Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2017, Vol. 13 ›› Issue (01): 71 -77. doi: 10.3877/cma.j.issn.1673-5250.2017.01.013

Special Issue:

Original Article

Changes of glycometabolic genes in placenta of intrahepatic cholestasis of pregnancy

Yun Chen1, Aiyun Xing1, Yayi Hu1,()   

  1. 1. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2016-11-05 Revised:2017-01-08 Published:2017-02-01
  • Corresponding author: Yayi Hu
  • About author:
    Corresponding author: Hu Yayi, Email:
Objective

To investigate the expression of glucose transporter (GLUT1), phosphoglycerate kinase(PGK1) and lactate dehydrogenase (LDHA) in placentas of women with intrahepatic cholestasis of pregnancy (ICP).

Methods

From June to October, 2014, a total of 20 samples of placentas from women with ICP were included as the study group, and another 20 samples of normal placentas were selected as control group according to random number table. The relative expression levels of GLUT1 mRNA, PGK1 mRNA and LDHA mRNA were measured by real-time polymerase chain reaction (RT-PCR), and the relative protein levels of GLUT1, PGK1, LDHA were detected by Western blotting assay and immunohistological analysis. There were no significant differences between two groups in age, gestational age, gravidity, parity, birth weight of newborns and placental weight (P>0.05). The study protocol was approved by the Ethical Review Board of Investigation in Human Being of West China Second University Hospital, Sichuan University. Informed consent was obtained from the parents of each participating patients.

Results

① There were no statistically significant difference between two groups in the relative expression levels of GLUT1 mRNA, PGK1 mRNA and LDHA mRNA (P>0.05). ② The relative protein levels of GLUT1, PGK1 and LDHA in control group were statistically lower than those in ICP group, which with significant difference (t=3.270, P=0.003; t=4.222, P<0.001; t=3.585, P=0.002). ③ All the proteins including GLUT1, PGK1 and LDHA were detected in the cytoplasma of cytotrophoblast and syncytiotrophoblast.

Conclusions

Under hypoxic conditions in pregnant women with ICP, the increased level of glycolysis may play a role in negative pregnancy outcomes.

表1 2组产妇胎盘组织中GLUT1、PGK1及LDHA mRNA相对表达水平比较(±s)
表2 2组产妇胎盘组织中GLUT1、PGK1及LDHA蛋白相对表达水平比较(±s)
图1 2组胎盘组织中GLUT1、PGK1及LDHA蛋白相对表达水平
图2 2组胎盘组织中GLUT1、PGK1及LDHA蛋白在细胞内的表达定位(图2A、2B:GLUT1蛋白;图2C、2D:PGK1蛋白;图2E、2F:LDHA蛋白)(SP染色,高倍镜)
[1]
Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution[J]. Ethn Health, 1999, 4(1-2): 35-37.
[2]
Luo XL, Zhang WY. Obstetrical disease spectrum in China: an epidemiological study of 111,767 cases in 2011[J]. Chin Med J (Engl), 2015, 128(9): 1137-1146.
[3]
王莉,叶晓秀.妊娠期肝内胆汁淤积症与围生儿结局关系的研究进展[J].中华妇幼临床医学杂志(电子版),2015,9(5): 666-670.
[4]
Wikström Shemer E, Marschall HU, Ludvigsson JF, et al. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study[J]. BJOG, 2013, 120(6): 717-723.
[5]
Zhou B, Wang CH, Ding RB, et al. The relationship between the internal oxidation-reduction system and fetal distress on pregnant patients with intrahepatic cholestasis[J]. European Rev Med Pharmacol Sci, 2015, 19(20): 3817-3821.
[6]
Kim JW, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia[J]. Cell Metab, 2006, 3(3): 177-185.
[7]
Papandreou I, Cairns RA, Fontana L, et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption[J]. Cell Metab, 2006, 3(3): 187-197.
[8]
Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system[J]. Nat Med, 2003, 9(6): 677-684.
[9]
曹泽毅,主编.中华妇产科. 2版[M]. 北京:人民卫生出版社,2004:468-475.
[10]
Reid R, Ivey KJ, Rencoret RH, et al. Fetal complications of obstetric cholestasis[J]. Br Med J, 1976, 1(6014): 870-872.
[11]
王晓东,刘淑云,衡正昌. 妊娠肝内胆汁淤积症胎儿宫内缺氧机理的初步探讨[J]. 中华妇产科杂志,1998,33(2): 68-70.
[12]
贺晶,陈璐,梁琤.妊娠期肝内胆汁淤积症发生死胎的临床因素分析[J].中华妇产科杂志,2011,46(5): 333-337.
[13]
Lammert F, Marschall HU, Glantz A, et al. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management[J]. J Hepatol, 2000, 33(6): 1012-1021.
[14]
Fisk NM, Storey GN. Fetal outcome in obstetric cholestasis[J]. Br J Obstet Gynaecol, 1988, 95(11): 1137-1143.
[15]
Sepúlveda WH, González C, Cruz MA, et al. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins[J]. Eur J Obstet Gynecol Reprod Biol, 1991, 42(3): 211-215.
[16]
Wikström Shemer E, Thorsell M, Östlund E, et al. Stereological assessment of placental morphology in intrahepatic cholestasis of pregnancy[J]. Placenta, 2012, 33(11): 914-918.
[17]
Perez MJ, Velasco E, Monte MJ, et al. Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver[J]. Toxicology, 2006, 225(2-3): 183-194.
[18]
胡雅毅,王晓东,刘淑芸. 急性缺氧对妊娠期肝内胆汁淤积症患者胎盘组织HIF-1α表达的影响及与P53相关性的研究[J]. 四川大学学报(医学版),2006,37(6): 901-903.
[19]
Tal R. The role of hypoxia and hypoxia-inducible factor-1alpha in preeclampsia pathogenesis[J]. Biol Reprod, 2012, 87(6): 134.
[20]
Hayashi M, Sakata M, Takeda T, et al. Induction of glucose transporter 1 expression through hypoxia-inducible factor 1alpha under hypoxic conditions in trophoblast-derived cells[J]. J Endocrinol, 2004, 183(1): 145-154.
[21]
Wagegg M, Gaber T, Lohanatha FL, et al. Hypoxia promotes osteogenesis but suppresses adipogenesis of human mesenchymal stromal cells in a hypoxia-inducible factor-1 dependent manner[J]. PLoS One, 2012, 7(9): e46483.
[22]
Barros LF, Yudilevich DL, Jarvis SM, et al. Quantitation and immunolocalization of glucose transporters in the human placenta[J]. Placenta, 1995, 16(7): 623-633.
[23]
胡雅毅,刘淑芸,王晓东,等. 妊娠肝内胆汁淤积症患者胎盘组织缺氧及复氧时缺氧诱导因子1α表达水平的变化[J]. 中华妇产科杂志,2007,42(1): 54-56.
[24]
Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response elements of the human vascular endothelial grown factor gene mediate transcriptional regulation by nitricoxide:control of hypoxia inducible factor 1α activity by nitricoxide[J]. Hemost Thrombs Vascul Biol, 2000, 95(1): 189-197.
[25]
Rajakumar A, Conrad KP. Expression, ontogeny, and regulation of hypoxia-inducible transcription factors in the human placenta[J]. Biol Reprod, 2000, 63(2): 559-569.
[26]
Huang LE, Arany Z, Livingston DM, et al. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit[J]. J Biol Chem, 1996, 271(50): 32253-32259.
[27]
Semenza GL. Oxygen homeostasis[J]. Wiley Interdiscip Rev Syst Biol Med, 2010, 2(3): 336-361.
[28]
Wei W, Hu YY. Expression of hypoxia-regulated genes and glycometabolic genes in placenta from patients with intrahepatic cholestasis of pregnancy[J]. Placenta, 2014, 35(9): 732-736.
[29]
丁依玲,唐玲玲.妊娠肝内胆汁淤积症患者胎盘合体滋养细胞超微结构的观察与脐静脉血总胆酸水平的测定[J].中华妇产科杂志,2005,40(7): 453-456.
[30]
张耀,刘淑芸,王晓东.妊娠肝内胆汁淤积症胆汁酸水平及羊水胎粪污染与胎儿宫内缺氧的关系[J].中国综合临床,2003,19(6): 568-569.
[31]
刘伯宁,沈宁,陶雯琪,等.妊娠期肝内胆汁淤积症胎盘的组织计量测定[J].中华妇产科杂志,1988,23(1): 9-12.
[32]
胡雅毅,刘淑芸,杨开选.急性缺氧对妊娠期肝内胆汁淤积症患者胎盘绒毛超微结构的影响[J].华西医学,2006,21(4): 741-743.
[33]
Williamson C, Gorelik J, Eaton BM, et al. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis[J]. Clin Sci (Lond), 2001, 100(4): 363-369.
[1] Haoyuan Yang, Jie Gong, Qingwei Zou, Hang Ruan. Current research status on adverse pregnancy outcomes of maternal and infant in pregnant women with asthma[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 522-529.
[2] Tiantian Chen, Xiaodong Wang, Haiyan Yu. Pregnancy outcome of twin pregnancy with Gitelman syndrome: a case report and literature review[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 559-568.
[3] Xiaoqing Ju, Yunjie Jin, Xiaoyan Wang. Influencing factors of uterine rupture during vaginal delivery in patients with scarred uterus after cesarean section[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 575-581.
[4] Juan Gu, Qingqing Sun, Fangfang Hu, Yijuan Cao, Yujuan Qi. Clinical application of endometrial receptivity array to improve pregnancy outcomes in women with repeated embryo implantation failure[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 582-587.
[5] Beibei Wang, Qixiu Dong, Hongyan Xi, Qingyun Yu, Lijun Zhang, Guang Shi. Analysis of influencing factors of medical abortion failure of pregnant women in early pregnancy and construction of related prediction model and its predictive value for medical abortion success[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 588-594.
[6] Xu Chen, Yuru Zhan, Chunhua Wang. Clinical value of ABO blood group combined with thyroid function in prediction of gestational diabetes mellitus[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 604-610.
[7] Mengling Zhou, Zhiwei Xue, Shu Zhou. Changes in size of uterine myoma during pregnancy and its association with adverse pregnancy outcomes[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 611-615.
[8] Chenxi Ran, Rufei Shen, Mingyu Liao, Qian Liao, Ling Zhou, Yuling Zhang, Min Long. Treatment and management of pituitary tumor during pregnancy[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 487-491.
[9] Jinke Hu, Wen Zhong. Management and outcome of ureteral calculi in pregnancy[J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(04): 377-381.
[10] Yuyan Zhang, Bin Hu, Weihong Zhang, Mei Xu, Hui Zhu, Xinyue Yang, Hailing Liu. Relationship between echocardiography parameters and liver function during the second trimester of pregnancy and their predictive value for adverse pregnancy outcomes[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 499-504.
[11] Xiuying Jin, Feng Chen. Diagnostic value of transabdominal and transvaginal ultrasonography combined with serumβ-HCG detection in cesarean scar pregnancy[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(03): 155-159.
[12] Xin Wang, Lin Liu, Zhejia Wen, Chunling Liu, Hong Zhang, Fang Lyu. Effect of stress exposure before pregnancy on subsequent pregnancy outcomes in mice[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(04): 431-437.
[13] Xueyun Liu, Ying Fan, Aijun Yao, Shengmiao Zhang, Yani Lv, Bingqing Zhang, Xiaoyu Zhang, Heng. Liu. Effects of individualized whole-course nursing intervention based on WeChat mini program on pregnancy weight and delivery outcome[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(04): 455-460.
[14] Lizi Zhang, Dunjin Chen. Adverse outcomes and long­term prognosis of placenta accreta spectrum disorders[J]. Chinese Journal of Obstetric Emergency(Electronic Edition), 2023, 12(03): 155-158.
[15] Yanli Zou, Wenjie Luan, Shujuan Wang, Yaqin Liu, Guizhi Chu, Songyang Li, Haoling Wang, Jinting Zhang, Xin Jiang, Zedong Luan. Ultrasonographic features of fetal right aortic arch in the first trimester[J]. Chinese Journal of Diagnostics(Electronic Edition), 2023, 11(04): 227-232.
Viewed
Full text


Abstract