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

Background: High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular Reactive Oxygen Species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2‑related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Herein, we sought to determine the relationship of hTERT and NRF2 in the progression of CRC and to elucidate the underlying molecular mechanisms.Methods: qPCR, Western blot, Immunohistochemistry, immunofluorescence assays were used to detect the mRNA and protein expression of hTERT, NRF2 and YBX1 in CRC cell lines and tissues.CCK8 and colony formation were used to detect the proliferation of CRC cells, transwell assay was used to detect the migration of CRC cells. Dual-luciferase reporter assays were used to detect the promoter activity of NRF2. DNA pull-down/MS analysis was used to identify NRF2 promoter binding proteins. ChIP-qPCR was used to detect the YBX1binding sequences of NRF2 promoter.Results: Both hTERT and NRF2 are highly expressed in CRC tissues and associated with poor diagnosis. hTERT increases NRF2 expression at both the mRNA and protein levels. hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. Moreover, hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability, and hTERT recruits YBX1 to upregulate NRF2 promoter activity thus increases NRF2 expression and enhances CRC proliferation and migration.Conclusions: hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter.

Colorectal cancer metastasis (CRC) is the main reason for patients’ death and remains a crucial clinical challenge. LncRNAs play kinds of important roles in the progression of CRC metastasis, but the implied mechanisms are still unclear. In our research, we studied the lncRNA small nucleolus host gene 1 (SNHG1) which was up-regulated in CRC tissues, and the high expression of lncRNA SNHG1 was correlated with poor prognosis of patients. Functionally, lncRNA SNHG1 acted as an oncogene and promoted CRC cells invasion and migration. Mechanistically, lncRNA SNHG1 mainly located in cell cytoplasm, in which it recruited heterogeneous nuclear ribonucleoprotein D (HNRNPD) and increased the mRNA stability of serpin family A member 3 (SERPINA3), and then subsequently upregulated SERPINA3 expression to facilitated CRC cells invasion and migration. Our finding demonstrated a different role of lncRNA SNHG1 in the cytoplasm and lncRNA SNHG1/HNRNPD-SERPINA3 might serve as a potential therapy for CRC.