2. Academic Validation
  3. IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis

IL-27 promotes decidualization via the STAT3-ESR/PGR regulatory axis

  • J Reprod Immunol. 2022 Jun;151:103623. doi: 10.1016/j.jri.2022.103623.
Xin-Yan Zhang 1,  Hui-Hui Shen 2,  Xue-Yun Qin 2,  Cheng-Jie Wang 2,  Wen-Ting Hu 2,  Song-Ping Liu 3,  Jiang-Nan Wu 4,  Feng Xie 5,  Feng-Yuan Xu 6,  Shi-Min Zhao 7,  Yi-Yuan Yuan 8,  Ming-Qing Li 9
Affiliations

Affiliations

  • 1 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China; NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China.
  • 2 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China.
  • 3 Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China.
  • 4 Clinical Epidemiology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200011, People's Republic of China.
  • 5 Center for Diagnosis and Treatment of Cervical and Uterine Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, People's Republic of China.
  • 6 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 7 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China. Electronic address: [email protected].
  • 8 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China; NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
  • 9 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China; NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 201203, People's Republic of China; Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200080, People's Republic of China. Electronic address: [email protected].
PMID: 35430461 DOI: 10.1016/j.jri.2022.103623
Abstract

Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from IL27RA-/- (knockout of IL27RA) female mice. Moreover, knockout of IL27RA did not affect the estrus cycle and folliculogenesis in mice but reduced implantation rate with the impairing decidualization. Mechanistically, IL-27 upregulated the expression of ESR1, ESR2 and PGR in ESCs and DSCs, as well as the phosphorylation level of STAT3. In the presence of estrogen plus progesterone, treatment with ESCs with anti-IL-27 inhibited the activation of STAT3. Also, the expression of ESR, PGR was decreased in IL27RA-/- mice. In conclusion, these findings demonstrate that IL-27 upregulated by estrogen and progestogen promotes decidualization possibly through a STAT3-dominant pathway.

Keywords

IL-27RA; Interleukin-27; STAT3; decidualization; progesterone.

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