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

• Published in: International journal of molecular sciences 2023-05, Vol.24 (11), p.9511
• Main Authors: Ontsouka, Edgar, Schroeder, Mariana, Ok, Linda, Vaillancourt, Cathy, Stroka, Deborah, Albrecht, Christiane
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Autocrine signalling; bile acid synthesis; Bile acids; Bile Acids and Salts - metabolism; Biosynthesis; Cholesterol; Cholesterol - metabolism; Communication; Enzymes; extrahepatic; Female; Gene Expression; Genes; Gestational age; human; Humans; Hydroxylation; Hydroxyprogesterone; Hypothalamus; Liver; Liver - metabolism; Metabolites; Mice; Placenta; Placenta - metabolism; Pregnancy; Pregnant women; RNA, Messenger - genetics; RNA, Messenger - metabolism; Steroid 12-alpha-Hydroxylase - genetics; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Steroids
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24119511

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 and mRNAs are lacking in the human placenta, while corresponding homologs were detected in the murine placenta. Conversely, and mRNA were undetected in the murine placenta, but these enzymes were found in the human placenta. and cholesterol 25-hydroxylase ( ) mRNA expression were detected in the placentas of both species. When comparing murine placentas and brains, and 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.