Maintenance of murine oocyte meiotic arrest: Uptake and metabolism of hypoxanthine and adenosine by cumulus cell-enclosed and denuded oocytes☆

摘要

Toanalyzethepotentialmechanismsbywhichhypoxanthineandadenosinemaintainmeioticarrestinmouseoocytesthisstudyfocusedon:(1)theuptakeandmetabolismofhypoxanthineandadenosine;(2)theeffectofinhibitorsofinosinemonophosphate(IMP)dehydrogenaseonpurine-mediatedmeioticarrest;and(3)theroleofadenosinemetabolismonthemaintenanceofmeioticarrest.Althoughthedenudedoocytecantakeupradiolabeledhypoxanthineandadenosine,anintactcumulusoophorusgreatlyaugmentsuptakeofthesemolecules(and/ormetabolites).Bothofthesecompoundswerecompletelymetabolizedduringincubationinvitro:hypoxanthinewasapparentlymetabolizedtouricacidandadenosinewasmetabolizedtoADP;asmallamountofeachcompoundwasalsoconvertedtoinosinebycumuluscellsandtransferredtotheoocyte.TheIMPdehydrogenaseinhibitors,bredininandmycophenolicacid(MA),induced,inadose-dependentmanner,theresumptionofmaturationincumuluscell-enclosedoocytesmaintainedinmeioticarrestbyhypoxanthinebuthadnoeffectondenudedoocytes.MAdidnotinducematurationwhenmeioticarrestwasmaintainedbyguanosine.NordidMAaltertheuptakeofhypoxanthinebycumuluscell-enclosedoocytes.Thepoorlymetabolizedanalogofadenosine,2-chloroadenosine,wasaseffectiveasadenosineinitssynergisticactionwithhypoxanthineinmaintainingmeioticarrest.Itisconcludedthat(1)hypoxanthineandadenosinearemetabolizedwithintheoocyte-cumuluscellcomplex;(2)xanthyland/orguanylcompoundsareproducedbyoocyte-cumuluscellcomplexesinthepresenceofhypoxanthineandplayanimportantroleinthemaintenanceofmeioticarrest;and(3)adenosineneednotbemetabolizedtoactsynergisticallywithhypoxanthineinmaintainingmeioticarrest.