Publication:
GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro

dc.contributor.coauthorInce, Umit
dc.contributor.coauthorGuzel, Yilmaz
dc.contributor.coauthorAyhan, Cem
dc.contributor.coauthorAlper, Ebru
dc.contributor.coauthorBalaban, Basak
dc.contributor.coauthorIwase, Akira
dc.contributor.departmentSchool of Medicine
dc.contributor.departmentGraduate School of Health Sciences
dc.contributor.kuauthorAkın, Nazlı
dc.contributor.kuauthorBildik, Gamze
dc.contributor.kuauthorÇetiner, Mustafa
dc.contributor.kuauthorEsen, Tarık
dc.contributor.kuauthorKarahüseyinoğlu, Serçin
dc.contributor.kuauthorMandel, Nil Molinas
dc.contributor.kuauthorÖktem, Özgür
dc.contributor.kuauthorŞahin, Gizem Nur
dc.contributor.kuauthorSelek, Uğur
dc.contributor.kuauthorŞenbabaoğlu, Filiz
dc.contributor.kuauthorTaşkıran, Çağatay
dc.contributor.kuauthorUrman, Cumhur Bülent
dc.contributor.kuauthorYakın, Kayhan
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF HEALTH SCIENCES
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T22:57:41Z
dc.date.issued2015
dc.description.abstractStudy question: Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? Summary answer: The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. What is known already: Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. Study design, settings, size and duration: This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. Participants/materials, setting, methods: Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. Main results and the role of chance: The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. Limitations, reasons for caution: Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo.Wider implications of the findings: GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue12
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipSchool of Medicine and the Graduate School of Health Sciences of Koc University
dc.description.sponsorshipAmerican Hospital Women's Health Center, Comprehensive Cancer Care and Fertility Preservation Programs, Istanbul, Turkey This study was funded by the School of Medicine and the Graduate School of Health Sciences of Koc University, and the American Hospital Women's Health Center, Comprehensive Cancer Care and Fertility Preservation Programs, Istanbul, Turkey.
dc.description.volume30
dc.identifier.doi10.1093/humrep/dev257
dc.identifier.eissn1460-2350
dc.identifier.issn0268-1161
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-84983096157
dc.identifier.urihttps://doi.org/10.1093/humrep/dev257
dc.identifier.urihttps://hdl.handle.net/20.500.14288/7575
dc.identifier.wos368437300025
dc.keywordsChemotherapy
dc.keywordsOvarian failure
dc.keywordsGnRH agonist
dc.keywordsApoptosis
dc.keywordsFollicle reserve
dc.keywordsGranulosa cells
dc.keywordsSteroidogenic activity
dc.language.isoeng
dc.publisherOxford University Press (OUP)
dc.relation.ispartofHuman Reproduction
dc.subjectObstetrics
dc.subjectGynecology
dc.subjectReproductive biology
dc.titleGnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorBildik, Gamze
local.contributor.kuauthorAkın, Nazlı
local.contributor.kuauthorŞenbabaoğlu, Filiz
local.contributor.kuauthorŞahin, Gizem Nur
local.contributor.kuauthorKarahüseyinoğlu, Serçin
local.contributor.kuauthorTaşkıran, Çağatay
local.contributor.kuauthorYakın, Kayhan
local.contributor.kuauthorUrman, Cumhur Bülent
local.contributor.kuauthorÖktem, Özgür
local.contributor.kuauthorSelek, Uğur
local.contributor.kuauthorÇetiner, Mustafa
local.contributor.kuauthorMandel, Nil Molinas
local.contributor.kuauthorEsen, Tarık
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1GRADUATE SCHOOL OF HEALTH SCIENCES
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Health Sciences
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