Dataset Information

Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survival.

ABSTRACT: The outer epithelial cell layer of human placenta, the syncytiotrophoblast, is a specialised terminally differentiated multinucleate tissue. It is generated and renewed from underlying cytotrophoblast cells that undergo proliferation, differentiation and fusion with syncytiotrophoblast. Acquisition of fresh cellular components is thought to be balanced by apoptosis and shedding of aged nuclei. This process of trophoblast cell turnover maintains a functional syncytiotrophoblast, capable of sufficient nutrient transfer from mother to foetus. Foetal growth restriction (FGR) is a pregnancy complication associated with aberrant trophoblast turnover and reduced activity of certain amino acid transporters, including the taurine transporter (TauT). Taurine is the most abundant amino acid in human placenta implying an important physiological role within this tissue. Unlike other amino acids, taurine is not incorporated into proteins and in non-placental cell types represents an important osmolyte involved in cell volume regulation, and is also cytoprotective. Here, we investigated the role of taurine in trophoblast turnover using RNA interference to deplete primary human trophoblast cells of TauT and reduce intracellular taurine content. Trophoblast differentiation was compromised in TauT-deficient cells, and susceptibility of these cells to an inflammatory cytokine that is elevated in FGR was increased, evidenced by elevated levels of apoptosis. These data suggest an important role for taurine in trophoblast turnover and cytoprotection.

SUBMITTER: Desforges M

PROVIDER: S-EPMC3618382 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:As gestation proceeds the human placenta is in a constant state of renewal and placental debris is released into the maternal circulation where it can trigger adverse physiological and immunological responses. Trophoblast cells of the placenta differentiate from mononuclear cytotrophoblast cells to fuse and form the syncytiotrophoblast, a multinuclear layer that covers the entire surface of the placenta. As part of this process there are significant changes to cellular cytoskeletal organization and organelle morphology. In this study we have examined the molecular changes that occur in mitochondria from these two cellular compartments and identified differential expression of key proteins that underpin changes in mitochondrial morphology, metabolism and function. Mitochondria were isolated for term placental tissue and separated according to size and density by sequential differential centrifugation. Isolated mitochondrial populations were then subjected to proteomics using HPLC separation of peptides and MS identification. Differential expression of proteins of interest was confirmed by western blots. Using a bioinformatics approach we also examined published protein databases to confirm our observations. In total 651 proteins were differentially regulated in mitochondria from cytotrophoblast versus syncytiotrophoblast. Of these 29 were statistically significant and chosen for subsequent analysis. These included subunits of ATP synthase that would affect ATP production and cristae structure, carbohydrate metabolizing enzymes phospoenolpyruvate carboxykinase-2, pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH), fatty acid metabolizing enzyme acyl-CoA dehydrogenase, stress responses such a glucose regulated protein-78 and protein disulfide isomerase, and mitochondrial dynamics proteins mitofusin 1 and 2. Placental cell biology and mitochondrial function is central to the pathogenesis of many gestational disorders such as preeclampsia, pre-term birth, fetal growth restriction and gestational diabetes. These studies show important shifts in mitochondrial metabolism and dynamics post trophoblast differentiation and provide key molecular targets for study in pathological pregnancies.

Dataset Information

Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survival.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets