Transcriptome analysis of eutopic endometrium in adenomyosis after GnRH agonist treatment

Reprod Biol Endocrinol. 2022 Jan 12;20(1):13. doi: 10.1186/s12958-021-00881-3.

Abstract

Background: Adenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer. In assisted reproductive technology (ART), gonadotropin-releasing hormone agonist (GnRHa) is often used to improve pregnancy rates in patients with adenomyosis, but the underlying mechanisms are poorly understood.

Methods: Eutopic endometrial specimens were collected from patients with adenomyosis before and after GnRHa treatment in the midsecretory phase. RNA sequencing (RNA-Seq) of these specimens was performed for transcriptome analysis. The differentially expressed genes (DEGs) of interest were confirmed by real-time PCR and immunohistochemistry.

Results: A total of 132 DEGs were identified in the endometrium of patients with adenomyosis after GnRHa treatment compared with the control group. Bioinformatics analysis predicted that immune system-associated signal transduction changed significantly after GnRHa treatment. Chemokine (C-C motif) ligand 21 (CCL21) was found to be highly expressed in the eutopic endometrium after GnRHa treatment, which may be involved in the improvement of endometrial receptivity in adenomyosis.

Conclusion: This study suggests that molecular regulation related to immune system-associated signal transduction is an important mechanism of GnRHa treatment in adenomyosis. Immunoreactive CCL21 is thought to regulate inflammatory events and participate in endometrial receptivity in adenomyosis.

Keywords: Adenomyosis; Chemokine ligand 21; Endometrial receptivity; Gonadotropin-releasing hormone agonist.

MeSH terms

  • Adenomyosis / drug therapy
  • Adenomyosis / genetics*
  • Adenomyosis / metabolism
  • Adenomyosis / pathology
  • Adult
  • Animals
  • Cohort Studies
  • Embryo Transfer / methods
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Fertility Agents, Female / pharmacology*
  • Fertility Agents, Female / therapeutic use
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gonadotropin-Releasing Hormone / agonists
  • Humans
  • Infertility, Female / etiology
  • Infertility, Female / genetics
  • Infertility, Female / metabolism
  • Infertility, Female / therapy
  • Mice
  • Mice, Inbred ICR
  • Pregnancy
  • Transcriptome / drug effects*

Substances

  • Fertility Agents, Female
  • Gonadotropin-Releasing Hormone