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SIRT1 与不孕女性体内的抗氧化剂:维生素 D 作用的探索。

SIRT1 and antioxidants in infertile females: Exploration of the role of vitamin D.

机构信息

PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Bandar Seri Begawan, Brunei Darussalam.

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

出版信息

PLoS One. 2023 Jul 10;18(7):e0287727. doi: 10.1371/journal.pone.0287727. eCollection 2023.

DOI:10.1371/journal.pone.0287727
PMID:37428803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10332578/
Abstract

BACKGROUND

Deficiency of silent information regulator 1 (SIRT1) can trigger inflammation, mitochondrial malfunctioning, and apoptosis through the hypothalamic-pituitary-ovarian axis, producing poor quality oocytes, leading to infertility. Normal vitamin D (VD) levels promote SIRT1 activity required for optimal fertility, and low levels of either may result in fertility problems owing to cell-membrane de-stabilization, increased autophagy, DNA damage leading to increased reactive oxygen species and mitochondrial dysfunction. Therefore, in this study, we want to estimate the levels of VD, SIRT1 and antioxidants (MnSOD; manganese superoxide dismutase, GR; glutathione reductase, visfatin) and oxidants (adrenaline & cortisol) in individuals living with infertility and explore the association of VD with SIRT1 expression (levels), antioxidants, and oxidants contributing to infertility in women. The significance of this study is that it highlights the importance of maintaining optimal levels of VD for reproductive health in females.

METHODS

This cross-sectional study included 342 (135 infertile and 207 fertile) female subjects. Serum levels of MnSOD, SIRT1, visfatin, GR, VD, adrenaline, and cortisol were analyzed by ELISA and were compared in fertile and infertile samples using the Mann Whitney U test.

RESULTS

There were significantly high levels of VD, SIRT1, GR, MnSOD and visfatin in fertile female participants. However, mean adrenaline and cortisol levels were higher in infertile samples with a significant negative correlation with VD. A significant negative correlation of VD with MnSOD, SIRT1, visfatin and GR was observed (p <0.01). In VD subset groups, MnSOD levels were significantly high in VD sufficient groups however, adrenaline and cortisol levels were significantly high in groups suffering from VD deficiency.

CONCLUSIONS

Deficiency of VD is associated with a decrease in SIRT1 and other antioxidants, which may deter natural reproductive functions leading to infertility. Further studies are required to determine the cause-effect relationship of VD deficiency on conception and interpretation of the involved mechanism.

摘要

背景

沉默信息调节因子 1(SIRT1)的缺乏可通过下丘脑-垂体-卵巢轴引发炎症、线粒体功能障碍和细胞凋亡,导致卵母细胞质量差,进而引起不孕。正常的维生素 D(VD)水平可促进 SIRT1 活性,这对最佳生育能力至关重要,而 VD 水平低或高都会导致生育问题,原因是细胞膜不稳定、自噬增加、导致活性氧和线粒体功能障碍的 DNA 损伤。因此,在这项研究中,我们旨在评估不孕患者体内的 VD、SIRT1 和抗氧化剂(MnSOD;锰超氧化物歧化酶、GR;谷胱甘肽还原酶、内脏脂肪素)和氧化剂(肾上腺素和皮质醇)水平,并探讨 VD 与 SIRT1 表达(水平)、抗氧化剂和氧化剂之间的关联,这些因素导致女性不孕。这项研究的意义在于,它强调了维持女性生殖健康的最佳 VD 水平的重要性。

方法

本横断面研究纳入了 342 名女性(135 名不孕和 207 名生育)。采用 ELISA 法检测血清 MnSOD、SIRT1、内脏脂肪素、GR、VD、肾上腺素和皮质醇水平,并采用 Mann Whitney U 检验比较生育和不孕样本之间的差异。

结果

生育女性参与者的 VD、SIRT1、GR、MnSOD 和内脏脂肪素水平显著较高。然而,不孕样本中的平均肾上腺素和皮质醇水平较高,且与 VD 呈显著负相关。VD 与 MnSOD、SIRT1、内脏脂肪素和 GR 呈显著负相关(p<0.01)。在 VD 亚组中,VD 充足组的 MnSOD 水平显著较高,而 VD 缺乏组的肾上腺素和皮质醇水平显著较高。

结论

VD 缺乏与 SIRT1 和其他抗氧化剂水平降低有关,这可能会抑制自然生殖功能,导致不孕。需要进一步研究来确定 VD 缺乏对受孕的因果关系,并解释所涉及的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56f0/10332578/dd1ea6bf637d/pone.0287727.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56f0/10332578/2e6c6f6e99ad/pone.0287727.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56f0/10332578/dd1ea6bf637d/pone.0287727.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56f0/10332578/2e6c6f6e99ad/pone.0287727.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56f0/10332578/dd1ea6bf637d/pone.0287727.g002.jpg

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