Elevated levels of KLF12 impair trophoblast syncytialization via GCM1 downregulation  

作　　者：Qing-Qing Shi Xing Wu Nan-Nan Kang Ji-Dong Zhou Xin Zhen Ze-Wu Li Gui-Jun Yan Hai-Xiang Sun Jing-Yu Liu Yang Liu 

机构地区：[1]Reproductive Medicine Center,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,Nanjing 210000,China [2]Center for Reproductive Medicine and Obstetrics and Gynecology,Nanjing Drum Tower Hospital,Nanjing University Medical School,Nanjing 210000,China [3]Center for Molecular Reproductive Medicine,Nanjing University,Nanjing 210000,China [4]Department of Obstetrics and Gynecology,Nanjing Drum Tower Hospital,Nanjing University Medical School,Nanjing 210000,China [5]Center for Reproductive Medicine,Affiliated Hospital of Jining Medical University,Jining 272000,China [6]Reproductive Medicine Center,Nanjing Drum Tower Hospital,State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210000,China

出　　处：《Reproductive and Developmental Medicine》2024年第3期131-137,共7页生殖与发育医学（英文版）

基　　金：supported by the National Natural Science Foundation of China(82030040,82301897,and 82171653);the Natural Science Foundation of Nanjing Drum Tower Hospital,Nanjing University Medical School(2022-JCYJ-QP-54);the Natural Science Foundation of Shandong(ZR202111300553 and ZR2022MH094).

摘　　要：Objective:Placental dysfunction is a major contributor to miscarriages in humans.We observed elevated expression of Kruppel-like factor 12(KLF12)in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies.This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.Methods:To investigate the role of KLF12 in placentation,we employed a model of forskolin-induced syncytialization in BeWo cells.Results:Our findings revealed that KLF12 expression is downregulated during normal syncytialization.Conversely,we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1(GCM1)expression.This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization.Furthermore,we observed placental deformities in KLF12-overexpressing mouse fetuses.Conclusion(s):This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression.These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.

关 键 词：KLF12 GCM1 Syncytialization MISCARRIAGE 

分 类 号：R714.8[医药卫生—妇产科学]