Experimental Induction of Reduced Ovarian Reserve in a Nonhuman Primate Model (Macaca fascicularis)

摘要

Chronicdiseasesincludingcoronaryheartdiseaseandosteoporosisrepresentasubstantialhealthburdentopostmenopausalwomen,yettheinitiationoftheseconditionsandtheirrelationshipswithreproductiveagingremainpoorlyunderstood.Thissituationisdue,inpart,tothelackofanimalmodelsreflectingovarianandhormonalcharacteristicsofperi-andpostmenopausalwomen.Ovariesofwomenapproachingmenopausearenearlydepletedofprimordialfolliclesbutretainapooloflargerdevelopingfolliclesandandrogen-producingstroma,aconditionknownasreducedovarianreserve(ROR).Thelong-termgoaloftheresearchpresentedherewastocreateamonkeymodelofreproductiveaging,beginningwithRORandprogressingtoperimenopauseandfinallypostmenopause.Herewesoughttodevelopamethodtoreduceprimordialfolliclesincynomolgusmonkeys(Macacafascicularis)anddocumenthormonalchangesassociatedwithfolliclereductionorROR.At30daftersurgicalplacementofabiodegradablefibercontainingapproximately200mgof4-vinlycyclohexenediepoxide(VCD)nexttooneovaryineachof8monkeys,primordialfollicleswerereducedbyapproximately70%,withacorrespondingdecrease(83%)inantimüllerianhormone(AMH,aserummarkerofovarianfolliclenumbers).At4moafterVCD-treatmentofbothovariesin29monkeys(approximately200mgVCDperovary),AMHwasreduced56%frombaseline,testosteronewasunchanged,andfollicularphaseestradiolwasslightlyincreased.ThesedataindicatethatVCDtreatmentmarkedlyreducedprimordialfollicleswhilepreservinglargerestradiol-andtestosterone-producingfolliclesandovarianstroma,aconditionthatmimicsRORinwomen.