Abstract
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.
| Original language | English |
|---|---|
| Article number | Article 74 |
| Journal | Biology of Reproduction |
| Volume | 87 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2012 |
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Keywords
- Long-chain acyl-CoA synthetase
- Meiotic arrest
- Meiotic maturation
- Oocyte maturation
- Palmitoylation
ASJC Scopus subject areas
- Cell Biology
Cite this
Activity of long-chain Acyl-CoA synthetase is required for maintaining meiotic arrest in Xenopus laevis. / Wang, Hua Weis; Fang, Jun Shun; Kuang, Xia; Miao, Li Yun; Wang, Chao; Xia, Guo Liang; King, Mary Lou L; Zhang, Jian.
In: Biology of Reproduction, Vol. 87, No. 3, Article 74, 01.09.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activity of long-chain Acyl-CoA synthetase is required for maintaining meiotic arrest in Xenopus laevis
AU - Wang, Hua Weis
AU - Fang, Jun Shun
AU - Kuang, Xia
AU - Miao, Li Yun
AU - Wang, Chao
AU - Xia, Guo Liang
AU - King, Mary Lou L
AU - Zhang, Jian
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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.
AB - 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.
KW - Long-chain acyl-CoA synthetase
KW - Meiotic arrest
KW - Meiotic maturation
KW - Oocyte maturation
KW - Palmitoylation
UR - http://www.scopus.com/inward/record.url?scp=84869392606&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869392606&partnerID=8YFLogxK
U2 - 10.1095/biolreprod.112.100511
DO - 10.1095/biolreprod.112.100511
M3 - Article
VL - 87
JO - Biology of Reproduction
JF - Biology of Reproduction
SN - 0006-3363
IS - 3
M1 - Article 74
ER -