicocele rats (Zhao et al, 2019). In cell models, HIF-1α induced GC-2 cell apoptosis by activating the mitochondrial pathway and death receptor pathway under hypoxic conditions (Yin et al, 2018a).…”

Section: Hif-1α Mediates Germ Cell Apoptosis and Proliferation Inhibitionmentioning

confidence: 99%

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Effects of Environmental and Pathological Hypoxia on Male Fertility

Wang

Gong

et al. 2021

Front. Cell Dev. Biol.

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Male infertility is a widespread health problem affecting approximately 6%–8% of the male population, and hypoxia may be a causative factor. In mammals, two types of hypoxia are known, including environmental and pathological hypoxia. Studies looking at the effects of hypoxia on male infertility have linked both types of hypoxia to poor sperm quality and pregnancy outcomes. Hypoxia damages testicular seminiferous tubule directly, leading to the disorder of seminiferous epithelium and shedding of spermatogenic cells. Hypoxia can also disrupt the balance between oxidative phosphorylation and glycolysis of spermatogenic cells, resulting in impaired self-renewal and differentiation of spermatogonia, and failure of meiosis. In addition, hypoxia disrupts the secretion of reproductive hormones, causing spermatogenic arrest and erectile dysfunction. The possible mechanisms involved in hypoxia on male reproductive toxicity mainly include excessive ROS mediated oxidative stress, HIF-1α mediated germ cell apoptosis and proliferation inhibition, systematic inflammation and epigenetic changes. In this review, we discuss the correlations between hypoxia and male infertility based on epidemiological, clinical and animal studies and enumerate the hypoxic factors causing male infertility in detail. Demonstration of the causal association between hypoxia and male infertility will provide more options for the treatment of male infertility

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Section: Hypoxic Factors Causing Male Infertilitymentioning

confidence: 99%

Section: Hif-1α Mediates Germ Cell Apoptosis and Proliferation Inhibitionmentioning

confidence: 99%

Effects of Environmental and Pathological Hypoxia on Male Fertility

Wang

Gong

et al. 2021

Front. Cell Dev. Biol.

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“…Hematoxylin and eosin staining HE staining was conducted according to routine protocols [7]. After xation in 4% paraformaldehyde and dehydrated sequentially with ethanol, the left testicle tissue was embedded in para n and sectioned at 5 um thickness.…”

Section: Establishment Of the Vc Modelmentioning

confidence: 99%

“…Western blot was conducted according to routine protocols [6,7]. The proteins were extracted from the left testicle tissue of rats.…”

Section: Western Blot To Con Rm Potential Proteinsmentioning

confidence: 99%

“…We also found the correlation between the apoptosis of spermatogenic cells and overexpression of hypoxia-induciblefactor-1α (HIF-1α) in VC rats. By decreasing the expression of HIF-1α, the apoptosis of spermatogenic cells was reduced, which is bene cial to the recovery of testicular function and the improvement of fertility [7]. Liang et al observed that increased expression level of reactive oxygen species (ROS) and p53 in VC rats and thought that the increased expression of p53 gene in testicular tissue was caused by the activation of ROS, and the abnormal increase of p53 may inhibit angiogenesis by generating anti-angiogenic factors, which lead to an increase in cell death [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Proteome Analysis of Testicular Tissue in Varicocele Rats Using iTRAQ Labeling Technology

feng

Zhao

rong

et al. 2020

Preprint

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Purpose Varicocele (VC) is considered as the main cause of male infertility, clear and definite molecular markers of varicocele disease are helpful for early prevention and timely treatment. This study was in order to examine the effect of varicocele on protein expression in testicular tissue.Methods The testicular tissue samples of normal rats and varicocele rats were used for proteomic analysis and functional bioinformatics analysis. The proteins with a fold change of > 1.2 or < 1.2, and with a P-value < 0.05 were used to identify up- and downregulation proteins between the varicocele and control rats, and two target proteins were selected and verified with western blot.Results It was found that seminiferous epithelium was disordered and spermatogenic cells were injured seriously in varicocele group. A total of 65 differentially expressed proteins were identified compared with normal group by liquid chromatography tandem mass spectrometry (LC-MS/MS) and isobaric tags for relative and absolute quantitation (iTRAQ) analysis, including 31 up-regulated proteins and 34 down-regulated proteins, respectively. Functions of those proteins were mainly related to the following processes: signal transduction, protein cycle, transmembrane transport, protein transport, vesicular mediated transport, cell division, and membrane tissue. Two down regulated proteins of ATPase and Cu2+-transporting alpha (ATP7A) and Calcium and integrin-binding protein 1 (CIB1) in varicocele rats were selected and confirmed.Conclusion Protein spectrum of testicular tissue in varicocele rats was different from that in normal rats. Low expressions of ATP7A and CIB1 may be affect testicular spermatogenic function and can be used as a potential biomarker for testicular tissue to maintain normal spermatogenic function.

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Lycopene improves testicular damage and sperm quality in experimentally induced varicocele: Relationship with apoptosis, hypoxia, and hyperthermia

Babaei

Asadpour

Mansouri

et al. 2022

Food Science & Nutrition

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Varicocele is defined as high pressure, stasis in the spermatic veins, and venous enlargement of the scrotal pampiniform plexus (Yetkin & Ozturk, 2018). The prevalence of varicocele disease is about 35% and 80% with primary and secondary infertility, respectively (Alsaikhan et al., 2016). The relationship between varicocele and infertility is unclear, but several articles have demonstrated that varicocele has

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Effect of silencing HIF-1α gene on testicle spermatogenesis function in varicocele rats

Cited by 22 publications

References 29 publications

Effects of Environmental and Pathological Hypoxia on Male Fertility

Effects of Environmental and Pathological Hypoxia on Male Fertility

Proteome Analysis of Testicular Tissue in Varicocele Rats Using iTRAQ Labeling Technology

Lycopene improves testicular damage and sperm quality in experimentally induced varicocele: Relationship with apoptosis, hypoxia, and hyperthermia

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