Targeted metabolomics analysis of maternal-placental-fetal metabolism in pregnant swine reveals links in fetal bile acid homeostasis and sulfation capacity.

Targeted metabolomics analysis of maternal-placental-fetal metabolism in pregnant swine reveals links in fetal bile acid homeostasis and sulfation capacity. Am J Physiol Gastrointest Liver Physiol. 2019 Apr 25;: Authors: Wang P, Zhong H, Song Y, Yuan P, Li Y, Lin S, Zhang X, Li J, Che L, Feng B, Lin Y, Xu S, Zhuo Y, Tian G, Chen D, Wu, Burrin DG, Fang Z Abstract Cholestasis of pregnancy endangers fetal and neonatal survival, yet systematic knowledge of the cause and effect of disrupted bile acid (BA) homeostasis in pregnancy is limited. Here we show that gestation stage-associated BA dysregulation in swine correlated with fetal death resulting from compromised capacity for BA secretion and increased alternative systemic efflux. The balance of BA input and output in the developing uterus suggested little uptake and metabolism of maternal BA by the placenta-fetus unit, implying a protection role of placenta in preventing maternal BA transported into fetus. We showed that the maternal origin of BA accounted for the increase in placental TBA leading to dysregulated expression of genes involved in BA transport and potentially impaired transplacental export of fetus-derived BA. Correspondingly, the secondary BA, mainly derived from the mother, gradually decreased in fetus. Finally, we identified that sulfation rather than glucuronidation played pivotal roles in maintaining BA homeostasis of developing fetus. These novel and systemic findin...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research