Ggps1 deficiency in the uterus results in dystocia by disrupting uterine contraction  

作　　者：Yong-Juan Sang Qiang Wang Feng Zheng Yue Hua Xin-Ying Wang Jing-Zi Zhang Kang Li Hai-Quan Wang Yue Zhao Min-Sheng Zhu Hai-Xiang Sun Chao-Jun Li 

机构地区：[1]State Key Laboratory of Pharmaceutical Biotechnology,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Model Animal Research Center,Nanjing University,Nanjing 210093,China [2]Department of Neurosurgery,Jingling Hospital,School of Medicine,Nanjing University,Nanjing 210002,China

出　　处：《Journal of Molecular Cell Biology》2021年第2期116-127,共12页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31530046);the National Science and Technology Major Project(SQ2018YFC100242).

摘　　要：Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality;thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.

关 键 词：uterine contraction protein prenylation DYSTOCIA STATIN RHOA 

分 类 号：R714.4[医药卫生—妇产科学]