Elevated levels of KLF12 impair trophoblast syncytialization via GCM1 downregulation

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

作者机构：Nanjing Med Univ Nanjing Drum Tower Hosp Reprod Med Ctr Clin Coll Nanjing 210000 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Ctr Reprod Med & Obstet & Gynecol Med Sch Nanjing Peoples R China Nanjing Univ Ctr Mol Reprod Med Nanjing 210000 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Med Sch Dept Obstet & Gynecol Nanjing 210000 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Reprod Med Ctr State Key Lab Pharmaceut Biotechnol Nanjing 210000 Peoples R China Jining Med Univ Affiliated Hosp Ctr Reprod Med Jining 272000 Peoples R China 

出 版 物：《REPRODUCTIVE AND DEVELOPMENTAL MEDICINE》 (Reproductive and Developmental Medicine)

年 卷 期：2024年第8卷第3期

页      面：131-137页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：National Natural Science Foundation of China [82030040, 82301897, 82171653] Natural Science Foundation of Nanjing Drum Tower Hospital, Nanjing University Medical School [2022-JCYJ-QP-54] Natural Science Foundation of Shandong [ZR202111300553, ZR2022MH094] 

主　　题：KLF12 GCM1 Syncytialization Miscarriage PLACENTAL DEVELOPMENT MISCARRIAGE DEFECTS 

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.