2. Academic Validation
  3. Fructose-1,6-bisphosphate prevents pregnancy loss by inducing decidual COX-2+ macrophage differentiation

Fructose-1,6-bisphosphate prevents pregnancy loss by inducing decidual COX-2+ macrophage differentiation

  • Sci Adv. 2022 Feb 25;8(8):eabj2488. doi: 10.1126/sciadv.abj2488.
Wen-Jie Zhou 1 2 3,  Hui-Li Yang 1,  Jie Mei 4,  Kai-Kai Chang 1,  Han Lu 1 3,  Zhen-Zhen Lai 1,  Jia-Wei Shi 1,  Xiao-Hui Wang 3,  Ke Wu 1,  Tao Zhang 5,  Jian Wang 1,  Jian-Song Sun 6,  Jiang-Feng Ye 7,  Da-Jin Li 1,  Jian-Yuan Zhao 8,  Li-Ping Jin 3,  Ming-Qing Li 1 9
Affiliations

Affiliations

  • 1 Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China.
  • 2 Reproductive Medical Center, Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
  • 3 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200040, People's Republic of China.
  • 4 Reproductive Medicine Center, Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medicine School, Nanjing 210000, People's Republic of China.
  • 5 Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
  • 6 National Research Centre for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, Jiangxi Province 330022, People's Republic of China.
  • 7 Division of Obstetrics and Gynecology, KK Women's and Children's Hospital, Singapore 229899, Singapore.
  • 8 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.
  • 9 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, People's Republic of China.
PMID: 35196096 DOI: 10.1126/sciadv.abj2488
Abstract

Decidualization is an intricate biological process in which extensive remodeling of the endometrium occurs to support the development of an implanting blastocyst. However, the immunometabolic mechanisms underlying this process are still largely unknown. We found that the decidualization process is accompanied by the accumulation of fructose-1,6-bisphosphate (FBP). The combination of FBP with Pyruvate Kinase M stimulated IL-27 secretion by endometrial stromal cells in an ERK/c-FOS-dependent manner. IL-27 induced decidual COX-2+ M2-like macrophage differentiation, which promotes decidualization, trophoblast invasion, and maternal-fetal tolerance. Transfer of Ptgs2+/COX-2+ macrophages prevented fetal loss in IL27RA-deleted pregnant mice. FBP levels were low in plasma and decidual tissues of patients with unexplained recurrent spontaneous abortion. In therapeutic studies, FBP supplementation significantly improved embryo loss by up-regulation of IL-27-induced COX-2+ macrophage differentiation in a mouse model of spontaneous abortion. These findings collectively provide a scientific basis for a potential therapeutic strategy to prevent pregnancy loss.

Figures
Products