Browse > Article
http://dx.doi.org/10.5653/cerm.2013.40.2.60

Effect of genistein administration on the recovery of spermatogenesis in the busulfan-treated rat testis  

Chi, Heejun (i-Dream Research Center, MizMedi Hospital)
Chun, Kangwoo (i-Dream Research Center, MizMedi Hospital)
Son, Hyukjun (i-Dream Research Center, MizMedi Hospital)
Kim, Jonghyun (i-Dream Research Center, MizMedi Hospital)
Kim, Giyoung (i-Dream Research Center, MizMedi Hospital)
Roh, Sungil (i-Dream Research Center, MizMedi Hospital)
Publication Information
Clinical and Experimental Reproductive Medicine / v.40, no.2, 2013 , pp. 60-66 More about this Journal
Abstract
Objective: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. Methods: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. Results: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. Conclusion: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.
Keywords
Drug therapy; Busulfan; Genistein; Recovery of spermatogenesis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Shuttlesworth GA, de Rooij DG, Huhtaniemi I, Reissmann T, Russell LD, Shetty G, et al. Enhancement of a spermatogonial proliferation and differentiation in irradiated rats by GnRH antagonist administration. Endocrinology 2000;141:37-49.   DOI
2 Kangasniemi M, Wilson G, Huhtaniemi I, Meistrich ML. Protection against procarbazine-induced testicular damage by GnRHagonist and antiandrogen treatment in the rat. Endocrinology 1995;136:3677-80.   DOI
3 Meistrich ML, Kangasniemi M. Hormone treatment after irradiation stimulates recovery of rat spermatogenesis from surviving spermatogonia. J Androl 1997;18:80-7.
4 Meistrich ML. Restoration of spermatogenesis by hormone treatment after cytotoxic therapy. Acta Paediatr Scand 1999;88:19-22.
5 Kangasniemi M, Wilson G, Parchuri N, Huhtaniemi I, Meistrich ML. Rapid protection of rat spermatogenic stem cells against procarbazine by treatment with a gonadotropin-releasing hormone antagonist (Nal-Glu) and an antiandrogen (flutamide). Endocrinology 1995;136:2881-8.   DOI
6 Shetty G, Wilson G, Huhtaniemi I, Shuttlesworth GA, Reissmann T, Meistrich ML. Gonadotropin-releasing hormone analogs stimulate and testosterone inhibits the recovery of spermatogenesis in irradiated rats. Endocrinology 2000;141:1735-45.   DOI
7 Ward JA, Robinson J, Furr BJA, Shalet SM, Morris ID. Protection of spermatogenesis in rats from the cytotoxic procarbazine by the depot formulation of Zoladex, a gonadotropin-releasing hormone agonist. Cancer spermatogenesis in rats from the cytotoxic procarbazine by the depot formulation of Zoladex, a gonadotropin- releasing hormone agonist. Cancer Res 1990;50:568-74.
8 Meistrich ML, Wilson G, Kangasniemi M, Huhtaniemi I. Mechanism of protection of rat spermatogenesis by hormonal pretreatment: stimulation of spermatogonial differentiation after irradiation. J Androl 2000;21:464-9.
9 Udagawa K, Ogawa T, Watanabe T, Yumura Y, Takeda M, Hosaka M. GnRH analog, leuprorelin acetate, promotes regeneration of rat spermatogenesis after severe chemical damage. Inter J Urolo 2001;8:615-22.   DOI
10 Blanchard KT, Lee J, Boekelheide K. Leuprolide, a gonadotropinreleasing hormone agonist, reestablishes spermatogenesis after 2,5-hexanedione-induced irreversible testicular injury in the rat, resulting in normalized stem cell factor expression. Endocrinology 1998;139:236-44.   DOI
11 Meistrich ML, Wilson G, Shuttlesworth G, Huhtaniemi I, Reissmann T. GnRH agonists and antagonists stimulate recovery of fertility in irradiated LBNF1 rats. J Androl 2001;22:809-17.
12 Schoenfeld HA, Hall SJ, Boekelheide K. Continuously proliferative stem germ cells partially repopulate the aged, atrophic rat testis after gonadotropin-releasing hormone agonist therapy. Biol Reprod 2001;64:1273-82.   DOI
13 Henriksson P, Carlstrom K, Pousette A, Gunnarsson PO, Johansson CJ, Eriksson B, et al. Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen. Prostate 1999;40:76-82.   DOI
14 Udagawa K, Takeda M, Hosaka M, Kubota Y, Ogawa T. Recovery of spermatogenesis by high dose gonadotropin-releasing hormone analogue treatment in rat cryptorchid testis after orchiopexy. J Urol 2002;168:1279-83.   DOI
15 Meistrich ML, Shetty G. Inhibition of spermatogonial differentiation by testosterone. J Androl 2003;24:135-48.   DOI
16 Shetty G, Weng CCY, Bolden-Tiller OU, Huhtaniemi I, Handelsman DJ, Meistrich ML. Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats. Endocrinology 2004;145:4461-9.   DOI
17 Adlercreutz H, Mazur W. Phyto-estrogens and Western diets. Ann Medici 1997;29:95-120.   DOI
18 Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggbald J, Nilsson S, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors $\alpha$ and $\beta$. Endocrinology 1997;138:863-70.   DOI
19 Shao ZM, Wu J, Shen ZZ, Barsky SH. Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Res 1998;58:4851-7.
20 Setchell KDR, Cassidy A. Dietary isoflavones - biological effects and relevance to human health. J Nutri 1999;129:758S-67S.
21 Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 2006;98:459-71.   DOI
22 Akingbemi BT, Braden TD, Kemppainen BW, Hancock KD, Sherrill JD, Cook SJ, et al. Exposure to phytoestrogens in the perinatal period affects androgen secretion by testicular Leydig cells in the adult rat. Endocrinology 2007;148:4475-88.   DOI
23 Valachovicova T, Slivova V, Bergman H, Shuherk J, Sliva D. Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways. Int J Oncol 2004;25:1389-95.
24 Anjamrooz SH, Movahedin M, Mowla SJ, Bairanvand SP. Assessment of morphological and functional changes in the mouse testis and epididymal sperms following busulfan treatment. Iran Biomedi J 2007;11:15-22.
25 Weber KS, Setchell KDR, Stocco DM, Lephart ED. Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague- Dawley rats. J Endocrinol 2001;170:591-9.   DOI
26 Skogseth H, Larsson E, Halgunset J. Inhibitors of tyrosine kinase inhibit the production of urokinase plasminogen activator in human prostatic cancer cells. APMIS 2005;113:332-9.   DOI
27 Hewitt AM, Singletary KW. Soy extract inhibits mammary adenocarcinoma growth in a syngeneic mouse model. Cancer Lett 2003;192:133-43.   DOI
28 Su SJ, Yeh TM, Chuang WJ, Ho CL, Chang KL, Cheng HL, et al. The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol 2005;69:307-18.   DOI
29 Farina HG, Pomies M, Alonso DF, Gomez DE. Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol Reports 2006;16:885-91.
30 McClive PJ, Sinclair AH. Type II and type IX collagen transcript isoforms are expressed during mouse testis development. Biol Reprod 2003;68:1742-7.   DOI
31 Karashima T, Zalatnai A, Schally AV. Protective effects of analogs of luteinizing hormone releasing hormone against chemotherapy- induced testicular damage in rats. Proc Natl Acad Sci USA 1988; 85:2329-33.   DOI
32 Kanatsu-Shinohara M, Toyokuni S, Morimoto T, Matsui S, Honjo T, Shinohara, T. Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation. Biol Reprod 2003;68:1801-7.   DOI
33 Fouchecourt S, Lareyre JJ, Chaurand P, DaGue BB, Suzuki K, Ong DE, et al. Identification, immunolocalization, regulation, and postnatal development of the lipocalin EP17 (epididymal protein of 17 kilodaltons) in the mouse and rat epididymis. Endocrinology 2003;144:887-900.   DOI
34 Porter KL, Shetty G, Meistrich ML. Testicular edema is associated with spermatogonial arrest in irradiated rats. Endocrinology 2006; 147:1297-305.   DOI
35 Adlercreutz H, Mazur W, Bartels P, Elomaa V, Watanabe S, Wahala K, et al. Phytoestrogens and prostate disease. J Nutri 2000;130: 658S-9S.
36 Hossaini A, Dalgaard M, Vinggaard AM, Pakarinen P, Larsen JJ. Male reproductive effects of octylphenol and estradiol in Fischer and Wistar rats. Reprod Toxicol 2003;17:607-15.   DOI
37 Shetty G, Wilson G, Hardy MP, Niu E, Huhtaniemi I, Meistrich ML. Inhibition of recovery of spermatogenesis in irradiated rats by different androgens. Endocrinology 2002;143:3385-96.   DOI
38 Sakaue M, Ishimura R, Kurosawa S, Fukuzawa NH, Kurohmaru M, Hayashi Y, et al. Administration of estradiol-3-benzoate downregulates the expression of testicular steroidogenic enzyme genes for testosterone production in the adult rat. J Vet Med Sci 2002; 64:107-13.   DOI
39 Sharpe RM. Pathways of endocrine disruption during male sexual differentiation and masculinization. Best Pract Res Clin Endocrinol Metab 2006;20:91-110.   DOI
40 Brennemann W, Brensing KA, Leipner N, Boldt I, Klingmuller D. Attempted protection of spermatogenesis from irradiation in patients with seminoma by D-tryptophan-6 luteinizing hormone releasing hormone. Clin Invest 1994;72:838-42.
41 Kamischke A, Kuhlmann M, Weinbauer GF, Luetjens M, Yeung CH, Kronholz HL, et al. Gonadal protection from radiation by GnRH antagonist or recombinant human FSH: a controlled trial in a male nonhuman primate (Macaca fascicularis). J Endocrinol 2003; 179:183-94.   DOI