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Background <p>Sheep are short-day breeder, and their reproductvie activity can be activated by short photoperiods, but the regulatory mechanism remains unclear. In this study, hypothalamic tissues were collected from ovariectomized and estradiol-treated (OVX + E<sub>2</sub>) Sunite ewes exposed to artificial short-day (SP) and long-day (LP) photoperiods. Integrated whole-genome DNA methylation and transcriptomic analyses were performed to elucidate the regulatory mechanisms underlying photoperiod-mediated seasonal reproduction.</p> Results <p>The DNA methylation profiles of the hypothalamus were examined, and whole-genome single-base resolution methylome maps of the sheep hypothalamus were generated across seven time points under various photoperiod treatments. The results revealed that photoperiod-induced changes in genome-wide DNA methylation constitute a dynamic and reversible regulatory process, with a potential transition point occurring approximately 15&#xa0;days after the switch from SP to LP. Following integrated analysis of differentially methylated regions-related genes (DMRGs) and differentially expressed genes (DEGs), it showed that the DNA methylation levels before the transcription start site (TSS) of the overlapping gene were different, and a negative correlation between gene expression levels and mCG levels in gene promoters was found (<i>P</i> &lt; 0.01). Functional analysis of the overlapping genes revealed that pathways involved in synapse development, thyroid hormone signaling, and circadian rhythm were regulated by photoperiod-induced DNA methylation, thereby influencing hypothalamic function in photoperiod-dependent seasonal reproduction.</p> Conclusion <p>This study generated the whole-genome single-base resolution DNA methylome maps of sheep hypothalamus under different photoperiods, and elucidated the regulatory relationship between DNA methylation and photoperiod-dependent seasonal reproduction in sheep hypothalamus tissues. Our findings provided a valuable resource for further research on the underlying mechanisms of the hypothalamic-regulated reproductive seasonality in sheep.</p>

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Photoperiodic responsiveness in the DNA methylation and gene expression in the hypothalamus of ovariectomized and estradiol-treated ewes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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  • Xiaoyun He,
  • Ran Di,
  • Xiangyu Wang,
  • Xiaofei Guo,
  • Xiaosheng Zhang,
  • Jinlong Zhang,
  • Qiuyue Liu,
  • Mingxing Chu

摘要

Background

Sheep are short-day breeder, and their reproductvie activity can be activated by short photoperiods, but the regulatory mechanism remains unclear. In this study, hypothalamic tissues were collected from ovariectomized and estradiol-treated (OVX + E2) Sunite ewes exposed to artificial short-day (SP) and long-day (LP) photoperiods. Integrated whole-genome DNA methylation and transcriptomic analyses were performed to elucidate the regulatory mechanisms underlying photoperiod-mediated seasonal reproduction.

Results

The DNA methylation profiles of the hypothalamus were examined, and whole-genome single-base resolution methylome maps of the sheep hypothalamus were generated across seven time points under various photoperiod treatments. The results revealed that photoperiod-induced changes in genome-wide DNA methylation constitute a dynamic and reversible regulatory process, with a potential transition point occurring approximately 15 days after the switch from SP to LP. Following integrated analysis of differentially methylated regions-related genes (DMRGs) and differentially expressed genes (DEGs), it showed that the DNA methylation levels before the transcription start site (TSS) of the overlapping gene were different, and a negative correlation between gene expression levels and mCG levels in gene promoters was found (P < 0.01). Functional analysis of the overlapping genes revealed that pathways involved in synapse development, thyroid hormone signaling, and circadian rhythm were regulated by photoperiod-induced DNA methylation, thereby influencing hypothalamic function in photoperiod-dependent seasonal reproduction.

Conclusion

This study generated the whole-genome single-base resolution DNA methylome maps of sheep hypothalamus under different photoperiods, and elucidated the regulatory relationship between DNA methylation and photoperiod-dependent seasonal reproduction in sheep hypothalamus tissues. Our findings provided a valuable resource for further research on the underlying mechanisms of the hypothalamic-regulated reproductive seasonality in sheep.