lncRNA/mRNA profiling of endometriosis rat uterine tissues during the implantation window

Int J Mol Med. 2019 Dec;44(6):2145-2160. doi: 10.3892/ijmm.2019.4370. Epub 2019 Oct 14.

Abstract

Endometriosis is associated with changes in long non‑coding RNA (lncRNA) and mRNA expression, but the exact changes during the implantation window are unknown. Therefore, this study aimed to explore the lncRNA and mRNA expression profiles in the uterus of rats with endometriosis during the implantation window. A total of 35 non‑pregnant female rats were randomized to the endometriosis (n=13), adipose tissue control (n=8) and blank control (n=14) groups. On the 5th day of pregnancy, the rats were sacrificed to obtain uterine tissues. lncRNA and mRNA were analyzed using gene chips. A total of five differentially expressed lncRNA and four mRNA were validated by reverse transcription‑quantitative (RT‑q)PCR. Immunohistochemistry and western blotting were used to determine the expression of the ADAM metallopeptidase with thrombospondin type 1 motif 7 (Adamts7), tumor protein p53 (Tp53), distal‑less homeobox 3 (Dlx3) and pyrimidinergic receptor P2Y6 (P2ry6) proteins. There were 115 upregulated lncRNAs, 51 downregulated lncRNAs, 97 upregulated mRNAs and 85 downregulated mRNAs in the endometriosis group. RT‑qPCR confirmed the trends for five lncRNAs and four mRNAs (Adamts7, Tp53, Dlx3 and P2ry6). The relative protein expression levels of Adamts7, P2ry6, Dlx3 and TP53 were significantly different in the endometriosis group (P<0.05 vs. controls). Bioinformatics predicted the co‑expression relationship of the selected five lncRNA and four mRNA. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes predicted that Adamts7, P2ry6, Dlx3 and TP53 were involved in endometriosis‑related inflammation and reproductive pathways. In conclusion, the changes in the expression of lncRNAs, mRNAs and proteins (Adamts7, P2ry6, Dlx3 and TP53) may possibly affect endometrial receptivity in rats with endometriosis during the implantation window, probably resulting in implantation failure of the embryo.

MeSH terms

  • ADAMTS7 Protein / genetics*
  • Animals
  • Embryo Implantation / genetics
  • Endometriosis / genetics*
  • Endometriosis / pathology
  • Endometrium / growth & development
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics*
  • Humans
  • Pregnancy
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Purinergic P2 / genetics*
  • Transcription Factors / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Uterus / growth & development
  • Uterus / pathology

Substances

  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Receptors, Purinergic P2
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • purinoceptor P2Y6
  • ADAMTS7 Protein
  • Adamts7 protein, rat