ABSTRACT
Background: Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor [PDGF] and stem cell factor [SCF] in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential
Methods: The mouse TM3 leydig cells were treated with 0 [control], 2.5, 5, 10 and 20 microM imatinib for 2, 4 and 6 days. Each experiment was repeated three times [15 experiments in each day]. The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant
Results: With increasing drug concentration, cellular viability decreased significantly [p<0.05] and in contrast, PDGF levels increased [p<0.05]. Different imatinib concentrations had no significant effect on SCF level. Increasing the duration of treatment from 2 to 6 days had no obvious effect on cellular viability, PDGF and SCF levels
Conclusion: Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug
Subject(s)
Animals, Laboratory , Platelet-Derived Growth Factor , Stem Cell Factor , Leydig Cells , MiceABSTRACT
Background: The anticancer agent imatinib [IM] is a small molecular analog of ATP that inhibits tyrosine kinase activity of platelet derived growth factors [PDGFs] and stem cell factor [SCF] receptor in cancer cells. However these factors have a key role in regulating growth and development of normal Sertoli, Leydig and germ cells
Objective: The aim of this study was to determine cell viability, PDGF and SCF levels in mouse normal Sertoli cells exposed to IM
Materials and Methods: In this experimental study, the mouse TM4 Sertoli cells were treated with 0, 2.5, 5, 10 and 20 micro M IM for 2, 4 or 6 days. The cell viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, One-Way ANOVA was performed
Results: IM showed significant decrease in Sertoli cell viability compared to control group [p=0.001]. However, IM increased PDGF and SCF level insignificantly [p>0.05]
Conclusion: Results suggested that IM treatment induced a dose dependent reduction of cell viability in Sertoli cells. It seems that treatment with this anticancer drug is involved in the fertility process. Further studies are needed to evaluate the role of PDGF and SCF in this cell
ABSTRACT
Background: Gonadotropin-releasing hormone [GnRH] has been found to be expressed in ovaries in addition to hypothalamus to modulate cell differentiation and induces atretic follicles. Since the death of granulosa cells during the process of follicular atresia occurs by apoptosis phenomenon, in this study, we investigated the occurrence of apoptosis of granulosa cells of rat ovarian follicles under the influence of Buserelin acetate, a GnRH agonist.
Materials and Methods: In this experimental case-control study, twelve 25-day-old female Wistar rats were randomly divided into 2 groups. The study and control groups received 0.2 mg/kg/d Buserelin acetate and normal saline, respectively, for 4 days. 24 hours after the last injection, the rats were anesthetized with a lethal dose of chloroform and ovaries were removed. Specimens were fixed in 10% formalin. After the passage, five-micron sections were prepared using a rotary microtome. Measurement of apoptosis was performed using a calibrated light microscope after TUNEL POD staining. Data were analyzed in GraphPad InStat software using independent t-test. P
Results: These data showed the average percentage of apoptotic cells in the control group 2/14 +/- 0/52, and in the experimental group 3/75 +/- 1/71. This difference was statistically significant [p
Conclusion: These findings suggest that Buserelin acetate increases apoptosis in the granulosa cells of ovarian follicles.