Physiological changes in oocyte-cumulus cell complexes from diabetic mice that potentially influence meiotic regulation.
We have previously shown that the type I diabetic condition significantly alters meiotic regulation in mouse oocytes. In the present study, possible physiological deficiencies underlying such meiotic dysfunction were examined in oocyte-cumulus cell complexes (OCC) from type I diabetic mice. Whereas the diabetic condition did not affect glycolysis or the tricarboxylic acid cycle, the increased flux of glucose through the pentose phosphate pathway in response to FSH treatment was suppressed. De novo purine synthesis was also compromised, and ATP levels were reduced in freshly isolated OCC. Additionally, diabetes resulted in a reduction in FSH-mediated cAMP synthesis. The responsiveness of the oocyte to cAMP was also affected; fewer oocytes were induced to resume maturation after a stimulatory pulse with cAMP analogs. Meiotic induction triggered by FSH was significantly reduced, but that stimulated by phorbol ester or epidermal growth factor was affected to a much lesser extent. In addition to metabolic deficiencies, the cell-cell communication between the oocyte and the cumulus cells was reduced in diabetic mice as determined by coupling assays. Thus, numerous physiological parameters are affected by type I diabetes, and these changes may collectively contribute to altered meiotic regulation.
Colton
Shannondoah A
SA
Biology Department, Marquette University, Milwaukee, Wisconsin 53202, USA.
Humpherson
Peter G
PG
Leese
Henry J
HJ
Downs
Stephen M
SM
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D016555:Matched-Pair Analysis; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000378:metabolism* / Q000473:pathology*; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology; D010060:Ovulation / Q000502:physiology; D010427:Pentose Phosphate Pathway / Q000502:physiology; D011687:Purines / Q000378:metabolism*
D011687:Purines; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D005947:Glucose