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

Qian Xing; Zhongyan Shan; Yun Gao; Jingyuan Mao; Xiu Liu; Jiashu Yu; Huakun Sun; Chenling Fan; Hong Wang; Hongmei Zhang; Weiping Teng

doi:10.1055/a-0658-2095

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2018; 50(09): 696-703
DOI: 10.1055/a-0658-2095

Endocrine Research

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

Authors

Qian Xing

¹Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China

³Department of Endocrinology and Metabolism, First Afﬁliated Hospital of Dalian Medical University, Dalian, China
Zhongyan Shan

¹Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China
Yun Gao

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Jingyuan Mao

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Xiu Liu

¹Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Jiashu Yu

¹Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China

³Department of Endocrinology and Metabolism, First Afﬁliated Hospital of Dalian Medical University, Dalian, China
Huakun Sun

¹Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, China

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Chenling Fan

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Hong Wang

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Hongmei Zhang

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China
Weiping Teng

²Key Laboratory of Endocrine Diseases, Liaoning Province, Shenyang, China

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

Full Text

References

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