Abstract

Background

Endometrial receptivity (ERE) is a transient uterine state that determines the success of blastocyst implantation; however, the epigenomic regulation underlying ERE establishment in goats remains unclear. Here, we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats, utilizing RNA-seq, ATAC-seq, and H3K27ac CUT&Tag.

Results

A total of 3,143 differentially expressed genes (DEGs) were identified, accompanied by significant alterations in chromatin accessibility and H3K27ac modifications between receptive and non-receptive endometria. The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion, immune tolerance, and embryo attachment. Motif enrichment and transcription factor (TF) footprinting analyses identified members of the FOS/JUN, SOX, HNF1, CEBP, and BATF families as candidate regulators, implicating downstream genes involved in ERE establishment, includingSPP1,FOXO1,KLF4/6,STAT1,IFI6,ITGB8,PLAC8,DUSP4,NR1D1,ISG15,RUFY4, andPIK3R3. In addition, numerous super-enhancers were identified, indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium. Integration of multi-omics datasets revealed a strong correlation (r> 0.7) among chromatin accessibility, H3K27ac activation, and the expression of 172 DEGs. Furthermore, a set of hub genes (KLF6,IFI6,MCL1,SDC4,SUSD6,MAFF, andIL6R) that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.

Conclusions

Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation. These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.

Data Availability

All data analyzed during this study are available in the article and/or supporting information; further inquiries can be directed to the corresponding author on reasonable request.

Abbreviations

  • ATAC-seq:: Assay for transposase-accessible chromatin using sequencing
  • CON:: Control group
  • CUT&Tag:: Cleavage under targets and tagmentation
  • DAR:: Differentially accessible regions
  • DEG:: Differentially expressed gene
  • DP:: Differential peaks
  • E2 :: 17β-Estradiol
  • EEC:: Endometrial epithelium cell
  • Enh:: Enhancer
  • ERE:: Endometrial receptivity
  • ESC:: Endometrial stromal cell
  • FAANG:: Functional Annotation of Animal Genomes
  • FarmGTEx:: Farm Animal Genotype-Tissue Expression
  • FDR:: False discovery rate
  • FIMO:: Find Individual Motif Occurrences
  • GO:: Gene Ontology
  • GTF:: General transcription factor
  • IDR:: Irreproducible discovery rate
  • IFN-τ:: Interferon-tau
  • IVF:: In-vitro fertilization
  • KEGG:: Kyoto Encyclopedia of Genes and Genomes
  • MEME:: Multiple Em for Motif Elicitation
  • P4 :: Progesterone
  • PMT:: Plasma membrane transformation
  • RNA-seq:: RNA-sequencing
  • RT-qPCR:: Real-time quantitative PCR
  • SEM:: Scanning electron microscope
  • sEnh:: Super-enhancer
  • tEnh:: Typical enhancer
  • TF:: Transcription factor
  • TSS:: Transcription start sites
  • UTR:: Untranslated Regions

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Acknowledgements

We thank the Chongqing Key Laboratory of Herbivore Science for providing data for this study and technical assistance, and Dr. Xiaochuan Chen’s contribution to this work. We also thank bioRender ( https://www.biorender.com/ ) and Figdraw ( https://www.figdraw.com ) for assisting in the creation of scientific illustrations.

Funding

This work was financially supported by the National Natural Science Foundation of China (No.32502862), the Collection, Utilization and Innovation of Animal Resources by Research Institutes and Enterprises of Chongqing (No. Cqnyncw-kqlhtxm), the Chongqing Modern Agricultural Industry Technology System (CQMAITS202513), and the Key Project of Chongqing Technology Innovation and Application Development Special Program (CTSB2025TIAD-KPX0079).

Ethics Declaration

Ethics approval and consent to participate

All animal studies were conducted in accordance with the Southwest University Institutional Animal Care and Use Committee (No. IACUC-20240506-06) regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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