Xenotransplantation as a model for human testicular development

Hutka, Marsida; Smith, Lee B.; Mitchell, Rod

doi:10.1016/j.diff.2017.09.001

Cited by 18 publications

(18 citation statements)

References 105 publications

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“…However, xenografting studies using fetal human tissue have been performed. As recently reviewed (51) administering exogenous gonadotropin treatment to mouse hosts revealed the stimulation of epithelial maturation and spermatogenic induction in human testicular grafts. First trimester human fetal grafts from hCG treated hosts produced lower testosterone output while second trimester human fetal xenografts produced significantly increased levels of testosterone (52).…”

Section: Discussionmentioning

confidence: 99%

“…Hosts treated with higher dose (10 IU) of hCG demonstrate significantly increased body weights and seminal vesicle weights compared to non-treated and lower dose (1 IU) groups (36). These studies reveal that exogenous treatment of mouse hosts with gonadotropins affects steroid release and gonadal development from primate xenografts and can therefore be used as a preclinical experimental tool (51). …”

Section: Discussionmentioning

confidence: 99%

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Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the Sex and Status of the Mouse Host

Sharma¹,

Sandhowe-Klaverkamp²,

Schlatt³

2018

Front. Endocrinol.

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This study investigates the effects of the endocrine milieu of immunodeficient mouse host (intact vs. castrated male, intact male vs. intact female) on prepubertal marmoset (Callithrix jacchus) testicular xenografts. Previous marmoset xenografting studies used castrated nude mouse hosts which did not support efficient graft survival and maturation. Due to the distinct endocrine milieu in marmosets with a deletion of exon 10 in the LH receptor, we wanted to explore whether the most efficient xenograft development occurs in intact male mouse hosts compared to intact females or castrated males. We xenografted freshly isolated tissue from prepubertal marmosets (age range 4–6 months) into the back skin of three groups of nude mice (intact male, castrated male, and intact female). We collected serum for endocrine determinations and grafts after 20 weeks and determined hormonal/reproductive status, graft survival, somatic cell development and initiation of germ cell differentiation. Graft development, tubular integrity, and germ cell differentiation status in the grafts retrieved from different hosts was scored by morphometric analysis. The influence of the different endocrine status was compared between groups of hosts. Endocrine readouts and histological endpoints in xenografts substantiate that grafts were exposed to different microenvironments and responded with host specific developmental patterns. The intact male hosts supported the most significant progression of germ cell development. Our data provide evidence for the important role of the host milieu on survival and differentiation of marmoset xenografts. The xenografting model offers innovative avenues to exploit development and endocrine effects in the primate marmoset testis using limited numbers of non-human primates for the experimental settings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the Sex and Status of the Mouse Host

Sharma¹,

Sandhowe-Klaverkamp²,

Schlatt³

2018

Front. Endocrinol.

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“…For males, animal studies have provided proof of principle for successful generation of functional gametes in re-transplanted testis tissue. This has been shown using testis tissue from several species transplanted subcutaneously into castrate-recipient mice (Hutka et al 2017). This includes sperm generated in immature non-human primate xenografts (Honaramooz et al 2004, Liu et al 2016.…”

Section: Generation Of Functional Sperm In Animal Models Of Testiculamentioning

confidence: 99%

“…Research into the development and function of human testis xenografts has increased over recent decades, including the use of fetal, prepubertal and adult tissues (Hutka et al 2017). For prepubertal xenografts, in which spermatogonia are the only germ cell type identified in pre-biopsy tissue, the most advanced germ cell type identified were spermatocytes (Wyns et al 2008, Sato et al 2010, Poels et al 2013, Van Saen et al 2013, whilst for some studies no differentiation of spermatogonia was identified (Wyns et al 2007, Goossens et al 2008.…”

Section: Transplantation Of Human Testicular Tissuementioning

confidence: 99%

FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

Kilcoyne

Mitchell

2019

Reproduction

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Transplantation of testicular tissues and cells has been proposed as a future clinical option for patients who have had testicular tissue cryopreserved prior to receiving gonadotoxic therapies. Whilst this approach remains experimental, success using animal models and successful transplantation of ovarian tissue resulting in live births in female patients provides optimism for the development of clinical applications involving transplantation of testicular tissue in males. Careful consideration must be given to patient groups that may benefit from this approach in the future. Current research is focused on optimising patient selection, methods for tissue cryopreservation and development of transplantation techniques that might restore sperm production or future fertility in males. Crucially, attention must be focused on ensuring safety of transplantation, including eliminating the potential for infection or re-introducing malignancy. Furthermore the genetic/epigenetic integrity of any gametes generated must be ensured to allow generation of normal offspring. This review will provide an overview of the current status of transplantation of testicular tissue and cells for fertility preservation in males.Reproduction (2019) 158 F1-F14

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“…Current strategies for restoring fertility after testicular or spermatogonial stem cell cryopreservation include; autotransplantation, via intratesticular spermatogonial stem cell injection or testicular tissue thaw and surgical graft . Promising evidence exists in these areas, particularly in murine models …”

Section: Fertility Preservationmentioning

confidence: 99%

Survival from cancer in young people: An overview of late effects focusing on reproductive health

Newton

Friend

Feltbower

et al. 2019

Acta Obstet Gynecol Scand

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This paper provides a summary of the areas of survival from childhood, teenage and young adult cancers and the significant late effects that can arise from treatment; with particular focus on the area of reproductive health and the impact on both fertility and pregnancy. To complete this review, Web of Science and MEDLINE were used. Search terms included: “"survival AND childhood OR teenage OR young adult cancer", "late effects", "childhood cancer", "teenage AND/OR young adult cancer", AND "fertility after cancer" OR "pregnancy AND cancer" OR "fertility preservation”. Additionally, the clinical expertise of the authors was drawn upon. Childhood cancer is a thankfully rare occurrence; however, the incidence is increasing. Survival rates remain high and this means that a growing population of childhood and young adult cancer survivors are reaching adulthood. For some of these adults, although cured of their cancer, they are now facing a future with lasting effects on their health from their treatments. These effects, commonly referred to as late effects, are defined as health problems related either directly to the underlying cancer or to its treatment and which occur months or years after treatment has finished. Reproductive health is an important consideration for these patients, and although many will be able to conceive naturally, some will exhibit impaired fertility after their treatments. This can include difficulties at all points along the path from conception to delivery of a live, healthy offspring. High‐quality, large‐population evidence is sparse in many areas relating to fertility risk from treatment and the maternal and fetal health of childhood cancer survivors. Yet given the potential for complications, the authors advocate consideration of fertility at the time of diagnosis and before potentially gonadotoxic treatment.

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Xenotransplantation as a model for human testicular development

Cited by 18 publications

References 105 publications

Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the Sex and Status of the Mouse Host

Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the Sex and Status of the Mouse Host

FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

Survival from cancer in young people: An overview of late effects focusing on reproductive health

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