Excretion of biliary compounds during intrauterine life

Abstract

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.

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother‐placenta‐foetus trio during cholestasis of pregnancy

“…As previously described in healthy pregnancies [15,25], the transplacental gradient for total bile acids was in the foetus-to-mother direction ( Figure 2A) with a mother : foetus ratio of 0.36. In pregnancies with ICP ( Figure 2B, C), there was a reversal in the gradient resulting in a mother : foetus ratio of 3.1.…”

“…Bile acids are transferred across the placenta for elimination by the maternal liver. The concerted action of several members of the organic anion transporting polypeptide (OATP) and the ATPbinding cassette (ABC) families located at the foetal and maternal poles of the trophoblast [12,13] accounts for this vectorial transfer (for reviews, see [14,15]). Among transporters involved, ABCG2, also known as breast cancer resistance protein (BCRP), plays a key role [16].…”

Recommendations for Pregnancies in Patients with Crigler-Najjar Syndrome

“…Unconjugated bilirubin can cross the placenta, and this is indeed the normal route for excretion during pregnancy as the foetal liver is unable to conjugate or excrete bilirubin (Macias et al 2009;Gajdos et al 2006;McDonagh 2007;2010). It is conceivable that phototherapy of the mother might reduce exposure of the foetal brain to a greater extent than reflected by serum bilirubin levels as the photoisomers of bilirubin are more water soluble and do not cross the blood-brain barrier or presumably the placenta to the same extent as unconjugated bilirubin (Mreihil 2010).…”

Congenital Neuroglial Heterotopia in a Neonatal Harbor Seal (Phoca vitulina richardsi ) with Evidence of Recent Exposure to Polycyclic Aromatic Hydrocarbons

“…Although maternal transfer of petroleum hydrocarbons to the developing fetus has been documented in humans, laboratory animals, and sea otters during the Exxon-Valdez oil spill (Tuomi and Williams, 1995;Perera et al, 1999;Tozuka et al, 2004), little is known about fetal metabolism of these compounds. During human fetal development, the immature hepatobiliary excretory system is not yet functional, so the placenta functions to metabolize and excrete toxins back to the maternal system for elimination and also acts as a barrier to protect the fetus from potentially toxic compounds in maternal blood (Macias et al, 2009). However, if one or both of these mechanisms is impaired or overwhelmed by an acute exposure, toxins could enter fetal circulation, resulting in deleterious effects to the fetus (Macias et al, 2009).…”

“…During human fetal development, the immature hepatobiliary excretory system is not yet functional, so the placenta functions to metabolize and excrete toxins back to the maternal system for elimination and also acts as a barrier to protect the fetus from potentially toxic compounds in maternal blood (Macias et al, 2009). However, if one or both of these mechanisms is impaired or overwhelmed by an acute exposure, toxins could enter fetal circulation, resulting in deleterious effects to the fetus (Macias et al, 2009). A large bunker fuel spill (58,000 gallons) occurred in San Francisco Bay in November 2007, which corresponds roughly with the late first trimester to early second trimester of this pup's gestation (Reidman, 1990); however, exposure may have occurred from petroleum products that entered the bay via nonpoint-source discharges.…”