Abstract
The study aimed to investigate the effect of imatinib coadministration on in vitro oocyte acquisition and subsequent embryo development in cyclophosphamide (Cp)-treated mice. Female BDF1 mice were injected with 5 IU equine chorionic gonadotropin (eCG) followed by 5 IU human chorionic gonadotropin 48 hours later and then oocytes were retrieved 14 hours later. Twenty-four hours prior to eCG administration, 25, 50, or 75 mg/kg Cp with or without 7.5 mg/kg imatinib was injected. In the 25 and 50 mg/kg Cp groups, imatinib coadministration significantly enhanced the percentage of mature oocytes (+16.4% and +10.4%) and significantly decreased the percentage of dead oocytes (−25.9% and −15.3%). Imatinib coadministration significantly enhanced the fertilization rate (FR) in the 50 mg/kg Cp group (+12.2%). Intraoocyte spindle integrity was significantly affected by Cp and was rescued by imatinib coadministration. Coadministration of imatinib prior to ovarian stimulation has the benefit of enhancing oocyte maturity and the in vitro FR in Cp-treated mice .
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References
Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007;110(10):2222–2229.
Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol Reprod. 2012; 86(2):27.
Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update. 2001;7(6): 535–543.
Gucer F, Balkanli-Kaplan P, Doganay L, et al. Effect of paclitaxel on primordial follicular reserve in mice. Fertil Steril. 2001;76(3): 628–629.
De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376(9744):911–921.
Anchan RM, Ginsburg ES. Fertility concerns and preservation in younger women with breast cancer. Crit Rev Oncol Hematol. 2010;74(3):175–192.
Donnez J, Dolmans MM. Preservation of fertility in females with haematological malignancy. Br J Haematol. 2011;154(2): 175–184.
Pydyn EF, Ataya KM. Effect of cyclophosphamide on mouse oocyte in vitro fertilization and cleavage: recovery. Reprod Toxicol. 1991;5(1):73–78.
Koike M, Kumasako Y, Otsu E, Arake Y, Utsunomiya T. The influence of the anti-cancer drug cyclophosphamide on fertilization and embryo growth in a mouse medel. Fertil Steril. 2012; 98(suppl 3):S117.
Barekati Z, Gourabi H, Valojerdi MR, Yazdi PE. Previous maternal chemotherapy by cyclophosphamide (Cp) causes numerical chromosome abnormalities in preimplantation mouse embryos. Reprod Toxicol. 2008;26(3–4):278–281.
Ataya KM, Pydyn EF, Sacco AG. Effect of “activated” cyclophosphamide on mouse oocyte in vitro fertilization and cleavage. Reprod Toxicol. 1988;2(2):105–109.
Jeong K, KArsy M, Oktay K. Impact of chemotherapy exposure on fertility preservation cycle outcomes. Fertil Steril. 2012; 98(suppl 3):S95.
Yuan ZP, Mailhes JB. Aneuploidy determination in C-banded mouse metaphase II oocytes following cyclophosphamide treatment in vivo. Mutat Res. 1987;179(2):209–214.
Meirow D, Epstein M, Lewis H, Nugent D, Gosden RG. Administration of cyclophosphamide at different stages of follicular maturation in mice: effects on reproductive performance and fetal malformations. Hum Reprod. 2001;16(4):632–637.
Visani G, Piccaluga P, Malagola M, Isidori A. Efficacy of dasati-nib in conjunction with alpha-interferon for the treatment of imatinib-resistant and dasatinib-resistant Ph+ acute lymphoblastic leukemia. Leukemia. 2009;23(9):1687–1688.
Gonfloni S, Di Telia L, Caldarola S, et al. Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nat Med. 2009;15(10):1179–1185.
Jo JW, Jee BC, Lee JR, Suh CS. Effect of antifreeze protein supplementation in vitrification medium on mouse oocyte developmental competence. Fertil Steril. 2011;96(5):1239–1245.
Jo JW, Jee BC, Suh CS, Kim SH. The beneficial effects of antifreeze proteins in the vitrification of immature mouse oocytes. PLoS One. 2012;7(5):e37043.
Hosten B, Abbara C, Cibert M, et al. Interleukin-2 treatment effect on imatinib pharmacokinetic, P-gp and BCRP expression in mice. Anticancer Drugs. 2010;21(2):193–201.
Kurita T, Cunha GR, Robboy SJ, Mills AA, Medina RT. Differential expression of p63 isoforms in female reproductive organs. Mech Dev. 2005;122(9):1043–1055.
Suh EK, Yang A, Kettenbach A, et al. p63 protects the female germ line during meiotic arrest. Nature. 2006;444(7119):624–628.
Barekati Z, Golkar-Narenji A, Totonchi M, Radpour R, Gourabi H. Effects of amifostine in combination with cyclophosphamide on female reproductive system. Reprod Sci. 2012;19(5): 539–546.
List AF, Heaton R, Glinsmann-Gibson B, Capizzi RL. Amifostine protects primitive hematopoietic progenitors against chemotherapy cytotoxicity. Semin Oncol. 1996;23(4 suppl 8):58–63.
Sanders JE, Hawley J, Levy W, et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood. 1996;87(7):3045–3052.
Green DM, Fiorello A, Zevon MA, Hall B, Seigelstein N. Birth defects and childhood cancer in offspring of survivors of childhood cancer. Arch Pediatr Adolesc Med. 1997;151(4):379–383.
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Chun, E.K., Jee, B.C., Kim, J.Y. et al. Effect of Imatinib Coadministration on in Vitro Oocyte Acquisition and Subsequent Embryo Development in Cyclophosphamide-Treated Mice. Reprod. Sci. 21, 906–914 (2014). https://doi.org/10.1177/1933719113518986
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DOI: https://doi.org/10.1177/1933719113518986