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Published on: September 13, 2022
Induction of meiotic maturation in mouse oocytes by adenosine analogs
1Biology Department, Marquette University, Milwaukee, Wisconsin 53233, USA. Downs@Marquette.edu
Abstract:
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-beta-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.
Insights
Certain adenosine analogs, like 8-bromo-adenosine, induce meiosis in mouse oocytes by activating AMP-activated protein kinase (AMPK). This kinase mediates the initiation and completion of oocyte maturation, though its role with other analogs is less clear.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cell Signaling
Background:
- Meiotic maturation in oocytes is a complex process crucial for female fertility.
- Adenosine and its analogs are known signaling molecules with diverse cellular effects.
- The role of specific signaling pathways, like AMP-activated protein kinase (AMPK), in oocyte maturation requires further elucidation.
Purpose of the Study:
- To investigate the meiosis-inducing potential of various adenosine analogs in mouse oocytes.
- To explore the involvement of AMP-activated protein kinase (AMPK) in mediating these effects.
- To determine the influence of adenosine analogs on the initiation and completion of oocyte meiotic maturation.
Main Methods:
- Culturing of mouse oocytes (cumulus cell-enclosed and denuded) arrested at the germinal vesicle stage.
- Treatment with various nucleosides, nucleotides, and adenosine analogs (e.g., 8-bromo-adenosine, methylmercaptopurine riboside).
- Assessment of meiotic progression (Germinal Vesicle Breakdown, Metaphase II) and measurement of AMPK activity.
Main Results:
- Halogenated adenosine analogs, particularly 8-bromo-adenosine, significantly induced meiosis in mouse oocytes.
- Meiosis induction correlated with increased AMPK activity, and inhibition of AMPK blocked this effect.
- Specific analogs influenced different stages of meiotic maturation, with varying effects on Metaphase II progression.
Conclusions:
- Oocyte AMPK activation is a key mediator for the meiosis-inducing effects of certain adenosine analogs (e.g., AICAR, 8-Br-Ado).
- Adenosine analogs can influence both the initiation and completion of meiotic maturation in mouse oocytes.
- The precise role of AMPK in the action of all tested adenosine analogs, such as MMPR, remains to be fully clarified.
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