Overexpression of CDC42 causes accumulation of DNA damage leading to failure of oogenesis in triploid Pacific oyster Crassostrea gigas.

Autor: Yang Q; Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China., Yu H; Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address: hongyu@ouc.edu.cn., Du S; Institute of Marine and Environmental Technology, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA., Li Q; Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China. Electronic address: qili66@ouc.edu.cn.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Dec; Vol. 282 (Pt 2), pp. 136769. Date of Electronic Publication: 2024 Oct 26.
DOI: 10.1016/j.ijbiomac.2024.136769
Abstrakt: Triploid Pacific oyster Crassostrea gigas exhibits notable differences in fecundity, with the majority being sterile individuals, referred to as female β, which produce few oocytes, while a minority are fertile individuals, referred to as female α, which produce abundant oocytes. However, the molecular mechanisms underlying these differences in triploid fecundity remain poorly understood. CDC42 has been implicated in processes related to increased DNA damage and genomic instability. Here, we investigate the crucial role of CDC42 in DNA damage repair during oogenesis in triploid C. gigas. Immunofluorescence analysis of γH2AX, a marker for DNA double-stranded breaks, showed significantly higher levels of DNA damage in gonadal cells of triploids compared to diploids, particularly in female β. Histological and ultrastructural analyses revealed abnormal germ cells, termed β gonia, characterized by giant nuclei condensed into irregular chromosome-like chromatin, present in triploid gonadal follicles. Analysis of mRNA and protein expression revealed significantly elevated CDC42 expression in triploid gonads compared to the diploids. Inhibition of CDC42 activity in triploids using ZCL278, a CDC42-specific inhibitor, resulted in a significant reduction in DNA damage, increased oocyte numbers, and a decrease in β gonia count. Transcriptome profiling revealed that CDC42 inhibition upregulated the PI3K-AKT signaling pathway along with DNA repair activation. Overall, our findings suggest that overexpression of CDC42 during oogenesis in triploid C. gigas impedes DNA repair, leading to the accumulation of DNA damage, and consequently, oogenesis blockade and abnormal germ cell differentiation. Conversely, inhibition of CDC42 activity activates the PI3K-AKT signaling pathway and promotes DNA repair, thereby mitigating DNA damage and facilitating oogenesis in triploids. This study provides new insights into the molecular mechanisms of sterility in female triploid C. gigas.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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