The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice.

BACKGROUND: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes. RESULTS: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1. CONCLUSIONS: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.

Association of methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis

ABSTRACT Recent studies have shown that two common methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis.

Recent studies have shown that two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.