Molecular bases of the excretion of fetal bile acids and pigments through the fetal liver-placenta-maternal liver pathway.
Since the excretion of potentially toxic cholephilic organic anions (COAs) produced by the fetus, such as bile acids and biliary pigments, cannot be performed by the fetal liver alone, the placenta and the maternal liver must play a key role collaborating in this function. COAs are transported across the plasma membranes of fetal and maternal hepatocytes and trophoblastic cells via similar carrier proteins. OATPs (organic anion-transporting polypeptides), mainly OATP1B1 and OATP1B3 are involved in COA uptake across the basal membrane of adult hepatocytes and trophoblastic cells. Certain OATPs may also play a role in COA efflux from fetal hepatocytes toward the fetal blood and from the trophoblast to the maternal blood. Either unmodified or biotransformed during their transit across the placenta, COAs are transferred to the maternal blood by MRPs (multidrug resistance-associated proteins), such as MRP1, MRP2 and MRP3. BCRP (breast cancer resistance protein) may also be involved in this step. Under physiological circumstances, fetal COAs are taken up by the maternal liver, which eliminates them across the canalicular membrane via MRP2 and BSEP (bile salt export pump). However, when normal biliary excretion is not possible, the accumulation of COAs, in particular in the fetal liver, placenta and maternal liver trio, induces oxidative stress and apoptosis, which has noxious repercussions on normal fetal development and even challenges pregnancy outcome. Treatment of pregnant rats with ursodeoxycholic acid, even though maternal hypercholanemia is not corrected, prevents oxidative damage and the subsequent deleterious effects on the placenta and fetal liver.
Marín
José J G
JJ
Department of Physiology and Pharmacology, University of Salamanca, 37007-Salamanca, Spain.
Macías
Rocio I R
RI
Briz
Oscar
O
Pérez
M J
MJ
Serrano
María Angeles
MA
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001654:Bile Pigments / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D001647:Bile Acids and Salts; D001654:Bile Pigments; D027361:Organic Anion Transporters; D012333:RNA, Messenger