Back
 JBM  Vol.6 No.6 , June 2018
Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy
Abstract: Aims: The abnormal increase of bile acid is found in intrahepatic cholestasis of pregnancy (ICP). It also can be observed the damage of placental tissue in ICP. The aim of this study was to find the associations of the bile acid in umbilical vein and the damage of placental tissue. Methods: Thirty women diagnosed with ICP and fifty normal pregnant women between September 2015 and September 2017 at Nanshan District Maternity & Child Healthcare Hospital of Shenzhen were included in this study. The glycocholic acid (GA), total bile acids (TBA), total bilirubin (TB), direct bilirubin (DB) and albumin level in umbilical vein were measured by cycle enzyme method in ICP and control group. The placental damage was analyzed by morphologic study using hematoxylin dyes in two groups. The correlation between the level of the bile acid in the umbilical vein and the damage of the placenta was assessed using SPSS software. Results: The GA, TBA, TB, DB and albumin level in umbilical vein were significantly higher in ICP than those of pregnant women, respectively. The placental villis were expanded and the structure was destroyed in ICP. The vessel was damaged and the cell trophoblast hyperplasia in ICP. It also can be seen that there was obvious nodules and a typical fibrous necrotic substance in ICP but not in control group. There is a positive correlation between the level of the TBA in the umbilical vein and the damage of the placenta in ICP. Conclusion: The TBAs were significantly higher in umbilical vein and were related to the placental damage in ICP.
Cite this paper: Xie, F. , Liu, X. , Xiao, P. , Huang, Y. , Chen, Q. and Zhou, L. (2018) Bile Acid Effects on Placental Damage in Intrahepatic Cholestasis of Pregnancy. Journal of Biosciences and Medicines, 6, 42-52. doi: 10.4236/jbm.2018.66003.
References

[1]   Floreani, A. and Gervasi, M.T. (2016) New Insights on Intrahepatic Cholestasis of Pregnancy. Insights on Intrahepatic Cholestasis of Pregnancy, 20, 177-189.
https://doi.org/10.1016/j.cld.2015.08.010

[2]   Zecca, E., De Luca, D., Marras, M., et al. (2006) Intrahepatic Cholestasis of Pregnancy and Neonatal Respiratory Distress Syndrome. Pediatrics, 117, 1669-1672.
https://doi.org/10.1542/peds.2005-1801

[3]   Zecca, E., De Luca, D., Baroni, S., et al. (2008) Bile Acid-Induced Lung Injury in Newborn Infants: A Bronchoalveolar Lavage Fluid Study. Pediatrics, 121, 141-149.
https://doi.org/10.1542/peds.2007-1220

[4]   Kondrackiene, J., Beuers, U., Zalinkevicius, R., et al. (2014) Predictors of Premature Delivery in Patients with Intrahepatic Cholestasis of Pregnancy. BMC Medical Genomics, 7, 42-53.

[5]   Wikstrom Shemer, E.A., Thorsell, M., Marschall, H.U., et al. (2013) Risks of Emergency Cesarean Section and Fetal Asphyxia after Induction of Labor in Intrahepatic Cholestasis of Pregnancy: A Hospital-Based Retrospective Cohort Study. Sexual & Reproductive Healthcare, 4, 17-22.
https://doi.org/10.1016/j.srhc.2012.11.005

[6]   Zecca, E., De Luca, D., Barbato, G., et al. (2008) Predicting Respiratory Distress Syndrome in Neonates from Mothers with Intrahepatic Cholestasis of Pregnancy. Early Human Development, 84, 337-341.
https://doi.org/10.1016/j.earlhumdev.2007.09.012

[7]   Salafia, C.M., Charles, A.K. and Maas, E.M. (2006) Placenta and Fetal Growth Restriction. Clinical Obstetrics & Gynecology, 49, 236-256.
https://doi.org/10.1097/00003081-200606000-00007

[8]   Du, Q., Pan, Y., Zhang, Y., et al. (2014) Placental Gene-Expression Profiles of Intrahepatic Cholestasis of Pregnancy Reveal Involvement of Multiple Molecular Pathways in Blood Vessel Formation and Inflammation. BMC Medical Genomics, 7, 42-53.
https://doi.org/10.1186/1755-8794-7-42

[9]   He, P., Wang, F., Jiang, Y., et al. (2014) Placental Proteome Alterations in Women with Intrahepatic Cholestasis of Pregnancy. International Journal of Gynecology and Obstetrics, 126, 256-259.
https://doi.org/10.1016/j.ijgo.2014.03.035

[10]   Marin, J.J., Serrano, M.A., El-Mir, M.Y., et al. (1990) Bile Acid Transport by Basal Membrane Vesicles of Human Term Placental Trophoblast. Gastroenterology, 99, 1431-1438.
https://doi.org/10.1016/0016-5085(90)91172-3

[11]   Chen, J., Deng, W., Wang, J., et al. (2013) Primary Bile Acids as Potential Biomarkers for the Clinical Grading of Intrahepatic Cholestasis of Pregnancy. International Journal of Gynecology and Obstetrics, 122, 5-8.
https://doi.org/10.1016/j.ijgo.2013.02.015

[12]   Marin, J.J., Macias, R.I., Briz, O., et al. (2008) Molecular Bases of the Fetal Liverplacenta-Maternal Liver Excretory Pathway for Cholephilic Compound. Liver International, 28, 435-454.
https://doi.org/10.1111/j.1478-3231.2008.01680.x

[13]   Geenes, V., Lovgren-Sandblom, A., Benthin, L., et al. (2014) The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid. PLoS ONE, 9, e83828.
https://doi.org/10.1371/journal.pone.0083828

[14]   Macias, R.I., Marin, J.J. and Serrano, M.A. (2009) Excretion of Biliary Compounds during Intrauterine Life. World Journal of Gastroenterology, 15, 817-828.
https://doi.org/10.3748/wjg.15.817

[15]   Bravo, P., Marin, J.J., Beveridge, M.J., et al. (1995) Reconstitution and Characterization of ATP-Dependent Bile acid Transport in Human and Rat Placenta. Biochemistry, 311, 479-485.
https://doi.org/10.1042/bj3110479

[16]   Hagenbuch, B. and Meier, P.J. (2004) Organic Anion Transporting Polypeptides of the OATP/SLC21 Family: Phylogenetic Classification as OATP/SLCO Superfamily, New Nomenclature and Molecu-lar/Functional Properties. Pflügers Archiv, 447, 653-665.

[17]   Kondrackiene, J. and Kupcinskas, L. (2008) Intrahepatic Cho-lestasis of Pregnancy-Current Achievements and Unsolved Problems. World Journal of Gastroenterology, 14, 5781-5788.
https://doi.org/10.3748/wjg.14.5781

[18]   Marin, J.J., Macias, R.I. and Serrano, M.A. (2003) The Hepatobiliary-Like Excretory Function of the Placenta. Placenta, 24, 431-438.
https://doi.org/10.1053/plac.2002.0951

[19]   Serrano, M.A., Macias, R.I., Briz, O., et al. (2007) Expression in Human Trophoblast and Choriocarcinoma Cell Lines, BeWo, Jeg-3 and Jar of Genes Involved in the Hepatobiliary-Like Excretory Function of the Placenta. Placenta, 28, 107-117.

[20]   Favre, N., Bourdel, N., Sapin, V., et al. (2010) Importance of Bile Acids for Intra-Hepatic Cholestasis of Pregnancy. Gynecologie, Obstetrique & Fertilite, 38, 293-295.
https://doi.org/10.1016/j.gyobfe.2010.02.011

[21]   Obstetrics Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association (2015) Guidelines for the Management of Intrahepatic Cholestasis of Pregnancy. Chinese Journal of Obstetrics and Gynecology, 50, 481-485.

[22]   Rook, M., Vargas, J., Caughey, A., et al. (2012) Fetal Outcomes in Pregnancies Complicated by Intrahepatic Cholestasis of Pregnancy in a Northern California Cohort. PLoS ONE, 7, e28343.

[23]   Monte, M.J., Rodriguez-Bravo, T., Macias, R.I., et al. (1995) Relationship between Bile Acid Transplacental Gradients and Transport across the Fetal-Facing Plasma Membrane of the Human Trophoblast. Pediatric Research, 38, 156-163.
https://doi.org/10.1203/00006450-199508000-00004

[24]   Glantz, A., Marschall, H. and Mattsson, L. (2010) Intrahepatic Cholestasis of Pregnancy: Relationships between Bile Acid Levels and Fetal Complication Rates. Hepatology, 40, 467-474.
https://doi.org/10.1002/hep.20336

[25]   Maillette de Buy Wenniger, L. and Beuers, U. (2010) Bile Salts and Cholestasis. Digestive and Liver Disease, 42, 409-418.
https://doi.org/10.1016/j.dld.2010.03.015

[26]   Myllynen, P., Immonen, E., Kummu, M., et al. (2009) Developmental Expression of Drug Metabolizing Enzymes and Transporter Proteins in Human Placenta and Fetal Tissues. Expert Opinion on Drug Metabolism & Toxicology, 5, 1483-1499.
https://doi.org/10.1517/17425250903304049

[27]   Geenes, V.L., Lim, Y.-H., Bowman, N., et al. (2011) A Placental Phenotype for Intrahepatic Cholestasis of Pregnancy. Placenta, 32, 1026-1032.

[28]   McIlvride, S. and Dixon, P.H. (2017) Catherine Williamson. Bile Acids and Gestation. Molecular Aspects of Medicine, 56, 90-100.

[29]   Wikstrom Shemer, E., Thorsell, M., Ostlund, E., et al. (2012) Stereological Assessment of Placental Morphology in Intrahepatic Cholestasis of Pregnancy. Placenta, 33, 914-918.

[30]   Du, Q.L., Pan, Y., Zhang, Y.H., et al. (2014) Placental Gene-Expression Profiles of Intrahepatic Cholestasis of Pregnancy Reveal Involvement of Multiple Molecular Pathways in Blood Vessel Formation and Inflammation. BMC Medical Genomics, 7, 42-53.

[31]   He, P., Wang, F., Jiang, Y., et al. (2014) Placental Proteome Alterations in Women with Intrahepatic Cholestasis of Pregnancy. International Journal of Gynecology and Obstetrics, 126, 256.

[32]   Wei, J., Wang, H., Yang, X., et al. (2010) Altered Gene Profile of Placenta from Women with Intrahepatic Cholestasis of Pregnancy. Archives of Gynecology and Obstetrics, 281, 801-810.
https://doi.org/10.1007/s00404-009-1156-3

[33]   Beninati, M., Seferovic, M.D., Liu, X., et al. (2016) The Placenta and Intrahepatic Cholestasis of Pregnancy (IHCP, Alterations to Bile Acid Transport Associated with Disease Duration and Reduction in Primary Bile Acid Concentrations. American Journal of Obstetrics and Gynecology, 214, S272-S272.

[34]   Sepúlveda, W.H., González, C., Cruz, M.A., et al. (1991) Vasoconstrictive Effect of Bile Acids on Isolated Human Placental Chorionic Veins. European Journal of Obstetrics & Gynecology and Reproductive Biology, 42, 211-215.
https://doi.org/10.1016/0028-2243(91)90222-7

[35]   Abu-Hayyeh, S., Papacleovoulou, G. and Williamson, C. (2013) Nuclear Receptors, Bile Acids and Cholesterol Homeostasis Series-Bile Acids and Pregnancy. Molecular and Cellular Endocri-nology, 368, 120-128.

[36]   Zhang, Y., Pan, Y., Lin, C., et al. (2016) Bile Acids Evoke Placental Inflammation by Activating Gpbar1/NF-κB Pathway in Intrahepatic Cholestasis of Pregnancy. Journal of Molecular Cell Biology, 8, 530-541.

[37]   Mella, M.T., Kohari, K., Jones, R., et al. (2016) Mitochondrial Gene Expression Profiles Are Associated with Intrahepatic Cholestasis of Pregnancy. Placenta, 45, 16-23.

[38]   Rezai, S., Lam, J. and Henderson, C.E. (2015) Intrahepatic Cholestasis of Pregnancy: Maternal and Fetal Outcomes Associated with Elevated Bile Acid Levels. American Journal of Obstetrics and Gynecology, 213, 114.
https://doi.org/10.1016/j.ajog.2015.03.040

 
 
Top