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...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.展开更多
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).
文摘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.
