Prenatal programming of adult thyroid function by alcohol and thyroid hormones

2004 ◽  
Vol 287 (2) ◽  
pp. E318-E326 ◽  
Author(s):  
Jennifer Slone Wilcoxon ◽  
Eva E. Redei

Increasing evidence associates environmental challenges early in life with permanent alterations of physiological functions in adulthood. These changes in fetal environment can trigger physiological adaptations by the fetus, called fetal programming, which may be beneficial before birth but permanently influence the physiology of the organism. In this study, we investigated the potential connection between alcohol-induced decreased maternal thyroid function and the hypothalamic-pituitary-thyroid (HPT) function of adult rat offspring. Plasma 3,5,3′-triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were decreased in alcohol-consuming (E) dams on gestational day 21 compared with ad libitum- (C) and pair-fed (PF) controls. No significant differences were found in HPT function in young offspring (3 wk of age) between diet groups. However, adult fetal alcohol-exposed (FAE) offspring had significantly decreased levels of T3 along with elevated TSH compared with control offspring. T4 administration to the mother did not normalize the hypothyroid state of the adult FAE offspring. Interestingly, administration of T4 to control pregnant dams decreased plasma T3 of the adult female offspring only, whereas T4 together with maternal alcohol consumption or pair-feeding led to decreased TSH and T4 in the adult female offspring. Our results suggest that ethanol consumption and T4 administration alter maternal HPT function, leading to prenatally programmed permanent alterations in the thyroid function of the adult offspring.

Author(s):  
Frank A. Quinn ◽  
Gennady N. Gridasov ◽  
Sergey A. Vdovenko ◽  
Natalia A. Krasnova ◽  
Nadezhda V. Vodopianova ◽  
...  

AbstractUndiagnosed thyroid disease is a common problem with significant public health implications. This is especially true during pregnancy, when the health of both the mother and the developing child can be adversely affected by abnormal maternal thyroid function. Measurement of serum thyroid stimulating hormone (TSH) and thyroid peroxidase antibodies (TPO-Ab) are two common ways to assess maternal thyroid status. The objective of our study was to determine the prevalence of abnormal TSH and TPO-Ab tests in a population of pregnant women in the Samara region of the Russian Federation. Serum samples were obtained from 1588 pregnant women as part of their routine antenatal care. TSH and TPO-Ab were measured, and trimester-specific reference values for TSH (2.5–97.5 percentiles) were calculated using TPO-Ab-negative women. TSH results outside these ranges were considered abnormal; TPO-Ab levels outside the manufacturer's reference range (>12IU/mL) were considered abnormal. Overall, the prevalence of abnormal results was 6.3% for TSH and 10.7% for TPO-Ab. High TSH (>97.5 trimester-specific percentile) and TPO-Ab-positive results were most common in the first trimester (5.7% and 13.8%, respectively). TSH levels were associated with gestational age and TPO-Ab status, and with maternal age in TPO-Ab-negative women. TPO-Ab status was associated with both maternal and gestational age. Women with TSH >2.5mIU/L had a significantly increased risk of being TPO-Ab-positive, and this risk increased with age. Based on our data, we conclude that abnormal TSH and TPO-Ab are common in pregnant women of the Samara region. Given the association of thyroid dysfunction to adverse pregnancy outcomes, screening of this population for abnormal thyroid function should be considered.


2000 ◽  
Vol 164 (1) ◽  
pp. 7-11 ◽  
Author(s):  
O Ogueh ◽  
AP Hawkins ◽  
A Abbas ◽  
GD Carter ◽  
KH Nicolaides ◽  
...  

The aim of the study was to investigate maternal thyroid function in pregnancy by monitoring the circulating concentrations of thyroid stimulating hormone (TSH), free thyroxine (fT(4)) and human chorionic gonadotrophin (hCG) in multifetal pregnancies before and after embryo reduction. We studied two groups of women: group 1 comprised singleton (n=12) and twin (n=12) pregnancies achieved after superovulation and in vitro fertilisation and embryo transfer (IVF-ET), and group 2 were multifetal pregnancies (n=39) undergoing selective fetal reduction to twin pregnancies. Blood samples were obtained initially at 10-12 weeks gestation (before fetal reduction) and then 4 and 8 weeks afterwards. Before fetal reduction, the circulating concentrations of fT(4) in multifetal pregnancies were significantly greater than those in singleton or twin pregnancies (singleton, mean 16.49 pmol/l (interquartile range 14.09-18.13 pmol/l); twins, 15.84 (15.36-16.95 pmol/l); multifetal, 21.08 (16. 64-26.29 pmol/l); P<0.005 for singleton and twins), and in a multiple regression analysis, fT(4) was significantly related to the number of fetuses (F=23.739, P=0.0001), but not to hCG. After fetal reduction to twins, the circulating concentrations of fT(4) in multifetal pregnancies decreased progressively towards those in control twin pregnancies, but remained significantly greater at both 4 (P=0.003) and 8 weeks (P=0.050). This pattern of change in the concentrations of fT(4) is similar to, but lags behind, that of hCG, which attains twin levels 4 weeks after fetal reduction. This may represent a delayed thyroid response to the decreasing concentrations of hCG, but the alternative is that the maternal thyroid function is controlled by a fetal factor in addition to hCG.


2013 ◽  
Vol 110 (5) ◽  
pp. 831-839 ◽  
Author(s):  
Piedad Santiago ◽  
Inés Velasco ◽  
Jose Antonio Muela ◽  
Baltasar Sánchez ◽  
Julia Martínez ◽  
...  

The benefits of iodine supplements during pregnancy remain controversial in areas with a mild-to-moderate iodine deficiency. The aim of the present study was to determine the effect of improving iodine intakes, with iodised salt (IS) or iodine supplements, in pregnant Spanish women. A total of 131 pregnant women in their first trimester were randomly assigned to three groups: (1) IS in cooking and at the table, (2) 200 μg potassium iodide (KI)/d or (3) 300 μg KI/d. No differences were found in thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) or thyroid volume (TV) between the three groups. Regardless of the group in which women were included, those who had been taking IS for at least 1 year before becoming pregnant had a significantly lower TV in the third trimester (P= 0·01) and a significantly higher urinary iodine in the first (173·7 (sd81·8)v. 113·8 (sd79·6) μg/l,P= 0·001) and third trimesters (206·3 (sd91·2)v. 160·4 (sd87·7) μg/l,P= 0·03). Also, no differences were seen in TSH, FT4 or FT3. Children's neurological development was not significantly associated with the consumption of IS for at least 1 year before becoming pregnant and no differences were found according to the treatment group. In conclusion, in pregnant women with insufficient iodine intake, the intake of IS before becoming pregnant was associated with a better maternal thyroid function. The form of iodide intake was not associated with maternal thyroid function or children's neurological development.


2005 ◽  
Vol 83 (4) ◽  
pp. 383-387 ◽  
Author(s):  
Parissa Sadri ◽  
Dallas J Legare ◽  
Shinichiro Takayama ◽  
W Wayne Lautt

Insulin causes the release of the hepatic insulin-sensitizing substance (HISS) from the liver. Hepatic parasympathetic nerves play a permissive role in the release of HISS. HISS-dependent insulin resistance (HDIR) occurs in the absence of HISS. Fetal ethanol exposure has been shown to cause dose-dependent HDIR in adult male rat offspring. Since female offspring are more severely affected by in utero ethanol toxicity, we hypothesized that fetal alcohol exposure causes higher incidence and more severe HDIR in adult female offspring. Adult female rat offspring prenatally exposed to different concentrations of ethanol (0%, 15%, and 20%) were tested for insulin sensitivity using the rapid insulin sensitivity test (RIST). The RIST index was significantly reduced in the 15% (134.1 ± 16.1 mg/kg) and the 20% (98.7 ± 9.7 mg/kg) group compared with the 0% (220.9 ± 27.6 mg/kg) group. Administration of atropine produced significant additional HDIR in the 15% group (82.9 ± 14.5 mg/kg) but not the 20% group (83.8 ± 20.5 mg/kg) indicating complete HDIR had been produced in this group, contrary to the adult male offspring in a previous study. The results are consistent with the hypothesis that adult-female offspring are more severely affected by in utero ethanol exposure compared with adult-male offspring.Key words: fetal, alcohol, insulin resistance, gender, HISS, teratology, diabetes.


2021 ◽  
Vol 9 ◽  
Author(s):  
Maya Berlin ◽  
Dana Barchel ◽  
Anna Brik ◽  
Elkana Kohn ◽  
Ayelet Livne ◽  
...  

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring.Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns.Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders.Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83–68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70–8.23) μIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27–13.53) μg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36–12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6–24.9) μg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) &lt; 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI &gt; 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19–24.9).Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.


2019 ◽  
Vol 32 (1) ◽  
pp. 189-196 ◽  
Author(s):  
Dagnachew Muluye Fetene ◽  
Kim S. Betts ◽  
Rosa Alati

AbstractMaternal thyroid dysfunction during pregnancy may contribute to offspring neurobehavioral disorders. In this paper, we investigate the relationship between maternal thyroid function during pregnancy and offspring depression and anxiety. Data were taken from the Avon Longitudinal Study of Parents and Children. A total of 2,920 mother-child pairs were included. Thyroid-stimulating hormone levels, free thyroxine (FT4), and thyroid peroxidase antibodies were assessed during the first trimester of pregnancy because maternal supply is the only source of thyroid hormone for the fetus during the first 12 weeks of gestation. Child symptoms of depression and anxiety were assessed using the Development and Well-Being Assessment at ages 7.5 and 15 years. The odds of presenting with depression and anxiety were estimated using the generalized estimating equation. The level of FT4 during the first trimester of pregnancy was associated with child depression combined at ages 7.5 and 15 (odds ratio = 1.21, 95% confidence interval [1.00, 1.14]. An increase of 1 standard deviation of FT4 during pregnancy increased the odds of child depression by 28% after adjustment made for potential confounders. No association was found among maternal levels of thyroid-stimulating hormone, FT4, and thyroid peroxidase antibodies and childhood anxiety. In conclusion, increased levels of FT4 during the first trimester of pregnancy appear be linked to greater risk of offspring depression.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meng Zuo ◽  
Guotao Liao ◽  
Wenqian Zhang ◽  
Dan Xu ◽  
Juan Lu ◽  
...  

Abstract Objective PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring. Methods After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice. Results The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05). Conclusions APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.


Author(s):  
Lakshmi Venugopalan ◽  
Aishwarya Rajan ◽  
Hemchand. K. Prasad ◽  
Anupama Sankaran ◽  
Gnanabalan Murugesan ◽  
...  

AbstractObjectivesPrevalence of Maternal and congenital hypothyroidism is on the rise. To present the thyroid stimulating hormone screening results in babies born to hypothyroid mothers and assess the burden, aetiology of hypothyroidism in these babiesMethodsAll antenatal mothers attending our hospital during the study period were enrolled into the study. Group I includes 249 term babies born to hypothyroid mothers and group II comprises 2154 newborns born to mothers who are euthyroid. Heel prick thyroid stimulating hormone was done for all newborns on day 3 for both groups. Confirmatory venous testing was done for all for babies in group I and screen positives belonging to group II. Evaluation and therapy done as per standard guidelines.ResultsThyroid stimulating hormone values in the two groups are presented. There was significant correlation between peak maternal thyroid stimulating hormone and neonatal day 3 heel prick in group I (r=0.7, P<0.05). The prevalence of positive screening test in groups I and II was 3.8 and 1.03% (p<0.05) whereas corresponding values for confirmed disease was 4.3 and 0.6%, respectively (p<0.05). Aetiological evaluation revealed both transient hypothyroidism (33.3%) and permanent hypothyroidism (66.6%).Conclusion4.3% of babies born to hypothyroid mothers develop congenital hypothyroidism; aetiology being both transient and permanent. A venous test by 3 weeks is helpful in these babies to improve case identification.


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