دورية أكاديمية
Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro.
العنوان: | Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro. |
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المؤلفون: | Lande Y; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel., Fisch B; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel., Tsur A; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel; Department of Obstetrics and Gynecology, The Chaim Sheba Medical, Ramat Gan, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Farhi J; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel; IVF Unit, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Prag-Rosenberg R; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel., Ben-Haroush A; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel., Kessler-Icekson G; The Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Israel., Zahalka MA; The Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Israel., Ludeman SM; Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA., Abir R; Infertility and IVF Unit, Beilinson's Women Hospital, Rabin Medical Center Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel. Electronic address: ronita@clalit.org.il. |
المصدر: | Reproductive biomedicine online [Reprod Biomed Online] 2017 Jan; Vol. 34 (1), pp. 104-114. Date of Electronic Publication: 2016 Oct 17. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101122473 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1472-6491 (Electronic) Linking ISSN: 14726483 NLM ISO Abbreviation: Reprod Biomed Online Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2009->: Amsterdam : Elsevier Original Publication: Cambridge, UK : Reproductive Healthcare Ltd. |
مواضيع طبية MeSH: | Cyclophosphamide/*therapeutic use , Ovarian Follicle/*drug effects, Adolescent ; Anti-Mullerian Hormone/therapeutic use ; Child ; Cryopreservation ; Culture Media ; Cyclophosphamide/analogs & derivatives ; Embryo Culture Techniques ; Estradiol/metabolism ; Female ; Freezing ; Humans ; Immunosuppressive Agents/therapeutic use ; Ki-67 Antigen/metabolism ; Ovary/metabolism ; Phosphoramide Mustards/therapeutic use ; Time Factors |
مستخلص: | How chemotherapy affects dormant ovarian primordial follicles is unclear. The 'burnout' theory, studied only in mice, suggests cyclophosphamide enhances primordial follicle activation. Using 4-hydroperoxycyclophosphamide (4hc) and phosphoramide mustard (PM), this study assessed how the active cyclophosphamide metabolites 4-hydroxycyclophosphamide (4-OHC) and PM, affect human primordial follicles. Frozen-thawed human ovarian samples were sliced and cultured with basic culture medium (cultured controls) or with 4hc/PM (3 µmol/l/10 µmol/l) (treated samples) for 24-48 h. Follicular counts and classification, Ki67 and anti-Müllerian hormone (AMH) immunohistochemistry and an apoptosis assay were used for evaluation, and 17β-oestradiol and AMH were measured in spent media samples. Generally, there was primordial follicle decrease and elevated developing follicle rates in treated samples compared with cultured (P = 0.04 to P < 0.0005) and uncultured controls (P < 0.05 to P < 0.0001). No traces of apoptosis were found. There were almost twicethe levels of AMH and 17β-oestradiol in treated compared with untreated samples (AMH with 4hc 3 µmol/l; P = 0.04). All follicles stained positively for AMHincluded treated samples. Ki67 positive staining was noted in all samples. Cyclophosphamide metabolites seem to enhance human primordial follicle activation to developing follicles, in vitro. Study findings support the 'burnout' theory as the mechanism of chemotherapy-induced ovarian toxicity. (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.) |
فهرسة مساهمة: | Keywords: 4-hydroperoxycyclophamide (4hc); 4-hydroxycyclophosphamide(4-OHC); cyclophosphamide metabolites; developing follicles; human primordial follicles; in vitro; phosphoramide mustard (PM); the ‘burnout’ theory |
المشرفين على المادة: | 0 (Culture Media) 0 (Immunosuppressive Agents) 0 (Ki-67 Antigen) 0 (Phosphoramide Mustards) 10159-53-2 (phosphoramide mustard) 1XBF4E50HS (4-hydroxycyclophosphamide) 4TI98Z838E (Estradiol) 80497-65-0 (Anti-Mullerian Hormone) 8N3DW7272P (Cyclophosphamide) |
تواريخ الأحداث: | Date Created: 20161106 Date Completed: 20170814 Latest Revision: 20180207 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.rbmo.2016.10.005 |
PMID: | 27815062 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1472-6491 |
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DOI: | 10.1016/j.rbmo.2016.10.005 |