Serial gene co-expression network approach to mine biological meanings from integrated transcriptomes of the porcine endometrium during estrous cycle

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The estrous cycle is a complex process regulated by several hormones. To understand the dynamic changes in gene expression that takes place in the swine endometrium during the estrous cycle relative to the day of estrus onset, we performed RNA-sequencing analysis on days 0, 3, 6, 9, 12, 15, and 18, resulting in the identification of 4495 differentially expressed genes (DEGs; Q ≤ 0.05 and |log2FC| ≥ 1) at various phases in the estrous cycle. These DEGs were integrated into multiple gene co-expression networks based on different fold changes and correlation coefficient (R2) thresholds and a suitable network, which included 899 genes (|log2FC| ≥ 2 and R2 ≥ 0.99), was identified for downstream analyses based on the biological relevance of the Gene Ontology (GO) terms enriched. The genes in this network were partitioned into 6 clusters based on the expression pattern. Several GO terms including cell cycle, apoptosis, hormone signaling, and lipid biosynthetic process were found to be enriched. Furthermore, we found 15 significant KEGG pathways, including cell adhesion molecules, cytokine-cytokine receptor signaling, steroid biosynthesis, and estrogen signaling pathways. We identified several genes and GO terms to be stage-specific. Moreover, the identified genes and pathways extend our understanding of porcine endometrial regulation during estrous cycle and will serve as a good resource for future studies.

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The authors would like to thank the Rural Development Administration and National Institute of Animal Science for providing the funding to carry out this research. JMK was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea, grant number NRF-2019R1F1A1061542

Availability of data

The data generated in this study are deposited in NCBI SRA data base under the accession no. SRP127622.


This study was carried out with the support of “Cooperative Research Program for Agriculture Science and Technology Development” (project title: Porcine epigenomic map construction and investigation of the imprinted genes, Project No. PJ011876), Rural Development Administration (RDA), Republic of Korea. KS is supported by a 2019 RDA Fellowship Program of National Institute of Animal Science, Rural Development Administration, Republic of Korea.

Author information

KS, WCP, and JMK analyzed the data. KS and JMK wrote the manuscript. JEP and JMK performed the experiment. HK and KTL designed and supervised the experiment and project. GWJ, DL, and JEP supervised the project. All authors reviewed the manuscript and approved.

Correspondence to Hakhyun Ka or Jong-Eun Park or Jun-Mo Kim.

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Srikanth, K., Park, W., Lim, D. et al. Serial gene co-expression network approach to mine biological meanings from integrated transcriptomes of the porcine endometrium during estrous cycle. Funct Integr Genomics 20, 117–131 (2020).

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  • DEGs
  • Estrous cycle
  • Gene co-expression network
  • Porcine endometrium
  • RNA-seq