title: Is caspase inhibition a valid therapeutic strategy in cryopreservation of ovarian tissue?
abstract: OBJECTIVE
  The aim of this study is to determine whether inclusion of caspase inhibitor can improve the efficacy of cryopreservation of ovarian tissue.
  
  
  METHODS
  Mice were randomly assigned to the Group A (fresh control group) Group B (inclusion of caspase inhibitor) and Group C (non-inclusion of caspase inhibitor). Ovarian tissue in Group B and Group C was vitrified-thawed. TUNEL assay and Bax protein detection were measured after cryopreservation. The mice in all groups received autotransplantation. The number of days before the resumption of estrous cycles was measured daily from the 5th day after surgery, and the percentage of cells expressing PCNA in grafts was measured one month following transplantation.
  
  
  RESULTS
  The incidence of TUNEL positive follicles in Group B was significantly higher than that in Group C. Similarly, the percentage of follicles expressing Bax protein in Group B was significantly higher than that in Group C. The number of days before the resumption of estrous cycles in Group B was significantly less than that in Group C. In addition, the percentage of follicular and stromal cells expressing PCNA of grafts in Group B was significantly higher than that in Group C.
  
  
  CONCLUSIONS
  The global caspase inhibitor Z-VAD-FMK decreases the incidence of apoptosis of ovarian tissue induced by cryopreservation, and inclusion of caspase inhibitor improves the efficacy of cryopreservation of ovarian tissue.
authors.affiliation: Department of Obstetrics and Gynecology, First People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200080, China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Zhang
authors.forename: Lin-Xia
authors.initials: LX
authors.lastname: Li
authors.forename: Yi-Xia
authors.initials: YX
authors.lastname: Yang
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Liu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wan
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D015925:Cryopreservation / Q000379:methods*; D003470:Culture Media; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008813:Mice, Inbred ICR; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; C494827:Bax protein, mouse; D061945:Caspase Inhibitors; D003470:Culture Media; D015853:Cysteine Proteinase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
references.citation: Blood Rev. 1995 Jun;9(2):93-116
references.pmid: 7580395
references.citation: Int J Oncol. 2005 Aug;27(2):345-53
references.pmid: 16010414
references.citation: Annu Rev Cell Dev Biol. 1999;15:269-90
references.pmid: 10611963
references.citation: Hum Reprod Update. 2003 Sep-Oct;9(5):471-81
references.pmid: 14640379
references.citation: Hum Reprod. 2008 Mar;23(3):606-18
references.pmid: 18216042
references.citation: J Biol Chem. 1998 Oct 9;273(41):26900-7
references.pmid: 9756937
references.citation: Am J Physiol. 1984 Sep;247(3 Pt 1):C125-42
references.pmid: 6383068
references.citation: Endocrinology. 1999 Jan;140(1):462-71
references.pmid: 9886858
references.citation: Biochemistry. 1989 Apr 4;28(7):2967-74
references.pmid: 2568123
references.citation: Genes Dev. 1998 Jun 1;12(11):1551-70
references.pmid: 9620844
references.citation: Annu Rev Biochem. 1999;68:383-424
references.pmid: 10872455
references.citation: JAMA. 2001 Sep 26;286(12):1490-3
references.pmid: 11572742
references.citation: J Cell Biochem. 1997 Jan;64(1):33-42
references.pmid: 9015752
references.citation: Cell. 1991 May 17;65(4):691-9
references.pmid: 1827756
references.citation: Domest Anim Endocrinol. 2005 Jan;28(1):17-33
references.pmid: 15620804
references.citation: J Clin Invest. 1996 May 15;97(10):2391-8
references.pmid: 8636421
references.citation: Nat Med. 2000 Oct;6(10):1109-14
references.pmid: 11017141
references.citation: Eur J Neurosci. 1998 Feb;10(2):777-81
references.pmid: 9749742
references.citation: ILAR J. 2000;41(4):187-96
references.pmid: 11123179
references.citation: Fertil Steril. 2007 May;87(5):1200-7
references.pmid: 17307173
references.citation: Cell Death Differ. 1999 Nov;6(11):1067-74
references.pmid: 10578175
references.citation: Eur J Obstet Gynecol Reprod Biol. 2006 Apr 1;125(2):233-8
references.pmid: 16443318
references.citation: Br J Pharmacol. 1998 Jun;124(4):756-62
references.pmid: 9690868
references.citation: J Bioenerg Biomembr. 1994 Oct;26(5):509-17
references.pmid: 7896766
references.citation: Mol Cell Endocrinol. 2000 May 25;163(1-2):125-9
references.pmid: 10963884
references.citation: Cell Death Differ. 1999 Nov;6(11):1028-42
references.pmid: 10578171
references.citation: Cell. 1997 Apr 18;89(2):175-84
references.pmid: 9108473
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13618-23
references.pmid: 9811849
references.citation: Science. 1998 Aug 28;281(5381):1309-12
references.pmid: 9721092
references.citation: J Exp Med. 1994 Aug 1;180(2):525-35
references.pmid: 8046331
references.citation: Science. 1998 Aug 28;281(5381):1312-6
references.pmid: 9721091
references.citation: Theriogenology. 2006 Nov;66(8):2008-16
references.pmid: 16870242
references.citation: Am J Obstet Gynecol. 1971 Jul 1;110(5):746-61
references.pmid: 4935165
references.citation: Nat Med. 1997 Nov;3(11):1228-32
references.pmid: 9359697
references.citation: Hum Reprod Update. 1997 May-Jun;3(3):267-80
references.pmid: 9322102