International journal of advanced scientific and technical research STUDY ON EFFECT OF IMATINIB: WITH SPECIAL REFERENCE TO ALTERATIONS IN HISTOPATHOLOGICAL PARAMETERS IN MALE SWISS ALBINO MICE (original) (raw)
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The Biological Effects of Imatinib on Male Fertility of Wistar Rats
International Journal of …, 2009
Background: Imatinib is used in chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. The major aim of this study was to investigate the effects of Imatinib on male fertility in Wistar rats. Materials and Methods: Three groups of rats were gavaged with 6, 9, and 12 mg/kg Imatinib dissolved in dH 2 O for 30 consecutive days. On days 7, 14 and 30, blood samples were collected and LH, FSH, and testosterone levels were measured by the ELISA method. The numbers of sperm located in the epididymis were counted by staining with aqueous Eosin Y. Other sections of the testes were stained with H & E, investigated histologically, and the results were statistically analyzed. Results: On day 7 of the experiment, testosterone concentrations in the experimental groups were decreased (p ≤ 0.01), LH and FSH increased significantly, and the number of sperm in both the epididymis and sertoli cells decreased (p ≤ 0.01). There was an increase in tunica albuginea thickness (p ≤ 0.05) but the diameter of the seminiferous tubules showed a significant decrease (p ≤ 0.01). There was also a decrease in the number of Leydig cells, spermatogonia, stem cells, primary spermatocyte and spermatid. In the second and third samples (14 and 30 days after treatment), the testosterone levels, numbers of spermatogenic cells, Sertoli and Leydig cells showed an increase when compared to the first sample. Conclusion: These findings suggest that a dose dependent administration of Imatinib has a profound effect on spermatogenesis.
The effect of imatinib administered in the prenatal period on testis development in rats
Human & Experimental Toxicology, 2020
Background: The purpose of this study was to examine the effects of exposure to imatinib in the prenatal period on testis development in rats. Methods: Although all the study groups received intraperitoneal imatinib on prenatal days 1-8, no pregnancy occurred in the Imatinib-80 group. Immunohistochemical analysis, TUNEL, c-kit and PDGF staining revealed no difference between the groups in terms of positivity scoring. Results: A significant decrease was detected in total sperm counts in the Imatinib-20 group compared to the control group, but the sperm count was higher in the Imatinib-60 group than in the Imatinib-20 group. At biochemical measurements, the drug increased oxidative stress in the testis and serum in the Imatinib-20 group, but caused a decrease in tissue in the Imatinib-60 group. Thiol measurements revealed a decrease in the testis and serum in the Imatinib-60 group, while an increase in serum measurements was observed in the Imatinib-40 group. Analysis revealed no difference between the groups in terms of protamine and histone gene expression levels in testis tissue exposed to imatinib. Conclusion: Our findings show that prenatal exposure to imatinib can lead to histopathological and biochemical changes in testis tissue, but that no adverse effect occurs in nuclear maturation of germ cells during spermiogenesis.
BMC Medicine
Background Clinical studies indicate chemotherapy agents used in childhood cancer treatment regimens may impact future fertility. However, effects of individual agents on prepubertal human testis, necessary to identify later risk, have not been determined. The study aimed to investigate the impact of cisplatin, commonly used in childhood cancer, on immature (foetal and prepubertal) human testicular tissues. Comparison was made with carboplatin, which is used as an alternative to cisplatin in order to reduce toxicity in healthy tissues. Methods We developed an organotypic culture system combined with xenografting to determine the effect of clinically-relevant exposure to platinum-based chemotherapeutics on human testis. Human foetal and prepubertal testicular tissues were cultured and exposed to cisplatin, carboplatin or vehicle for 24 h, followed by 24–240 h in culture or long-term xenografting. Survival, proliferation and apoptosis of prepubertal germ stem cell populations (gonocyt...
Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies
JNCI …, 2005
Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors who were treated before or during their reproductive years may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time to pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that infl uence the risk for transmitted genetic damage including agent, dose, end point, and germ cell susceptibility profi les that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm fl uorescent in situ hybridization have corroborated the differences in germ cell susceptibilities. The available evidence indicates that the risk of producing chromosomally defective sperm is highest during the fi rst few weeks after the end of chemotherapy and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring. [
Decreased spermatogonial quantity in prepubertal boys with leukaemia treated with alkylating agents
Leukemia, 2017
Cancer therapies are known to cause fertility impairment as a long-term treatment side effect. Although postpubertal male cancer patients have the possibility to cryopreserve semen before gonadotoxic treatment, prepubertal boys do not yet produce spermatozoa. 1 Therefore, proposed fertility-preservation strategies for these boys are cryopreservation of testicular tissue followed by autotransplantation of spermatogonial stem cells, tissue grafting or in vitro maturation. 1-3 Numerous animal studies, including those of non-human primates, have proven the successful accelerated recovery of spermatogenesis following the application of fertility-restoration techniques. Hence, at this moment, testicular tissue cryopreservation is offered to patients as a part of clinical research programs, while the fertility-restoration strategy remains experimental. 3 Male patients with leukaemia who are at a high risk of infertility include those receiving allogenic haematopoietic stem cell transplantation, while conventional chemotherapy is associated with a low risk of infertility. 4,5 Therefore, the majority of patients with haematological malignancies do not meet the criteria for testicular tissue cryopreservation at the time of the original diagnosis. However, disease response or relapse may result in patients undergoing potentially sterilizing therapy regimens. This means that many patients with leukaemia have already received chemotherapy before testicular tissue cryopreservation is offered. 1 The potential effect of previous chemotherapy must be taken into account when testis biopsy and storage are considered for these patients. In order to optimize the cryobanking of prepubertal testicular tissue, more information on the effects of cancer therapies on spermatogonial quantities is required. Recently, reference values concerning spermatogonial quantity in human testes throughout healthy prepuberty were established. 6 In the present study, these reference values were used to evaluate the effects of leukaemia treatment on spermatogonial quantity and hence spermatogenic recovery in prepubertal boys with acute lymphoblastic leukaemia. The study material consisted of testis samples from prepubertal boys with acute lymphoblastic leukaemia who had undergone routine bilateral/unilateral testicular biopsy to examine possible testicular leukaemia at the cessation of antileukaemia therapy at University Central Hospitals in Helsinki and Turku between 1979 and 1995. The Research Ethics Committees of Helsinki University Hospital (No 192/13/03/03/2013) and Turku University Hospital (DNR 1905-32/300/05) approved the study. Altogether, 37 boys were identified through hospital records and enrolled in the study. Eighteen of these boys had earlier been included in a study to evaluate the expression of spermatogonial markers during leukaemia therapy, as previously described. 7 Testicular biopsies were performed at the end of the treatment, during the last days of the per oral maintenance therapy. Four of the 37 boys were subjected to two biopsies-one at the end of induction therapy (50 days after diagnosis) and a second biopsy at the end of the treatment (Figure 1). Antileukaemia therapy was carried out as described earlier. 8,9 Briefly, the therapy involved the use of antimetabolites, vinca-alkaloids and anthracyclines. Of the 37
Reproductive toxicology (Elmsford, N.Y.), 2016
Cisplatin (CP) is used to treat a number of cancers, including testicular cancer. Studies indicate that CP-treatment can impair spermatogenesis in humans and rodents by germ cell DNA binding, through different modes of action. CP-paternal exposure resulted in adverse effects in F1 male offspring. In this study F1 female offspring was assessed for reproductive development after CP-paternal exposure. Peri-pubertal male rats, treated with 1mg/Kg/day of CP or vehicle for 3 weeks, were mated with unexposed females. F1 female offspring of CP-treated fathers showed a decrease in fetal ovary germ cells, in estrous cycle length and FSH levels, and an increase in the percentage of antral follicles in adults. Based on our previous results and the findings of the present work we concluded that CP-paternal exposure leads to adverse effects on rat male and female reproductive development, raising concern, in humans, for children born to men exposed to CP.
Journal of reproduction & infertility
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. The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM 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...