Dataset Information

Glucocorticoid Exposure of Preimplantation Embryos Increases Offspring Anxiety-Like Behavior by Upregulating miR-211-5p via Trpm1 Demethylation.

ABSTRACT: Most studies on mechanisms by which prenatal stress affects offspring behavior were conducted during late pregnancy using in vivo models; studies on the effect of preimplantation stress are rare. In vivo models do not allow accurate specification of the roles of different hormones and cells within the complicated living organism, and cannot verify whether hormones act directly on embryos or indirectly to alter progeny behavior. Furthermore, the number of anxiety-related miRNAs identified are limited. This study showed that both mouse embryculture with corticosterone (ECC) and maternal preimplantation restraint stress (PIRS) increased anxiety-like behavior (ALB) while decreasing hippocampal expression of glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) in offspring. ECC/PIRS downregulated GR and BDNF expression by increasing miR-211-5p expression via promoter demethylation of its host gene Trpm1, and this epigenetic cell fate determination was exclusively perpetuated during development into mature hippocampus. Transfection with miR-211-5p mimic/inhibitor in cultured hippocampal cell lines confirmed that miR-211-5p downregulated Gr and Bdnf. Intrahippocampal injection of miR-211-5p agomir/antagomir validated that miR-211-5p dose-dependently increased ALB while decreasing hippocampal GR/BDNF expression. In conclusion, preimplantation exposure to glucocorticoids increased ALB by upregulating miR-211-5p via Trpm1 demethylation, and miR-211-5p may be used as therapeutic targets and biomarkers for anxiety-related diseases.

SUBMITTER: Yuan HJ

PROVIDER: S-EPMC9011152 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Glucocorticoid Exposure of Preimplantation Embryos Increases Offspring Anxiety-Like Behavior by Upregulating miR-211-5p via Trpm1 Demethylation.

Yuan Hong-Jie HJ Han Xiao X Wang Guo-Liang GL Wu Jia-Shun JS He Nan N Zhang Jie J Kong Qiao-Qiao QQ Gong Shuai S Luo Ming-Jiu MJ Tan Jing-He JH

Frontiers in cell and developmental biology 20220401

Most studies on mechanisms by which prenatal stress affects offspring behavior were conducted during late pregnancy using in vivo models; studies on the effect of preimplantation stress are rare. In vivo models do not allow accurate specification of the roles of different hormones and cells within the complicated living organism, and cannot verify whether hormones act directly on embryos or indirectly to alter progeny behavior. Furthermore, the number of anxiety-related miRNAs iden ...[more]

PMID: 35433692

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Project description:Clinical studies have proven that ultraviolet B (UVB) based phototherapy can induce perifollicular and marginal repigmentation patterns in the skin of vitiligo patients. It is, however, difficult to conceive how melanocytes can easily exit from their tightly interconnected epidermal microenvironment to re?enter a different location in the skin to establish a new network with neighboring keratinocytes. While it is known that matrix metalloprotease 9 (MMP9) is involved in the degradation of the extracellular matrix in physiological or pathological processes, little is known about whether MMP9 affects melanocyte migration in vitiligo repigmentation. To investigate the effects of the p53? transient receptor potential cation channel subfamily M member 1 (TRPM1)/microRNA (miR/miRNA)?211?MMP9 axis to regulate melanocyte migration following exposure to UVB, the expression profile of MMP9 in cultured human melanocytes transfected with or without the miR?211?mimic and p53?GFP lentiviral vector, respectively were determined. Quantitative polymerase chain reaction and western blotting were used to examine p53, TRPM1 and MMP9 mRNA and protein levels in UVB?exposed and unexposed cells. The capacity of melanocytes to migrate on collagen IV substrate was estimated using a Transwell migration assay. Interestingly, the upregulation of p53 and MMP9 at the mRNA and protein levels was evident in melanocytes treated with single or repeat exposures to UVB, whereas levels of TRPM1 and miR?211 were significantly suppressed in UVB?exposed melanocytes compared with the UVB?unexposed control cells. These results indicate that the p53?TRPM1/miR?211?MMP9 axis is significantly activated in melanocytes exposed to UVB. Notably, the ability of melanocyte migration was altered by the overexpression of p53 using a lentiviral vector and by the upregulation of miR?211 using an miRNA mimic. That altered migration could be neutralized by co?treatment with GM6001 (a broad?spectrum MMP inhibitor). Overall, these results show that the MMP9?mediated migration of melanocytes is regulated by a novel mechanism driven by the p53?TRPM1/miR?211?MMP9 axis. Activation of the p53?TRPM1/miR?211?MMP9 axis potentially represents an attractive therapeutic target to improve repigmentation outcomes in vitiligo patients.

Dataset Information

Glucocorticoid Exposure of Preimplantation Embryos Increases Offspring Anxiety-Like Behavior by Upregulating miR-211-5p via Trpm1 Demethylation.

Publications

Glucocorticoid Exposure of Preimplantation Embryos Increases Offspring Anxiety-Like Behavior by Upregulating miR-211-5p <i>via</i> Trpm1 Demethylation.

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