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Horm Metab Res 2018; 50(09): 696-703
DOI: 10.1055/a-0658-2095
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF Expression in the Rat Fetal Brain Following Maternal Hypothyroidism

Qian Xing
1   Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
3   Department of Endocrinology and Metabolism, First Affiliated Hospital of Dalian Medical University, Dalian, China
,
Zhongyan Shan
1   Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China
,
Yun Gao
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Jingyuan Mao
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Xiu Liu
1   Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Jiashu Yu
1   Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
3   Department of Endocrinology and Metabolism, First Affiliated Hospital of Dalian Medical University, Dalian, China
,
Huakun Sun
1   Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Chenling Fan
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Hong Wang
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Hongmei Zhang
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
,
Weiping Teng
2   Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
› Author Affiliations
Further Information

Publication History

received 15 August 2017

accepted 04 July 2018

Publication Date:
17 August 2018 (online)

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Abstract

To investigate the mechanism responsible for the neurological alterations, miRNA expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in brain tissues of fetal or neonatal rats and from maternal rats with hypothyroidism. Ninety female Wistar rats were divided into a control and a hypothyroid group, which were mated. Brain samples of the offspring were obtained at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7, and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested by real-time PCR and protein expression by Western blot. Luciferase assays were used to confirm that miR-206 targets the 3′-untranslated region (3′-UTR) of BDNF. In the brain tissues of fetal and neonatal rats from maternal rats with hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and P7. Compared with the control group, miR-206 levels in the hypothyroidism group were increased by 3.1-fold by micro-array, and were higher as measured by SYBR green real-time qRT–PCR (p<0.01). There was no significant difference in the BDNF mRNA levels at E13 between the hypothyroidism group and the control group (1.767±0.477 vs. 1.798±0.462, respectively; p>0.05), but pro-BDNF and mature BDNF protein levels in the hypothyroid group at E13 were significantly lower than those in the control group (p<0.05). miR-206 targeted 3′-UTR of BDNF. Our data highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13 in pregnant hypothyroid rats.

Key words

pregnancy - hypothyroidism - BDNF - microRNA - brain development

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