Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age

Title：Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age

Authors：Tang Y, Gan H, Wang B, Wang X, Li M, Yang Q, Geng M, Zhu P, Shao S, Tao F.

Source：BMC Public Health. 2023 Sep 15;23(1):1802.  

DOI: 10.1186/s12889-023-16681-w.

原文链接：https://doi.org/10.1186/s12889-023-16681-w

Abstract

Background: This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association.

Methods: This study is a population-based case-control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package "mediation".

Results: The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01-0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%.

Conclusion: These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Keywords: DNA methylation; Epigenetics; Infertility; Ovulation disorders; Sleep quality.

摘要

背景:本研究旨在探讨女性睡眠质量与不孕症之间的关系，并探讨DNA甲基化在这一关系中的中介作用。

方法:本研究为基于人群的病例对照研究。研究无排卵性不孕症患者(n = 43)和健康对照组(n = 43)的睡眠质量与不孕症的关系。使用Illumina Infinium Human methylation 850k BeadChip对外周血样本进行全基因组DNA甲基化分析。使用ChAMP R包鉴定病例和对照组之间甲基化CpGs的差异。采用R包“mediation”提供的贝叶斯估计方法，研究DNA甲基化在女性睡眠质量与不孕之间的中介作用。

结果:该调查包括86名育龄妇女，病例组和对照组各43名参与者。患者平均年龄27.6±2.8岁(病例组27.8±3.0岁，对照组27.4±2.7岁)。共鉴定出185个基因对应的262个差异甲基化CpGs。入睡困难是女性不孕症的危险因素(OR = 3.69, 95%CI = 1.14, 11.99)，发现DNA甲基化CpGs有因果中介作用。cg08298632的介导效应系数为0.10 (95%CI = 0.01 ~ 0.22)，该甲基化位点介导的总效应比例增加至64.3%。

结论:DNA甲基化CpGs (cg08298632)在女性入睡困难与不孕之间的关系中发挥重要作用。这些发现有助于我们理解女性入睡困难和不孕之间的潜在机制。为了充分了解这些发现的生物学意义和潜在的治疗应用，需要进一步的研究。发现的DNA甲基化位点为未来预防和治疗女性不孕症的研究提供了新的有价值的见解和潜在的靶点。

关键词:DNA甲基化;表观遗传学;不孕症;排卵障碍;睡眠质量。