Transcriptome Profiling of Placenta through Pregnancy Reveals Dysregulation of Bile Acids Transport and Detoxification Function

Abstract

Placenta performs the function of several adult organs for the fetus during intrauterine life. Because of the dramatic physiological and metabolic changes during pregnancy and the strong association between maternal metabolism and placental function, the possibility that variation in gene expression patterns during pregnancy might be linked to fetal health warrants investigation. Here, next-generation RNA sequencing was used to investigate the expression profile, including mRNAs and long non-coding RNAs (lncRNAs) of placentas on day 60 of gestation (G60), day 90 of gestation (G90), and on the farrowing day (L0) in pregnant swine. Bioinformatics analysis of differentially expressed mRNAs and lncRNAs consistently showed dysregulation of bile acids transport and detoxification as pregnancy progress. We found the differentially expressed mRNAs, particularly bile salt export pump (ABCB11), organic anion-transporting polypeptide 1A2 (OATP1A2), carbonic anhydrase II (CA2), Na+-HCO3− cotransporter (NBC1), and hydroxysteroid sulfotransferases (SULT2A1) play an important role in bile acids transport and sulfation in placentas during pregnancy. We also found the potential regulation role of ALDBSSCG0000000220 and XLOC_1301271 on placental SULT2A1. These findings have uncovered a previously unclear function and its genetic basis for bile acids metabolism in developing placentas and have important implications for exploring the potential physiological and pathological pathway to improve fetal outcomes.

Transcriptomic and ChIP-seq Integrative Analysis Reveals Important Roles of Epigenetically Regulated lncRNAs in Placental Development in Meishan Pigs

“…We reported here the lncRNAs that were differentially expressed in the placentas (chorioallantoic tissues) of Meishan gilts from the two crucial placental fold developmental stages: gestational days 50 (establishment stage of placental fold) and 95 (expanding stage of placental fold) and the differential expression of the DElncRNAs was validated by using qRT-PCR. Our finding is in agreement with the previous report demonstrating the role of lncRNAs in regulating the gene expression in the placentas of pigs [44]. On the other hand, in addition to vasculature development, it has been documented that the placental trophoblast cells undergo differentiation and change in cell shape during the development of the placental fold in pigs [3,[45][46][47][48].…”

“…Recently, RNA-seq data analysis was performed on the placentas of Landrace × Yorkshire gilts on gestational days 60 and 90, as well as the farrowing day. The mRNAs and lncRNAs that were responsible for the bile acid metabolism in placentas were identified [44]. We reported here the lncRNAs that were differentially expressed in the placentas (chorioallantoic tissues) of Meishan gilts from the two crucial placental fold developmental stages: gestational days 50 (establishment stage of placental fold) and 95 (expanding stage of placental fold) and the differential expression of the DElncRNAs was validated by using qRT-PCR.…”

Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model

“…Studies of pregnant women and rodents have revealed the physiological change of BA and reproductive hormones during pregnancy, particularly the role of estrogen or its glucuronidated forms [ 1 , 22 , 26 ]. However, glucuronidation was a minor pathway for steroid metabolism in humans, rodents, minipigs, and pregnant sows [ 27 , 28 ]. The most important finding in this study was that the dysregulation of BA homeostasis was associated with changes in PMSs metabolism during the latter stages of pregnancy in sows.…”

Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis

“…This onset might be due to the foetus's capacity to produce but not metabolize BA properly. Recent research has shown that BA metabolites are released from the placenta to the bloodstream during the second and third trimesters in order to be metabolized by the maternal liver, increasing significantly serum BA concentrations in the mother 26,27 …”

“…Recent research has shown that BA metabolites are released from the placenta to the bloodstream during the second and third trimesters in order to be metabolized by the maternal liver, increasing significantly serum BA concentrations in the mother. 26,27 The multiple significant correlations found between BA subcategories and hepatic insulin sensitivity markers provide interesting insights on the impacts of elevated BA production. Theoretically, activated FXR inhibits the pathway leading to glucose release from the liver into the bloodstream.…”