The role of Cetrorelix in preservation of morphological and ultrastructural changes in the germinal epithelium of testicular tissue following Cyclophosphamide-induced toxicity in mice
Subject Areas :
Veterinary Clinical Pathology
daryosh mohammadnejad
1
(Associate Professor, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.)
jamal eivazi
2
(Associate Professor, Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.)
Ayda Azami
3
(M.Sc., Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.)
Mohammadreza Valilou
4
(Assistant Professor, Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.)
hussein Rasta
5
(Associate Professor, Department of Medical Physics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.)
Ali Abedelahi
6
(Associate Professor, Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.)
Received: 2020-09-13
Accepted : 2020-12-26
Published : 2020-10-22
Keywords:
Testis,
Cetrorelix,
Mouse,
Cyclophosphamide,
Abstract :
Anticancer drugs used in the treatment of neoplasia have harmful effects on organs with rapid cell division such as testicular tissue. Gonadotropin releasing hormone (GnRH) antagonists may have a preventive effect on spermatogenic defect produced by anticancer drugs such as cyclophosphamide. Therefore, the aim of the present study was to investigate the preventive effect of GnRH antagonist (Cetrorelix) on cyclophosphamide-induced toxicity in testicular tissue of mice. For this purpose, 30 adult 6-8 week old male mice were divided into three groups of control (no treatment), treatment 1 (50mg/kg intraperitoneal cyclophosphamide) and treatment 2 (0.25 mg/kg subcutaneous cetrorelix plus 50 mg/kg intraperitoneal cyclophosphamide). The mice were sacrificed 35 days after the last injection of cetrorelix and testicular speciemens were isolated for histomorphological and ultrastructural studies. Histomorphometric studies of the seminiferous tubules in the first treatment group showed significant decrease in the number of sertoli cells and the thickness of germinal epithelium (p <0.05). Ultrastructural study revealed that several intercellular spaces appear between sertoli cells and spermatogenic cells, and also there were a lot of degenerated mitochondria in the sertoli cells. In the second treatment group, conditions were similar to the control group to some extent. These results demonstrated that cetrorelix can protect the germinal epithelium of testis to some extent against side effects of cyclophosphamide.
References:
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Andriana, B.B., Tay, T.W., Maki, I., Awal, M.A., Kanai, Y., Kurohmaru, M., et al. (2004). An ultra structural study on cytotoxic effect of mono (2-ethlyhexyl) phthalate (MEHP) on testes in Shiba goat in vitro.Journal of Veterinary Science, 5(3): 235-240.
Bakhtiary, Z., Shahrooz, R., Ahmadi, A. and Soltanalinejad, F. (2020). Protective effect of ethyl pyruvate on testicular histology and fertilization potential in cyclophosphamide treated mice. Veterinary Research Forum, 11(1): 7-13.
Bhattacharya, I., Basu, S., Pradhan, B.S., Sarkar, H., Nagarajan, P. and Majumdar, S.S. (2019). Testosterone augments FSH signaling by upregulating the expression and activity of FSH-Receptor in Pubertal Primate Sertoli cells. Molecular and Cellular Endocrinology, 482: 70-80.
Bustos-Obregon, E., Carvallo, M., Hartley-Belmar, R., Sarabia, L. and Ponce, C. (2007). Histopathological and histometrical assessment of boron exposure effects on mouse spermatogenesis. International Journal of Morphology, 25(4): 919-925.
Cao, Y., Wang, X., Li, S., Wang, H., Yu, L. and Wang, P. (2017). The effects of l-carnitine against cyclophosphamide-induced injuries in mouse testis. Basic Clinical Pharmacology Toxicology, 120(2): 152-158.
Charak, B.S., Gupta, R., Mandrekar, P., Sheth, N.A., Banavali, S.D., Saikia, T.K., et al. (1990). Testicular dysfunction after cyclophosphamide-vincristine procarbazine-prednisolone chemotherapy for advanced Hodgkin’s disease. A long-term follow-up study. Cancer, 65(9): 1903-1906.
Cook, T. and Sheridan, W.P. (2000). Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist, 5(2): 162-168.
de Jong, W.K., Groen, H.J., Koolen, M. G., Biesma, B., Willems, L.N., Kwa, H.B., et al. (2007). Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer. European Journal of Cancer, 43(16): 2345-2350.
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El-Awady, R.A., Semreen, M.H., Saber-Ayad, M.M., Cyprian, F., Menon, V. and Al-Tel, T.H. (2016). Modulation of DNA damage response and induction of apoptosis mediates synergism between doxorubicin and anew imidazopyridine derivative in breast and lung cancer cells. DNA Repair (Amst), 37: 1-11.
Francavilla, S.P., D Abrizio, P., Cordeschi, G., Pelliccione, F., Necozione, S., Ulisse, S., et al. (2002). Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis. Molecular Human Reproduction, 8(3): 213-220.
Glode, L.M., Robinson, J. and Gould, S.F. (1981). Protection from CP induced testicular damage with an analogue of gonadotrophin-releasing hormone. Lancet, 1(8230): 1132-1136.
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Harel, S., Fermé, C. and Poirot, C. (2011). Management of fertility in patients treated for Hodgkin’s lymphoma. Haematologica, 96(11): 1692-9169.
Haywood, H., Spaliviero, J., Jimenz, M., King, N.J., Handelsman, D.J. and Allan, C.M. (2003). Sertoli cell and germ cell development in hypogonadal mice (hpg) expressing transgenic follicle stimulating hormone alone or in combination with resttosterone. Endocrinology, 144(2): 509-517.
Hild, S.A., Meistrich, M.L., Blye, R.P. and Reel, J.R. (2001). Lupron depot prevention of antispernatogenic/antifertility activity of the indenopyridine, CDB-4022 in the rat. Biology of Reproduction, 65(1): 165-172.
Hou, M., Chrysis, D., Nurmio, M., Parvinen, M., Eksborg. S., Söder, O., et al. (2005). Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostin can not protect against this cytotoxicity. Cancer Research, 65(21): 9999-10005.
Howell, S.J. and Shatel, S.M. (2005). Spermatogenesis after cancer treatment: Damage and Recovery.Journal of the National Cancer Institute Monographs, 34: 12-17.
Jonat, W., Kaufmann, M., Sauerbrei, W., Blamey, R., Cuzick, J., Namer, M., et al. (2002) Goserelin versus CP, methotrexate and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study. Journal of Clinical Oncology, 20(24): 4628-4635.
Kaffashielahi, R. (2013). Protective effects of Resveratrol against chemotherapy drug cisplatin induced hepatotoxicity in the rat. Journal of Veterinary Clinical Pathology, 7(4): 286-299. [In Persian]
Kenney, L.B., Laufer, M.R., Grant, F.D., Grier, H. and Diller, L. (2001). High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer, 91(3): 613-621.
Krüger-Genge, A., Steinbrecht, S., Küpper, J.H., Lendlein, A. and Jung, F. (2018). Evidence for cytostatic effect of cyclophosphamide on human vein endothelial cells in cancer therapy: Preliminary in vitro results. Clinical Hemorheology and Microcirculation, 69(1-2): 267-276.
Li, D.J., Xu, Z.S., Zhang, Z.H. and Huang, Q.Y. (2006). Antagonistic effects of vitamin E on the testicular injury by cyclophosphamide in mice. Zhonghua Nan Ke Xue, 12(4): 318-322.
Meistrich, M.L. and Shetty, G. (2003). Inhibition of spermatogonial differentiation by testosterone. Journal of Andrology, 24(2): 135-148.
Mohammad Ghasemi, F., Dezfolyan, A., Mohmoudzadeh Sagheb, H.R. and Shohani, B. (2000). Appilication of the stereology technique in evaluation the addictive effects of morphine on the cerebella cortex volum in male rat. Journal of Sabzevar University of Medical Sciences, 7(15): 3-13.
Mohammadnejad, D., Abedelahi, A. and Rashtbar, M. (2013). Protective role of GnRH on chemotherapy-induced spermatogenesis disorder: a morphological study. Advanced Pharmaceutical Bulletin, 3(2): 323-328.
Mohammadnejad, D., Abedelahi, A., Soleimani-rad, J., Mohammadi-roshandeh, A., Rashtbar, M. and Azami, A. (2012). Degenerative effect of cisplatin on testicular germinal epithelium. Advanced Pharmaceutical Bulletin, 2(2): 173-177.
Mohammadnejad, D., Soleimani-rad, J., Abedelahi, A. and Peirovi, T. (2013). Study of the preventive effects of cetronelix on blood-testis barrier and spermatogenesis injuries caused by chemotherapy wich cisplatin in adult Balb/C mice. Journal of Veterinary Clinical Pathology, 7(1): 1774-1785. [In Persian]
Nanomura, M., Okada, K., Hida, S. and Yoshid, O. (1991). Does a gonadotropin releasing hormone analogue prevent cisplatin–induced spermatogenic impairment? An experimental study in the mouse. Urological Research, 19(2): 135-140.
Nejad, D.M., Rad, J.S., Roshankar, L., Karimipor, M., Ghanbari, A.A., Aazami, A., et al. (2008). A study on the effect of thiotepa on mice spermatogenesis using light and electronic microscope. Pakistan Journal of Biological Sciences, 11(15): 1929-1934.
Nejad, D.M., Rad, J.S. and Roshandeh, M.A. (2013). Preventive effects of Cetrorelix on the changes induced by Cisplatin on spermatogenic and myoid cells and basal lamina of seminiferous ducts in the testis of Balb/C mouse. Journal of Veterinary Clinical Pathology, 6(4): 1665-1674. [In Persian]
Newton, S.C., Blaschuk, O.W. and Millette, C.F. (1993). N-cadherin mediates sertoli cell-spernatogenic cell adhesion. Developmental Dynamics, 197(1): 1-13.
O'Donnell, L., Stanton, P.G., Bartles, J.R. and Robertson, D.M. (2000). Sertoli cell ectoplasmic specialization in the seminiferous epithelium of the testosterone suppressed adult rat. Biology of Reproduction, 63(1): 99-108.
Okuda, D.T. (2014). Immunosuppressive treatments in multiple sclerosis. Handbook of Clinical Neurology, 122: 503-511.
Reissmann, T., Schally, A.V., Bouchard, P., Riethmiiller, H. and Engel, J. (2000). The LHRH antagonist cetrorelix: a review. Human Reproduction Update, 6(4): 322-331.
Shetty, G. and Meistrich, M.L. (2005). Hormonal approaches to preservation and restoration of male fertility after cancer treatment. Journal of the National Cancer Institute Monographs, 34: 36-39.
Shetty, G., Wilson, G., Hardy, M.P., Niu, E., Huhtaniemi, I. and Meistrich, M.L. (2002). Inhibition of recovery of spermatogenesis in irradiated rats by different androgens. Endocrinology, 143(9): 3385-3396.
Shetty, G., Wilson, G., Huhtaniemi, I., Shuttlesworth, G.A., Reissmann, T. and Meistrich, M.L. (2000). Gonadotropin-releasing hormone analogs stimulate and testosterone inhibits the recovery of spermatogenesis in irradiated rats. Endocrinology, 141(15): 1735-1745.
Sieniawski, M., Reineke, T., Nogova, L., Josting, A., Pfistner, B., Diehl, V., et al. (2008). Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: a report of the German Hodgkin study Group (GHSG). Blood, 111(1): 71-76.
Smart, E., Lopes, F., Rice, S., Nagy, B., Anderson, R.A., Mitchell, R.T., et al. (2018). Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis. Scientific Reports, 8(1): 1773.
Su, L., Mruk, D.D. and Cheng, C.Y. (2011). Drug transporters, the blood-testis barrier, and spermatogenesis. Journal of Endocrinology, 208(3): 207-223.
Uber, W.E., Self, S.E., Van Bakel, A.B. and Pereira, N.L. (2007). Acute antibody-mediated rejection following heart transplantation. American Journal of Transplantation, 7(9): 2064-2074.
Udagawa, K., Ogawa, T., Watanabe, T., Yumura, Y., Takeda, M. and Hosaka, M. (2001). GnRH analog, leuprorelin acetate, promotes regeneration of rat spermatogenesis after severe chemical damage. International Journal of Urology, 8(11): 615-622.
Vaisheva, F., Delbes, G., Hales, B.F. and Robaire, B. (2007). Effects of the chemotherapeutic agents for non-hodgkin lymphoma, CP, doxorubicin, vincristine, and prednisone (CHOP), on the male rat reproductive system and progeny outcome. Journal of Andrology, 28(4): 578-587.
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Aich, S. and Manna, C.K. (2001). Histo physiological changes of the testicular tissue due to busulphan administration in the wild Indian. Acta Biologica Hungarica, 52(1): 105-116.
Allan, C.M., Garcia, A., Spaliviero, J., Zhang, F.D. and Jimenz, M. (2004). Complete sertoli cell proliferation induced by follicle stimulation hormone (FSH) Independently of luteinizing hormone activity: Evidence from genetic models of isolated FSH action. Endocrinology, 145(4): 1587-1593.
Andriana, B.B., Tay, T.W., Maki, I., Awal, M.A., Kanai, Y., Kurohmaru, M., et al. (2004). An ultra structural study on cytotoxic effect of mono (2-ethlyhexyl) phthalate (MEHP) on testes in Shiba goat in vitro.Journal of Veterinary Science, 5(3): 235-240.
Bakhtiary, Z., Shahrooz, R., Ahmadi, A. and Soltanalinejad, F. (2020). Protective effect of ethyl pyruvate on testicular histology and fertilization potential in cyclophosphamide treated mice. Veterinary Research Forum, 11(1): 7-13.
Bhattacharya, I., Basu, S., Pradhan, B.S., Sarkar, H., Nagarajan, P. and Majumdar, S.S. (2019). Testosterone augments FSH signaling by upregulating the expression and activity of FSH-Receptor in Pubertal Primate Sertoli cells. Molecular and Cellular Endocrinology, 482: 70-80.
Bustos-Obregon, E., Carvallo, M., Hartley-Belmar, R., Sarabia, L. and Ponce, C. (2007). Histopathological and histometrical assessment of boron exposure effects on mouse spermatogenesis. International Journal of Morphology, 25(4): 919-925.
Cao, Y., Wang, X., Li, S., Wang, H., Yu, L. and Wang, P. (2017). The effects of l-carnitine against cyclophosphamide-induced injuries in mouse testis. Basic Clinical Pharmacology Toxicology, 120(2): 152-158.
Charak, B.S., Gupta, R., Mandrekar, P., Sheth, N.A., Banavali, S.D., Saikia, T.K., et al. (1990). Testicular dysfunction after cyclophosphamide-vincristine procarbazine-prednisolone chemotherapy for advanced Hodgkin’s disease. A long-term follow-up study. Cancer, 65(9): 1903-1906.
Cook, T. and Sheridan, W.P. (2000). Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist, 5(2): 162-168.
de Jong, W.K., Groen, H.J., Koolen, M. G., Biesma, B., Willems, L.N., Kwa, H.B., et al. (2007). Phase III study of cyclophosphamide, doxorubicin, and etoposide compared with carboplatin and paclitaxel in patients with extensive disease small-cell lung cancer. European Journal of Cancer, 43(16): 2345-2350.
Dere, E., Anderson, L.M., Hwang, K. and Boekelheide, K. (2013). Biomarkers of chemotherapy-induced testicular damage. Fertility and Sterility, 100(5): 1192-1202.
DeVita, V.T., Rosenberg, S.A. and Lawrence, T.L. (2018). Cancer: Principles and Practice of Oncology. 11th ed., Philadelphia: Lippincott, pp: 1533-1577.
Drumond, A.L., Weng, C.C., Wang, G., Chiarini-Garcia, H., Eras-Garcia, L. and Meistrich, M.L. (2011). Effects of multiple doses of cyclophosphamide on mouse testes: accessing the germ cells lost, and the functional damage of stem cells. Reproductive Toxicology, 32(4): 395-406.
Elangovan, N., Chiou, T.J., Tzeng, W.F., and Chu, S.T. (2006). Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice. Toxicology, 222(1-2): 60-70.
El-Awady, R.A., Semreen, M.H., Saber-Ayad, M.M., Cyprian, F., Menon, V. and Al-Tel, T.H. (2016). Modulation of DNA damage response and induction of apoptosis mediates synergism between doxorubicin and anew imidazopyridine derivative in breast and lung cancer cells. DNA Repair (Amst), 37: 1-11.
Francavilla, S.P., D Abrizio, P., Cordeschi, G., Pelliccione, F., Necozione, S., Ulisse, S., et al. (2002). Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis. Molecular Human Reproduction, 8(3): 213-220.
Glode, L.M., Robinson, J. and Gould, S.F. (1981). Protection from CP induced testicular damage with an analogue of gonadotrophin-releasing hormone. Lancet, 1(8230): 1132-1136.
Gründker, C., Schlotawa, L., Viereck, V., Eicke, N., Horst, A., Kairies, B., et al. (2004). Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor. European Journal of Endocrinology, 151(1): 141-149.
Harel, S., Fermé, C. and Poirot, C. (2011). Management of fertility in patients treated for Hodgkin’s lymphoma. Haematologica, 96(11): 1692-9169.
Haywood, H., Spaliviero, J., Jimenz, M., King, N.J., Handelsman, D.J. and Allan, C.M. (2003). Sertoli cell and germ cell development in hypogonadal mice (hpg) expressing transgenic follicle stimulating hormone alone or in combination with resttosterone. Endocrinology, 144(2): 509-517.
Hild, S.A., Meistrich, M.L., Blye, R.P. and Reel, J.R. (2001). Lupron depot prevention of antispernatogenic/antifertility activity of the indenopyridine, CDB-4022 in the rat. Biology of Reproduction, 65(1): 165-172.
Hou, M., Chrysis, D., Nurmio, M., Parvinen, M., Eksborg. S., Söder, O., et al. (2005). Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostin can not protect against this cytotoxicity. Cancer Research, 65(21): 9999-10005.
Howell, S.J. and Shatel, S.M. (2005). Spermatogenesis after cancer treatment: Damage and Recovery.Journal of the National Cancer Institute Monographs, 34: 12-17.
Jonat, W., Kaufmann, M., Sauerbrei, W., Blamey, R., Cuzick, J., Namer, M., et al. (2002) Goserelin versus CP, methotrexate and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study. Journal of Clinical Oncology, 20(24): 4628-4635.
Kaffashielahi, R. (2013). Protective effects of Resveratrol against chemotherapy drug cisplatin induced hepatotoxicity in the rat. Journal of Veterinary Clinical Pathology, 7(4): 286-299. [In Persian]
Kenney, L.B., Laufer, M.R., Grant, F.D., Grier, H. and Diller, L. (2001). High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer, 91(3): 613-621.
Krüger-Genge, A., Steinbrecht, S., Küpper, J.H., Lendlein, A. and Jung, F. (2018). Evidence for cytostatic effect of cyclophosphamide on human vein endothelial cells in cancer therapy: Preliminary in vitro results. Clinical Hemorheology and Microcirculation, 69(1-2): 267-276.
Li, D.J., Xu, Z.S., Zhang, Z.H. and Huang, Q.Y. (2006). Antagonistic effects of vitamin E on the testicular injury by cyclophosphamide in mice. Zhonghua Nan Ke Xue, 12(4): 318-322.
Meistrich, M.L. and Shetty, G. (2003). Inhibition of spermatogonial differentiation by testosterone. Journal of Andrology, 24(2): 135-148.
Mohammad Ghasemi, F., Dezfolyan, A., Mohmoudzadeh Sagheb, H.R. and Shohani, B. (2000). Appilication of the stereology technique in evaluation the addictive effects of morphine on the cerebella cortex volum in male rat. Journal of Sabzevar University of Medical Sciences, 7(15): 3-13.
Mohammadnejad, D., Abedelahi, A. and Rashtbar, M. (2013). Protective role of GnRH on chemotherapy-induced spermatogenesis disorder: a morphological study. Advanced Pharmaceutical Bulletin, 3(2): 323-328.
Mohammadnejad, D., Abedelahi, A., Soleimani-rad, J., Mohammadi-roshandeh, A., Rashtbar, M. and Azami, A. (2012). Degenerative effect of cisplatin on testicular germinal epithelium. Advanced Pharmaceutical Bulletin, 2(2): 173-177.
Mohammadnejad, D., Soleimani-rad, J., Abedelahi, A. and Peirovi, T. (2013). Study of the preventive effects of cetronelix on blood-testis barrier and spermatogenesis injuries caused by chemotherapy wich cisplatin in adult Balb/C mice. Journal of Veterinary Clinical Pathology, 7(1): 1774-1785. [In Persian]
Nanomura, M., Okada, K., Hida, S. and Yoshid, O. (1991). Does a gonadotropin releasing hormone analogue prevent cisplatin–induced spermatogenic impairment? An experimental study in the mouse. Urological Research, 19(2): 135-140.
Nejad, D.M., Rad, J.S., Roshankar, L., Karimipor, M., Ghanbari, A.A., Aazami, A., et al. (2008). A study on the effect of thiotepa on mice spermatogenesis using light and electronic microscope. Pakistan Journal of Biological Sciences, 11(15): 1929-1934.
Nejad, D.M., Rad, J.S. and Roshandeh, M.A. (2013). Preventive effects of Cetrorelix on the changes induced by Cisplatin on spermatogenic and myoid cells and basal lamina of seminiferous ducts in the testis of Balb/C mouse. Journal of Veterinary Clinical Pathology, 6(4): 1665-1674. [In Persian]
Newton, S.C., Blaschuk, O.W. and Millette, C.F. (1993). N-cadherin mediates sertoli cell-spernatogenic cell adhesion. Developmental Dynamics, 197(1): 1-13.
O'Donnell, L., Stanton, P.G., Bartles, J.R. and Robertson, D.M. (2000). Sertoli cell ectoplasmic specialization in the seminiferous epithelium of the testosterone suppressed adult rat. Biology of Reproduction, 63(1): 99-108.
Okuda, D.T. (2014). Immunosuppressive treatments in multiple sclerosis. Handbook of Clinical Neurology, 122: 503-511.
Reissmann, T., Schally, A.V., Bouchard, P., Riethmiiller, H. and Engel, J. (2000). The LHRH antagonist cetrorelix: a review. Human Reproduction Update, 6(4): 322-331.
Shetty, G. and Meistrich, M.L. (2005). Hormonal approaches to preservation and restoration of male fertility after cancer treatment. Journal of the National Cancer Institute Monographs, 34: 36-39.
Shetty, G., Wilson, G., Hardy, M.P., Niu, E., Huhtaniemi, I. and Meistrich, M.L. (2002). Inhibition of recovery of spermatogenesis in irradiated rats by different androgens. Endocrinology, 143(9): 3385-3396.
Shetty, G., Wilson, G., Huhtaniemi, I., Shuttlesworth, G.A., Reissmann, T. and Meistrich, M.L. (2000). Gonadotropin-releasing hormone analogs stimulate and testosterone inhibits the recovery of spermatogenesis in irradiated rats. Endocrinology, 141(15): 1735-1745.
Sieniawski, M., Reineke, T., Nogova, L., Josting, A., Pfistner, B., Diehl, V., et al. (2008). Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: a report of the German Hodgkin study Group (GHSG). Blood, 111(1): 71-76.
Smart, E., Lopes, F., Rice, S., Nagy, B., Anderson, R.A., Mitchell, R.T., et al. (2018). Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell loss in an in vitro model of the prepubertal testis. Scientific Reports, 8(1): 1773.
Su, L., Mruk, D.D. and Cheng, C.Y. (2011). Drug transporters, the blood-testis barrier, and spermatogenesis. Journal of Endocrinology, 208(3): 207-223.
Uber, W.E., Self, S.E., Van Bakel, A.B. and Pereira, N.L. (2007). Acute antibody-mediated rejection following heart transplantation. American Journal of Transplantation, 7(9): 2064-2074.
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