Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination

Shinohara, Takashi; Inoue, Kimiko; Ogonuki, Narumi; Kanatsu-Shinohara, Mito; Miki, Hiromi; Nakata, Kumiko; Kurome, Mayuko; Nagashima, Hiroshi; Toyokuni, Shinya; Kogishi, Kumiko; Honjo, Tasuku; Ogura, Atsuo

doi:10.1093/humrep/17.12.3039

Cited by 242 publications

(201 citation statements)

References 40 publications

(56 reference statements)

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“…Mammalian testis tissue xenografted into mice has resulted in production of viable spermatozoa (Snedaker et al 2004) that are capable of fertilization (Honaramooz et al 2002, Shinohara et al 2002, Schlatt et al 2003. Spermatogenesis in bovine testis tissue xenografts has not been very efficient, with only 5 -10% of seminiferous tubules producing elongated spermatids (Oatley et al 2004(Oatley et al , 2005.…”

Section: Introductionmentioning

confidence: 99%

Germ cell fate and seminiferous tubule development in bovine testis xenografts

Rathi¹,

Honaramooz²,

Zeng³

et al. 2005

Reproduction

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Spermatogenesis can occur in testis tissue from immature bulls ectopically grafted into mouse hosts; however, efficiency of sperm production is lower than in other donor species. To elucidate a possible mechanism for the impaired spermatogenesis in bovine testis xenografts, germ cell fate and xenograft development were investigated at different time points and compared with testis tissue from age-matched calves as controls. Histologically, an initial decrease in germ cell number was noticed in xenografts recovered up to 2 months post-grafting without an increase in germ cell apoptosis. From 2 months onward, the number of germ cells increased. In contrast, a continuous increase in germ cell number was seen in control tissue. Pachytene spermatocytes were observed in some grafts before 4 months, whereas in the control tissue they were not present until 5 months of age. Beyond 4 months post-grafting spermatogenesis appeared to be arrested at the pachytene spermatocyte stage in most grafts. Elongated spermatids were observed between 6 and 8 months post-grafting, similar to the controls, albeit in much lower numbers. Lumen formation started earlier in grafts compared with controls and by 6 months post-grafting tubules with extensively dilated lumen were observed. A donor effect on efficiency of spermatogenesis was also observed. These results indicate that the low efficiency of sperm production in bovine xenografts is due to an initial deficit of germ cells and impaired meiotic and post-meiotic differentiation. The characterization of spermatogenic efficiency will provide the basis to understand the control of spermatogenesis in testis grafts.

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Section: Introductionmentioning

confidence: 99%

Germ cell fate and seminiferous tubule development in bovine testis xenografts

Rathi¹,

Honaramooz²,

Zeng³

et al. 2005

Reproduction

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“…There have been several reports of animal experiments based on such an idea 3,[5][6][7] . These reports demonstrated the efficacy of testis tissue cryopreservation as a means to preserve fertility.…”

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confidence: 99%

Offspring production with sperm grown in vitro from cryopreserved testis tissues

et al. 2014

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With the increasing cure rate of paediatric cancers, infertility, as one of the adverse effects of treatments, has become an important concern for patients and their families. Since semen cryopreservation is applicable only for post-pubertal patients, alternative pre-pubertal measures are necessary. Here we demonstrate that testis tissue cryopreservation is a realistic measure for preserving the fertility of an individual. Testis tissues of neonatal mice were cryopreserved either by slow freezing or by vitrification. After thawing, they were cultured on agarose gel and showed spermatogenesis up to sperm formation. Microinsemination was performed with round spermatids and sperm, leading to eight offspring in total. They grew healthily and produced progeny upon natural mating between them. This strategy, the cryopreservation of testis tissues followed by in vitro spermatogenesis, is promising to preserve the fertility of male paediatric cancer patients in the future.

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“…Ectopic testis xenografting has been performed using many different species as donors (Honaramooz et al 2002;Schlatt et al 2002Schlatt et al , 2006Shinohara et al 2002;Snedaker et al 2004;Oatley et al 2005;Rathi et al 2006). However, as noted above, there have been great discrepancies between species in terms of the timing of xenograft spermatozoa production v. that seen under normal physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…This technique is performed by transplanting millimetre-sized pieces of testis tissue from a variety of species into immunodeficient mice, in which the xenografts can grow and produce sperm of the donor species. It has been performed with tissue from various donor species, including pigs and goats (Honaramooz et al 2002), hamster and monkey (Schlatt et al 2002), cattle (Oatley et al 2005;Rathi et al 2005), rabbits (Shinohara et al 2002), cats (Snedaker et al 2004), humans (Schlatt et al 2006) and horses .…”

Section: Introductionmentioning

confidence: 99%

Effect of donor age on success of spermatogenesis in feline testis xenografts

Kim

Selvaraj

Pukazhenthi

et al. 2007

Reprod. Fertil. Dev.

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Abstract. Ectopic xenografting of 'donor' feline testicular tissue into a 'recipient' immunodeficient mouse is a promising tool to preserve the male genome from genetically valuable felids. To define parameters under which the technique can succeed, we compared the effect of donor age on xenograft spermatogenesis among four age groups of domestic cats (Felis catus; age range 8 weeks to 15 months). In all cases, fresh tissue was grafted into castrated mice and collected 10, 30 and 50 weeks later. The percentage of xenografts recovered decreased as donor age increased. Mature testicular spermatozoa were observed in xenografts from the 8 and 9-16 week age groups; only a single 7-month-old donor produced elongating spermatids and xenografts from donors ≥8 months of age degenerated. Seminal vesicle weight, an indicator of bioactive testosterone, was not significantly different between donors aged 8 weeks to 7 months and controls, suggesting that xenograft Leydig cells were ultimately functional even in the 5-7 month age group. Regardless of donor age, production of mature spermatozoa from xenografts was markedly delayed compared with controls. Comparison of xenografts that produced sperm with normal controls revealed a decrease in tubule cross-sections having post-meiotic germ cells. Together, these results indicate that the maximum practical donor age was just before the onset of puberty and that even successful xenografts had abnormalities in spermatogenesis.

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Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination

Abstract: This approach of 'testicular tissue banking' is a promising technique for the preservation of fertility in prepubertal male oncology patients. Xenogeneic transplantation into immunodeficient mice may provide a system for studying spermatogenic failure in infertile men.

Cited by 242 publications

References 40 publications

Germ cell fate and seminiferous tubule development in bovine testis xenografts

Germ cell fate and seminiferous tubule development in bovine testis xenografts

Offspring production with sperm grown in vitro from cryopreserved testis tissues

Effect of donor age on success of spermatogenesis in feline testis xenografts

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