Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress.

Autor:	Gao W; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Jin Y; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Hao J; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Huang S; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Wang D; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Quan F; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Zhang M; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Zhang J; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Ren W; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China., Yu X; Jilin Provincial Key Laboratory of Animal Model, College of Animal Science, Jilin University, Changchun 130062, China.
Jazyk:	angličtina
Zdroj:	Bioscience reports [Biosci Rep] 2021 Apr 30; Vol. 41 (4).
DOI:	10.1042/BSR20203091
Abstrakt:	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. (© 2021 The Author(s).)
Databáze:	MEDLINE
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