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Aberrant expression of sperm?specific glycolytic enzymes are associated with poor sperm quality.

ABSTRACT: The energy required for normal sperm function is mainly generated by glycolysis and oxidative phosphorylation. Testis?specific glycolytic enzymes are expressed in germ cells and present in mature spermatozoa. The objective of the present study was to investigate the association between aberrant expression of glycolytic enzymes and human sperm quality. In silico analysis of glyceraldehyde?3?phosphate dehydrogenase, testis?specific (GAPDHS), phosphoglycerate kinase 2 (PGK2) and lactate dehydrogenase (LDHC) identified that they were exclusively expressed in post?meiotic germ cells and this was validated in human testes using immunohistochemistry. Compared with the testes of young adults, markedly lower expression levels of these glycolytic enzymes were observed in the testes of elderly adults. Similarly, low levels were observed in immature and asthenozoospermic spermatozoa. The expression levels of GAPDHS, PGK2 and LDHC in the spermatozoa were closely correlated with progressive sperm motility. The results indicated that the expression of GAPDHS, PGK2 and LDHC in sperm may be associated with sperm quality, and there may be a similar molecular mechanism underlying sperm quality in immature and asthenozoospermic spermatozoa. This study reveals a close association of glycolytic enzymes with sperm quality. The data may greatly contribute to the molecular evaluation of sperm quality and the diagnosis and treatment of asthenozoospermia.

SUBMITTER: Liu X

PROVIDER: S-EPMC6423621 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Aberrant expression of sperm‑specific glycolytic enzymes are associated with poor sperm quality.

Liu Xuexia X Li Qian Q Wang Wenjuan W Liu Fujun F

Molecular medicine reports 20190201 4

The energy required for normal sperm function is mainly generated by glycolysis and oxidative phosphorylation. Testis‑specific glycolytic enzymes are expressed in germ cells and present in mature spermatozoa. The objective of the present study was to investigate the association between aberrant expression of glycolytic enzymes and human sperm quality. In silico analysis of glyceraldehyde‑3‑phosphate dehydrogenase, testis‑specific (GAPDHS), phosphoglycerate kinase 2 (PGK2) and lactate dehydrogena ...[more]

PMID: 30720094

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Project description:BackgroundGlutathione-S transferases (GSTs) comprise a series of critical enzymes involved in detoxification of endogenous or xenobiotic compounds. Among several GSTs, Glutathione S-transferases mu (GSTM) has been implicated in a number of cancer types. However, the prognostic value and potential functions of the GSTM family genes have not been investigated in lung adenocarcinoma (LUAD).MethodsWe examined the expression of GSTM5 in LUAD and identified associations among GSTM5 expression, clinicopathological features, survival data from the Cancer Genome Atlas (TCGA). The correlation between GSTM5 DNA methylation and its expression was analyzed using the MEXPRESS tool and UCSC Xena browser. The methylation status of GSTM5 in the promoter region in lung cancer cells was measured by methylation-specific PCR (MSP). After 5-aza-2'-deoxycytidine treatment of lung cancer cells, expression of GSTM5, cell proliferation and migration were assessed by RT-PCR, CCK-8 and transwell assays, respectively.ResultsThe results showed that GSTM5 was abnormally down-regulated in LUAD patients' tissues, and patients with low GSTM5 expression level had significantly shorter OS. Cox regression analyses revealed that GSTM5 was associated with overall survival (OS) of LUAD patients, which expression was an independent prognostic indicator in terms of OS (hazard ratio: 0.848; 95% CI: 0.762-0.945; P = 0.003). In addition, we found the promoter region of GSTM5 was hypermethylated in the tumor tissue compared with adjacent normal tissues, and the average methylation level of GSTM5 were moderately correlated with its expression. Moreover, methylation-specific PCR also showed that the GSTM5 gene promoter was hypermethylated in lung cancer cells, and treatment with 5-Aza-CdR can restore the gene expression and inhibit cell proliferation and migration. Finally, Gene Set Enrichment Analysis (GSEA) revealed that low GSTM5 expression was significantly related to DNA repair pathways.ConclusionOur data demonstrate that low GSTM5 expression and its high DNA methylation status may act as a novel putative molecular target gene for LUAD.

Project description:BackgroundNovel therapeutic approaches are required to treat ovarian cancer and dependency on glycolysis may provide new targets for treatment. This study sought to investigate the variation of expression of molecular components (GLUT1, HKII, PKM2, LDHA) of the glycolytic pathway in ovarian cancers and the effectiveness of targeting this pathway in ovarian cancer cell lines with inhibitors.MethodsExpression of GLUT1, HKII, PKM2, LDHA were analysed by quantitative immunofluorescence in a tissue microarray (TMA) analysis of 380 ovarian cancers and associations with clinicopathological features were sought. The effect of glycolysis pathway inhibitors on the growth of a panel of ovarian cancer cell lines was assessed by use of the SRB proliferation assay. Combination studies were undertaken combining these inhibitors with cytotoxic agents.ResultsMean expression levels of GLUT1 and HKII were higher in high grade serous ovarian cancer (HGSOC), the most frequently occurring subtype, than in non-HGSOC. GLUT1 expression was also significantly higher in advanced stage (III/IV) ovarian cancer than early stage (I/II) disease. Growth dependency of ovarian cancer cells on glucose was demonstrated in a panel of ovarian cancer cell lines. Inhibitors of the glycolytic pathway (STF31, IOM-1190, 3PO and oxamic acid) attenuated cell proliferation in platinum-sensitive and platinum-resistant HGSOC cell line models in a concentration dependent manner. In combination with either cisplatin or paclitaxel, 3PO (a novel PFKFB3 inhibitor) enhanced the cytotoxic effect in both platinum sensitive and platinum resistant ovarian cancer cells. Furthermore, synergy was identified between STF31 (a novel GLUT1 inhibitor) or oxamic acid (an LDH inhibitor) when combined with metformin, an inhibitor of oxidative phosphorylation, resulting in marked inhibition of ovarian cancer cell growth.ConclusionsThe findings of this study provide further support for targeting the glycolytic pathway in ovarian cancer and several useful combinations were identified.

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Aberrant expression of sperm?specific glycolytic enzymes are associated with poor sperm quality.

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Aberrant expression of sperm‑specific glycolytic enzymes are associated with poor sperm quality.

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