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<p>In this cohort, we explored the DNA methylation changes of 3 genes of the canonical Wnt/β-catenin and RANKL/OPG pathways related to bone homeostasis in cord blood at birth. Those mothers with poor sleep quality in the first trimester of pregnancy had 5.9 times higher odds of complete <i>OPG</i> methylation compared to those with good sleep (adjusted OR = 5.9; 95% CI 1.04–33.0; <i>p</i> = 0.045). Maternal lifestyle factors during pregnancy can influence fetal development through epigenetic mechanisms, potentially affecting neonatal skeletal programming and long-term bone health. Sleep quality is an important, modifiable maternal factor, but its role in shaping epigenetic regulation of bone development remains unclear. We aimed to investigate the association between maternal sleep quality during pregnancy and DNA methylation of key genes of the canonical Wnt/β-catenin signaling pathway, Wnt Family Member 10B (<i>WNT10B</i>), β-catenin (<i>CTNNB1</i>), and osteoprotegerin (<i>OPG or TNFRSF11B</i>) in the offspring's cord blood samples at birth. A total of 300 pregnant women were recruited as a sub-study of the PERSIAN Birth Cohort-Isfahan. Maternal sleep patterns were assessed using the Pittsburgh Sleep Quality Index (PSQI). Methylation at cytosine-guanine (CpG) dinucleotide sites within the promoters of <i>WNT10B,</i> β-catenin, and <i>OPG</i> was quantified in offspring’s cord blood at birth, and associations with maternal sleep quality across all trimesters were assessed. Poor sleep quality in the first trimester was significantly associated with increased <i>OPG</i> methylation (adjusted OR = 1.40, 95% CI 1.05–1.8, <i>p</i> = 0.023). Mothers with poor sleep quality (PSQI ≥ 5) in the first trimester had 5.9 times higher odds of complete <i>OPG</i> methylation compared to those with good sleep quality (adjusted OR = 5.9, 95% CI 1.04–33.0, <i>p</i> = 0.045). However, associations with <i>WNT10B</i> and β-catenin were not statistically significant. Maternal sleep quality during early gestation may influence the DNA methylation and epigenetic programming of bone-related genes in neonatal cord blood, emphasizing the importance of maternal lifestyle as a modifiable factor shaping early-life bone health.</p> Graphical Abstract <p></p>

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Maternal Sleep Quality and Early-Life Epigenetic Programming of Bone-Related Genes in Neonatal Cord Blood: Findings from the PERSIAN Birth Cohort, Isfahan

  • 期刊论文

  • 发表日期：

    2026年5月28日

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  • Sadegh Baradaran Mahdavi,
  • Anoosha Niazmand,
  • Seyed Morteza Javadirad,
  • Seyede Shahrbanoo Daniali,
  • Nafiseh Mozafarian,
  • Shekoufeh Roudashti,
  • Motahar Heidari-Beni,
  • Mahsa Rafieian,
  • Maryam Bemanalizadeh,
  • Parnian Poursafa,
  • Vajihe Azimian Zavareh,
  • Awat Feizi,
  • Rasoul Salehi,
  • Roya Kelishadi

摘要

In this cohort, we explored the DNA methylation changes of 3 genes of the canonical Wnt/β-catenin and RANKL/OPG pathways related to bone homeostasis in cord blood at birth. Those mothers with poor sleep quality in the first trimester of pregnancy had 5.9 times higher odds of complete OPG methylation compared to those with good sleep (adjusted OR = 5.9; 95% CI 1.04–33.0; p = 0.045). Maternal lifestyle factors during pregnancy can influence fetal development through epigenetic mechanisms, potentially affecting neonatal skeletal programming and long-term bone health. Sleep quality is an important, modifiable maternal factor, but its role in shaping epigenetic regulation of bone development remains unclear. We aimed to investigate the association between maternal sleep quality during pregnancy and DNA methylation of key genes of the canonical Wnt/β-catenin signaling pathway, Wnt Family Member 10B (WNT10B), β-catenin (CTNNB1), and osteoprotegerin (OPG or TNFRSF11B) in the offspring's cord blood samples at birth. A total of 300 pregnant women were recruited as a sub-study of the PERSIAN Birth Cohort-Isfahan. Maternal sleep patterns were assessed using the Pittsburgh Sleep Quality Index (PSQI). Methylation at cytosine-guanine (CpG) dinucleotide sites within the promoters of WNT10B, β-catenin, and OPG was quantified in offspring’s cord blood at birth, and associations with maternal sleep quality across all trimesters were assessed. Poor sleep quality in the first trimester was significantly associated with increased OPG methylation (adjusted OR = 1.40, 95% CI 1.05–1.8, p = 0.023). Mothers with poor sleep quality (PSQI ≥ 5) in the first trimester had 5.9 times higher odds of complete OPG methylation compared to those with good sleep quality (adjusted OR = 5.9, 95% CI 1.04–33.0, p = 0.045). However, associations with WNT10B and β-catenin were not statistically significant. Maternal sleep quality during early gestation may influence the DNA methylation and epigenetic programming of bone-related genes in neonatal cord blood, emphasizing the importance of maternal lifestyle as a modifiable factor shaping early-life bone health.

Graphical Abstract