Transplacental thyroxine and fetal brain development

Zoeller, R. Thomas

doi:10.1172/jci18236

Cited by 64 publications

(17 citation statements)

References 21 publications

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“…During the embryonic and fetal periods of life the critical importance of THs of maternal origin becomes apparent in light of the consideration that while the effects of congenital hypothyroidism can be largely prevented by early postnatal TH substitution therapy, the effects of severe TH deficiency secondary to an inadequate supply from the mother, which include cognitive and motor defects, growth retardation, defects of hearing and speech and other defects, are irreversible after birth (this syndrome is known as neurological cretinism; de Escobar et al, 2004, Gilbert et al, 2012). Moreover, recent evidence additionally suggests that even more subtle forms of maternal thyroid dysfunction during pregnancy may impair her offspring’s cognitive and motor development (Zoeller, 2003, de Escobar et al, 2008, McLeod and McIntyre, 2010). In addition to iodine deficiency, maternal thyroid dysfunction can arise from autoimmune processes (e.g.…”

mentioning

confidence: 99%

Influence of maternal thyroid hormones during gestation on fetal brain development

et al. 2017

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Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention.

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confidence: 99%

Influence of maternal thyroid hormones during gestation on fetal brain development

et al. 2017

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“…Decreased production of this hormone can lead to hypothyroidism and clinical symptoms such as fatigue, muscle weakness, sensitivity to cold, constipation, weight gain, depression, and impaired memory. In the fetus and child, thyroid hormone is required for proper brain and neurological development (20). The fetal thyroid does not begin producing significant amounts of thyroid hormone until later in pregnancy, so in early pregnancy maternal T4 that crosses the placenta is the major source to serum T4 in the fetus (21).…”

Section: Human Pharmacokinetics and Toxicitymentioning

confidence: 99%

Perchlorate in Water Supplies: Sources, Exposures, and Health Effects

Steinmaus

2016

Curr Envir Health Rpt

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Perchlorate exposure occurs from ingestion of natural or manmade perchlorate in food or water. Perchlorate is used in a variety of industrial products including missile fuel, fireworks, and fertilizers, and industrial contamination of drinking water supplies has occurred in a number of areas. Perchlorate blocks iodide uptake into the thyroid, and decreases the production of thyroid hormone, a critical hormone for metabolism, neurodevelopment, and other physiologic functions. Occupational and clinical dosing studies have not identified clear adverse effects, but may be limited by small sample sizes, short study durations, and the inclusion of mostly healthy adults. Expanding evidence suggests that young children, pregnant women, fetuses, and people co-exposed to similarly acting agents may be especially susceptible to perchlorate. Given the ubiquitous nature of perchlorate exposure, and the importance of thyroid hormone for brain development, studying the impact of perchlorate on human health could have far-reaching public health implications.

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“…Neuronal cells are more sensitive to PCB metabolites than other cells [72], and Purkinje cells seem to be especially sensitive to endocrine disruptions [75]. Hypothyroidism leads to region-specific alterations of the expression pattern of TR isoforms, of which TRα2 is a non-T 3 -binding isoform [76], and such subtle changes lead to molecular and histological changes [19,73,77,78] that finally may translate into clinical and epidemiological effects of hypothyroidism in humans. …”

Section: Effects Of Low Ths On the Developing Human Brainmentioning

confidence: 99%

“…Low TH is associated with alterations of cell migration in the developing brain [19,77,78], decreased myelination and cell migration and maturation [77] resulting in permanent changes of the cytoarchitecture, especially of the somatosensory cortex and the hippocampus [21], and for these effects, critical windows of sensibility exist during fetal and embryonic development [13]. …”

Section: Effects Of Low Ths On the Developing Human Brainmentioning

confidence: 99%

“…Generally, decreased TH levels during pregnancy result in serious alterations of the neurodevelopment of the developing fetus [13,18]. Mandatory screening for thyroid function in pregnant women is therefore warranted [19,20], especially in the light of the permanent effects of hypothyroxinemia on brain development [21,22]. Therefore, the potential of chemicals interfering with TH homeostasis needs careful attention, and the main aspects and long-term effects of TH-disrupting compound (THDC) activities and exposure for humans are discussed below.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Endocrine Disruptors on the Thyroid Hormone System

Gutleb

Cambier

Serchi³

2016

Horm Res Paediatr

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The thyroid hormone (TH) system plays a central role in central physiological processes of many species, including mammals and humans, ranging from growth and cell differentiation, energy metabolism, thermoregulation and phasing of hibernation or annual movements of migratory species, metamorphosis from larvae to adult forms, brain development, reproduction, or the cardiovascular system. Several chemicals are known to be TH-disrupting compounds (THDCs) and have been shown to interact with virtually all elements of TH homeostasis such as feedback mechanisms with the hypothalamus-pituitary axis, TH synthesis, TH storage and release from the thyroid gland, transport protein binding and TH distribution in tissues and organs, cellular TH uptake, intracellular TH metabolism, and TH receptor binding. Therefore, chemicals interfering with the TH homeostasis have the potential to interact with many of these important processes, and especially early-life stage exposure results in permanent alterations of tissue organization and homeostatic regulation of adaptive processes. This is not only of theoretical importance as the reported plasma concentrations of THDCs in human plasma fall well within the range of reported in vitro effect concentrations, and this is of even higher importance as the developing fetus and young children are in a sensitive developmental stage.

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Transplacental thyroxine and fetal brain development

Cited by 64 publications

References 21 publications

Influence of maternal thyroid hormones during gestation on fetal brain development

Influence of maternal thyroid hormones during gestation on fetal brain development

Perchlorate in Water Supplies: Sources, Exposures, and Health Effects

Impact of Endocrine Disruptors on the Thyroid Hormone System

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