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

Authors：Ying Tang, Hong Gan, Baolin Wang, Xiaorui Wang , Mengdie Li, Qianhui Yang, Menglong Geng, Peng Zhu, Shanshan Shao, Fangbiao Tao

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

DOI: 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：本研究旨在调查女性睡眠质量与不孕症之间的关联，并探讨DNA甲基化在这种关联中的中介作用。

方法：本研究是一项基于人群的病例对照研究。在无排卵性不孕症（n = 43）和健康对照组（n = 43）的女性中调查了睡眠质量与不孕症之间的关系。使用Illumina Infinium人甲基化850k BeadChip从外周血样本中分析全基因组DNA甲基化。使用ChAMP R包鉴定病例和对照组之间的差异甲基化CpG。使用R包“中介”提供的贝叶斯估计方法研究了DNA甲基化在女性睡眠质量与不孕症之间的中介作用。

结果：该调查包括86名育龄妇女，病例组和对照组各有43名参与者。妇女的平均年龄为27.6岁±2.8岁（病例组：27.8±3.0岁，对照组：27.4±2.7岁）。共鉴定出262个差异甲基化CpG，对应于185个基因。入睡困难是女性不孕症的危险因素（OR = 3.69,95%CI = 1.14,11.99），并且发现了DNA甲基化CpGs的因果介导效应。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提高到64.3%。

结论：这些结果表明，DNA甲基化CpGs（cg08298632）在女性入睡困难与不孕之间的关系中起重要作用。这些发现有助于我们了解将女性入睡困难和不孕症联系起来的潜在机制。需要进一步的研究来充分了解这些发现的生物学意义和潜在的治疗应用。已确定的DNA甲基化位点为旨在预防和治疗女性不孕症的未来研究提供了新的有价值的见解和潜在靶点。

关键词：DNA甲基化；表观遗传学；不孕症；排卵障碍；睡眠质量