Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells

Tze Sing Huang, Yi Jen Chen*, Teh Ying Chou, Chih Yao Chen, Hsin Yang Li, Ben Shian Huang, Hsiao Wen Tsai, Hsin Yi Lan, Cheng Hsuan Chang, Nae Fang Twu, Ming Shyen Yen, Peng Hui Wang, Kuan Chong Chao, Chun Chung Lee, Muh Hwa Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Adenomyosis is an oestrogen-dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen-associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen-induced Slug expression was critical for endometrial epithelial-mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a Slug-VEGF axis in endometrial epithelial cells, and also induced pro-angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen-induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2-Slug-VEGF pathway.

Original languageEnglish
Pages (from-to)1358-1371
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Issue number7
StatePublished - Jul 2014


  • Adenomyosis
  • Angiogenesis
  • Epithelial-mesenchymal transition
  • Oestrogen
  • Slug


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