Inhibition of endoplasmic reticulum stress improves mouse embryo development.

X-box binding protein-1 (XBP-1) is an important regulator of a subset of genes during endoplasmic reticulum (ER) stress. In the current study, we analyzed endogenous XBP-1 expression and localization, with a view to determining the effects of ER stress on the developmental competency of preimplantat...

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Autores principales: Jin Yu Zhang, Yun Fei Diao, Hong Rye Kim, Dong Il Jin
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:af1573464ad840d9837ebb156f25a26b2021-11-18T07:12:34ZInhibition of endoplasmic reticulum stress improves mouse embryo development.1932-620310.1371/journal.pone.0040433https://doaj.org/article/af1573464ad840d9837ebb156f25a26b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22808162/?tool=EBIhttps://doaj.org/toc/1932-6203X-box binding protein-1 (XBP-1) is an important regulator of a subset of genes during endoplasmic reticulum (ER) stress. In the current study, we analyzed endogenous XBP-1 expression and localization, with a view to determining the effects of ER stress on the developmental competency of preimplantation embryos in mice. Fluorescence staining revealed that functional XBP-1 is localized on mature oocyte spindles and abundant in the nucleus at the germinal vesicle (GV) stage. However, in preimplantation embryos, XBP-1 was solely detected in the cytoplasm at the one-cell stage. The density of XBP-1 was higher in the nucleus than the cytoplasm at the two-cell, four-cell, eight-cell, morula, and blastocyst stages. Furthermore, RT-PCR analysis confirmed active XBP-1 mRNA splicing at all preimplantation embryo stages, except the one-cell stage. Tunicamycin (TM), an ER stress inducer used as a positive control, promoted an increase in the density of nuclear XBP-1 at the one-cell and two-cell stages. Similarly, culture medium supplemented with 25 mM sorbitol displayed a remarkable increase active XBP-1 expression in the nuclei of 1-cell and 2-cell embryos. Conversely, high concentrations of TM or sorbitol led to reduced nuclear XBP-1 density and significant ER stress-induced apoptosis. Tauroursodeoxycholic acid (TUDCA), a known inhibitor of ER stress, improved the rate of two-cell embryo development to blastocysts by attenuating the expression of active XBP-1 protein in the nucleus at the two-cell stage. Our data collectively suggest that endogenous XBP-1 plays a role in normal preimplantation embryonic development. Moreover, XBP-1 splicing is activated to generate a functional form in mouse preimplantation embryos during culture stress. TUDCA inhibits hyperosmolar-induced ER stress as well as ER stress-induced apoptosis during mouse preimplantation embryo development.Jin Yu ZhangYun Fei DiaoHong Rye KimDong Il JinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e40433 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jin Yu Zhang
Yun Fei Diao
Hong Rye Kim
Dong Il Jin
Inhibition of endoplasmic reticulum stress improves mouse embryo development.
description X-box binding protein-1 (XBP-1) is an important regulator of a subset of genes during endoplasmic reticulum (ER) stress. In the current study, we analyzed endogenous XBP-1 expression and localization, with a view to determining the effects of ER stress on the developmental competency of preimplantation embryos in mice. Fluorescence staining revealed that functional XBP-1 is localized on mature oocyte spindles and abundant in the nucleus at the germinal vesicle (GV) stage. However, in preimplantation embryos, XBP-1 was solely detected in the cytoplasm at the one-cell stage. The density of XBP-1 was higher in the nucleus than the cytoplasm at the two-cell, four-cell, eight-cell, morula, and blastocyst stages. Furthermore, RT-PCR analysis confirmed active XBP-1 mRNA splicing at all preimplantation embryo stages, except the one-cell stage. Tunicamycin (TM), an ER stress inducer used as a positive control, promoted an increase in the density of nuclear XBP-1 at the one-cell and two-cell stages. Similarly, culture medium supplemented with 25 mM sorbitol displayed a remarkable increase active XBP-1 expression in the nuclei of 1-cell and 2-cell embryos. Conversely, high concentrations of TM or sorbitol led to reduced nuclear XBP-1 density and significant ER stress-induced apoptosis. Tauroursodeoxycholic acid (TUDCA), a known inhibitor of ER stress, improved the rate of two-cell embryo development to blastocysts by attenuating the expression of active XBP-1 protein in the nucleus at the two-cell stage. Our data collectively suggest that endogenous XBP-1 plays a role in normal preimplantation embryonic development. Moreover, XBP-1 splicing is activated to generate a functional form in mouse preimplantation embryos during culture stress. TUDCA inhibits hyperosmolar-induced ER stress as well as ER stress-induced apoptosis during mouse preimplantation embryo development.
format article
author Jin Yu Zhang
Yun Fei Diao
Hong Rye Kim
Dong Il Jin
author_facet Jin Yu Zhang
Yun Fei Diao
Hong Rye Kim
Dong Il Jin
author_sort Jin Yu Zhang
title Inhibition of endoplasmic reticulum stress improves mouse embryo development.
title_short Inhibition of endoplasmic reticulum stress improves mouse embryo development.
title_full Inhibition of endoplasmic reticulum stress improves mouse embryo development.
title_fullStr Inhibition of endoplasmic reticulum stress improves mouse embryo development.
title_full_unstemmed Inhibition of endoplasmic reticulum stress improves mouse embryo development.
title_sort inhibition of endoplasmic reticulum stress improves mouse embryo development.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/af1573464ad840d9837ebb156f25a26b
work_keys_str_mv AT jinyuzhang inhibitionofendoplasmicreticulumstressimprovesmouseembryodevelopment
AT yunfeidiao inhibitionofendoplasmicreticulumstressimprovesmouseembryodevelopment
AT hongryekim inhibitionofendoplasmicreticulumstressimprovesmouseembryodevelopment
AT dongiljin inhibitionofendoplasmicreticulumstressimprovesmouseembryodevelopment
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