Endoplasmic reticulum stress in mouse decidua during early pregnancy.
Unfolded or misfolded protein accumulation in the endoplasmic reticulum lumen leads to endoplasmic reticulum stress (ER stress). Although it is known that ER stress is crucial for mammalian reproduction, little is known about its physiological significance and underlying mechanism during decidualization. Here we show that Ire-Xbp1 signal transduction pathway of unfolded protein response (UPR) is activated in decidual cells. The process of decidualization is compromised by ER stress inhibitor tauroursodeoxycholic acid sodium (TUDCA) and Ire specific inhibitor STF-083010 both in vivo and in vitro. A high concentration of ER stress inducer tunicamycin (TM) suppresses stromal cells proliferation and decidualization, while a lower concentration is beneficial. We further show that ER stress induces DNA damage and polyploidization in stromal cells. In conclusion, our data suggest that the GRP78/Ire1/Xbp1 signaling pathway of ER stress-UPR is activated and involved in mouse decidualization.
Department of Biology, Shantou University, Shantou 515063, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Xiao-Wei
XW
Gu
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Jia-Qi
JQ
Yan
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Hai-Ting
HT
Dou
Department of Biology, Shantou University, Shantou 515063, China.
Jie
J
Liu
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Li
L
Liu
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Meng-Long
ML
Zhao
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Xiao-Huan
XH
Liang
Department of Biology, Shantou University, Shantou 515063, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address: zmyang@scau.edu.cn.
Zeng-Ming
ZM
Yang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1 / Q000378:metabolism*
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; C556690:STF 083010; D013449:Sulfonamides; D013876:Thiophenes; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D014415:Tunicamycin; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
DNA damage; Decidualization; Endoplasmic reticulum stress; Polyploidization