Dataset Information

Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes.

ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR), an enzyme expressed in mammalian testes, exerts a direct effect on spermatogenesis; however, its protein characteristics in bovine testes remain unknown. Here, we analysed bovine testicular structure, MTHFR bioinformatics profile, mRNA, and protein expression characteristics in yellow-cattle (y-c) and yak testis using histological procedures, bioinformatics analysis, qRT-PCR, and western blot. Testes from 13 bovines, ≤2 years juvenile (y-c, n = 3; yak, n = 3) and ≥3 years adult (y-c, n = 3; yak, n = 4) were collected and analysed. Anatomical characteristics of testis in y-c and yak were similar except the weight or size for which that of y-c was significantly higher or greater than yak. In y-c, an open reading frame (ORF) for 2600 nucleotides sequence, encoding 655 amino acids showed high homology with zebu cattle (99.51%) and wild yak (98.68%). Secondary and 3D protein structures were similar to that of humans with differences in the number of nucleotides, amino acids, and some physico-chemical characteristics. MTHFR mRNA expression in y-c and yak were significantly higher in adult testes compared with juvenile ones. However, its protein expression was higher, but not statistically significant, in adult y-c and yak compared to the juvenile ones. The highlights and inferences of these and other findings are discussed.

SUBMITTER: Afedo SY

PROVIDER: S-EPMC7598625 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes.

Afedo Seth Yaw SY Cui Yan Y Yu Sijiu S Liao Bo B Zhao Zihan Z Li Hui H Zhang Huizhu H Zou Shengnan S Li De Hong H Zhang Peng P

Animals : an open access journal from MDPI 20200923 10

Methylenetetrahydrofolate reductase (MTHFR), an enzyme expressed in mammalian testes, exerts a direct effect on spermatogenesis; however, its protein characteristics in bovine testes remain unknown. Here, we analysed bovine testicular structure, MTHFR bioinformatics profile, mRNA, and protein expression characteristics in yellow-cattle (y-c) and yak testis using histological procedures, bioinformatics analysis, qRT-PCR, and western blot. Testes from 13 bovines, ≤2 years juvenile (y-c, <i>n</i> = ...[more]

PMID: 32977696

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Project description:BackgroundThe association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis.MethodsThe previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping.ResultsNeither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72-0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69-1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53-1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99-1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97-1.51).ConclusionsThe MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.

Project description:Background and objectiveMethylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism and one-carbon metabolism. MTHFR gene polymorphism affects enzyme activity. MTHFR gene polymorphism is closely related to many human diseases, such as cardiocerebrovascular diseases, diabetes, neural tube defects (NTDs), tumors, and so on. In the field of Andrology, MTHFR gene polymorphism may be associated with male infertility and erectile dysfunction (ED), and there is a possibility of treating male infertility and ED by supplementing with folic acid. However, its exact pathophysiologic mechanism is not fully understood. We sought to obtain a robust understanding of the interactions between MTHFR gene polymorphism, oxidative stress, DNA methylation, hyperhomocysteinemia (HHcy), male infertility, and ED.MethodsWe performed a non-systematic literature review using the PubMed database to identify articles specifically related to MTHFR, male infertility and ED.Key content and findingsOur literature review on MTHFR gene polymorphism in male infertility patients indicates a significant association between C677T gene polymorphism and male infertility. There is limited literature on the correlation between ED and MTHFR gene polymorphism, and there are two different conclusions, related and unrelated. More clinical data are needed to clarify the conclusion. There is a possibility of using folic acid supplementation to treat male infertility and ED, especially for patients with thymine-thymine (TT) genotype. Future research is necessary to further understand the relationship between MTHFR gene polymorphism and male infertility and ED.ConclusionsOur literature review on MTHFR gene polymorphism in male infertility patients indicates a significant association between C677T gene polymorphism and male infertility. Folic acid supplementation can improve sperm quality. The correlation between MTHFR gene polymorphisms and ED is questionable and needs to be confirmed by more clinical data. MTHFR gene polymorphisms are associated with homocysteine (Hcy) levels, which affects vascular endothelial function and may be related to the development of vascular ED (VED). Folic acid supplementation improves International Index for Erectile Function (IIEF) questionnaire scores in ED patients in whom phosphodiesterase 5 inhibitor (PDE5i) alone is ineffective.

Project description:What is already known about this subject* Numerous clinical studies, including a few prospective ones, have reported conflicting results on the impact of gene polymorphisms related to fluorouracil (FU) and oxaliplatin pharmacodynamics.What this study adds* This prospective study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C-->T and 1298A-->C), with a response rate of 37, 53, 63 and 80% in patients harbouring no, one, two or three favourable MTHFR alleles, respectively. * Only polymorphisms of genes related to oxaliplatin pharmacodynamics (GSTpi 105Ile-->Val and XPD 751Ly-->Gln) influenced progression-free survival. * These results corroborate the observation that response was related to the cumulative FU dose, whereas progression-free survival was related to the cumulative oxaliplatin dose.AimsTo test prospectively the predictive value of germinal gene polymorphisms related to fluorouracil (FU) and oxaliplatin (Oxa) pharmacodynamics on toxicity and responsiveness of colorectal cancer (CRC) patients receiving FOLFOX therapy.MethodsAdvanced CRC patients (n= 117) receiving FOLFOX 7 therapy were enrolled. Gene polymorphisms relevant for FU [thymidylate synthase (TYMS, 28 bp repeats including the G-->C mutation + 6 bp deletion in 3'UTR), methylenetetrahydrofolate reductase (MTHFR, 677C-->T, 1298A-->C), dihydropyrimidine deshydrogenase (IVS14+1G-->A) and Oxa: glutathione S-transferase (GST) pi (105Ile-->Val, 114Ala-->Val), excision repair cross-complementing group 1 (ERCC1) (118AAT-->AAC), ERCC2 (XPD, 751Lys-->Gln) and XRCC1 (399Arg-->Gln)] were determined (blood mononuclear cells).ResultsNone of the genotypes was predictive of toxicity. Response rate (54.7% complete response + partial response) was related to FU pharmacogenetics, with both 677C-->T (P= 0.042) and 1298A-->C (P= 0.004) MTHFR genotypes linked to clinical response. Importantly, the score of favourable MTHFR alleles (677T and 1298C) was positively linked to response, with response rates of 37.1, 53.3, 62.5 and 80.0% in patients bearing no, one, two or three favourable alleles, respectively (P= 0.040). Polymorphisms of genes related to Oxa pharmacodynamics showed an influence on progression-free survival, with a better outcome in patients bearing GSTpi 105 Val/Val genotype or XPD 751Lys-containing genotype (P= 0.054).ConclusionsThese results show that response to FOLFOX therapy in CRC patients may be driven by MTHFR germinal polymorphisms.

Project description:BackgroundDNA hypomethylation and uracil misincorporation into DNA, both of which have a very important correlation with colorectal carcinogenesis. Folate plays a crucial role in DNA synthesis, acting as a coenzyme in one-carbon metabolism, which involves the synthesis of purines, pyrimidines, and methyl groups. MTHFR, a key enzyme in folate metabolism, has been widely studied in relation to neural tube defects and hypertension, but its role in colorectal cancer remains underexplored. Therefore, understanding the role of folate and MTHFR genes in colorectal cancer may be helpful for potential preventive or therapeutic interventions. In this meta-analysis, the effects of MTHFR genotype and folate intake on colorectal cancer incidence were analyzed.MethodsWe searched PubMed,Embase, Web of Science, and CNKI database to identify relevant studies up to January 2024. We included a series of studies on the association of MTHFR C677T genotype and folate intake with colorectal cancer incidence. The meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). It included 100 studies (39702 cases and 55718 controls),that investigated the association between the MTHFR C677T polymorphism and colorectal cancer (CRC). Additionally, the analysis incorporated further stratification by ethnic population and geographical region. Furthermore, Six of the studies which clarified high amount of folate might be a protective factor for CRC in all three MTHFR C677T genotype, especially in TT genotype.ResultsMTHFR 677TT genotype was negatively associated with CRC incidence compared with CC genotype (OR = 0.89; 95% CI: 0.85-0.93; P < 0.00001; Z = 5.17). MTHFR 677CT genotype was not significantly associated with colorectal cancer incidence (OR = 1.00; 95% CI: 0.98,1.03). A negative correlation between TT genotype and CRC was observed in ethnics of Asians (OR = 0.83, 95% CI: 0.76, 0.91), Caucasians (OR = 0.93, 95% CI: 0.88, 0.99) and the region of USA (OR = 0.77, 95% CI: 0.71, 0.85), Asia (OR = 0.93, 95% CI: 0.86, 1.00) and Europe (OR = 0.93, 95% CI:0.87, 1.00),but not in Indian (TT: OR = 1.67, 95% CI: 1.06, 2.63; CT: OR = 1.31, 95% CI: 1.00, 1.73)). Amount folate intakes might reduce the morbidity of CRC for people in MTHFR 677TT genotype (OR = 0.68; 95% CI: 0.48,0.96; P = 0.03).ConclusionThe analysis showed that the incidence of colorectal cancer was reduced among individuals with TT genotype. The individuals with TT genotype and amount folate intake may collectively improve the incidence of colorectal cancer. While the MTHFR 677TT genotype is associated with a reduced risk of CRC, especially in certain populations, these findings should be interpreted with caution due to the limitations of retrospective studies.

Dataset Information

Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes.

Publications

Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes.

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