Endocrine Abstracts

The link between thyroid hormone deficiency and optimal neurodevelopment in early childhood is well established. More recently, data from animal model experiments and epidemiological databases have indicated that perturbations in maternal and fetal thyroid hormone concentrations may affect fetal outcome and, in particular, have an adverse effect on neurodevelopmental outcome. Epidemiological evidence in human pregnancies has indicated that hypothyroxinaemia in the fetus in the...

Background: Thyroid hormones (TH) are vital for fetal and placental development. TH transporters including monocarboxylate transporters 8 and 10 (MCT8, MCT10), organic anion transporters (OATP1A2, OATP4A1) and system-L amino acid transporters (LAT1, LAT2) are expressed in human placenta from 6 weeks of gestation. All of these TH transporters have been localized to the human syncytiotrophoblast layer of placental villi, which is in direct contact with maternal bl...

Vitamin D deficiency is prevalent in pregnant women and associated with adverse pregnancy outcomes, including pre-eclampsia. Active vitamin-D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) appears a key target. Uterine natural killer cells (uNKs) are the most prominent decidual immune cell during early pregnancy. Given their critical role in fetal implantation and placentation, we hypothesised uNKs are a local source...

Vitamin D deficiency is prevalent in pregnant women and associated with adverse pregnancy outcomes, including pre-eclampsia. Active vitamin-D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) appears a key target. Uterine natural killer cells (uNKs) are the most prominent decidual immune cell during early pregnancy. Given their critical role in fetal implantation and placentation, we hypothesised uNKs are a local source...

Vitamin D-deficiency during pregnancy has been associated with increased complications of pregnancy including a high risk of pre-eclampsia (PET). Current analysis of vitamin D ‘status’ is based exclusively on analysis of maternal serum 25-hydroxyvitamin D3 (25(OH)D3), the circulating precursor form of vitamin D. We hypothesised that comprehensive profiling of vitamin D metabolites may provide a more accurate determination of vitamin D function i...

Vitamin D deficiency is prevalent in pregnant women. Active vitamin D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) is a potential target for this. CD56+ -uterine natural killer (uNK) cells are the most prominent cell type in the decidua during early pregnancy. Given their critical role in foetal implantation and placentation, we hypothesised that uNK cells are a pivotal immunomodula...

The plasma membrane thyroid hormone (TH) transporter, MCT8, is present in the human placenta from early gestation and is postulated to participate in transplacental transfer of TH. In vitro, MCT8 overexpression decreases the survival of human cytotrophoblast in a TH-independent manner.Objective: To examine the role of Mct8 in fetoplacental growth using the Mct8 knockout (ko) mouse model.Methods: Heterozygous females were mat...

Thyroid hormones (THs) are important for fetal and placental development. Monocarboxylate transporters 8 and 10 (MCT8 and MCT10) are effective plasma membrane TH transporters expressed in the human placenta from 6 weeks of gestation. Both have been localized to human villous trophoblasts and extravillous trophoblasts (EVTs).Aims: Using HTR-8/SVneo cells as a model of 1st trimester EVTs, we assessed 1) T3 effects on gene expression, cell prolif...

Thyroid hormones (TH) are important for the development of the fetus and placenta. We have previously reported increased placental expression of the potent TH transporter, MCT8, with advancing gestation. The amino acid plasma membrane transporters, MCT10, LAT1, LAT2, and the organic anion transporters, OATP1A2 and OATP4A1, are also known to transport TH.Objective: To describe the ontogeny of these TH transporters and the obligate heterodimer of the LATs,...

Thyroid hormones play vital roles in fetal brain development. Mutations in MCT8, recently recognised as a specific thyroid hormone transporter, define a novel syndrome of severe X-linked psychomotor retardation and thyroid hormone resistance.N-TERA-2 (NT2) cells (human embryonal cells with characteristics of CNS precursors) were transiently transfected with either WT MCT8 or its L471P, R271H or S448X mutations, described in males affected by severe psych...