Effect of Low Dietary Folate on Mouse Spermatogenesis and Spindle Assembly Checkpoint Dysfunction May Contribute to Folate Deficiency-Induced Chromosomal Instability in Cultured Mouse Spermatogonia.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Huanhuan Ren, Kaixian Wang, Zirui Liu, Xuansheng Zhong, Meng Liang, Yaping Liao
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引用次数: 0

Abstract

Folate, as the initial substrate in one-carbon metabolism, is involved in the synthesis of important substances such as DNA, RNA, and protein. Folate deficiency (FD) is associated with male subfertility and impaired spermatogenesis, yet the underlying mechanisms are poorly understood. In the present study, we established an animal model of FD to investigate the effect of FD on spermatogenesis. GC-1 spermatogonia were used as a model to investigate the effect of FD on proliferation, viability, and chromosomal instability (CIN). Furthermore, we explored the expression of core genes and proteins of spindle assembly checkpoint (SAC), a signaling cascade ensuring accurate chromosome segregation and preventing CIN during mitosis. Cells were maintained in medium containing 0, 20, 200, or 2000 nM folate for 14 days. CIN was measured by using a cytokinesis-blocked micronucleus cytome assay. We found that sperm counts decreased significantly (p < 0.001) and the rate of sperm with defects in the head increased significantly (p < 0.05) in FD diet mice. We also found, relative to the folate-sufficient conditions (2000 nM), cells cultured with 0, 20, or 200 nM folate exhibited delayed growth and increased apoptosis in an inverse dose-dependent manner. FD (0, 20, or 200 nM) significantly induced CIN (p < 0.001, p < 0.001, and p < 0.05, respectively). Moreover, FD significantly and inverse dose dependently increased the mRNA and protein expression of several key SAC-related genes. The results indicate that FD impairs SAC activity, which contributes to mitotic aberrations and CIN. These findings establish a novel association between FD and SAC dysfunction. Thus, FD-impaired spermatogenesis may be partly due to genomic instability and proliferation inhibition of spermatogonia.

低叶酸饮食对小鼠精子发生的影响和纺锤体组装检查点功能障碍可能是叶酸缺乏诱导的培养小鼠精原细胞染色体不稳定的原因之一。
叶酸作为单碳代谢的初始底物,参与DNA、RNA、蛋白质等重要物质的合成。叶酸缺乏(FD)与男性生育能力低下和精子发生受损有关,但其潜在机制尚不清楚。在本研究中,我们建立了FD动物模型,研究FD对精子发生的影响。以GC-1精原细胞为模型,探讨FD对细胞增殖、活力和染色体不稳定性(CIN)的影响。此外,我们还探索了纺锤体组装检查点(SAC)的核心基因和蛋白质的表达,这是一个信号级联,确保染色体准确分离并防止有丝分裂过程中的CIN。细胞在含有0、20、200或2000 nM叶酸的培养基中维持14天。使用细胞动力学阻断微核细胞组测定CIN。我们发现精子数量显著下降(p p p p p
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来源期刊
DNA and cell biology
DNA and cell biology 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
93
审稿时长
1.5 months
期刊介绍: DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.
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