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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...

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Autores principales: Gao, Wei, Jin, Yongxun, Hao, Jindong, Huang, Siyi, Wang, Dongxu, Quan, Fushi, Zhang, Mingjun, Zhang, Jiabao, Ren, Wenzhi, Yu, Xianfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
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.
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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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