Transplantation of germ cells and testis tissue for the study and preservation of fertility.

Center for Animal Transgenesis and Germ Cell Research, 145 Myrin Bldg., New Bolton Center, School of Veterinary Medicine. University of Pennsylvania, 382 West Street Rd., Kennett Square, PA 19348, USA.
Society of Reproduction and Fertility supplement 02/2007; 65:447-58.
Source: PubMed

ABSTRACT The germ line stem cells in the mammalian testis form the basis of male fertility. When these stem cells are transplanted from the testis of a fertile donor animal to the testis of an infertile recipient they can establish donor-derived spermatogenesis in the recipient testis, and the resulting sperm can transmit the genotype of the donor to the offspring of the recipient. Germ cell transplantation provides a system to study the biology of germ line stem cells, to explore stem cell isolation and culture, to examine defects in spermatogenesis and to overcome male infertility. Although most widely studied in rodents, germ cell transplantation is now applied to larger mammals, including primates. Germ cell transplantation can preserve fertility from valuable animals and potentially restore fertility in patients that underwent cytotoxic treatments for cancer. In addition, genetic manipulation of germ cells prior to transplantation provides a new approach to germ line modification and transgenesis. As an alternative to transplantation of isolated germ cells to a recipient testis, ectopic grafting of testis tissue from diverse mammalian donor species, including primates, into a mouse host represents a model to study spermatogenesis, to investigate the effects of substances with the potential to enhance or suppress male fertility, and to produce fertile sperm from immature donors. Therefore, transplantation of germ cells or testis tissue are uniquely valuable approaches for the study, preservation and manipulation of male fertility in mammalian species.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Spermatogonial stem cells open novel strategies for preservation of testicular tissue and fertility preservation in boys and men exposed to gonadotoxic therapies. This review provides an update on the physiology of spermatogonial stem cells in rodent and primate testes. Species-specific differences must be considered when new technologies on testicular stem cells are considered. Germ cell transplantation is presented as one novel and promising strategy. Whereas this technique has become an important research tool in rodents, a clinical application must still be regarded as experimental and many aspects of the procedure need to be optimized prior to a safe and efficient clinical application in men. Testicular grafting opens another exciting strategy for fertility preservation. Autologous and xenologous transfer of immature tissue revealed a high regenerative potential of immature testicular tissue. Grafting was applied in rodents and primates and resulted in the generation of sperm. Further research is needed before an application in humans can be considered safe and efficient. Despite the current limitations in regard to the generation of sperm from cryopreserved male germline cells and tissues, protocols for cryopreservation of testicular tissue are available and reveal a promising outcome. Since future improvements of germ cell transplantation and grafting approaches can be assumed, bioptic retrieval and cryopreservation of testicular tissue fragments should be performed in oncological patients at high risk of fertility loss since this is their only option to maintain their fertility potential.
    Pediatric Blood & Cancer 06/2009; 53(2):274-80. · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review describes the regulation of spermatogenesis taking into consideration the hypothalamic-pituitary gonadal axis, the male reproductive organs and the endocrine and paracrine factors involved in the control of sperm production and the release of androgens. Instead of detailed descriptions of many hormones and growth factors, we attempt to provide an integrative and evolutionary view by comparing different species and considering their specific needs for successful male reproduction. The review focuses on species specific differences in the structural organization of spermatogenesis and indicates that the crucial regulatory mechanisms controlling sperm output are targeted towards differentiating spermatogonia when they initiate clonal expansion. We argue that the further differentiation of germ cells is following a highly coordinated and strictly predetermined morphogenetic cascade widely independent of hormonal control. We propose a hypothetical "ancient" model. Spermatogenesis and steroidogenesis are controlled by a master switch (GnRH pulse generator) under whose control two separate feedback systems provide independent control of androgen (LH-testosterone) and sperm production (FSH-inhibin). This scenario offers high flexibility and has seen uncountable adaptions to optimize the specific needs of different species. Models for the hormonal regulation in hamsters, laboratory rodents and primates are presented to illustrate the species specific diversity.
    Seminars in Cell and Developmental Biology 03/2014; · 6.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In cattle,assisted reproductive technologies (ART) can be defined as techniques that manipulate reproductive-related events and/or structures to achieve pregnancy with the final goal of producing healthy offspring in bovine females. The present review includes manipulation of female reproductive tract physiology, artificial insemination, multiple ovulation and embryo transfer, in vitro production of embryos, in vitro assisted fertilization, cloning, transgenesis, xenografting-germ cell transplantation, preimplantation genetic diagnosis and sperm sexing. This review shows that several ART are being currently applied commercially in the cattle industry with acceptable results. On the other hand, others have low efficiency in producing cattle offspring and are predominantly applied in experimental settings. Several of these ART can cause detrimental effects at the prenatal and postnatal period and therefore they need to be improved. However, even if thesebovine-related biotechnologies are properly improved, they might be more useful in the conservation of endangered ungulates, production of pharmaceuticals, or as experimental models for human reproduction.
    Annual Review of Biomedical Sciences. 02/2008;