Abstract
Introduction: Chemotherapy has cytotoxic effect that induces follicular damage and abnormal folliculogenesisleads to ovarian failure. Two crucial growth factors in abnormal folliculogenesis, Growth Differentiation Factor-9 (GDF-9) and Kit-Ligand, will be disrupted and affect follicular development. In this study, we evaluate whether bone marrow transplantation (BMT) has a role on oocyte-granulosa cell interaction by analyzing GDF-9 and Kit-Ligand expressions and also follicular development by analyzing primordial, primary, secondary and graafian follicles of cisplatin-induced ovarian failure in rat. Material and method: Forty eight rats were divided into three groups: control, cisplatin and cisplatin+BMT. Ovarian failure was induced by administration of intraperitoneal cisplatin 5 mg/kg body weight for 1 week. BMT 2 × 107 cells were injected through rat tail vein after cisplatin administration. Bone marrow was isolated from rat femur and characterized by CD44(+), CD45(-), CD105(+). Immunohistochemistry examinations for ovarian GDF-9, Kit-Ligand and follicle development evaluation were performed after 2 weeks of BMT injection. Results: The expressions of Kit-Ligand among three groups by ANOVA were significant different (p=0.00), whereas by Post Hoc: cisplatin group lower than control group (p=0.00); cisplatin+BMT group higher than cisplatin group (p=0.00); and no significant different between control group and cisplatin+BMT group (p=0.955). The expressions of GDF-9 by Kruskal Wallis showed significant different (p=0.00) among three groups whereas cisplatin+BMT group higher than cisplatin group and control group. In cisplatin+BMT group the number of primordial, primary, secondary and graafian follicles were higher than those in cisplatin group; but were lower than those in control group (p=0.000). Positive Paul Karl Horan (PKH) labeling was seen in cisplatin+BMT group only. Conclusion: In cisplatin-induced ovarian failure in rat, bone marrow transplantation may improve oocytegranulosa cell interaction and follicular development.
Highlights
Chemotherapy has cytotoxic effect that induces follicular damage and abnormal folliculogenesisleads to ovarian failure
Positive Paul Karl Horan (PKH) labeling was seen in cisplatin+bone marrow transplantation (BMT) group only
The first group was the control group, injected with 0.9% NaCl intraperitoneum, the second group was the group of rat models with ovarian failure, administered with cisplatin 5 mg/kg intraperitoneally for 1 week, and the third group was the group of rat models with ovarian failure, which, after receiving cisplatin, were administered with bone marrow stem cell transplantation (BMT) for 2 weeks
Summary
Chemotherapy has cytotoxic effect that induces follicular damage and abnormal folliculogenesisleads to ovarian failure. Two crucial growth factors in abnormal folliculogenesis, Growth Differentiation Factor-9 (GDF-9) and Kit-Ligand, will be disrupted and affect follicular development. We evaluate whether bone marrow transplantation (BMT) has a role on oocyte-granulosa cell interaction by analyzing GDF-9 and Kit-Ligand expressions and follicular development by analyzing primordial, primary, secondary and graafian follicles of cisplatin-induced ovarian failure in rat. Ovarian failure is a consequence of chemotherapy in cancer patients due to cytotoxic effects that will damage the granulosa cells and induces acute damage in ovarian follicle growth so that folliculogenesis disruption may take place [3,4]. Various methods of treatment have been made to overcome ovarian failure due to chemotherapy, such as stem cell therapy. To date the effect of stem cell transplantation to repair folliculogenesisdisruption in ovarian failure remains a debate
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