1. Academic Validation
  2. An IGF1-expressing endometrial stromal cell population is associated with human decidualization

An IGF1-expressing endometrial stromal cell population is associated with human decidualization

  • BMC Biol. 2022 Dec 8;20(1):276. doi: 10.1186/s12915-022-01483-0.
Jia-Wei Shi 1 2 Zhen-Zhen Lai 2 Hui-Li Yang 1 Wen-Jie Zhou 3 Xiao-Ya Zhao 4 Feng Xie 5 Song-Ping Liu 6 Wei-Dong Chen 7 Tao Zhang 8 Jiang-Feng Ye 9 Xiang-Yu Zhou 1 10 Ming-Qing Li 11 12 13
Affiliations

Affiliations

  • 1 NHC Key Lab of Reproduction Regulation, Hospital of Obstetrics and Gynecology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, 200080, China.
  • 2 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200080, China.
  • 3 Center of Reproductive Medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 4 Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China.
  • 5 Center for Diagnosis and Treatment of Cervical and Uterine Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, China.
  • 6 Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai, 201508, China.
  • 7 NovelBio Bio-Pharm Technology Co., Ltd, Shanghai, 201112, China.
  • 8 Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
  • 9 Institute for Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, 138632, Singapore.
  • 10 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.
  • 11 NHC Key Lab of Reproduction Regulation, Hospital of Obstetrics and Gynecology, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, 200080, China. mqli@fudan.edu.cn.
  • 12 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200080, China. mqli@fudan.edu.cn.
  • 13 Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai, 201508, China. mqli@fudan.edu.cn.
Abstract

Background: Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization.

Results: We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA Sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients.

Conclusions: Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

Keywords

Decidual stromal cells; Decidualization; IGF1; IGF1R; IL1B; Recurrent implantation failure.

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