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Journal of Assisted Reproduction and Genetics

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01-10-2019 | Embryo Biology

FoxO transcription factors 1 regulate mouse preimplantation embryo development

Authors: Nilay Kuscu, Nazli Ece Gungor-Ordueri, Berna Sozen, Dileyra Adiguzel, Ciler Celik-Ozenci

Published in: Journal of Assisted Reproduction and Genetics | Issue 10/2019

Abstract

Purpose

The aim of the present study is to investigate role of FoxO transcription factors in preimplantation embryo development by knocking down FoxO1, FoxO3, and FoxO4 genes and also to assess cell cycle arrest related proteins, p53 and p21, and apoptosis-related proteins, fas ligand (FASL), and cleaved caspase 3.

Methods

Knockdown of FoxOs using siRNA was confirmed utilizing RT-PCR and qRT-PCR in gene level and using immunofluorescence in protein level. Following knockdown of FoxO1, FoxO3, and FoxO4 in two-cell mouse embryos with or without resveratrol treatment; developmental competence of embryos and expression patterns of SIRT1, p53, p21, FASL, and CLEAVED CASPASE 3 proteins in embryos by immunofluorescence were assessed after 48 h. ROS levels were measured in knockdown embryos. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to determine resveratrol dose.

Results

Successful knockdown of FoxO genes in mouse embryos utilizing a non-invasive siRNA method was achieved. Significantly, knockdown of FoxO genes impaired preimplantation embryo development which cannot be prevented by resveratrol treatment. Immunofluorescence results showed that resveratrol could protect embryos from cell cycle arrest and apoptosis. FOXO proteins regulate apoptosis and cell cycle related proteins in mouse preimplantation embryos. Moreover, there might be an autofeedback mechanism where FOXO1, FOXO3, and FOXO4 regulate SIRT1 protein expression.

Conclusions

These results suggest that FOXO transcription factors could contribute to mouse preimplantation embryo development, and it remains to investigate whether they have crucial roles in human preimplantation embryo and infertility.

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Title: FoxO transcription factors 1 regulate mouse preimplantation embryo development
Authors: Nilay Kuscu
Nazli Ece Gungor-Ordueri
Berna Sozen
Dileyra Adiguzel
Ciler Celik-Ozenci
Publication date: 01-10-2019
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 10/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-019-01555-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

FoxO transcription factors 1 regulate mouse preimplantation embryo development

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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