Dataset Information

Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.

ABSTRACT: Our previous studies have shown that maternal high estradiol (E₂) environment increased the risk of thyroid dysfunction in offspring. However, the mechanism involved remains unexplored. To evaluate the thyroid function of offspring after high E₂ exposure and to explore the underlying mechanism, we established a high E₂ mouse model of early pregnancy, and detected thyroid hormones of their offspring. In thyroids of offspring, the expressions of Tg, Nis, Tpo, Pax8, and Titf1 and CpG island methylation status of Pax8 and genes involved in methylation were analyzed. We found that thyroxine (T4) and FT4 levels of offspring were obviously increased in the high-E₂ group, especially in females. In both 3- and 8-week-old offspring of the high-E₂ group, Pax8 was significantly up-regulated in thyroid glands, accompanied by the abnormal CpG island methylation status in the promoter region. Furthermore, Dnmt3a and Mbd1 were obviously down-regulated in thyroids of the high E₂ group. Besides, the disturbance of thyroid function in females was more severe than that in males, implying that the effects were related to gender. In summary, our study indicated that maternal high E₂ exposure disturbed the thyroid function of offspring through the dysregulation and abnormal DNA methylation of Pax8.

SUBMITTER: Lv PP

PROVIDER: S-EPMC5101534 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.

Lv Ping-Ping PP Tian Shen S Feng Chun C Li Jing-Yi JY Yu Dan-Qin DQ Jin Li L Shen Yan Y Yu Tian-Tian TT Meng Ye Y Ding Guo-Lian GL Jin Min M Chen Xi-Jing XJ Sheng Jian-Zhong JZ Zhang Dan D Huang He-Feng HF

Scientific reports 20161109

Our previous studies have shown that maternal high estradiol (E2) environment increased the risk of thyroid dysfunction in offspring. However, the mechanism involved remains unexplored. To evaluate the thyroid function of offspring after high E2 exposure and to explore the underlying mechanism, we established a high E2 mouse model of early pregnancy, and detected thyroid hormones of their offspring. In thyroids of offspring, the expressions of Tg, Nis, Tpo, Pax8, ...[more]

PMID: 27827435

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Project description:The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis.

Dataset Information

Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.

Publications

Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.

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