The Phosphodiesterase Inhibitor, Isobutyl-1-Methylxanthine Prevents the Sudden Drop in Cyclic Adenosine Monophosphate Concentration and Modulates Glucose Metabolism of Equine Cumulus-Oocyte Complexes Matured in Vitro.
Abstract: Spontaneous nuclear maturation of mammalian oocytes can occur when physically removed from the ovarian follicle during in vitro oocyte maturation (IVM), largely because of a decrease in cyclic adenosine monophosphate (cAMP) concentration. Modulation of oocyte cAMP during IVM by using phosphodiesterase inhibitors has been shown to maintain elevated oocyte cAMP concentrations and control meiotic resumption of bovine and ovine oocytes. This study determined the effect of inclusion of isobutyl-1-methylxanthine (IBMX) during collection and the first 12 hours of incubation of equine oocytes on cAMP concentration and glucose metabolism of cumulus-oocyte complexes (COCs). Abattoir-derived COCs were collected in aspiration medium with (Asp-IBMX) or without (Asp) IBMX. Cumulus-oocyte complexes were then incubated for 12 hours in IVM medium with (Mat-IBMX) or without (Mat) IBMX, followed by additional 24 hours in Mat medium. The cAMP concentration, glucose consumption, lactate production, and metaphase II rates of the COCs were assessed. Cumulus-oocyte complexes aspirated into Asp-IBMX (62.2 ± 2.6 fmol per COC) medium had higher cAMP concentration than Asp (31.8 ± 2.8 fmol per COC) control group (P < .05). Likewise, at 12 hours of IVM, Mat-IBMX group (33.2 ± 2.1 fmol per COC) had higher cAMP concentration than the Mat group (7.68 ± 0.5 fmol per COC; P < .05). Glucose consumption and lactate production were lower during the first 12 hours of incubation in COCs cultured in Mat-IBMX (P < .05). Isobutyl-1-methylxanthine prevented the rapid drop in cAMP concentration and altered metabolism of glucose by the COC. Preventing the sudden drop in cAMP prevents the premature nuclear maturation of in vitro-matured oocytes causing poor developmental competence.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication Date: 2020-05-07 PubMed ID: 32684257DOI: 10.1016/j.jevs.2020.103112Google Scholar: Lookup
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Summary
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The study explores how a phosphodiesterase inhibitor named Isobutyl-1-Methylxanthine (IBMX) impacts the concentration of cyclic Adenosine Monophosphate (cAMP) and glucose metabolism in horse egg cells (oocytes) during in-vitro maturation. It discovers that IBMX prevents the abrupt drop in cAMP levels, reducing premature maturation, and affecting glucose metabolism in the oocytes.
Research Objectives
The research was conducted with the following objectives:
- To explore the effect of IBMX during the collection and the first twelve hours of in vitro maturation of horse egg cells [Cumulus-Oocyte Complexes (COCs)] on cAMP concentration and glucose metabolism.
- To study the effect of IBMX on the maintenance of elevated oocyte cAMP concentrations and control of meiotic resumption, a process previously observed in bovine and ovine oocytes.
Methodology
The researchers used the following methods:
- Collection of COCs from slaughtered horses in aspiration medium with or without IBMX.
- Incubation of COCs for twelve hours in in-vitro maturation medium with or without IBMX, followed by an additional 24 hours in Mat medium.
- Assessment of cAMP concentration, glucose consumption, lactate production, and metaphase II rates of the COCs.
Findings
The study discovered the following:
- COCs collected and incubated with IBMX [in Asp-IBMX and Mat-IBMX medium] had higher cAMP concentrations compared to the control groups, indicating the role of IBMX in preventing the sudden drop in cAMP levels.
- The COCs cultured in Mat-IBMX showed lower glucose consumption and lactate production during the first 12 hours of incubation, revealing that IBMX altered the glucose metabolism of COC.
- The use of IBMX can prevent the premature nuclear maturation of in-vitro matured oocytes, reducing their poor developmental competence.
Conclusion
The results suggest that IBMX has a significant impact on controlling the cAMP concentration and glucose metabolism of horse egg cells during in vitro maturation, effectively minimizing premature maturation. This opens potential opportunities for the use of IBMX to improve in vitro maturation processes of oocytes in mammals.
Cite This Article
APA
Tscharke M, Kind K, Kelly J, Kleemann D, Len J.
(2020).
The Phosphodiesterase Inhibitor, Isobutyl-1-Methylxanthine Prevents the Sudden Drop in Cyclic Adenosine Monophosphate Concentration and Modulates Glucose Metabolism of Equine Cumulus-Oocyte Complexes Matured in Vitro.
J Equine Vet Sci, 91, 103112.
https://doi.org/10.1016/j.jevs.2020.103112 Publication
Researcher Affiliations
- School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia.
- School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia.
- South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, South Australia, Australia.
- South Australian Research and Development Institute, Turretfield Research Centre, Rosedale, South Australia, Australia.
- School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia. Electronic address: jose@lenmedvet.com.
MeSH Terms
- Adenosine Monophosphate
- Animals
- Cattle
- Female
- Glucose
- Horses
- Oocytes
- Phosphodiesterase Inhibitors / pharmacology
- Sheep
- Xanthines
Citations
This article has been cited 1 times.- Medina-Chávez DA, Sánchez-Ajofrín I, Peris-Frau P, Maside C, Montoro V, Fernández-Santos R, Garde JJ, Soler AJ. cAMP Modulators before In Vitro Maturation Decrease DNA Damage and Boost Developmental Potential of Sheep Oocytes. Animals (Basel) 2021 Aug 26;11(9).
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