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Induction of meiotic maturation in mouse oocytes by adenosine analogs
Author(s) -
Downs Stephen M.,
Chen Jing
Publication year - 2006
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.20439
Subject(s) - adenosine , germinal vesicle , biology , oocyte , meiosis , nucleotidase , ampk , adenosine kinase , microbiology and biotechnology , protein kinase a , endocrinology , medicine , biochemistry , kinase , adenosine deaminase , embryo , gene
In this study we have examined the meiosis‐inducing influence of adenosine analogs in mouse oocytes. When a varied group of nucleosides and nucleotides were tested on overnight cultures of hypoxanthine‐arrested, cumulus cell‐enclosed oocytes (CEO), halogenated adenosine nucleosides, but not native adenosine, exhibited a significant meiosis‐inducing capability. When tested under a variety of conditions, meiotic induction by 8‐bromo‐adenosine (8‐Br‐Ado) and a second adenosine analog, methylmercaptopurine riboside (MMPR), was especially potent in denuded oocytes (DO) compared to CEO and was not dependent on the type of inhibitor chosen to maintain meiotic arrest. Germinal vesicle breakdown (GVB) was stimulated with rapid kinetics and was preceded by an increase in AMP‐activated protein kinase (AMPK) activity. Moreover, compound C, an inhibitor of AMPK, blocked the meiosis‐inducing activities of both adenosine analogs. When tested for an effect on meiotic progression to metaphase II (MII) in spontaneously maturing CEO, 8‐Br‐Ado and the AMPK activator, 5‐aminoimidazole‐4‐carboxamide 1‐β‐ D ‐ribofuranoside (AICAR), increased the percentage of MII‐stage oocytes, but MMPR decreased this number. Adenosine and inhibitors of de novo purine synthesis had no effect on the completion of maturation, while compound C suppressed this process. These results support the proposition that oocyte AMPK mediates the positive influence of AICAR and 8‐Br‐Ado on both the initiation and completion of meiotic maturation. The role of AMPK in MMPR action is less clear. Mol. Reprod. Dev. 1159–1168, 2006. © 2006 Wiley‐Liss, Inc.