Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro
| Autor: | Susan M. Ludeman, Jacob Farhi, Gania Kessler-Icekson, Ronit Abir, Abraham Tsur, Roni Prag-Rosenberg, Muayad A. Zahalka, Avi Ben-Haroush, Yechezkel Lande, Benjamin Fisch |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Anti-Mullerian Hormone medicine.medical_specialty Time Factors Cyclophosphamide Adolescent medicine.medical_treatment Biology Embryo Culture Techniques 03 medical and health sciences Follicle 0302 clinical medicine Ovarian Follicle Internal medicine Follicular phase Freezing medicine Humans Child Cryopreservation Chemotherapy 030219 obstetrics & reproductive medicine Estradiol Ovary Obstetrics and Gynecology Culture Media 030104 developmental biology Endocrinology Ki-67 Antigen Reproductive Medicine Apoptosis Immunohistochemistry Female Phosphoramide Mustards Folliculogenesis Immunosuppressive Agents Developmental Biology Hormone medicine.drug |
| Zdroj: | Reproductive biomedicine online. 34(1) |
| ISSN: | 1472-6491 |
| Popis: | 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 P0.0005) and uncultured controls (P0.05 to P0.0001). 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. |
| Databáze: | OpenAIRE |
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