Fetal Thyroid Research Articles

Maternal nutrient restriction alters thyroid hormone dynamics in placentae of sheep having small for gestational age fetuses

Thyroid hormones regulate a multitude of metabolic and cellular processes involved in placental and fetal growth, while maternal nutrient restriction (NR) has the potential to influence these processes. Those fetuses most impacted by NR, as categorized by weight, are termed small for gestational age (SGA), but the role of thyroid hormones in these pregnancies is not fully understood. Therefore, the aims of the present study were to determine effects of NR during pregnancy on maternal and fetal thyroid hormone concentrations, as well as temporal and cell-specific expression of mRNAs and proteins for placental thyroid hormone transporters, thyroid hormone receptors, and deiodinases in ewes having either SGA or normal weight fetuses. Ewes with singleton pregnancies were fed either a 100% NRC (n = 8) or 50% NRC (NR; n = 28) diet from Days 35 to 135 of pregnancy with a single placentome surgically collected on Day 70. Fetal weight at necropsy on Day 135 was used to designate the fetuses as NR NonSGA (n = 7; heaviest NR fetuses) or NR SGA (n = 7; lightest NR fetuses). Thyroid hormone levels were lower in NR SGA compared to NR NonSGA ewes, while all NR fetuses had lower concentrations of thyroxine at Day 135. Expression of mRNAs for thyroid hormone transporters SLC16A2, SLC16A10, SLCO1C1, and SLCO4A1 were altered by day, but not nutrient restriction. Expression of THRA mRNA and protein was dysregulated in NR SGA fetuses with protein localized to syncytial and stromal cells in placentomes in all groups. The ratio of deiodinases DIO2 and DIO3 was greater for NR SGA placentae at Day 70, while DIO3 protein was less abundant in placentae from NR SGA than 100% NRC ewes. These results identify mid-gestational modifications in thyroid hormone-associated proteins in placentomes of ewes having SGA fetuses, as well as a potential for placentomes from NonSGA pregnancies to adapt to, and overcome, nutritional restrictions during pregnancy.

Complex immunogenomic control of serum thyroid hormone levels in fetuses and piglets challenged with Porcine Reproductive and Respiratory Syndrome Virus

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) causes respiratory disease in piglets and reproductive disease in sows. However, the interaction between host immunity and hormone homeostasis is not completely understood but piglet and fetal serum thyroid hormone (i.e., T3 and T4) levels decrease rapidly in response to PRRSV infection. Our objective was to estimate genetic parameters, identify QTL, and uncover nearby candidate genes for T3 and/or T4 levels of piglets and fetuses challenged with PRRSV2. Serum from 5-week old pigs (N=1792) at 11 days post infection (dpi) with PRRSV2 were assayed for T3 levels (piglet_T3). While serum from fetuses (N=1267) at 12 or 21 dpi from sows (N=150) challenged with PRRSV2 in late gestation were assayed for T3 (fetal_T3) and T4 (fetal_T4) levels. Animals were genotyped for 60K or 650K SNPs, heritabilities were estimated and genome wide association studies were performed for each trait separately. We found all three traits to be moderately heritable (18–28%) and the significant QTL (N=37) across several chromosomes collectively explained 24–34% of the genetic variation. A shared QTL identified for all traits on chromosome 6 contained the IL12RB2 and IFI44 genes. The largest QTL identified for both piglet_T3 and fetal_T3 on chromosome 5 contained IL17RA. A large QTL identified for piglet_T3 on chromosome 7 contained 9 MHC genes (e.g., SLA-DMA, SLA-DOA, SLA-DQA, SLA-DRA, and MHC-IA7). In conclusion, our data support the concept that there are complex interactions between thyroid hormone levels and multiple immunogenetic pathways during PRRSV infection, and that there is potential to select for pleiotropic QTL to simultaneously improve host immunity for reproductive and respiratory PRRS.

X-RAY AND MOLECULAR IMAGING DURING PREGNANCY AND BREASTFEEDING-WHEN SHOULD WE BE WORRIED?

Some of the ethically most sensitive issues in radiation protection arise at imaging of pregnant—and potentially pregnant—patients and of newborn.This article reviews the current literature and recommendations on imaging during pregnancy and breastfeeding. Risks related to alternative non-ionizing radiation methods are also considered.With few exceptions, exposure of the fetus through radiography, computed tomography (CT) and nuclear medicine imaging can be limited to safe levels, although studies such as abdominal-pelvic CT cannot avoid significant exposure to fetuses. Eight to 10 weeks post-conception, the fetus has a thyroid which starts to concentrate iodide having crossed the placenta barrier resulting in unacceptably high doses to the fetal thyroid after administration of 131I- and even 123I-iodide and other radiopharmaceuticals with a high content of free radioiodine.Many radiopharmaceuticals are excreted through breast milk. Breastfeeding interruption recommendations should be followed to keep the effective dose to the infant below 1 mSv.

Histological Studies on Foetal Thyroid Gland of Developing Human Foetuses

Introduction: Thyroid gland is the first endocrine gland to develop. It is one of the organs of interest for researchers since a long time. Though, detailed study about adult thyroid is there in the literature but histological study of thyroid gland at different stages in the foetal period is far and few. The present study aims to assess the histogenesis of thyroid gland and also to correlate the functional activity with structural changes in thyroid gland.
 Methods: The study was carried out on 30 foetal thyroid gland of known gestational age ranging from 10 to 38 weeks foetuses. The midline dissection of neck was done to expose the thyroid gland. After tissue processing, paraffin blocks were prepared. All sections were stained with Haematoxylin-Eosin stain.
 Results: In the foetuses, below 12th gestational week no colloid was detected in thyroid gland. First appearance of colloid was observed at 14th gestational week. Parafollicular cells were found after 17th gestational week. Capsule thickness and gland vascularity increased with advancement of gestational age. The size of the peripheral follicles is larger than the central follicles.
 Conclusions: The study concluded the developmental stage of foetal thyroid as Precolloidal stage, Colloid formation stage, Follicular stage and Maturation stage in different gestational weeks. The knowledge on the growth and differentiation of foetal thyroid will be helpful to the clinicians to judge the thyroid structure in preterm babies.

Application of Ultrasonographic Imaging in Fetal Thyroid Function Measurement of Amniotic Hormone Concentration

Objective: To investigate the fetal thyroid function using ultrasound imaging combined with amniotic fluid hormone concentration. Method: 380 pregnant women who did pregnancy test in our hospital from August 2015 to August 2017 were selected as the subjects. 260 of them had normal fetal growth indicators, all of them were singletons, with a gestational time of 18–41 weeks. 120 pregnant women underwent cesarean section, parturition, and amniocentesis. All pregnant women had no thyroid related diseases, hypertension, or autoimmune diseases. 3DUS (Three-dimensional ultrasound) and 2DUS (two-dimensional ultrasound) were used to measure the size of fetal thyroid gland, and the amniotic hormone content was measured. Result: The repeatability and consistency of the 3DUS-VOCAL (Voual organ computerized analysis) technique were superior to 2DUS in the measurement of fetal thyroid volume in 20 cases. There were 243 fetal thyroid size-related data collected from 260 fetuses at 18 weeks and 41 weeks of pregnancy. Amniotic fluid FT3, T3 had a certain correlation with gestational age, but amniotic fluid FT4, T4, TSH had no significant correlation with gestational age. 4 cases of fetal hypothyroidism were screened by ultrasound combined with amniotic fluid hormone measurement. Conclusion: The volume of fetal thyroid measured by 3DUS-VOCAL is better than that of 2DUS. Ultrasound combined with amniotic fluid thyroid associated hormone detection is helpful to evaluate fetal thyroid function.

Antenatal diagnosis and treatment of fetal goitrous hypothyroidism

Fetal goitre secondary to hypothyroidism is the leading cause of intellectual disability. Despite its rarity, many cases of fetal goitre are diagnosed and require prenatal management. We present a comprehensive review about the pre­na­tal diagnosis and treatment of fetal hypo­thy­roid goitre. Fetal thyroid size can be measured by transvaginal ultra­so­no­gra­phy from 14 weeks, and by trans­ab­do­mi­nal ultrasonography from 18 weeks of ges­ta­tion. The size of the fetal thyroid de­pends on ges­ta­tio­nal age. Because fetal goitre can lead to intra­ute­rine, perinatal and obstetrical complications, the op­ti­mal treat­ment is required. Fetal com­pli­cations are: fetal growth res­tric­tion, polyhydramnios, pleural effusion, preterm de­li­ve­ry, craniosynostosis, neuro­developmental disorders and neo­na­tal asphyxia or fetal death. The optimal intraamniotic L-thiroxine treatment did not normalize the thyroid hormonal le­vels, but these infants have normal neuromotor and psy­cho­­emo­­tio­nal development.

Interpretation of Chinese and American Guidelines for Diagnosis and Treatment of Thyroid Diseases During Pregnancy

More and more studies have found that thyrotoxicosis and hypothyroidism are related to adverse pregnancy outcomes, and maternal thyroid diseases also have a certain impact on fetal development. Drugs used to treat maternal hyperthyroidism can pass through the placenta and affect fetal thyroid development and thyroid function, and may cause fetal development malformations . Due to the lack of in-depth knowledge of this disease, timely screening, medical consultation and treatment rates for thyroid diseases during pregnancy are relatively low. Like this, if the treatment is not timely, it may cause irreversible effects on the pregnancy process and the fetus, such as increasing the risk of high blood pressure during pregnancy, miscarriage, premature delivery, low birth weight, stillbirth, thyroid crisis and maternal congestive heart failure, and impairing the neurological and intellectual development of offspring. This article intends to provide a reference for clinicians in the standardized diagnosis and treatment of thyroid diseases during pregnancy and postpartum through a comparative analysis of the latest guidelines for the diagnosis and treatment of thyroid diseases during pregnancy in China and the United States in 2020. It is hoped that through this article, various related complications and risks of mothers, fetuses and pregnancy caused by abnormal thyroid function will be reduced, and the quality of the population will be improved.

Ambient air pollution exposure during the late gestational period is linked with lower placental iodine load in a Belgian birth cohort

BackgroundAdequate intake of iodine is required for the production of thyroid hormones and contributes in pregnant women to a healthy brain development and growth in their offspring. To date, some evidence exists that fine particulate air pollution is linked with the fetal thyroid hormone homeostasis. However, possible effects of air pollutants on the placental iodine storage have not been investigated so far. ObjectivesWe investigated the association between air pollution exposure to particulate matter with a diameter less than 2.5 µm (PM2.5), NO2, and black carbon and the placental iodine load. MethodsThe current study is part of the ENVIRONAGE birth cohort and included 470 mother-newborn pairs. Iodine concentrations were measured in placental tissue. A high-resolution air pollution model was used to estimate the daily exposure to PM2.5, NO2, and black carbon over the entire pregnancy based on the maternal residential addresses. Distributed lag nonlinear models (DLNMs) were used to estimate gestational week-specific associations between placental iodine concentrations and the air pollutants to understand the impact of specific exposure windows. ResultsPM2.5 showed a positive association with placental iodine concentration between the 16th and 22nd week of gestation. In contrast, a significant inverse association between PM2.5 and placental iodine concentration was observed in gestational weeks 29–35. The effect estimate, for a 5 µg/m3 increment in PM2.5 concentration, was the strongest at week 32 (β −0.11 µg/kg; 95%CI: −0.18 to −0.03). No associations were observed between placental iodine concentrations and NO2 or black carbon. Assuming causality, we estimated that placental iodine mediated 26% (−0.33 pmol/L; 95%CI: −0.70 to 0.04 pmol/L) of the estimated effect of a 5 µg/m3 increment in PM2.5 exposure on cord blood free thyroxine (FT4) concentrations. ConclusionIn utero exposure to particulate matter during the third trimester of pregnancy is linked with a lower placental iodine load. Furthermore, the effect of air pollution on cord blood FT4 levels was partially mediated by the placental iodine load.

A study on evaluation of foetal thyroid volume in aborted foetus by ellipsoid method in relation to gestational age

Introduction: Thyroid volume measurement is a better reflection of thyroid gland growth than any other linear dimension of the organ. Foetal thyroid volume is significantly correlated with gestational age and foetal weight. Aim: To evaluate the foetal thyroid volume in relation to the gestational weeks. Materials and Methods: A total of 22 (Male - 9; Female - 13) aborted foetuses were collected from the department of Anatomy, ESIC Medical College & PGIMSR, Chennai. Results: We have observed there was significant increase in thyroid volume with the correction factor (CF-0.479) by ellipsoid method in relation to gestational weeks. Thyroid volume with correction factor was noted to be more in males as compared to females in all gestational age groups. There was a gradual increase in thyroid weight in relation to thyroid volume in all groups of gestational ages in our study. Conclusion: The present study evaluated the foetal thyroid volume in relation to the gestational age in aborted foetuses and also suggested the volume related changes of the thyroid gland in foetal life and its abnormalities. Keywords: Evaluation, Gestation, Thyroid, Volume.

Prenatal exposure to perfluoroalkyl substances and thyroid hormone concentrations in cord plasma in a Chinese birth cohort

BackgroundEvidence of associations between prenatal exposure to perfluoroalkyl substances (PFASs) and fetal thyroid hormones (THs) is controversial, and few studies have estimated the associations, while addressing the high correlations among multiple PFASs. We aimed to examine the associations between prenatal PFAS exposure and thyroid hormone concentrations in cord blood.MethodsA total of 300 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study were included. We measured the concentrations of eight PFASs in maternal plasma samples collected at 12–16 gestational weeks, as well as those of total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. We estimated the associations between maternal PFAS concentrations and TH concentrations using linear regression and Bayesian kernel machine regression (BKMR) models.ResultsIn BKMR models, higher PFAS mixture concentrations were associated with increased T3 concentrations, and there were suggestive associations with increased FT3 concentrations. For single-exposure effects in BKMR models, a change in PFDA, PFUdA, and PFOA concentrations from the 25th to 75th percentile was associated with a 0.04 (95%CrI: − 0.01, 0.09), 0.02 (95%CrI: − 0.03, 0.07), and 0.03 (95%CrI: − 0.001, 0.06) nmol/L increase in T3 concentrations, respectively. PFOA, PFNA, and PFDA were the predominant compounds in PFASs-FT3 associations, and the corresponding estimates were 0.11 (95% CrI: 0.02, 0.19), − 0.17 (95% CrI: − 0.28, − 0.07), and 0.12 (95% CrI: − 0.004, 0.24) pmol/L, respectively. A change in PFNA and PFOA concentrations from the 25th to 75th percentile was associated with a − 1.69 (95% CrI: − 2.98, − 0.41) μIU/mL decrease and a 1.51 (95% CrI: 0.48, 2.55) μIU/mL increase in TSH concentrations. The associations of PFOA and PFNA with T3/FT3 were more pronounced in boys, while those with TSH were more pronounced in girls.ConclusionOur results suggest that prenatal exposure to multiple PFASs was associated with thyroid hormones in cord blood. However, individual PFAS had varied effects—differing in magnitude and direction—on fetal thyroid hormones.

New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way.

In recent years, the presence in the environment of chemical compounds with thyroid-disrupting effects is progressively increased. This phenomenon has risen concern for human health as the preservation of thyroid system homeostasis is essential for fetal development and for maintaining psychological and physiological wellbeing. An increasing number of studies explored the role of different classes of toxicants in the occurrence and severity of thyroid diseases, but large epidemiological studies are limited and only a few animal or in vitro studies have attempted to identify the mechanisms of chemical action. Recently, epigenetic changes such as alteration of methylation status or modification of non-coding RNAs have been suggested as correlated to possible deleterious effects leading to different thyroid disorders in susceptible individuals. This review aims to analyze the epigenetic alterations putatively induced by chemical exposures and involved in the onset of frequent thyroid diseases such as thyroid cancer, autoimmune thyroiditis and disruption of fetal thyroid homeostasis.

Exposure to organophosphate ester flame retardants and plasticizers during pregnancy: Thyroid endocrine disruption and mediation role of oxidative stress

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer and industrial products. Human exposure to OPEs raises concerns due to their endocrine disruptive potentials. Till now, the effects of OPEs on thyroid hormones (THs) and the mediating role of oxidative stress in pregnant women have not been studied. In this study, prenatal urinary concentrations of OPE metabolites (mOPEs), levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and oxidative stress levels of 8-hydroxy-2-deoxy guanosine (8-OHdG) and malondialdehyde (MDA) were measured in pregnant women (n = 360) from a coastal urbanized region and moderate socioeconomic status. Neonatal TSH in heel blood was also measured in newborns (n = 309). Dibutyl phosphate (DBP) and diphenyl phosphate (DPHP) were extensively detected with a median creatinine-adjusted level of 0.19 μg/g and 0.66 μg/g, respectively, and the median of ∑mOPEs was 1.82 μg/g. DBP and DPHP were included in the analysis. The concentrations of DBP and DPHP were positively associated with either maternal or neonatal TSH levels, while not for maternal FT3 and FT4 levels. Positive associations for maternal and neonatal TSH were particularly observed in girls as stratified by newborn sex suggesting a sex-selective difference. Furthermore, 8-OHdG, the biomarker of DNA damage, was found to be a major mediator (>60%) for the association between neonatal TSH and DPHP, suggesting that DNA damage is involved in fetal thyroid function disruption. On the other hand, MDA showed a partially suppressing effect (<40%) for the associations between mOPEs and neonatal TSH, which needs further clarification. For maternal TSH, both 8-OHdG and MDA showed moderate mediating effects while the direct effects of mOPEs on maternal TSH also contributed. These results suggest thyroid disrupting effects of OPE exposure on mothers and fetuses during pregnancy and the potential influence mediated by the oxidative stresses of DNA damage and lipid peroxidation.

Morphometric features of the fetal thyroid gland: ultrasound examination findings

The article discusses features of morphometric parameters of the thyroid gland based on results of ultrasound examination. The need to study development of the thyroid gland in the fetus is due to the high prevalence of thyroid pathology and the possibility of its early prenatal diagnostics.The aim of the study was to characterize morphometric parameters of the fetal thyroid gland at 20–24 weeks of gestation using ultrasound examination. Material and methods. In the study the thyroid glands of 70 fetuses, both male and female, at the age of 20-24 weeks, were exposed to ultrasound examination. During ultrasound examination, the authors evaluated linear parameters, an organ perimeter, thyroid volume, and growth rate. Results. Ultrasound examination of fetuses aged 20–24 weeks demonstrated that all anatomical structures of the thyroid gland were well visualized on the images. The period from the 20th to the 24th week of the fetal intrauterine development was accompanied by an increase in the studied parameters of the thyroid gland, the growth intensity ranged from 3% (width of the left lobe) to 37% (thyroid volume). In female fetuses, the lobe sizes of the thyroid gland and the index of the thyroid volume prevailed. This period was also characterized by a low (up to 14%) growth intensity of certain linear parameters in male and female fetuses in different age subgroups.Conclusion. Starting from the 20th week of intrauterine development, ultrasound examination allows detecting features of the topography, quantitative anatomy and growth intensity of the fetal thyroid gland. The data obtained evidence the possibility of assessing the state of the thyroid gland during ultrasound screening of a fetus.

Iodine contrast prior to or during pregnancy and neonatal thyroid function: a systematic review.

Thyroid dysfunction is a known side effect of iodinated contrast media. There is some evidence to suggest that iodinated contrast media administered to pregnant women may cause thyroid dysfunction not only in themselves but also in their offspring. Here, we systematically evaluated literature on the use of iodinated contrast media prior to or during pregnancy on the offspring's thyroid function. Systematic review of published literature. Relevant studies were identified by PubMed, EMBASE and The Cochrane Library up to June 5, 2020. All study designs, reporting on the foetal or neonatal thyroid function after exposure to iodinated contrast media prior to or during pregnancy, were included. We undertook random effects meta-analysis and pooled the estimates as proportions with 95% CIs. We identified 402 articles, of which 26 were included. Six studies reported (n = 369) on exposure to iodinated contrast media prior to pregnancy by hysterosalpingography and 20 studies (n = 670) on exposure to these media during pregnancy by amniofetography, urography or CT. There was low to high risk of bias. The proportion of (transient) neonatal thyroid dysfunction was 0.0% (95% CI: 0.0-2.9% based on 3 studies) for hysterosalpingography, 2.25% (95% CI: 0.03-6.55% based on 2 studies) for amniofetography and 0.0% (95% CI: 0.0-0.02% based on 5 studies) for CT. There was a tendency towards an increased risk of thyroid dysfunction with higher amounts of contrast used. Exposure to iodinated contrast media prior to or during pregnancy may increase the risk of thyroid dysfunction in offspring. We recommend keeping the amount of contrast used as low as possible.

VP10.03: Fetal thyroid hypothyroidism diagnosed prenatally with an ultrasound score to predict thyroid function of fetal goiter

VP10.03: Fetal thyroid hypothyroidism diagnosed prenatally with an ultrasound score to predict thyroid function of fetal goiter

Characterization of Fetal Thyroid Levels at Delivery among Appalachian Infants.

Thyroid disorders are a frequently encountered issue during pregnancy and a cause of maternal and fetal morbidity. In regions like Appalachia that are particularly susceptible to health disparities, descriptive studies are needed to assist in identifying pathologic derangements. We sought to characterize fetal thyroid hormone levels at delivery and investigate whether or not maternal demographic characteristics affect the prevalence of neonatal thyroid disease. A cross-sectional analysis was conducted on 130 pregnant women recruited from the Tri-State region, incorporating areas of Kentucky, Ohio, and West Virginia. Total triiodothyronine (T3) (p = 0.4799), free T3 (p = 0.6323), T3 uptake (p = 0.0926), total thyroxine (T4) (p = 0.8316), free T4 (p = 0.0566), and Thyroid stimulating hormone (TSH) (p = 0.8745) levels were comparable between urban and rural newborns. We found no effect of hypertension status or nicotine levels on fetal umbilical cord thyroid hormone levels. Maternal diabetic status was associated with lower T4 (p = 0.0099) and free T4 (p = 0.0025) levels. Cotinine affected levels of T4 (p = 0.0339). In regard to maternal Body Mass Index (BMI), there was an increase in total T3 as BMI increased (p = 0.0367) and no significant difference in free T3, T3 uptake, T4, free T4, or TSH. There was a negative correlation between TSH and 1 min Apgar scores (p = 0.0058). Lead and cadmium have been implicated to alter TSH levels, but no correlation was found in our study (r2 = 0.0277). There were no differences in cord blood between urban (37.3 ± 10.3 fmol/ug DNA) and rural (70.5 ± 26.8 fmol/ug DNA) benzo(a)pyrene DNA adducts (p = 0.174). Thyroid disorders present a unique opportunity for the prevention of perinatal morbidity and mortality, since maternal treatment, as well as maternal demographic characteristics, can have direct fetal effects.

Defending Effects of Iodide Transfer in Placental Barrier Against Maternal Iodine Deficiency.

Objective: Placental iodide transport is necessary for maintaining an adequate iodide supply to the developing fetus. We hypothesized that compounds from the placental barrier can compensate for decreases in maternal iodine intake and normalize fetal iodine levels. Methods: Pregnant rats administered different amounts of iodine (1.24, 2.5, 5, or 10 μg/day) were evaluated on gestational day (gd) 16 and 20. The iodine levels in maternal blood, amniotic fluid (AF), and placental tissue were estimated using As-Ce catalytic spectrophotometry. The protein and/or messenger RNA (mRNA) levels of sodium iodide symporter (NIS), pendrin, alpha-smooth muscle actin (α-SMA), and CD31 in the placental labyrinth, trophoblast cells isolated using laser capture microdissection (LCM), and/or fetomaternal thyroid were detected using immunoblotting, real-time polymerase chain reaction, and/or immunohistochemistry. Results: When iodine intake was reduced, iodine levels in maternal blood gradually decreased; however, placental iodine levels were not significantly different between groups on gd16 and gd20. Minimal changes were observed in AF iodine levels on gd16, and a mild decreasing trend was observed (iodine dose, 10 to 1.24 μg/day) on gd20. NIS protein, which was linearly distributed along the basolateral membrane of maternal-fetal thyroid follicles, gradually increased with decreasing iodine levels. Regarding iodine deficiency in the placental labyrinth on gd16 and gd20, pendrin and glycosylated NIS proteins were significantly upregulated in a dose-dependent manner. However, the mRNA levels were unchanged. Furthermore, the conversion of NIS protein from the nonglycosylated to the glycosylated form increased. In trophoblast cells isolated using LCM, PDS mRNA levels increased in the 1.24-μg/day group on gd16 but not NIS mRNA levels. There was a smaller α-SMA+ area in the labyrinth zone on gd16 and gd20; however, the proportional CD31+ area increased on gd16 and reduced on gd20 with decreased iodine levels. Conclusions: All mechanisms upregulating the expression of iodine transporters and changes in villous stroma and microvessel area in the placental labyrinth can promote iodide transfer from mother to fetus in iodine deficiency, especially before the onset of fetal thyroid function. Compensatory NIS protein regulation in the placenta against decreased iodine intake mainly occurs during translation and glycosylation modification after translation. Pendrin may be more important than NIS in the mediation of placental iodide transport.

Dose-Dependent Influence of Antithyroid Drugs on the Difference in Free Thyroxine Levels between Mothers with Graves’ Hyperthyroidism and Their Neonates

Background: Several guidelines have recommended that the use of the lowest effective dose of antithyroid drugs (ATDs) that maintains maternal serum free thyroxine (FT4) levels at or moderately above the upper limit of the reference range is appropriate for fetal euthyroid status. However, little is known about whether ATD dosage affects the difference in serum FT4 levels between the mother and neonate. We conducted a retrospective study at a tertiary hospital in Japan to investigate the dose-dependent influence of ATDs on both maternal and fetal thyroid hormone status. Materials and Methods: We retrospectively examined 62 pregnant women who delivered between 2007 and 2016 and were treated for Graves’ hyperthyroidism with ATD at any stage during pregnancy. We selected individuals whose data on maternal FT4 level within 4 weeks of their deliveries and cord FT4 level of their infants at the time of delivery were available. Those with multiple pregnancies, iodine or glucocorticoid treatment, and fetal goiter detected by ultrasonography were excluded. Results: After the exclusion criteria were applied, we recruited 40 individuals. The cord FT4 levels were significantly lower than the maternal FT4 levels in patients treated with high-dosage ATDs (methimazole >5 mg daily or propylthiouracil >100 mg daily). However, there were no significant differences between maternal and cord FT4 levels in patients treated with low-dosage ATDs (methimazole ≤5 mg daily or propylthiouracil ≤100 mg daily). We selected 35 individuals whose data on maternal thyrotropin receptor-binding inhibitory immunoglobulin (TBII) level were available. Multiple linear regression analysis adjusted for ATD dosage, maternal TBII level, and gestational period found that ATD dosage was a significant predictor of the difference in serum FT4 levels between the mother and neonate. In terms of maternal complications, multiple logistic regression analysis identified maternal free triiodothyronine (FT3) level as a significant predictor of the incidence of preterm delivery. Conclusions: We found a dose-dependent influence of ATDs on the difference in serum FT4 levels between mothers with Graves’ hyperthyroidism and their neonates. Further studies to evaluate the optimal target FT4 and FT3 levels for the mother and neonate during pregnancy may improve the outcome of pregnant women with Graves’ hyperthyroidism.

Ultrasonographic assessment of fetal thyroid in Japan: thyroid circumference and distal femoral and proximal tibial ossification.

The present study established a nomogram of fetal thyroid circumference (FTC) and the appearance timing of fetal distal femoral and proximal tibial ossification to assess fetal thyroid function in Japan. Between April 2015 and July 2019, normal pregnant women at our hospital were recruited for the study. FTC was measured by the automatic ellipse outline and plotted against gestational age (GA). Fetal distal femoral and proximal tibial ossification measurements were obtained with standard electronic calipers from outer-to-outer margins (> 1mm as the presence of ossification). A total of 199 pregnant women were examined. FTC increased logarithmically to GA. A nomogram of FTC was expressed by a logarithmic formula: [Formula: see text]. The respective 5-95th percentiles of FTC at each GA were 20.2-36.2mm at 22weeks, 25.0-44.8mm at 26weeks, 29.2-52.3mm at 30weeks, and 32.9-59.0mm at 34weeks. The fetal distal femoral epiphysis was not visualized before 30weeks, but was visualized in 100% of fetuses after 35weeks of gestation. The fetal proximal tibial epiphysis was not visualized before 33weeks, but was visualized in 73.7% of fetuses at 37weeks of gestation. We generated a GA-dependent FTC nomogram for Japanese fetuses. We also confirmed the appearance timing of fetal distal femoral and proximal tibial ossification to assess bone maturation. These assessments may be very useful for evaluating fetal thyroid function in Japan.

Effects of repetitive Iodine thyroid blocking on the foetal brain and thyroid in rats: a systems biology approach

A single administration of an iodine thyroid blocking agent is usually sufficient to protect thyroid from radioactive iodine and prevent thyroid cancer. Repeated administration of stable iodine (rKI) may be necessary during prolonged or repeated exposure to radioactive iodine. We previously showed that rKI for eight days offers protection without toxic effects in adult rats. However, the effect of rKI administration in the developing foetus is unknown, especially on brain development, although a correlation between impaired maternal thyroid status and a decrease in intelligence quotient of the progeny has been observed. This study revealed distinct gene expression profiles between the progeny of rats receiving either rKI or saline during pregnancy. To understand the implication of these differentially expressed (DE) genes, a systems biology approach was used to construct networks for each organ using three different techniques: Bayesian statistics, sPLS-DA and manual construction of a Process Descriptive (PD) network. The PD network showed DE genes from both organs participating in the same cellular processes that affect mitophagy and neuronal outgrowth. This work may help to evaluate the doctrine for using rKI in case of repetitive or prolonged exposure to radioactive particles upon nuclear accidents.