Dysregulated glycolysis underpins high-fat-associated endometrial decidualization impairment during early pregnancy in mice

作者全名："Chen, Zixuan; E, Yiwen; Xiong, Jun; Li, Weike; Chen, Xuemei; Li, Na; Long, Jing; Tong, Chao; He, Junlin; Li, Fangfang; Zhang, Cuihua; Wang, Yingxiong; Gao, Rufei"

作者地址："[Chen, Zixuan; E, Yiwen; Xiong, Jun; Li, Weike; Chen, Xuemei; Li, Na; Long, Jing; He, Junlin; Li, Fangfang; Wang, Yingxiong; Gao, Rufei] Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Li, Weike; Li, Na; Long, Jing; Wang, Yingxiong] Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China; [Tong, Chao] Chongqing Med Univ, State Key Lab Maternal & Fetal Med Chongqing Munic, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Zhang, Cuihua; Gao, Rufei] Chongqing Med Univ, Chongqing Hlth Ctr Women & Children, Women & Childrens Hosp, Chongqing, Peoples R China; [Gao, Rufei] Chongqing Hlth Ctr Women & Children, Chongqing Key Lab Human Embryo Engn, Chongqing, Peoples R China; [Gao, Rufei] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China"

通信作者："Gao, RF (通讯作者)，Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China."

来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000999064400001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：1869

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Obesity; High -fat diet; Early pregnancy; Decidualization; Glycolysis

摘要："Pregnancy complications are more likely to occur in obese women because of defective decidualization. However, the specific mechanism of glycolysis in decidual modulation associated with obesity remains unknown. Therefore, we explored the role of glycolysis in the endometrium of obese pregnant mice during decidualization. C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. All obesity related parameters were significantly higher in the HFD mice than control. Furthermore, the HFD mice had fewer implantation sites, a smaller decidual area growth, and decreased decidualization marker protein expression than control. The HFD mice also had significantly decreased lactate production and glycolytic enzyme expression. To confirm the functional role of glycolysis during the decidual period in obese pregnant mice, we extracted endometrial stromal cells (ESCs) and treated them with oleic acid (OA) and palmitic acid (PA) to mimic a high-fat environment. Decidualization and glycolysis were significantly restricted in the OA-and PA-treated groups. Moreover, we administered a glycolytic inhibitor, 2-DG, and an agonist, pioglitazone. 2-DG treatment considerably decreased the cells' glycolysis and decidualization. However, pioglitazone treatment improved glycolysis and alleviated defective decidualization. In conclusion, obesity-induced endometrial glycolysis modifications and key glycolytic enzyme downregulation during early pregnancy might cause abnormal decidualization, leading to an unsustainable pregnancy."

基金机构："Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0041]; CQMU Program for Youth Innovation in Future Medicine [W0039]; open project of Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Health Center for Women and Children [2020KFKT002]; Chongqing post-graduate scientific research innovation project [CYS20207]"

基金资助正文："This work was supported by the Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0041) , the CQMU Program for Youth Innovation in Future Medicine (W0039) , the open project of Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Health Center for Women and Children (2020KFKT002) and Chongqing post-graduate scientific research innovation project (CYS20207) ."