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Molehin D.,University of Queensland | Dekker Nitert M.,University of Queensland | Richard K.,University of Queensland | Richard K.,Conjoint Endocrine Laboratory | Richard K.,Queensland University of Technology
Journal of Thyroid Research | Year: 2016

Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. Copyright © 2016 Deborah Molehin et al.

Li H.,Conjoint Endocrine Laboratory | Landers K.,Conjoint Endocrine Laboratory | Patel J.,Conjoint Endocrine Laboratory | Patel J.,University of Queensland | And 4 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2011

Normal human fetal development requires an adequate supply of thyroid hormone from conception. Until about 16 wk gestation this is supplied entirely by placental transfer of maternal hormone. Subsequently, the fetal thyroid synthesizes thyroid hormones, requiring a supply of maternal iodide. Trophoblast iodide transfer is mediated by the apical sodium iodide symporter (NIS). Placental oxygen levels are low in early pregnancy (~1%), rising with placental vascularisation to a plateau of ~8% at about 16 wk. Although the impact of these changing oxygen levels on placental implantation is well recognized, effects on trophoblast materno-fetal exchange are less understood. We investigated expression of the NIS regulator hCG, NIS mRNA expression, and I125 uptake in choriocarcinoma BeWo cells (a model of the trophoblast) cultured in 1 and 8% oxygen and in room air (21% oxygen). Expression of NIS and hCG mRNA and protein was low at 1% oxygen but rose significantly at 8 and at 21%. This was reflected in significant increases in I125 uptake. Desferrioxamine, an iron chelator and hypoxia mimic, decreased NIS and hCG expression and I125 uptake in BeWo cells. NIS expression and I125 uptake in cells grown at 1% oxygen were not increased by addition of hCG (2,500 IU/l). We infer that placental NIS mRNA and protein expression are regulated by oxygen, rising with vascularization of the placenta in the late first trimester, a time when fetal iodide requirements are increasing. © 2011 the American Physiological Society.

Landers K.A.,Conjoint Endocrine Laboratory | Mortimer R.H.,University of Queensland | Richard K.,Conjoint Endocrine Laboratory | Richard K.,University of Queensland
Placenta | Year: 2013

Since its discovery, transthyretin (TTR) has been regarded as an important hepatically derived protein carrier of thyroid hormones and retinol in blood. However, in more recent years it has been shown that TTR has other important functions. TTR is abundant in cerebrospinal fluid, where it may be involved in transport of thyroid hormones into the brain. TTR derived amyloid is associated with diseases such as senile systemic amyloidosis, familial amyloid polyneuropathy and familial amyloid cardiomyopathy. Recently, synthesis, secretion and uptake of TTR by human placenta have been reported. TTR appears to play an important role in the delivery of maternal thyroid hormone to the developing fetus. This review explores the various proposed roles of TTR and more recent findings on TTR synthesis and expression in the placenta. © 2013 Elsevier Ltd. All rights reserved.

Li H.,Conjoint Endocrine Laboratory | Patel J.,University of Queensland | Mortimer R.H.,Conjoint Endocrine Laboratory | Mortimer R.H.,University of Queensland | And 2 more authors.
Placenta | Year: 2012

The human fetus requires a maternal supply of iodide to synthesize thyroid hormone from 16 weeks gestation. Placental iodide transport is regulated by the sodium iodide symporter (NIS). We studied the ontogeny of NIS in placentas from surgically terminated pregnancies and from normal term pregnancies. NIS mRNA was low at 6 weeks gestation and peaked at 12 weeks gestation. Placental NIS protein levels are significantly correlated with gestational age during early pregnancy and increase with increased placental vascularization. This would lead to increased iodide supply to meet increased fetal requirements for thyroid hormone synthesis as the pregnancy progresses. Crown Copyright © 2012 Published by Elsevier Ltd. All rights reserved.

Patel J.,University of Queensland | Patel J.,Conjoint Endocrine Laboratory | Landers K.,Conjoint Endocrine Laboratory | Li H.,Conjoint Endocrine Laboratory | And 4 more authors.
Placenta | Year: 2011

Maternal thyroid hormone is provided to the fetus before the onset of fetal thyroid function (at about 16 weeks) and is essential for normal neurologic development. Mechanisms of transport are uncertain but transthyretin (TTR), a thyroxine binding protein produced by the placenta may be involved. Placental oxygen concentrations in early pregnancy are low, about 1% early in the first trimester and rising to 8% over the next 12 weeks. This study investigated the regulation of TTR expression, secretion and uptake in JEG-3 placental cells cultured at different oxygen concentrations. TTR mRNA and protein expression and 125I-TTR and Alexa-Fluor594-TTR uptake were significantly higher in cells cultured at 1% and 3% O 2, than at 8% O 2. This suggests that increased carrier mediated T 4 transport by placental TTR may be induced by the low oxygen environment of early pregnancy, a time when the fetus has its highest requirement for transport of maternal T 4. © 2010 Elsevier Ltd. All rights reserved.

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