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11 July 2012 Activity of Long-Chain Acyl-CoA Synthetase Is Required for Maintaining Meiotic Arrest in Xenopus laevis
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In most vertebrates, fully grown oocytes are arrested in meiotic prophase I and only resume the cell cycle upon external stimuli, such as hormones. The proper arrest and resumption of the meiotic cycle is critical for reproduction. A GalphaS signaling pathway essential for the arrest is conserved in organisms from Xenopus to mouse and human. A previous gene association study implicated that mutations of human ACSL6 may be related to premature ovarian failure. However, functional roles of ACSL6 in human infertility have yet to be reported. In the present study, we found that triacsin C, a potent and specific inhibitor for ACSL, triggers maturation in Xenopus and mouse oocytes in the absence of hormone, suggesting ACSL activity is required for the oocyte arrest. In Xenopus, acsl1b may fulfill a major role in the process, because inhibition of acsl1b by knocking down its RNA results in abnormal acceleration of oocyte maturation. Such abnormally matured eggs cannot support early embryonic development. Moreover, direct inhibition of protein palmitoylation, which lies downstream of ACSLs, also causes oocyte maturation. Furthermore, palmitoylation of Galphas, which is essential for its function, is inhibited when the ACSL activity is blocked by triacsin C in Xenopus. Thus, disruption of ACSL activity causes inhibition of the Galphas signaling pathway in the oocytes, which may result in premature ovarian failure in human.

© 2012 by the Society for the Study of Reproduction, Inc.
Hua-wei Wang, Jun-shun Fang, Xia Kuang, Li-yun Miao, Chao Wang, Guo-liang Xia, Mary Lou King, and Jian Zhang "Activity of Long-Chain Acyl-CoA Synthetase Is Required for Maintaining Meiotic Arrest in Xenopus laevis," Biology of Reproduction 87(3), (11 July 2012).
Received: 9 March 2012; Accepted: 1 June 2012; Published: 11 July 2012

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