Full Text:   <2447>

CLC number: Q95

On-line Access: 2013-04-03

Received: 2012-06-29

Revision Accepted: 2012-11-08

Crosschecked: 2013-03-13

Cited: 10

Clicked: 4405

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2013 Vol.14 No.4 P.318-324

http://doi.org/10.1631/jzus.B1200181


Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide


Author(s):  Yan Jiang, Jing Zhao, Hui-jing Qi, Xiao-lin Li, Shi-rong Zhang, Daniel W. Song, Chi-yang Yu, Jian-gang Gao

Affiliation(s):  Key Laboratory of the Ministry of Education for Experimental Teratology and School of Life Science, Shandong University, Jinan 250100, China; more

Corresponding email(s):   chiyangyu@hotmail.com, jggao@sdu.edu.cn

Key Words:  Premature ovarian failure, Busulfan, Cyclophosphamide, Chemotherapy, Mouse model


Yan Jiang, Jing Zhao, Hui-jing Qi, Xiao-lin Li, Shi-rong Zhang, Daniel W. Song, Chi-yang Yu, Jian-gang Gao. Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide[J]. Journal of Zhejiang University Science B, 2013, 14(4): 318-324.

@article{title="Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide",
author="Yan Jiang, Jing Zhao, Hui-jing Qi, Xiao-lin Li, Shi-rong Zhang, Daniel W. Song, Chi-yang Yu, Jian-gang Gao",
journal="Journal of Zhejiang University Science B",
volume="14",
number="4",
pages="318-324",
year="2013",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1200181"
}

%0 Journal Article
%T Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide
%A Yan Jiang
%A Jing Zhao
%A Hui-jing Qi
%A Xiao-lin Li
%A Shi-rong Zhang
%A Daniel W. Song
%A Chi-yang Yu
%A Jian-gang Gao
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 4
%P 318-324
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200181

TY - JOUR
T1 - Accelerated ovarian aging in mice by treatment of busulfan and cyclophosphamide
A1 - Yan Jiang
A1 - Jing Zhao
A1 - Hui-jing Qi
A1 - Xiao-lin Li
A1 - Shi-rong Zhang
A1 - Daniel W. Song
A1 - Chi-yang Yu
A1 - Jian-gang Gao
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 4
SP - 318
EP - 324
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200181


Abstract: 
busulfan/cyclophosphamide (Bu/Cy) conditioning regimen has been widely used to treat cancer patients, while their effects on major internal organs in females are not fully understood. We treated female mice with Bu/Cy, and examined the histopathology of major internal organs on Day 30 after the treatment. The results show that Bu/Cy treatment affected the ovaries most extensively, while it had less effect on the spleen, lungs, and kidneys, and no effect on the heart, liver, stomach, and pancreas. To better understand the effect of Bu/Cy on the ovaries, we counted follicles, and determined the levels of ovarian steroids. The Bu/Cy-treated mice showed a reduction of primordial and primary follicles (P<0.01) on Day 30 and a marked loss of follicles at all developmental stages (P<0.01) on Day 60. Plasma levels of estradiol and progesterone in Bu/Cy-treated mice decreased by 43.9% and 61.4%, respectively. Thus, there was a gradual process of follicle loss and low estradiol in Bu/Cy-treated mice; this is a profile similar to what is found in women with premature ovarian failure (POF). The Bu/Cy-treated mice may serve as a useful animal model to study the dynamics of follicle loss in women undergoing POF.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Al-Hashmi, S., Hassan, Z., Sadeghi, B., Rozell, B., Hassan, M., 2011. Dynamics of early histopathological changes in GVHD after busulphan/cyclophosphamide conditioning regimen. Int. J. Clin. Exp. Pathol., 4(6):596-605.

[2]Barrett-Connor, E., Stuenkel, C., 1999. Hormones and heart disease in women: heart and estrogen/progestin replacement study in perspective. J. Clin. Endocrinol. Metab., 84(6):1848-1853.

[3]Benedict, J.C., Lin, T.M., Loeffler, I.K., Peterson, R.E., Flaws, J.A., 2000. Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol. Sci., 56(2):382-388.

[4]Burkl, W., Schiechl, H., 1978. The growth of follicles in the rat ovary under the influence of busulphan and endoxan. Cell Tissue Res., 186(2):351-359.

[5]Copelan, E.A., Biggs, J.C., Szer, J., Thompson, J.M., Crilley, P., Brodsky, I., Klein, J.L., Kapoor, N., Harman, G.S., Avalos, B.R., 1993. Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2). Semin. Oncol., 20(Suppl. 4):33-38.

[6]Coulam, C.B., Adamson, S.C., Annegers, J.F., 1986. Incidence of premature ovarian failure. Obstet. Gynecol., 67(4):604-606.

[7]Danilovich, N., Ram Sairam, M., 2006. Recent female mouse models displaying advanced reproductive aging. Exp. Gerontol., 41(2):117-122.

[8]de Magalhaes-Silverman, M., Lister, J., Rybka, W., Wilson, J., Ball, E., 1997. Busulfan and cyclophosphamide (Bu/Cy2) as preparative regimen for patients with lymphoma. Bone Marrow Transplant., 19(8):777-781.

[9]Dierich, A., Sairam, M.R., Monaco, L., Fimia, G.M., Gansmuller, A., LeMeur, M., Sassone-Corsi, P., 1998. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. PNAS, 95(23):13612-13617.

[10]Dixit, H., Rao, L., Padmalatha, V., Raseswari, T., Kapu, A.K., Panda, B., Murthy, K., Tosh, D., Nallari, P., Deenadayal, M., et al., 2010. Genes governing premature ovarian failure. Reprod. Biomed. Online, 20(6):724-740.

[11]Grigg, A.P., McLachlan, R., Zaja, J., Szer, J., 2000. Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg). Bone Marrow Transplant., 26(10):1089-1095.

[12]Hankins, D.G., Sanders, S., MacDonald, F.M., Drage, C.W., 1978. Pulmonary toxicity recurring after a six week course of busulfan therapy and after subsequent therapy with uracil mustard. Chest, 73(3):415-416.

[13]Hemsworth, B.N., Jackson, H., 1963. Effect of busulphan on the developing ovary in the rat. J. Reprod. Fertil., 6(2):229-233.

[14]Jemal, A., Siegel, R., Xu, J., Ward, E., 2010. Cancer statistics. CA Cancer J. Clin., 60(5):277-300.

[15]Johnson, J., Bagley, J., Skaznik-Wikiel, M., Lee, H.J., Adams, G.B., Niikura, Y., Tschudy, K.S., Tilly, J.C., Cortes, M.L., Forkert, R., et al., 2005. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell, 122(2):303-315.

[16]Jopling, C., Rosendaal, M., 2001. A cautionary tale: how to delete mouse haemopoietic stem cells with busulphan. Br. J. Haematol., 113(4):970-974.

[17]Kaaks, R., Lukanova, A., Kurzer, M.S., 2002. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol. Biomarkers Prev., 11(12):1531-1543.

[18]Lopez, S.G., Luderer, U., 2004. Effects of cyclophosphamide and buthionine sulfoximine on ovarian glutathione and apoptosis. Free Radic. Biol. Med., 36(11):1366-1377.

[19]Maltaris, T., Seufert, R., Fischl, F., Schaffrath, M., Pollow, K., Koelbl, H., Dittrich, R., 2007. The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur. J. Obstet. Gynecol. Reprod. Biol., 130(2):148-155.

[20]Mayer, L.P., Devine, P.J., Dyer, C.A., Hoyer, P.B., 2004. The follicle-deplete mouse ovary produces androgen. Biol. Reprod., 71(1):130-138.

[21]Meirow, D., Nugent, D., 2001. The effects of radiotherapy and chemotherapy on female reproduction. Hum. Reprod. Update, 7(6):535-543.

[22]Meirow, D., Lewis, H., Nugent, D., Epstein, M., 1999. Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool. Hum. Reprod., 14(7):1903-1907.

[23]Myers, M., Britt, K.L., Wreford, N.G., Ebling, F.J., Kerr, J.B., 2004. Methods for quantifying follicular numbers within the mouse ovary. Reproduction, 127(5):569-580.

[24]Nair, G.V., Herrington, D.M., 2000. The ERA trial: findings and implications for the future. Climacteric, 3(4):227-232.

[25]Pelloux, M.C., Picon, R., Gangnerau, M.N., Darmoul, D., 1988. Effects of busulfan on ovarian folliculogenesis, steroidogenesis and anti-müllerian activity of rat neonates. Acta Endocrinol. (Copenh), 118(2):218-226.

[26]Rossouw, J.E., Anderson, G.L., Prentice, R.L., LaCroix, A.Z., Kooperberg, C., Stefanick, M.L., Jackson, R.D., Beresford, S.A., Howard, B.V., Johnson, K.C., et al., 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. JAMA, 288(3):321-333.

[27]Schallier, D., Impens, N., Warson, F., van Belle, S., de Wasch, G., 1983. Additive pulmonary toxicity with melphalan and busulfan therapy. Chest, 84(4):492-493.

[28]Shelling, A.N., 2010. Premature ovarian failure. Reproduction, 140(5):633-641.

[29]Shirota, M., Soda, S., Katoh, C., Asai, S., Sato, M., Ohta, R., Watanabe, G., Taya, K., Shirota, K., 2003. Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats. Reproduction, 125(1):85-94.

[30]Sklar, C., 2005. Maintenance of ovarian function and risk of premature menopause related to cancer treatment. J. Natl. Cancer Inst. Monogr., 2005(34):25-27.

[31]Soble, A.R., Perry, H., 1977. Fatal radiation pneumonia following subclinical busulfin injury. AJR Am. J. Roentgenol., 128(1):15-18.

[32]Ulrickson, M., Aldridge, J., Kim, H.T., Hochberg, E.P., Hammerman, P., Dube, C., Attar, E., Ballen, K.K., Dey, B.R., McAfee, S.L., et al., 2009. Busulfan and cyclophosphamide (Bu/Cy) as a preparative regimen for autologous stem cell transplantation in patients with non-Hodgkin lymphoma: a single-institution experience. Biol. Blood Marrow Transplant., 15(11):1447-1454.

[33]Vergnon, J.M., Boucheron, S., Riffat, J., Guy, C., Blanc, P., Emonot, A., 1988. Interstitial pneumopathies caused by busulfan. Histologic, developmental and bronchoalveolar lavage analysis of 3 cases. Rev. Med. Interne, 9(4):377-383.

[34]Woad, K.J., Watkins, W.J., Prendergast, D., Shelling, A.N., 2006. The genetic basis of premature ovarian failure. Austr. N. Z. J. Obstet. Gynaecol., 46(3):242-244.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE