Placental Iodine Research Articles

Mechanism of multi-organ compensation under different iodine intake in pregnant rats: results from a repeated-measures study of iodine metabolism.

This study aimed to explore the differences in iodine metabolism and expression of NIS and Pendrin in pregnant rats under different iodine nutritional status. Female Wistar rats were divided into four groups: low iodine (LI), normal iodine (NI), tenfold high iodine (10HI), and fifty fold high iodine (50HI). The intervention began after one week of adaptive feeding. Iodine metabolism experiments were performed beginning on the 15th day of pregnancy. 24-h iodine intake and excretion were calculated. The concentrations of iodine in urine, fecal, thyroid, and placenta were measured by ICP-MS. PCR and Western Blot were used to detect the mRNA levels and cell membrane protein of sodium/iodide symporter (NIS) and Pendrin in the small intestine, thyroid, kidney, and placenta. Fecal iodine excretion (FIE) and urinary iodine excretion (UIE) in the 50HI group were significantly higher than those in the NI group (P < 0.05). The NIS protein and mRNA in the kidney and small intestine have an upward trend in iodine deficiency and a downward trend in iodine excess. Thyroid and placental iodine storage in the 50HI group were significantly higher than those in the NI group (P < 0.05). NIS, Pendrin protein, and mRNA in the thyroid and placenta tend to increase when iodine is deficient and decrease when there is excess. Iodine excretion and iodine stores in the placenta and thyroid gland are positively correlated with iodine intake. NIS and Pendrin are also regulated by iodine intake.

Adverse Effects of Black Carbon (BC) Exposure during Pregnancy on Maternal and Fetal Health: A Contemporary Review.

Black carbon (BC) is a major component of ambient particulate matter (PM), one of the six Environmental Protection Agency (EPA) Criteria air pollutants. The majority of research on the adverse effects of BC exposure so far has been focused on respiratory and cardiovascular systems in children. Few studies have also explored whether prenatal BC exposure affects the fetus, the placenta and/or the course of pregnancy itself. Thus, this contemporary review seeks to elucidate state-of-the-art research on this understudied topic. Epidemiological studies have shown a correlation between BC and a variety of adverse effects on fetal health, including low birth weight for gestational age and increased risk of preterm birth, as well as cardiometabolic and respiratory system complications following maternal exposure during pregnancy. There is epidemiological evidence suggesting that BC exposure increases the risk of gestational diabetes mellitus, as well as other maternal health issues, such as pregnancy loss, all of which need to be more thoroughly investigated. Adverse placental effects from BC exposure include inflammatory responses, interference with placental iodine uptake, and expression of DNA repair and tumor suppressor genes. Taking into account the differences in BC exposure around the world, as well as interracial disparities and the need to better understand the underlying mechanisms of the health effects associated with prenatal exposure, toxicological research examining the effects of early life exposure to BC is needed.

Lower iodine storage in the placenta is associated with gestational diabetes mellitus

BackgroundThe micronutrient iodine is essential for a healthy intrauterine environment and is required for optimal fetal growth and neurodevelopment. Evidence linking urinary iodine concentrations, which mainly reflects short-term iodine intake, to gestational diabetes mellitus (GDM) is inconclusive. Although the placental concentrations would better reflect the long-term gestational iodine status, no studies to date have investigated the association between the placental iodine load and the risk at GDM. Moreover, evidence is lacking whether placental iodine could play a role in biomarkers of insulin resistance and β-cell activity.MethodsWe assessed the incidence of GDM between weeks 24 and 28 of gestation for 471 mother-neonate pairs from the ENVIRONAGE birth cohort. In placentas, we determined the iodine concentrations. In maternal and cord blood, we measured the insulin concentrations, the Homeostasis Model Assessment (HOMA) for insulin resistance (IR) index, and β-cell activity. Logistic regression was used to estimate the odds ratios (OR) of GDM, and the population attributable factor (PAF) was calculated. Generalized linear models estimated the changes in insulin, HOMA-IR, and β-cell activity for a 5 μg/kg increase in placental iodine.ResultsHigher placental iodine concentrations decreased the risk at GDM (OR = 0.82; 95%CI 0.72 to 0.93; p = 0.003). According to the PAF, 54.2% (95%CI 11.4 to 82.3%; p = 0.0006) of the GDM cases could be prevented if the mothers of the lowest tertile of placental iodine would have placental iodine levels as those belonging to the highest tertile. In cord blood, the plasma insulin concentration was inversely associated with the placental iodine load (β = − 4.8%; 95%CI − 8.9 to − 0.6%; p = 0.026).ConclusionsHigher concentrations of placental iodine are linked with a lower incidence of GDM. Moreover, a lower placental iodine load is associated with an altered plasma insulin concentration, HOMA-IR index, and β-cell activity. These findings postulate that a mild-to-moderate iodine deficiency could be linked with subclinical and early-onset alterations in the normal insulin homeostasis in healthy pregnant women. Nevertheless, the functional link between gestational iodine status and GDM warrants further research.

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.

Determinants of placental iodine concentrations in a mild-to-moderate iodine-deficient population: an ENVIRONAGE cohort study

BackgroundIodine is an essential trace element for the production of thyroid hormones, and plays a key role during the gestational period for optimal foetal growth and (neuro-)development. To this day, iodine deficiency remains a global burden. Previous studies indicate that the placenta can store iodine in a concentration-dependent manner and serve as a long-term storage supply, but studies on the determinants of long-term placental iodine load are limited.MethodsThe placental iodine concentrations were determined for 462 mother-neonate pairs from the ENVIRONAGE birth cohort (Limburg, Belgium). Sociodemographic and clinical variables were obtained from questionnaires and medical files. Determinants of placental iodine concentration were identified using stepwise multiple regression procedures (p value < 0.15). The biological significance of our findings was investigated by measuring the plasma thyroid hormones in maternal and cord blood of 378 participants.ResultsA higher pre-pregnancy BMI, higher gestational weight gain, and alcohol consumption during pregnancy were linked with lower placental iodine storage. Multi-vitamin supplementation during pregnancy and longer gestation were associated with higher levels of placental iodine. Children born during the winter period had on average higher placental iodine levels. Besides, we found a significant positive time trend for placental iodine load over the study period 2013 to 2017. Lastly, we observed positive associations of both the maternal and cord plasma thyroxine concentrations with placental iodine load, emphasizing their biological link.ConclusionsThis study identified some determinants likely presenting a risk of reduced iodine storage during the gestational period of life. Future studies should elucidate the effects of lower placental iodine load on neonatal health, and health later in life.

Lower placental iodine concentrations are linked with higher concentrations of ambient PM2.5 exposure during the last trimester of pregnancy.

Background - The essential trace element iodine is needed for an optimal (neuro)-development of the fetus via the production of thyroid hormones. Recent findings indicate that exposure to ambient air pollution was linked with mild thyroid dysfunction during pregnancy. We hypothesize that air pollution might alter the placental iodine concentrations during gestation. Methods -We determined the placental iodine concentrations in 470 mother newborn pairs included in the ENVIRONAGE birth cohort. Maternal residential PM2.5 (particulate matter with a diameter &lt; 2.5 µm), NO2, and black carbon concentrations were determined during the pregnancy using a high-resolution air pollution model. Using distributed lag nonlinear models (DLNM), we modeled the gestational week-specific association between placental iodine concentrations and air pollutants. Results - Significant inverse associations were observed between gestational exposure to PM2.5 at weeks 28 to 35 and placental iodine concentrations. Cumulative estimates over the trimesters of pregnancy showed that in the third trimester of pregnancy (week 27 until delivery) an increase of 5 µg/m³ in PM2.5 exposure was associated with a decrease of 0.85 µg/kg in placental iodine concentration (95%CI: -1.56 to -0.14). These associations were adjusted for maternal pre-pregnancy BMI, gestational weight gain, household smoking behavior, maternal alcohol consumption, maternal education, maternal age, vitamin use, gestational age, date and season at delivery, and newborns’ sex. No significance was found between placental iodine load and the ambient NO2 or black carbon exposure.Conclusions- Gestational exposure to PM2.5 is linked with a lower placental iodine concentration. This decrease indicates that ambient air pollution might interfere with the normal uptake mechanisms of iodine, which could results in worse neurocognitive health outcomes later in life.

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.

The role of placental iodine storage in the neonatal thyroid stimulating hormone surge: iodine as a driving force to adapt the terrestrial life.

Iodine plays a pivotal role in adaptation during the transition from intrauterine to extrauterine life. Although it is well known that the placenta plays a role in iodine storage, a relationship between the neonatal thyroid stimulating hormone (TSH) peak and placental iodine concentration has not been established. This study focuses on the role of placental iodine concentration in the TSH surge after delivery. This study included 42 mothers and their newborns, none of whom had perinatal risk factors. The following samples were collected to analyze iodine: placental tissue, amniotic fluid (AF), and 24-h maternal urine. Blood was drawn from the umbilical cord (uc), newborns (at the 1st-24th hours), and mothers (at 1st hour) to analyze the following hormones: TSH, freeT4/T3(fT4/fT3), human chorionic gonadotrophin (hCG), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), and cortisol. The mean iodine levels of placental tissue, AF, and 24-h maternal urine were as follows: 29.06 ± 45.88μg/kg, 182.80 ± 446.51µg/L, and 498.35 ± 708.34µg/L, respectively. The mean TSH and hCG values were 32.41 ± 13.96mIU/ml and 30.66 ± 18.55mIU/ml, respectively, at the 1st hour. Placental iodine had strong, very strong, and weak negative correlations with TSH, hCG, and PRL, respectively (rTSH = - 0.763, p < 0.001;rHCG = - 0.919, p < 0.001; rPRL = - 0.312, p = 0.044). This study showed that the placental iodine level was inversely correlated with neonatal TSH, hCG, and PRL. It indicates that placental iodine concentration is an efficient driving force shaping the dynamic pattern of the neonatal TSH peak in addition to hCG and PRL surges, which reflects the adaptive effort in the transition from intrauterine to extrauterine life.

Variability of iodine concentrations in the human placenta

Iodine is an essential trace element, necessary for the production of thyroid hormones, which play a key role in optimal foetal growth and (neuro-) development. To date, iodine deficiency remains a health burden in many countries. We investigated the variability of placental iodine concentrations within and between individuals. We used 20 mother-neonate pairs from the ENVIRONAGE birth cohort, took samples at three standardized locations of the placentas, pooled and digested them, and determined the iodine concentrations using an ICP-MS method as an alternative for the Sandell-Kolthoff method. The variability between and within the three sample regions was calculated using the intra-class correlation coefficient (ICC) from the variance components of mixed models. With the Friedman test, the differences between placental biopsies were assessed. The ICC showed a higher between-placenta (68.6%) than within-placenta (31.4%) variability. Subsequently, we used our optimized method to determine iodine concentrations in 498 mother-neonate pairs, which averaged 26.1 μg/kg. For 96 mothers, the urinary iodine concentrations were also determined, which showed no correlation with the placental iodine storage, as was expected. Future studies are necessary to explore the effects of these placental iodine concentrations in relation to health outcomes of mother and child at birth and later in life.

Host and environmental determinants of placental iodine concentrations

Host and environmental determinants of placental iodine concentrations

Expression and function of placental uric acid transporter GLUT9

Expression and function of placental uric acid transporter GLUT9

Maintenance of iodine intake

Maintenance of iodine intake

Is placental iodine content related to dietary iodine intake?

Delivery of iodine to the foetus depends not only on maternal dietary iodine intake but also on the presence of a functioning placental transport system. A role for the placenta as an iodine storage organ has been suggested, and this study compares the iodine content of placentas from women giving birth at term in Ireland and Iran, areas with median urinary iodine of 79 and 206 μg/l respectively. Placental cotyledon iodine was measured using an alkaline ashing technique with Sandell-Kolthoff kinetic colorimetry. Samples were taken from six sites from the centre and periphery of each cotyledon. Placentas (Ireland n = 58; Iran n = 45) were obtained from consecutive euthyroid women delivering at term. The median placental iodine (μg/g wet weight) was significantly higher in Iranian than in Irish women (187·2 μg/g vs 34·3 μg/g; P < 0·001). The distribution of individual placental iodine values showed that values >50μg/g were found in 71·0% of Iranian and in only 21·0% of Irish samples. In Irish subjects, the relationship of placental iodine to pregnant population urinary iodine (UI) (ng/g:μg/l) was 1:2 (40:79), while in Iranians this ratio is closer to 1:1 (211:206). These findings, by demonstrating an apparent ability of the placenta to store iodine in a concentration-dependent manner, suggest a hitherto undetected role for the placenta. Whether placental iodine has a role in protecting the foetus from inadequacies in maternal dietary iodine intake is as yet unknown.

The Placenta as a Compensatory Iodine Storage Organ

The production of iodine-containing thyroid hormones necessary for brain development in the fetus depends not only on maternal dietary intake but also on placental iodine transport. The optimum level of iodine nutrition during pregnancy and the proportion of the pregnant population reaching this level have previously been evaluated. Little information exists on the ability of the placenta to either accumulate or store iodine. This study aims to investigate iodine uptake and tissue iodine content within placental tissue obtained from women delivering at term. Samples (∼1 cm(3)) obtained from placental cotyledons (n = 19), thyroid (n = 4), and uterine myometrial (n = 4) tissue were incubated for 6 hours with (125)I in the presence and absence of potassium perchlorate. To account for variation in tissue composition, results were expressed in cpm (125)I/μg DNA. Placental uptake of (125)I (375 cpm/μg DNA) was significantly higher than that of control myometrial tissue (226 cpm/μg DNA) (p < 0.05) and was ∼25% that of thyroid tissue (1702 cpm/μg DNA). Uptake of (125)I could be partially blocked in the thyroid and placenta, respectively, by potassium perchlorate (100 μM), which had no effect on uptake by myometrial tissue. Iodine content of tissue samples measured using an alkaline ashing technique with Sandell-Kolthoff colorimetry gave a mean value for total iodine of 30.4 ng/g placental tissue (range 21-50 ng/g), 1.74 ng/g myometrial tissue, and 1037 ng/g thyroid tissue. Placental iodine content was only ∼3% that of the thyroid, but on the basis that neonatal iodine stores are very low and highly sensitive to fluctuations in maternal iodine supply, we postulate that placental iodine bioavailability makes a significant contribution to protection against neonatal hypothyroidism. These findings suggest that the placenta has a role not only in uptake but also in storing iodine as a possible means of protecting the fetus from inadequacies in maternal dietary iodine intake.

202: The placenta as a significant modulator of iodine supply to the fetus

Iodide supply to the developing fetus is dependent on maternal dietary iodine intake and on functioning placental iodine transport; maternal iodine excretion falls precipitously at delivery. The aim of this study was to evaluate iodide uptake, tissue iodine content and transporter expression in placental tissue obtained from women undergoing prelabor cesarean section (CS) at term. The influences of different pregnancy-associated hormones on placental iodine uptake and its relationship to alterations in the expression levels of the iodide transporters, sodium iodide symporter (NIS) and Pendrin (PDS) were also assessed.