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A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats.

ABSTRACT: Thyroid disorders are relatively frequently observed in pregnant women. However, the impact of pregnancy on maternal thyroid has not been systematically evaluated. In the present study, using the rat as an animal model, we observed that the weight of maternal thyroid increased by about 18% in late pregnancy. To gain an insight into the molecular mechanisms, we took advantage of RNA-seq approaches to investigate global gene expression changes in the maternal thyroid. We identified a total of 615 differentially expressed genes, most of which (558 genes or 90.7%) were up-regulated in late pregnancy compared to the non-pregnant control. Gene ontology analysis showed that genes involved in cell cycle and metabolism were significantly enriched among up-regulated genes. Unexpectedly, pathway analysis revealed that expression levels for key components of the thyroid hormone synthesis pathway were not significantly altered. In addition, by examining of the promoter regions of up-regulated genes, we identified MAZ (MYC-associated zinc finger protein) and TFCP2 (transcription factor CP2) as two causal transcription factors. Our study contributes to an increase in the knowledge on the maternal thyroid adaptation to pregnancy.

SUBMITTER: Liu JL

PROVIDER: S-EPMC4661888 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats.

Liu Ji-Long JL Wang Tong-Song TS Zhao Miao M Peng Ying Y Fu Yong-Sheng YS

International journal of molecular sciences 20151113 11

Thyroid disorders are relatively frequently observed in pregnant women. However, the impact of pregnancy on maternal thyroid has not been systematically evaluated. In the present study, using the rat as an animal model, we observed that the weight of maternal thyroid increased by about 18% in late pregnancy. To gain an insight into the molecular mechanisms, we took advantage of RNA-seq approaches to investigate global gene expression changes in the maternal thyroid. We identified a total of 615 ...[more]

PMID: 26580608

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Project description:BACKGROUND:Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent. OBJECTIVES:In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns. METHODS:We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n?=?202) and cord serum at delivery (n?=?276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones. RESULTS:With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT4) decreased by 0.52??g/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT4 (WQS beta?=?-0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta?=?-0.11; 95% CI: -0.20, -0.03) and TT4 (WQS beta?=?-0.53; 95% CI: -0.90, -0.16). CONCLUSION:Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology.

Project description:BackgroundHypertensive disorders of pregnancy (HDP) are characterized by hemodynamic disturbances. Altered thyroid function is a risk factor for poor outcomes of pregnancy. However, the associations between thyroid function biomarkers and maternal hemodynamics during pregnancy in HDP remain unclear.MethodsFrom January 2016 to January 2018, pregnant women diagnosed with HDP admitted to the Nanjing Maternity and Child Health Care Hospital were prospectively enrolled in the third trimester. Normally distributed variables were expressed as mean ± standard deviation and skewed variables were expressed as median (25th percentile, 75th percentile). Correlations between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) and maternal hemodynamic parameters were assessed by Pearson's correlation coefficient and 95% confidence interval (95%CI). Bonferroni's correction for multiple correlations was performed. Logistic regression models with odd ratio (OR) and 95%CI were applied to confirm the associations.ResultsA total of 163 third-trimester pregnant women with HDP with a mean gestational age of 35.62 ± 2.83 weeks were recruited. The infant birth weight of patients with elevated TSH levels was lower than that of patients with normal TSH levels (2635 ± 867 g vs. 3037 ± 673 g, p = 0.002). Reduced cardiac output (CO) was defined as CO < 3.5 L/min. The infant birth weight of patients with reduced CO was lower than that of patients with normal CO (2250 ± 510 g vs. 2890 ± 774 g, p = 0.002). TSH levels were significantly and negatively correlated with CO (r = - 0.260, 95%CI: - 0.392- -0.103, p < 0.001). FT4 levels were not significantly correlated with any of the maternal hemodynamic parameters (all p > 0.05). TSH level (OR = 1.371, 95%CI: 1.086-1.733, p = 0.008) was confirmed associated with reduced CO in the logistic regression analysis.ConclusionsElevated TSH levels are associated with reduced CO in HDP during the third trimester.

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A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats.

Publications

A Transcriptomic Study of Maternal Thyroid Adaptation to Pregnancy in Rats.

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