Biliary Bile Acid Composition of the Human Fetus in Early Gestation

Colombo, Carla; Zuliani, G.; Ronchi, M; Breidenstein, J; Setchell, Kenneth D.R.

doi:10.1203/00006450-198702000-00017

Cited by 81 publications

(34 citation statements)

References 25 publications

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“…However, the results obtained in the present work confirm previous findings by other groups on the relative fetal and, to a lesser extent, also maternal hypercholanemia in uncomplicated pregnancies. Moreover, in spite of the large variability in the bile acid profiles of both fetal and maternal blood (I), these studies indicate that, in agreement with previous reports by other authors (41,42), in normal term infants at birth, bile acid profiles for major bile acid species are generally different from those of their mothers. With regard to the ratio of two major primary bile acid families in the fetal and adult bile acid pool, the mean value for the cholic acid:CDC ratio was 0.61 in the fetuses and 1.79 in their mothers.…”

Section: Discussionsupporting

confidence: 89%

Relationship between Bile Acid Transplacental Gradients and Transport across the Fetal-Facing Plasma Membrane of the Human Trophoblast

Monte

Rodriguez-Bravo²,

Macias

et al. 1995

Pediatr Res

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Section: Discussionsupporting

confidence: 89%

Relationship between Bile Acid Transplacental Gradients and Transport across the Fetal-Facing Plasma Membrane of the Human Trophoblast

Monte

Rodriguez-Bravo²,

Macias

et al. 1995

Pediatr Res

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“…However, the fetus does synthesise bile acids, including cholate, relatively early in gestation. 18,19 There are also data that suggest that the fetus synthesises lithocholate, a hydrophobic and therefore potentially cardiotoxic bile acid, as a primary bile acid. 20 Fetal gallbladder bile collected at 16-19 weeks of gestation and analysed by gas chromatographymass spectrometry (GC-MS) demonstrated a relatively high proportion of bile acids that are not typically seen in adult bile and which are characterised by hydroxy groups at the C1 and C6 carbon positions of the steroid nucleus.…”

Section: Discussionmentioning

confidence: 99%

Basic science: Genes encoding bile acid, phospholipid and anion transporters are expressed in a human fetal cardiomyocyte culture

Gorelik

Patel

Ng'andwe

et al. 2006

BJOG

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Objectives To establish a human fetal cardiomyocyte culture and to investigate whether the genes that encode transporters that may influence influx or efflux of bile acids are expressed in human fetal cardiomyocytes. Design Laboratory study. Setting Imperial College London. Sample Six fetal hearts were obtained at the time of termination of pregnancy at 12–13 weeks of gestation and used to generate primary human cardiomyocyte cultures. Methods To confirm the presence of cardiomyocytes, the cells were incubated with monoclonal antibodies to sarcomeric α‐actinin and anticardiac myosin heavy chain. Real‐time reverse transcription polymerase chain reaction was used to establish whether transcripts of genes that may influence bile acid transport are present in the culture (NTCP, BSEP, MDR3, FIC1, MRP2, MRP3, OATP‐A, OATP‐C, OATP‐D, OATP‐E) and whether taurocholate administration alters messenger RNA (mRNA) expression. Main outcome measures Relative mRNA expression of genes of interest. Results Real‐time polymerase chain reaction demonstrated the presence of mRNA for BSEP, MDR3, FIC1, OATP‐C, OATP‐D and OATP‐E in fetal heart. Four transcripts remained in the cardiomyocyte culture (BSEP, MDR3, FIC1 and OATP‐D), and we demonstrated the influence of taurocholate on gene expression. Conclusions We have developed an in vitro model of the fetal heart that may be used for studies of the cardiac effect of endobiotics, e.g. bile acids, or of specific agents that may be used to treat the mother or fetus in pregnancy.

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“…In spite of the immaturity of fetal bile secretion, small amounts of bile acids have been detected in the gallbladder bile collected from human fetuses obtained from abortions older than 12 wk of age [32] . Regarding bile pigments, although the IXβ isomer of bilirubin constitutes only a small fraction of the total amount produced in the fetus [33] , this more water-soluble isomer is the most abundant isomer found in fetal gallbladder bile and meconium [34,35] .…”

Section: The Hepatobiliary Excretory Function During Intrauterine Lifementioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

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Biliary Bile Acid Composition of the Human Fetus in Early Gestation

Cited by 81 publications

References 25 publications

Relationship between Bile Acid Transplacental Gradients and Transport across the Fetal-Facing Plasma Membrane of the Human Trophoblast

Relationship between Bile Acid Transplacental Gradients and Transport across the Fetal-Facing Plasma Membrane of the Human Trophoblast

Basic science: Genes encoding bile acid, phospholipid and anion transporters are expressed in a human fetal cardiomyocyte culture

Excretion of biliary compounds during intrauterine life

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