The Placenta—A New Source of Bile Acids during Healthy Pregnancy? First Results of a Gene Expression Study in Humans and Mice

Edgar Ontsouka, Mariana Schroeder, Linda Ok, Cathy Vaillancourt, Deborah Stroka, Christiane Albrecht

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1 Scopus citations


Bile acids (BAs) are natural ligands for several receptors modulating cell activities. BAs are synthesized via the classic (neutral) and alternative (acidic) pathways. The classic pathway is initiated by CYP7A1/Cyp7a1, converting cholesterol to 7α-hydroxycholesterol, while the alternative pathway starts with hydroxylation of the cholesterol side chain, producing an oxysterol. In addition to originating from the liver, BAs are reported to be synthesized in the brain. We aimed at determining if the placenta potentially represents an extrahepatic source of BAs. Therefore, the mRNAs coding for selected enzymes involved in the hepatic BA synthesis machinery were screened in human term and CD1 mouse late gestation placentas from healthy pregnancies. Additionally, data from murine placenta and brain tissue were compared to determine whether the BA synthetic machinery is comparable in these organs. We found that CYP7A1, CYP46A1, and BAAT mRNAs are lacking in the human placenta, while corresponding homologs were detected in the murine placenta. Conversely, Cyp8b1 and Hsd17b1 mRNAs were undetected in the murine placenta, but these enzymes were found in the human placenta. CYP39A1/Cyp39a1 and cholesterol 25-hydroxylase (CH25H/Ch25h) mRNA expression were detected in the placentas of both species. When comparing murine placentas and brains, Cyp8b1 and Hsd17b1 mRNAs were only detected in the brain. We conclude that BA synthesis-related genes are placentally expressed in a species-specific manner. The potential placentally synthesized BAs could serve as endocrine and autocrine stimuli, which may play a role in fetoplacental growth and adaptation.

Original languageEnglish
Article number9511
JournalInternational Journal of Molecular Sciences
Issue number11
StatePublished - Jun 2023
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded by the Swiss National Science Foundation (Grant No. 310030_197408, C.A.) and the National Center of Competence in Research (NCCR) TransCure (Grant No. 51NF40-185544, C.A.), as well as the Lindenhof Foundation, Bern, Switzerland (Grant No. 17-15-F, C.A.). L.O. was supported by a Mitac-RQR fellowship and the NSERC (Grant No. RGPIN/06778-2019, C.V.) and NIH (Grant No. 5R01HD089713-04, C.V.).

Publisher Copyright:
© 2023 by the authors.


  • bile acid synthesis
  • extrahepatic
  • human
  • mice
  • pregnancy


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