The identification and functional analysis of CircRNAs in endometrial receptivity of mice with polycystic ovary

Environ Toxicol. 2024 Mar;39(3):1456-1470. doi: 10.1002/tox.24052. Epub 2023 Nov 21.

Abstract

The disorders of endometrial receptivity and ovulatory dysfunction are both significant causes of infertility in patients with polycystic ovary syndrome (PCOS). In this study, we investigated the expression profile and functional implications of circular RNAs (circRNAs) in the endometrial receptivity of PCOS-affected mice. Twenty-four female C57BL/6 mice were divided into PCOS and normal control groups. The PCOS group received subcutaneous DHEA treatment, while the control group remained untreated. Gene chip technology was utilized to analyze circRNA expression in endometrial tissues on the fourth day of gestation with subsequent bioinformatics analyses into circRNA functions. Furthermore, endometrial epithelial cells were used to determine represented circRNA functions. Results showed that the PCOS group exhibited 205 differentially expressed circRNAs, with 147 upregulated and 58 downregulated ones. qRT-PCR confirmed differential expression of circRNAs, including circRNA_38548, circRNA_001686, circRNA_38550, and circRNA_27938. Predicted target genes and a circRNA-miRNA-mRNA regulatory network were constructed. Additionally, four circRNAs (circRNA_38548, circRNA_38550, and circRNA_001686) were identified to contribute to abnormal endometrial receptivity by regulating genes such as Lifr, FOXK1, FOXO1, HOXA10, through interactions with miRNAs. Further research is warranted to elucidate the underlying mechanisms involving these circRNAs.

Keywords: PCOS; circular RNA; endometrial receptivity; expression profiling.

MeSH terms

  • Animals
  • Female
  • Forkhead Transcription Factors
  • Gene Expression Profiling / methods
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • Polycystic Ovary Syndrome* / genetics
  • RNA, Circular / metabolism

Substances

  • RNA, Circular
  • MicroRNAs
  • FOXK1 protein, human
  • Forkhead Transcription Factors