Genetic and Epigenetic Changes After Spermatogonial Stem Cell Culture and Transplantation.
Men with testicular failure, either primary or secondary, have been shown to be interested in fertility preservation. Spermatogonial stem cell (SSC) transplantation is currently being investigated as a treatment for this. Currently this experimental technique consists of cryopreservation of a testicular biopsy prior to cancer treatment, followed by optional in vitro expansion of SSCs and auto transplantation after cancer treatment. This technique may restore the pool of SSCs resulting in restoration of spermatogenesis. While this technique has not been applied to humans due to its highly experimental nature and concerns of malignant contamination, animal studies have been successful. While the offspring obtained from SSCs appear to be healthy in rodent models, there is relatively little data on any genetic and epigenetic changes that occur in either the transplanted SSCs or offspring. In humans, male germ cells undergo unique and extensive chromatin and epigenetic remodeling soon after their destiny as a spermatocyte has been secured. Errors in this remodeling may cause altered genetic information to be transmitted to offspring, resulting in abnormalities. This is particularly pertinent for cancer patients as SSCs obtained from these men may have a predisposition for genetic instability even prior to starting gonadotoxic therapies. In this article, landmarks in the evolution of SSC transplantation are reviewed, along with presently known genetic, epigenetic, and imprinting abnormalities that may occur after in vitro propagation and transplantation.
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto , Toronto, Ontario, Canada.
Mary K
MK
Samplaski
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto , Toronto, Ontario, Canada.
Marie
M
Deault-Bonin
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Kirk C
KC
Lo
Epigenetic; Fertility preservation; Genetic; Spermatogonial; Stem cel
Hum Reprod. 2010 Jul;25(7):1836-42
20488806
Science. 2001 Jul 6;293(5527):95-7
11441181
Mol Hum Reprod. 2008 Feb;14(2):67-74
18178607
Nature. 1993 Apr 22;362(6422):747-9
8385745
Hum Reprod. 2009 Sep;24(9):2255-63
19525299
Reprod Biomed Online. 2011 Aug;23(2):160-86
21676653
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11298-302
7972053
Biol Reprod. 2003 Aug;69(2):612-6
12700182
Hum Mol Genet. 2007 Nov 1;16(21):2542-51
17636251
Hum Reprod. 1991 Aug;6(7):992-4
1761672
Hum Reprod Update. 2010 May-Jun;16(3):312-28
20047952
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10567-70
12149477
J Cell Sci. 2002 Jun 1;115(Pt 11):2381-8
12006622
Nat Biotechnol. 2002 Jul;20(7):675-81
12089551
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3586-90
11891338
JAMA. 2009 Nov 18;302(19):2127-34
19920237
Hum Reprod. 2002 Dec;17(12):3039-45
12456600
Mol Hum Reprod. 2010 Jan;16(1):37-47
19906823
Theriogenology. 2010 Jan;73(1):86-96
19853904
Hum Reprod. 2009 Oct;24(10):2457-67
19561041
Hum Reprod. 2001 Jun;16(6):1191-9
11387291
Development. 2005 Sep;132(18):4155-63
16107472
Biomaterials. 1996 Feb;17(3):243-56
8745321
Hum Reprod. 2008 Nov;23(11):2402-14
18664476
Hum Reprod. 2011 Dec;26(12):3388-400
21984576
Hum Reprod. 2013 Mar;28(3):578-89
23315062
Hum Reprod. 2003 Sep;18(9):1874-80
12923142
Nat Biotechnol. 2004 Jan;22(1):53-4
14661028
J Clin Oncol. 2006 Jun 20;24(18):2917-31
16651642
Fertil Steril. 2012 May;97(5):1152-7.e1-2
22369773
Hum Reprod. 2013 Jul;28(7):1816-26
23569082
Adv Exp Med Biol. 2014;791:53-66
23955672
Int J Androl. 2010 Aug 1;33(4):642-9
19878521
Fertil Steril. 2010 Mar 1;93(4):1147-56
19135665
Development. 1998 Jun;125(12):2273-82
9584126
Fertil Steril. 2011 May;95(6):2123.e9-12
21300331
Reprod Fertil Dev. 2009;21(3):489-97
19261226
Biol Reprod. 2000 Jun;62(6):1526-35
10819752
Fertil Steril. 2011 Mar 15;95(4):1229-34.e1
20541745
Hum Reprod. 2006 Aug;21(8):2057-60
16601006
Mutat Res. 1993 Dec;290(2):193-200
7694110
Hum Reprod Update. 2008 Mar-Apr;14(2):121-30
18187526
J Assist Reprod Genet. 2012 Sep;29(9):943-50
22692281
JAMA. 2011 Jun 15;305(23):2416-8
21673293
Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1595-600
14747652
Hum Reprod. 2002 Jan;17(1):55-62
11756362
Theriogenology. 2012 Mar 15;77(5):1008-13
22153273
Fertil Steril. 2012 Aug;98(2):284-9
22608314
PLoS One. 2009 Nov 19;4(11):e7909
19936070
Biol Reprod. 2009 Mar;80(3):518-27
19020300
Hum Reprod. 2004 Dec;19(12):2702-10
15489240
J Clin Oncol. 2002 Apr 1;20(7):1880-9
11919248
Transgenic Res. 1997 Sep;6(5):321-8
9322369
J Cell Mol Med. 2011 Mar;15(3):468-83
21155977
Int J Androl. 1999 Jun;22(3):155-62
10367235
Biol Reprod. 2008 Apr;78(4):681-7
18199882
Nat Med. 1996 Jun;2(6):693-6
8640563
Hum Reprod. 2011 Feb;26(2):282-93
21123192
Hum Reprod. 2006 Jul;21(7):1759-64
16495303
Cell Res. 2011 Aug;21(8):1164-71
21747415
PLoS One. 2013 Jun 21;8(6):e67614
23805321
Hum Reprod. 2003 Dec;18(12):2660-7
14645188
Hum Reprod. 2012 May;27(5):1249-59
22416011
Methods Mol Biol. 2008;450:109-18
18370054