Recent developments in testis tissue xenografting

Abstract

Development of the mammalian testis and spermatogenesis involve complex processes of cell migration, proliferation, differentiation, and cell-cell interactions. Although our knowledge of these processes has increased in the last few decades, many aspects still remain unclear. The lack of suitable systems that allow to recapitulate and manipulate both testis development and spermatogenesis ex situ has limited our ability to study these processes. In the last few years, two observations suggested novel strategies that will improve our ability to study and manipulate mammalian spermatogenesis: i) testis tissue from immature animals transplanted ectopically into immunodeficient mice is able to respond to mouse gonadotropins and to initiate and complete differentiation to the level where fertilization-competent sperm are obtained, and ii) isolated testis cells are able to organize and rearrange into seminiferous cords that subsequently undergo complete development, including production of viable sperm. The current paper reviews recent advances that have been obtained with both techniques that represent novel opportunities to explore testis development and spermatogenesis in diverse mammalian species.

Development of strips of ovine testes after xenografting under the skin of mice and co-transplantation of exogenous spermatogonia with grafts

“…Since the publication of the first reports, xenografting of testicular tissue has emerged as an attractive technology for preserving the genetics of valuable males and to study postnatal development of spermatogenesis (Rodriguez-Sosa & Dobrinski 2009). It is an especially economical way to study large animal spermatogenesis because multiple mice can be engrafted from a single testis, and these can be given different treatments and collected at multiple time points.…”

“…Engrafting of testicular tissue from newborns of a variety of species to immune-deficient mice has resulted in production of spermatozoa (Rodriguez-Sosa & Dobrinski 2009), although average percentage of tubules with spermatozoa has varied with species, notably from !15% in grafts from calves (Oatley et al 2004, Rathi et al 2005, Schmidt et al 2006a, 2006b) to 64% in grafts from sheep . The applications of xenografting of testicular tissue make it desirable that a high number of seminiferous tubules obtain full spermatogenesis.…”

Optimal dose of busulfan for depleting testicular germ cells of recipient mice before spermatogonial transplantation

“…During the past decade, spermatogonial transplantation has become a powerful tool for investigators to gain insight into the biology of male germline stem cells and their niche, to restore fertility in infertile animals and to produce transgenic animals with genetically modified germline cells. In addition, spermatogonial transplantation is a potentially powerful technique for assisted reproductive strategies [10,11].…”

Generation of macaques with sperm derived from juvenile monkey testicular xenografts

“…The testis tissue from young mammals, including mice and monkeys, is capable of undergoing complete spermatogenesis in xenografts, and sperms obtained from monkey testicular tissue xenografts have yielded monkey blastocysts after intracytoplasmic sperm injection (ICSI), although no successful production of primates has been reported [2][3][4]. Achieving the latter is important because of its potential implication for restoring fertility of young cancer patients undergoing radiotherapy and chemotherapy.…”