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.
Highlights
Despite the controversy surrounding the life cycle of apoptotic nuclei during normal trophoblast turnover, it is agreed that there is increased trophoblast cell death in placentas from pregnancies complicated by foetal growth restriction (FGR).[3]
Our observations provide the first evidence that TauTmediated taurine transport in human placenta is important for the normal process of trophoblast turnover
In order to carry out these important roles, it is essential that intracellular taurine concentration is maintained by appropriate regulation of cellular taurine uptake and efflux
Summary
Despite the controversy surrounding the life cycle of apoptotic nuclei during normal trophoblast turnover, it is agreed that there is increased trophoblast cell death in placentas from pregnancies complicated by foetal growth restriction (FGR).[3]. Abnormal turnover compromises syncytiotrophoblast integrity and renewal with consequences for nutrient delivery to the foetus, and this is thought to be a major contributing factor to FGR. Consistent with this is the finding that in addition to aberrant trophoblast turnover in FGR, there is reduced activity of certain amino acid transporters in the syncytiotrophoblast including that of system b6 responsible for taurine uptake into the placenta. We further hypothesised that reduced taurine uptake by syncytiotrophoblast could compromise cytoprotection against TNFa, an inflammatory cytokine that is elevated in FGR, and increase susceptibility to inappropriate apoptosis
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