Aurora B inhibitor barasertib prevents meiotic maturation and subsequent embryo development in pig oocytes

Aurora B inhibitor barasertib prevents meiotic maturation and subsequent embryo development in pig oocytes

Barasertib, a highly selective Aurora B inhibitor, has been widely used in a variety of cells to investigate the role of Aurora B kinase, which has been implicated in various functions in the mitotic process. However, effects of barasertib on the meiotic maturation process are not fully understood,...

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Published in:Theriogenology Vol. 86; no. 2; pp. 503 - 515
Main Authors: Ju, Shiqiang, Peng, Xu, Yang, Xiaoliu, Sozar, Sparksi, Muneri, Caroline W., Xu, Yaping, Chen, Changchao, Cui, Panpan, Xu, Weichao, Rui, Rong
Format: Journal Article
Language:English
Published: United States Elsevier Inc 15-07-2016
Subjects:
Animals
Aurora B
Aurora Kinase B - antagonists & inhibitors
Aurora Kinase B - metabolism
Barasertib
Chromosome alignment
Embryonic Development - drug effects
Embryonic Development - physiology
Gene Expression Regulation, Developmental - drug effects
In Vitro Oocyte Maturation Techniques - veterinary
Meiosis - drug effects
Meiosis - physiology
Oocytes maturation
Organophosphates - pharmacology
Quinazolines - pharmacology
Spindle formation
Swine - embryology
Barasertib
Oocytes maturation
Aurora B
Spindle formation
Chromosome alignment
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Summary:Barasertib, a highly selective Aurora B inhibitor, has been widely used in a variety of cells to investigate the role of Aurora B kinase, which has been implicated in various functions in the mitotic process. However, effects of barasertib on the meiotic maturation process are not fully understood, particularly in porcine oocyte meiotic maturation. In the present study, the effects of barasertib on the meiotic maturation and developmental competence of pig oocytes were investigated, and the possible roles of Aurora B were also evaluated in porcine oocytes undergoing meiosis. Initially, we examined the expression and subcellular localization of Aurora B using Western blot analysis and immunofluorescent staining. Aurora B was found to express and exhibit specific dynamic intracellular localization during porcine oocyte meiotic maturation. Aurora B was observed around the chromosomes after germinal vesicle breakdown. Then it was transferred to the spindle region after metaphase I stage, and was particularly concentrated at the central spindles at telophase I stage. barasertib treatment resulted in the failure of polar body extrusion in pig oocytes, with a larger percentage of barasertib-treated oocytes remaining at the pro–metaphase I stage. Additional results reported that barasertib treatment had no effect on chromosome condensation but resulted in a significantly higher percentage of the treated oocytes with aberrant spindles and misaligned chromosomes during the first meiotic division. In addition, inhibition of Aurora B with lower concentrations of barasertib during pig oocyte meiotic maturation decreased the subsequent embryo developmental competence. Thus, these results illustrate that barasertib has significant effects on porcine oocyte meiotic maturation and subsequent development through Aurora B inhibition, and this regulation is related to its effects on spindle formation and chromosome alignment during the first meiotic division in porcine oocytes.
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ISSN:0093-691X
1879-3231
DOI:10.1016/j.theriogenology.2016.01.030