Germ cell development in equine testis tissue xenografted into mice

Abstract

Grafting of testis tissue from immature animals to immunodeficient mice results in complete spermatogenesis, albeit with varying efficiency in different species. The objectives of this study were to investigate if grafting of horse testis tissue would result in spermatogenesis, and to assess the effect of exogenous gonadotropins on xenograft development. Small fragments of testis tissue from 7 colts (2 week to 4 years of age) were grafted under the back skin of castrated male immunodeficient mice. For 2 donor animals, half of the mice were treated with gonadotropins. Xenografts were analyzed at 4 and 8 months post-transplantation. Spermatogenic differentiation following grafting ranged from no differentiation to progression through meiosis with appearance of haploid cells. Administration of exogenous gonadotropins appeared to support post-meiotic differentiation. For more mature donor testis samples where spermatogenesis had progressed into or through meiosis, after grafting an initial loss of differentiated germ cells was observed followed by a resurgence of spermatogenesis. However, if haploid cells had been present prior to grafting, spermatogenesis did not progress beyond meiotic division. In all host mice with spermatogenic differentiation in grafts, increased weight of the seminal vesicles compared to castrated mice showed that xenografts were releasing testosterone. These results indicate that horse spermatogenesis occurs in a mouse host albeit with low efficiency. In most cases, spermatogenesis arrested at meiosis. The underlying mechanisms of this spermatogenic arrest require further investigation.

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

“…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.…”

“…Therefore, in the castrated recipients, seminal vesicle development is commonly used as a marker for xenograft production of bioactive testosterone (Schlatt et al 2003;Rathi et al 2006;Schmidt et al 2006). The average weight of recipient seminal vesicles varied only slightly between the three youngest donor age groups (174.2 ± 41.2, 157.3 ± 53.7 and 215.0 ± 29.2 mg for 8-and 9-16-week-old and 5-7-month-old donors, respectively; Fig.…”

“…In addition, differences in the age of the donor may have effects on the ability of xenografts to support spermatogenesis. In most species, full spermatogenesis can be observed in xenografts from neonatal donors (Honaramooz et al 2002;Schlatt et al 2003;Snedaker et al 2004;Oatley et al 2005), whereas limited attempts with fully adult testicular tissue have not supported spermatogenesis (Geens et al 2006;Rathi et al 2006;Schlatt et al 2006). Beyond this broad division, only two studies have examined the effect of donor age on xenograft success.…”

Cryopreservation of Testicular Tissue

“…The approach has especially been successful using neonatal/immature donors (Fig. 5), from laboratory animals to domestic animals, primates, and even humans (Honaramooz et al, 2002aSchlatt et al, 2002;Oatley et al, 2004;Snedaker et al, 2004;Rathi et al, 2005Rathi et al, , 2006Arregui et al, 2008;Abrishami et al, 2010b). .…”

Can we grow sperm? A translational perspective on the current animal and human spermatogenesis models

“…Grafting of immature (neonatal) donor testis on an immunodeficient recipient mouse can lead to complete spermatogenesis and production of offspring using the mature sperm obtained from the graft (Figure 2). Successful xenografts of fresh and cryopreserved testicular tissue have been reported in a variety of species, including: mouse, 26,27 hamster, 28 rabbit, 29 pig, 30 goat, 26 sheep, 26,31 cattle, 32,33 cat, 34 horse 35 and nonhuman primates. 36 Although the risk of retroviral genetic contamination does exist using this xenograft model, consistent graft recovery and complete spermatogenesis have made this model a valuable tool for animal reproductive and toxicology studies.…”