Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of Education, Guizhou University; College of Animal Science, Guizhou University, Guiyang, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Wen-Wen Shi
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Yu-Qian Lin
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Zhen-Shan Yang
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Ying Wang
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Meng-Yuan Li
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Yue Li
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
Ai-Xia Liu
Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Zhejiang, China
Yali Hu
Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Key Laboratory of Plateau Mountain Animal Genetics, Breeding and Reproduction, Ministry of Education, Guizhou University; College of Animal Science, Guizhou University, Guiyang, China
Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI2 and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI2-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.