Placental Expression of Bile Acid Transporters in Intrahepatic Cholestasis of Pregnancy
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related condition characterized by increased maternal circulating bile acids (BAs) having adverse fetal effects. We investigated whether the human placenta expresses specific regulation patterns to prevent fetal exposition to harmful amounts...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/19/10434 |
| Summary: | Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related condition characterized by increased maternal circulating bile acids (BAs) having adverse fetal effects. We investigated whether the human placenta expresses specific regulation patterns to prevent fetal exposition to harmful amounts of BAs during ICP. Using real-time quantitative PCR, we screened placentae from healthy pregnancies (<i>n</i> = 12) and corresponding trophoblast cells (<i>n</i> = 3) for the expression of 21 solute carriers and ATP-binding cassette transporter proteins, all acknowledged as BA- and/or cholestasis-related genes. The placental gene expression pattern was compared between healthy women and ICP patients (<i>n</i> = 12 each). Placental <i>SLCO3A1</i> (OATP3A1) gene expression was significantly altered in ICP compared with controls. The other 20 genes, including <i>SLC10A2</i> (ASBT) and <i>EPHX1</i> (EPOX, mEH) reported for the first time in trophoblasts, were comparably abundant in healthy and ICP placentae. <i>ABCG5</i> was undetectable in all placentae. Placental <i>SLC10A2</i> (ASBT), <i>SLCO4A1</i> (OATP4A1), and <i>ABCC2</i> mRNA levels were positively correlated with BA concentrations in ICP. Placental <i>SLC10A2</i> (ASBT) mRNA was also correlated with maternal body mass index. We conclude that at the transcriptional level only a limited response of BA transport systems is found under ICP conditions. However, the extent of the transcriptional response may also depend on the severity of the ICP condition and the magnitude by which the maternal BA levels are increased. |
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| ISSN: | 1661-6596 1422-0067 |