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Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress
Hydroxyurea (HU) is an FDA-approved drug used to treat a variety of diseases, especially malignancies, but is harmful to fertility. We used porcine oocytes as an experimental model to study the effect of HU during oocyte maturation. Exposure of cumulus–oocyte complexes (COCs) to 20 µM (P<0.01) an...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062957/ https://www.ncbi.nlm.nih.gov/pubmed/33844009 http://dx.doi.org/10.1042/BSR20203091 |
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author | Gao, Wei Jin, Yongxun Hao, Jindong Huang, Siyi Wang, Dongxu Quan, Fushi Zhang, Mingjun Zhang, Jiabao Ren, Wenzhi Yu, Xianfeng |
author_facet | Gao, Wei Jin, Yongxun Hao, Jindong Huang, Siyi Wang, Dongxu Quan, Fushi Zhang, Mingjun Zhang, Jiabao Ren, Wenzhi Yu, Xianfeng |
author_sort | Gao, Wei |
collection | PubMed |
description | Hydroxyurea (HU) is an FDA-approved drug used to treat a variety of diseases, especially malignancies, but is harmful to fertility. We used porcine oocytes as an experimental model to study the effect of HU during oocyte maturation. Exposure of cumulus–oocyte complexes (COCs) to 20 µM (P<0.01) and 50 µM (P<0.001) HU reduced oocyte maturation. Exposure to 20 µM HU induced approximately 1.5- and 2-fold increases in Caspase-3 (P<0.001) and P53 (P<0.01) gene expression levels in cumulus cells, respectively, increased Caspase-3 (P<0.01) and P53 (P<0.001) protein expression levels in metaphase II (MII) oocytes and increased the percentage of apoptotic cumulus cells (P<0.001). In addition, HU decreased the mitochondrial membrane potential (Δφm) (P<0.01 and P<0.001) and glutathione (GSH) levels (P<0.01 and P<0.001) of both cumulus cells and MII oocytes, while increasing their reactive oxygen species (ROS) levels (P<0.001). Following parthenogenetic activation of embryos derived from MII oocytes, exposure to 20 µM HU significantly reduced total blastocyst cell numbers (P<0.001) and increased apoptosis of blastocyst cells (P<0.001). Moreover, HU exposure reduced the rate of development of two-celled, four- to eight-celled, blastocyst, and hatching stages after parthenogenetic activation (P<0.05). Our findings indicate that exposure to 20 µM HU caused significant oxidative stress and apoptosis of MII oocytes during maturation, which affected their developmental ability. These results provide valuable information for safety assessments of HU. |
format | Online Article Text |
id | pubmed-8062957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80629572021-05-04 Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress Gao, Wei Jin, Yongxun Hao, Jindong Huang, Siyi Wang, Dongxu Quan, Fushi Zhang, Mingjun Zhang, Jiabao Ren, Wenzhi Yu, Xianfeng Biosci Rep Developmental Biology Hydroxyurea (HU) is an FDA-approved drug used to treat a variety of diseases, especially malignancies, but is harmful to fertility. We used porcine oocytes as an experimental model to study the effect of HU during oocyte maturation. Exposure of cumulus–oocyte complexes (COCs) to 20 µM (P<0.01) and 50 µM (P<0.001) HU reduced oocyte maturation. Exposure to 20 µM HU induced approximately 1.5- and 2-fold increases in Caspase-3 (P<0.001) and P53 (P<0.01) gene expression levels in cumulus cells, respectively, increased Caspase-3 (P<0.01) and P53 (P<0.001) protein expression levels in metaphase II (MII) oocytes and increased the percentage of apoptotic cumulus cells (P<0.001). In addition, HU decreased the mitochondrial membrane potential (Δφm) (P<0.01 and P<0.001) and glutathione (GSH) levels (P<0.01 and P<0.001) of both cumulus cells and MII oocytes, while increasing their reactive oxygen species (ROS) levels (P<0.001). Following parthenogenetic activation of embryos derived from MII oocytes, exposure to 20 µM HU significantly reduced total blastocyst cell numbers (P<0.001) and increased apoptosis of blastocyst cells (P<0.001). Moreover, HU exposure reduced the rate of development of two-celled, four- to eight-celled, blastocyst, and hatching stages after parthenogenetic activation (P<0.05). Our findings indicate that exposure to 20 µM HU caused significant oxidative stress and apoptosis of MII oocytes during maturation, which affected their developmental ability. These results provide valuable information for safety assessments of HU. Portland Press Ltd. 2021-04-22 /pmc/articles/PMC8062957/ /pubmed/33844009 http://dx.doi.org/10.1042/BSR20203091 Text en © 2021 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Developmental Biology Gao, Wei Jin, Yongxun Hao, Jindong Huang, Siyi Wang, Dongxu Quan, Fushi Zhang, Mingjun Zhang, Jiabao Ren, Wenzhi Yu, Xianfeng Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
title | Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
title_full | Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
title_fullStr | Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
title_full_unstemmed | Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
title_short | Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
title_sort | hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062957/ https://www.ncbi.nlm.nih.gov/pubmed/33844009 http://dx.doi.org/10.1042/BSR20203091 |
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