title: In search of the most efficient fertility preservation strategy for prepubertal boys.
abstract: Fertility preservation strategies are currently being developed for boys facing spermatogonial stem cell (SSC) loss. However, it is not clear yet which transplantation strategy would be the best choice. Therefore, the aim of the work presented in this thesis was both to compare these strategies and to study how to improve their efficiency. The efficiency to restore spermatogenesis after transplantation of SSCs or testicular tissue was evaluated. In addition, we investigated the potential of transplanted adult bone marrow stem cells (BMSCs) to repopulate the testis. We aimed to improve the efficiency of human intratesticular xenografting by exogenous administration of FSH. Since spermatogonial loss was observed in human intratesticular xenografts, we finally evaluated whether early cell death was the cause of this loss. Compared to SSC transplantation, more donor-derived spermatogenesis was observed after intratesticular tissue grafting. Human SSCs were able to survive for at least 12 months inside the mouse testis and meiotic activity was observed. However, the attempt to improve germ cell survival and induce full differentiation by the exogenous administration of FSH failed. Spermatogonia-specific apoptosis could not explain the SSC loss. Differentiation towards the germ line was not observed after intra-testicular injection of BMSCs, neither did we observe any protective effect for SSC loss. Intra-testicular tissue grafting seems to be the most efficient fertility preservation strategy. However, this strategy can not be applied in patients at risk of malignant contamination. For these patients SSC transplantation should be performed after decontamination of the cell suspension.
authors.affiliation: Research Group Biology of the testis (BITE), Research Department Embryology and Genetics, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Van Saen
keywords: Fertility; grafting; spermatogonial stem cells; testis; transplantation
references.citation: Endocrinology. 2006 Sep;147(9):4104-11
references.pmid: 16728492
references.citation: Int J Androl. 2009 Feb;32(1):66-73
references.pmid: 17916184
references.citation: Hum Reprod. 2006 Feb;21(2):384-9
references.pmid: 16239313
references.citation: Biol Reprod. 2003 Aug;69(2):612-6
references.pmid: 12700182
references.citation: Reprod Biomed Online. 2009 Jul;19(1):99-105
references.pmid: 19573297
references.citation: Hum Reprod. 2002 Dec;17(12):3039-45
references.pmid: 12456600
references.citation: Br J Haematol. 2011 Jul;154(2):175-84
references.pmid: 21564077
references.citation: Lab Invest. 2006 Jul;86(7):654-63
references.pmid: 16652109
references.citation: JAMA. 2009 Nov 18;302(19):2127-34
references.pmid: 19920237
references.citation: Reproduction. 2008 Dec;136(6):823-31
references.pmid: 18768666
references.citation: Prog Brain Res. 1987;71:293-308
references.pmid: 3588950
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11303-7
references.pmid: 7972054
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11298-302
references.pmid: 7972053
references.citation: Biol Reprod. 2003 Jun;68(6):2331-5
references.pmid: 12606381
references.citation: Theriogenology. 2010 Mar 1;73(4):512-22
references.pmid: 19962749
references.citation: Endocrinology. 2008 Oct;149(10):5288-96
references.pmid: 18566126
references.citation: Cell Stem Cell. 2012 Nov 2;11(5):715-26
references.pmid: 23122294
references.citation: Biol Reprod. 2006 Apr;74(4):706-13
references.pmid: 16371588
references.citation: Biol Reprod. 2006 Aug;75(2):167-75
references.pmid: 16571874
references.citation: Biol Reprod. 2002 Jan;66(1):21-8
references.pmid: 11751259
references.citation: Biochim Biophys Acta. 2002 May 23;1582(1-3):204-15
references.pmid: 12069830
references.citation: Hum Reprod. 2006 Aug;21(8):2057-60
references.pmid: 16601006
references.citation: PLoS One. 2011 Apr 29;6(4):e19475
references.pmid: 21559342
references.citation: Nat Med. 1996 Jun;2(6):693-6
references.pmid: 8640563
references.citation: Nature. 2002 Aug 15;418(6899):778-81
references.pmid: 12181567
references.citation: J Androl. 2004 Nov-Dec;25(6):926-30
references.pmid: 15477365
references.citation: Reproduction. 2005 Dec;130(6):923-9
references.pmid: 16322552
references.citation: Hum Reprod. 2008 Nov;23(11):2402-14
references.pmid: 18664476
references.citation: Biol Reprod. 2002 Feb;66(2):486-94
references.pmid: 11804966
references.citation: Cell Stem Cell. 2008 Nov 6;3(5):533-42
references.pmid: 18983968
references.citation: J Clin Invest. 2005 Jul;115(7):1855-61
references.pmid: 15965502
references.citation: Tissue Cell. 1999 Oct;31(5):461-72
references.pmid: 10612257
references.citation: J Steroid Biochem Mol Biol. 2008 Apr;109(3-5):323-30
references.pmid: 18400489
references.citation: Reprod Biomed Online. 2013 Mar;26(3):286-98
references.pmid: 23352099
references.citation: JAMA. 2011 Jun 15;305(23):2416-8
references.pmid: 21673293
references.citation: Fertil Steril. 2009 Apr;91(4 Suppl):1549-52
references.pmid: 19006799
references.citation: Fertil Steril. 2013 Apr;99(5):1264-1272.e1
references.pmid: 23312508
references.citation: Biol Reprod. 2004 May;70(5):1500-3
references.pmid: 14736818
references.citation: Hum Reprod. 2007 Jun;22(6):1603-11
references.pmid: 17483089
references.citation: Stem Cells. 2008 May;26(5):1385-6
references.pmid: 18339770
references.citation: Bull Exp Biol Med. 2006 Jan;141(1):124-8
references.pmid: 16929983
references.citation: Reproduction. 2002 Sep;124(3):339-46
references.pmid: 12201807
references.citation: Hum Reprod. 2011 Feb;26(2):282-93
references.pmid: 21123192
references.citation: Hum Reprod. 1999 Jan;14(1):144-50
references.pmid: 10374111
references.citation: Hum Reprod. 2010 May;25(5):1113-22
references.pmid: 20172867
references.citation: Hum Reprod. 2007 Mar;22(3):733-42
references.pmid: 17082221
references.citation: Hum Reprod. 2006 Feb;21(2):390-6
references.pmid: 16311289
references.citation: Reproduction. 2006 Jun;131(6):1091-8
references.pmid: 16735548
references.citation: Endocrinology. 2008 Apr;149(4):1736-47
references.pmid: 18174281
references.citation: Am J Pathol. 2007 Mar;170(3):899-908
references.pmid: 17322375
references.citation: Biol Reprod. 2008 Apr;78(4):705-13
references.pmid: 18094353
references.citation: Stem Cells. 2004;22(4):487-500
references.pmid: 15277695
references.citation: Cancer Res. 2006 Dec 1;66(23):11166-71
references.pmid: 17145860
references.citation: Fertil Steril. 2008 Nov;90(5):2019-22
references.pmid: 18439593
references.citation: Biol Reprod. 2004 Aug;71(2):494-501
references.pmid: 15070832
references.citation: Fertil Steril. 2009 May;91(5 Suppl):2264-72
references.pmid: 18394623
references.citation: Exp Neurol. 2000 Oct;165(2):268-77
references.pmid: 10993687
references.citation: Reproduction. 2009 Oct;138(4):667-77
references.pmid: 19633133
references.citation: Biol Reprod. 2003 Oct;69(4):1260-4
references.pmid: 12801978
references.citation: Fertil Steril. 2012 Dec;98(6):1443-8.e1
references.pmid: 22981175
references.citation: Mol Reprod Dev. 1999 Jun;53(2):142-8
references.pmid: 10331452
references.citation: J Clin Oncol. 2007 Aug 1;25(22):3198-204
references.pmid: 17664466
references.citation: Biol Reprod. 2004 Dec;71(6):2087-91
references.pmid: 15317690
references.citation: Reproduction. 2003 Dec;126(6):765-74
references.pmid: 14748695
references.citation: Biol Reprod. 2006 Oct;75(4):575-81
references.pmid: 16807385
references.citation: J Clin Endocrinol Metab. 1999 Oct;84(10):3836-44
references.pmid: 10523039
references.citation: Pediatr Blood Cancer. 2009 Aug;53(2):261-6
references.pmid: 19326418
references.citation: Leukemia. 2010 Dec;24(12):2039-47
references.pmid: 20861916
references.citation: J Androl. 2006 Jul-Aug;27(4):527-33
references.pmid: 16598031