J Gynecol Oncol.  2014 Oct;25(4):328-333. 10.3802/jgo.2014.25.4.328.

Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model

Affiliations
  • 1Department of Obstetrics and Gynecology, Ege University School of Medicine, Izmir, Turkey. burak.zeybek@ege.edu.tr
  • 2Department of Physiology, Ege University School of Medicine, Izmir, Turkey.
  • 3Department of Histology and Embryology, Ege University School of Medicine, Izmir, Turkey.

Abstract


OBJECTIVE
To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment.
METHODS
Twenty-one adult female Sprague-Dawley rats were used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 microg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4degrees C for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30degrees C for hormone assays.
RESULTS
All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Mullerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group.
CONCLUSION
G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.

Keyword

Anti-Mullerian hormone; Cisplatin; Granulocyte-colony stimulating factor; Ovarian follicle; Ovary

MeSH Terms

Animals
Anti-Mullerian Hormone/blood
Antineoplastic Agents/*toxicity
Biological Markers/blood
Cisplatin/*toxicity
Disease Models, Animal
Drug Evaluation, Preclinical/methods
Female
Fertility Preservation/methods
Granulocyte Colony-Stimulating Factor/*therapeutic use
Ovarian Follicle/drug effects/pathology
Primary Ovarian Insufficiency/blood/chemically induced/pathology/*prevention & control
Rats, Sprague-Dawley
Antineoplastic Agents
Anti-Mullerian Hormone
Biological Markers
Cisplatin
Granulocyte Colony-Stimulating Factor

Figure

  • Fig. 1 Histological evaluation of ovaries in control (A), cisplatin (CP)+physiological saline (PS) (B), and cisplatin+granulocyte-colony stimulating factor (G-CSF) group (C). Cisplatin+PS group showed stromal and follicular damage. G-CSF treatment significantly reduced cisplatin-induced changes in ovaries (H&E, ×20). CL, corpus luteum; pr, primary follicle; sf, secondary follicle; tf, tertiary follicle; v, vessel.


Cited by  1 articles

Consequences of chemotherapeutic agents on primordial follicles and future clinical applications
So-Youn Kim, Geum Joon Cho, John S. Davis
Obstet Gynecol Sci. 2019;62(6):382-390.    doi: 10.5468/ogs.2019.62.6.382.


Reference

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012; 62:10–29.
2. Anderson RA, Themmen AP, Al-Qahtani A, Groome NP, Cameron DA. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod. 2006; 21:2583–2592.
3. Meraner V, Gamper EM, Grahmann A, Giesinger JM, Wiesbauer P, Sztankay M, et al. Monitoring physical and psychosocial symptom trajectories in ovarian cancer patients receiving chemotherapy. BMC Cancer. 2012; 12:77.
4. Sugiyama S, Hayakawa M, Kato T, Hanaki Y, Shimizu K, Ozawa T. Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity. Biochem Biophys Res Commun. 1989; 159:1121–1127.
5. Brady HR, Kone BC, Stromski ME, Zeidel ML, Giebisch G, Gullans SR. Mitochondrial injury: an early event in cisplatin toxicity to renal proximal tubules. Am J Physiol. 1990; 258(5 Pt 2):F1181–F1187.
6. Leibbrandt ME, Wolfgang GH, Metz AL, Ozobia AA, Haskins JR. Critical subcellular targets of cisplatin and related platinum analogs in rat renal proximal tubule cells. Kidney Int. 1995; 48:761–770.
7. Li X, Kang X, Deng Q, Cai J, Wang Z. Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study. Reprod Biol Endocrinol. 2013; 11:16.
8. Hubner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, De La Fuente R, et al. Derivation of oocytes from mouse embryonic stem cells. Science. 2003; 300:1251–1256.
9. Geijsen N, Horoschak M, Kim K, Gribnau J, Eggan K, Daley GQ. Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature. 2004; 427:148–154.
10. Dyce PW, Wen L, Li J. In vitro germline potential of stem cells derived from fetal porcine skin. Nat Cell Biol. 2006; 8:384–390.
11. Danner S, Kajahn J, Geismann C, Klink E, Kruse C. Derivation of oocyte-like cells from a clonal pancreatic stem cell line. Mol Hum Reprod. 2007; 13:11–20.
12. Lee HJ, Selesniemi K, Niikura Y, Niikura T, Klein R, Dombkowski DM, et al. Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure. J Clin Oncol. 2007; 25:3198–3204.
13. Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005; 122:303–315.
14. Weisbart RH, Gasson JC, Golde DW. Colony-stimulating factors and host defense. Ann Intern Med. 1989; 110:297–303.
15. Martino M, Fedele R, Massara E, Recchia AG, Irrera G, Morabito F. Long-term safety of granulocyte colony-stimulating factor in normal donors: is it all clear? Expert Opin Biol Ther. 2012; 12:609–621.
16. Kudo T, Matsumoto T, Nakamichi I, Yada S, Esaki M, Jo Y, et al. Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis. Scand J Gastroenterol. 2008; 43:689–697.
17. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A. 2001; 98:10344–10349.
18. Spahr L, Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, et al. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology. 2008; 48:221–229.
19. Iwasaki M, Adachi Y, Minamino K, Suzuki Y, Zhang Y, Okigaki M, et al. Mobilization of bone marrow cells by G-CSF rescues mice from cisplatin-induced renal failure, and M-CSF enhances the effects of G-CSF. J Am Soc Nephrol. 2005; 16:658–666.
20. Solaroglu I, Tsubokawa T, Cahill J, Zhang JH. Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat. Neuroscience. 2006; 143:965–974.
21. Sehara Y, Hayashi T, Deguchi K, Zhang H, Tsuchiya A, Yamashita T, et al. Decreased focal inflammatory response by G-CSF may improve stroke outcome after transient middle cerebral artery occlusion in rats. J Neurosci Res. 2007; 85:2167–2174.
22. Authier N, Gillet JP, Fialip J, Eschalier A, Coudore F. An animal model of nociceptive peripheral neuropathy following repeated cisplatin injections. Exp Neurol. 2003; 182:12–20.
23. Sugiyama Y, Yagita Y, Oyama N, Terasaki Y, Omura-Matsuoka E, Sasaki T, et al. Granulocyte colony-stimulating factor enhances arteriogenesis and ameliorates cerebral damage in a mouse model of ischemic stroke. Stroke. 2011; 42:770–775.
24. Shima C, Adachi Y, Minamino K, Okigaki M, Shi M, Imai Y, et al. Neuroprotective effects of granulocyte colony-stimulating factor on ischemia-reperfusion injury of the retina. Ophthalmic Res. 2012; 48:199–207.
25. Oktay K, Schenken RS, Nelson JF. Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat. Biol Reprod. 1995; 53:295–301.
26. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest. 2005; 115:2083–2098.
27. Oishi A, Otani A, Sasahara M, Kojima H, Nakamura H, Yodoi Y, et al. Granulocyte colony-stimulating factor protects retinal photoreceptor cells against light-induced damage. Invest Ophthalmol Vis Sci. 2008; 49:5629–5635.
28. Pastuszko P, Schears GJ, Pirzadeh A, Kubin J, Greeley WJ, Wilson DF, et al. Effect of granulocyte-colony stimulating factor on expression of selected proteins involved in regulation of apoptosis in the brain of newborn piglets after cardiopulmonary bypass and deep hypothermic circulatory arrest. J Thorac Cardiovasc Surg. 2012; 143:1436–1442.
29. Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med. 2005; 11:305–311.
30. Xu Y, Hunt NH, Bao S. The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation. Cell Res. 2008; 18:1220–1229.
31. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel). 2010; 2:2490–2518.
32. Lee ST, Chu K, Jung KH, Ko SY, Kim EH, Sinn DI, et al. Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res. 2005; 1058:120–128.
33. Deindl E, Zaruba MM, Brunner S, Huber B, Mehl U, Assmann G, et al. G-CSF administration after myocardial infarction in mice attenuates late ischemic cardiomyopathy by enhanced arteriogenesis. FASEB J. 2006; 20:956–958.
34. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001; 7:430–436.
35. Skaznik-Wikiel ME, McGuire MM, Sukhwani M, Donohue J, Chu T, Krivak TC, et al. Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy. Fertil Steril. 2013; 99:2045–2054.e3.
36. Al-Awqati Q, Oliver JA. Stem cells in the kidney. Kidney Int. 2002; 61:387–395.
37. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature. 2003; 422:897–901.
38. Yannaki E, Athanasiou E, Xagorari A, Constantinou V, Batsis I, Kaloyannidis P, et al. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol. 2005; 33:108–119.
39. Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B, et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol. 2003; 21:763–770.
40. Ledee N, Lombroso R, Lombardelli L, Selva J, Dubanchet S, Chaouat G, et al. Cytokines and chemokines in follicular fluids and potential of the corresponding embryo: the role of granulocyte colony-stimulating factor. Hum Reprod. 2008; 23:2001–2009.
41. Masuda H, Tanaka T, Tateishi M, Naito M, Tamai H. Detection and cytotoxicity of cisplatin-induced superoxide anion in monolayer cultures of a human ovarian cancer cell line. Cancer Chemother Pharmacol. 2001; 47:155–160.
42. Park KW, Kwon YW, Cho HJ, Shin JI, Kim YJ, Lee SE, et al. G-CSF exerts dual effects on endothelial cells: opposing actions of direct eNOS induction versus indirect CRP elevation. J Mol Cell Cardiol. 2008; 45:670–678.
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