Granulocyte colony-stimulating factor in conjunction with vascular endothelial growth factor maintains primordial follicle numbers in transplanted mouse ovaries.
OBJECTIVE
To determine whether granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or vascular endothelial growth factor (VEGF) improve the outcome of ovarian grafting.


METHODS
Experimental animal study.


METHODS
Tertiary care hospital, animal facilities.


METHODS
Young adult (6- to 8-week-old) C57BL/6 female mice.


METHODS
Orthotopic transplantation of the frozen-thawed ovary. Group 1 (n = 6) received VEGF (8 g/kg/day); group 2 (n = 6) received VEGF and G-CSF (50 g/kg/day), group 3 (n = 6) received G-CSF and SCF (100 g/kg/day), and group 4 (n = 5) received saline (vehicle controls). All injections were given once daily for 5 days starting the day after surgery. Ovaries were collected 2 weeks after transplantation.


METHODS
Number of nonatretic immature (primordial, primary, and small preantral) follicles.


RESULTS
Transplanted ovaries in mice injected with VEGF concurrently with G-CSF maintained a statistically significantly larger pool of primordial follicles compared with transplanted ovaries in saline-injected controls. Follicle numbers (total immature and primordial) in transplanted ovaries showed no statistically significant difference in mice injected with VEGF alone or G-CSF plus SCF compared with saline-injected controls.


CONCLUSIONS
After ovarian transplantation, mice treated with VEGF and G-CSF maintain a significantly greater number of primordial follicles compared with the transplanted ovaries in control animals, suggesting that the combination of G-CSF and VEGF minimizes ischemic damage and thus improves the viability and function of the ovarian graft.
Obstetrics, Gynecology, and Women's Health Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Malgorzata E
ME
Skaznik-Wikiel
Rakesh K
RK
Sharma
Kaisa
K
Selesniemi
Ho-Joon
HJ
Lee
Jonathan L
JL
Tilly
Tommaso
T
Falcone
D000818:Animals; D002452:Cell Count / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation*; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor
Nature. 2004 Mar 11;428(6979):145-50
15014492
Hum Reprod. 2000 Jun;15(6):1300-4
10831559
Obstet Gynecol. 1992 Sep;80(3 Pt 2):541-3
1386664
J Clin Invest. 1998 Dec 1;102(11):1978-85
9835623
Cancer. 2004 Jul 1;101(1):3-27
15221985
Fertil Steril. 2008 Oct;90(4 Suppl):1550-8
18291375
Int Rev Exp Pathol. 1993;34 Pt A:215-33
7681048
Endocrinology. 1999 Sep;140(9):4262-71
10465300
Cancer Res. 1985 Aug;45(8):3651-6
3926307
Expert Opin Biol Ther. 2002 Dec;2(8):985-92
12517276
Hum Reprod Update. 2004 May-Jun;10(3):251-66
15140872
J Clin Endocrinol Metab. 1996 Aug;81(8):3112-8
8768883
Nat Med. 2000 Oct;6(10):1109-14
11017141
Cancer. 1999 Nov 15;86(10):2138-42
10570443
Differentiation. 2010 Mar;79(3):159-70
20138422
Hum Reprod Update. 1998 May-Jun;4(3):248-59
9741709
Development. 1990 Dec;110(4):1057-69
1712701
Dev Biol. 1993 May;157(1):100-9
7683280
Hum Reprod Update. 2003 Sep-Oct;9(5):471-81
14640379
Blood. 1991 Aug 15;78(4):961-6
1714329
Lancet. 2004 Mar 13;363(9412):837-40
15031026
Kidney Int. 1999 Sep;56(3):794-814
10469350
Lancet. 1994 Jul 23;344(8917):235-6
7913160
Curr Opin Obstet Gynecol. 2005 Aug;17(4):333-8
15976536
Biol Reprod. 2009 Jan;80(1):2-12
18753611
Fertil Steril. 1998 Jan;69(1):1-7
9457923
Hum Reprod. 1995 Sep;10(9):2334-8
8530662
Dev Biol. 1994 Jan;161(1):194-205
7507447
Nat Med. 1995 Jan;1(1):27-31
7584949
Reprod Biol Endocrinol. 2003 Feb 06;1:11
12646064
Science. 1989 Dec 8;246(4935):1306-9
2479986
Cell. 2005 Jul 29;122(2):303-15
16051153
J Clin Oncol. 2004 Oct 15;22(20):4174-83
15483028
Fertil Steril. 2007 Jan;87(1):195-7
17074335
Endocrinology. 1992 Jul;131(1):254-60
1612003
Biol Reprod. 1995 Feb;52(2):365-72
7711205
Endocrinology. 1990 Aug;127(2):965-7
2197082
Cardiovasc Res. 2005 Jan 1;65(1):52-63
15621033
Eur J Cancer. 1996 Dec;32A(14):2413-22
9059329
Fertil Steril. 2002 Feb;77(2):403-8
11821105
Nature. 1996 Apr 4;380(6573):435-9
8602241
J Reprod Dev. 2005 Feb;51(1):161-8
15750308
Expert Opin Biol Ther. 2002 Apr;2(4):361-70
11955275
Hum Reprod. 2004 Jun;19(6):1287-93
15117903
Cardiovasc Res. 2006 Apr 1;70(1):117-25
16497284
N Engl J Med. 2000 Jun 22;342(25):1919
10877641
Nat Cell Biol. 2009 May;11(5):631-6
19363485
Dev Biol. 1993 May;157(1):85-99
7683286
Fertil Steril. 2004 Feb;81(2):243-57
14967351