Toxic effects of AZD1208 on mouse oocytes and its possible mechanisms

AZD1208, a pan‐inhibitor that can effectively inhibit PIM kinase, is used for the treatment of advanced solid tumors and malignant lymphomas. Numerous studies have proved its curative effects while its potential cellular toxicity on reproduction was still little known. In this study, we investigated...

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Bibliographic Details
Published in:Journal of cellular physiology 2022-09, Vol.237 (9), p.3661-3670
Main Authors: Yan, Feng‐Ze, Ouyang, Ying‐Chun, Meng, Tie‐Gang, Zhang, Hong‐Yong, Yue, Wei, Zhang, Xin‐Ran, Xue, Yue, Wang, Zhen‐Bo, Sun, Qing‐Yuan
Format: Article
Language:English
Subjects:
Assembly
AZD1208
Extrusion
Gametocytes
Kinases
Lymphoma
Meiosis
meiotic progression
Membrane potential
Mitochondria
oocyte quality
Oocytes
Oxidative stress
Reactive oxygen species
Solid tumors
Spindles
Toxicity
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Summary:AZD1208, a pan‐inhibitor that can effectively inhibit PIM kinase, is used for the treatment of advanced solid tumors and malignant lymphomas. Numerous studies have proved its curative effects while its potential cellular toxicity on reproduction was still little known. In this study, we investigated the toxic effects of AZD1208 on mouse oocytes. The results showed that AZD1208 treatment did not affect meiotic resumption, but postponed oocyte maturation as indicated by delayed first polar body extrusion. Further mechanistic study showed that AZD1208 treatment delayed spindle assembly. In addition, we found that oocytes treated with AZD1208 showed mitochondrial dysfunction. Abnormal mitochondrial clusters with decreased mitochondrial membrane potential were observed in oocytes during incubation in vitro. Moreover, increased oxidative stress was observed by testing the level of reactive oxygen species. In summary, our results suggest that AZD1208 treatment influences oocyte meiotic progression by causing mitochondrial dysfunctions and subsequent delayed spindle assembly. AZD1208 treatment influences oocyte meiotic progression by causing mitochondrial dysfunctions and subsequent delayed spindle assembly.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.30835