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.
Publication Date: 2006-06-01 PubMed ID: 16735548DOI: 10.1530/rep.1.01101Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research examines the development of horse testis tissue grafted into immunodeficient mice with or without exogenous gonadotropins. The results show that horse spermatogenesis does occur in a mouse host but generally stops at meiosis.
Research Methodology
- Testis tissue from seven young horses aged 2 weeks to 4 years old were grafted onto castrated, immunodeficient mice. Half of these mice were treated with gonadotropins for two of the donor horses.
- Xenografts were analyzed 4 and 8 months following the transplantation procedure.
Research Findings
- The study found that spermatogenic differentiation, or the development from germ cells to mature sperm cells, varied after the grafting. In some instances, no differentiation was observed, while in others, haploid cells emerged as a result of the meiotic process.
- Results showed that gonadotropins seem to promote post-meiotic differentiation where maturation of sperms occurred after the division of the cells.
- The researchers observed an initial loss of differentiated germ cells after grafting in the more mature horse testis samples, but then a subsequent resurgence in spermatogenesis. If haploid cells were already present before grafting, the process did not progress beyond the meiotic cell division.
Impact of the Research
- In all host mice demonstrating spermatogenic differentiation, a notable increase in the weight of the seminal vesicles (suggesting the release of testosterone) was observed, as compared to the castrated mice. This finding indicates functioning testosterone production by the grafted testis tissues.
- However, the efficiency of horse spermatogenesis in a mouse host was found to be low. In most cases, the sperm cell development arrested at the meiosis stage. The researchers recommend further investigation into the underlying mechanisms of this developmental arrest.
Cite This Article
APA
Rathi R, Honaramooz A, Zeng W, Turner R, Dobrinski I.
(2006).
Germ cell development in equine testis tissue xenografted into mice.
Reproduction, 131(6), 1091-1098.
https://doi.org/10.1530/rep.1.01101 Publication
Researcher Affiliations
- Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, 19348, USA.
MeSH Terms
- Animals
- Gonadotropins, Equine / pharmacology
- Graft Survival
- Male
- Meiosis
- Mice
- Mice, SCID
- Orchiectomy
- Seminiferous Tubules / growth & development
- Spermatogenesis
- Spermatozoa / cytology
- Testis / metabolism
- Testis / transplantation
- Testosterone / biosynthesis
- Transplantation, Heterologous
Citations
This article has been cited 40 times.- Quach CC, Fulton JE, Benson JD, Walker P, Auckland C, Lessard C. Major Histocompatibility Complex-B haplotype and ovarian graft response. Poult Sci 2023 Sep;102(9):102850.
- Horvath-Pereira BO, Almeida GHDR, da Silva Júnior LN, do Nascimento PG, Horvath Pereira BO, Fireman JVBT, Pereira MLDRF, Carreira ACO, Miglino MA. Biomaterials for Testicular Bioengineering: How far have we come and where do we have to go?. Front Endocrinol (Lausanne) 2023;14:1085872.
- Eugeni E, Arato I, Del Sordo R, Sidoni A, Garolla A, Ferlin A, Calafiore R, Brancorsini S, Mancuso F, Luca G. Fertility Preservation and Restoration Options for Pre-Pubertal Male Cancer Patients: Current Approaches. Front Endocrinol (Lausanne) 2022;13:877537.
- Tran KTD, Valli-Pulaski H, Colvin A, Orwig KE. Male fertility preservation and restoration strategies for patients undergoing gonadotoxic therapies†. Biol Reprod 2022 Aug 9;107(2):382-405.
- Teves ME, Roldan ERS. Sperm bauplan and function and underlying processes of sperm formation and selection. Physiol Rev 2022 Jan 1;102(1):7-60.
- Huleihel M, Lunenfeld E. Approaches and Technologies in Male Fertility Preservation. Int J Mol Sci 2020 Jul 31;21(15).
- Goossens E, Jahnukainen K, Mitchell RT, van Pelt A, Pennings G, Rives N, Poels J, Wyns C, Lane S, Rodriguez-Wallberg KA, Rives A, Valli-Pulaski H, Steimer S, Kliesch S, Braye A, Andres MM, Medrano J, Ramos L, Kristensen SG, Andersen CY, Bjarnason R, Orwig KE, Neuhaus N, Stukenborg JB. Fertility preservation in boys: recent developments and new insights (†). Hum Reprod Open 2020;2020(3):hoaa016.
- Goel S, Minami N. Altered hormonal milieu and dysregulated protein expression can cause spermatogenic arrest in ectopic xenografted immature rat testis. Sci Rep 2019 Mar 11;9(1):4036.
- Ntemou E, Kadam P, Van Saen D, Wistuba J, Mitchell RT, Schlatt S, Goossens E. Complete spermatogenesis in intratesticular testis tissue xenotransplants from immature non-human primate. Hum Reprod 2019 Mar 1;34(3):403-413.
- Del Vento F, Vermeulen M, de Michele F, Giudice MG, Poels J, des Rieux A, Wyns C. Tissue Engineering to Improve Immature Testicular Tissue and Cell Transplantation Outcomes: One Step Closer to Fertility Restoration for Prepubertal Boys Exposed to Gonadotoxic Treatments. Int J Mol Sci 2018 Jan 18;19(1).
- Devi L, Pothana L, Goel S. Dysregulation of angiogenesis-specific signalling in adult testis results in xenograft degeneration. Sci Rep 2017 Jun 1;7(1):2605.
- Zeng W, Alpaugh W, Stefanovski D, Schlingmann K, Dobrinski I, Turner RM. Xenografting of isolated equine (Equus caballus) testis cells results in de novo morphogenesis of seminiferous tubules but not spermatogenesis. Andrology 2017 Mar;5(2):336-346.
- Pukazhenthi BS, Nagashima J, Travis AJ, Costa GM, Escobar EN, França LR, Wildt DE. Slow freezing, but not vitrification supports complete spermatogenesis in cryopreserved, neonatal sheep testicular xenografts. PLoS One 2015;10(4):e0123957.
- Poels J, Abou-Ghannam G, Herman S, Van Langendonckt A, Wese FX, Wyns C. In Search of Better Spermatogonial Preservation by Supplementation of Cryopreserved Human Immature Testicular Tissue Xenografts with N-acetylcysteine and Testosterone. Front Surg 2014;1:47.
- Wyns C. Male fertility preservation before gonadotoxic therapies. Facts Views Vis Obgyn 2010;2(2):88-108.
- Arregui L, Dobrinski I. Xenografting of testicular tissue pieces: 12 years of an in vivo spermatogenesis system. Reproduction 2014 Nov;148(5):R71-84.
- Lim JJ, Seol DW, Choi KH, Shin DH, Kim HJ, Song SH, Lee DR. Spermatogonial stem cell enrichment using simple grafting of testis and in vitro cultivation. Sci Rep 2014 Aug 1;4:5923.
- Van Saen D. In search of the most efficient fertility preservation strategy for prepubertal boys. Facts Views Vis Obgyn 2013;5(1):45-58.
- Kaneko H, Kikuchi K, Nakai M, Somfai T, Noguchi J, Tanihara F, Ito J, Kashiwazaki N. Generation of live piglets for the first time using sperm retrieved from immature testicular tissue cryopreserved and grafted into nude mice. PLoS One 2013;8(7):e70989.
- Arregui L, Dobrinski I, Roldan ER. Germ cell survival and differentiation after xenotransplantation of testis tissue from three endangered species: Iberian lynx (Lynx pardinus), Cuvier's gazelle (Gazella cuvieri) and Mohor gazelle (G. dama mhorr). Reprod Fertil Dev 2014;26(6):817-26.
- Jahnukainen K, Ehmcke J, Nurmio M, Schlatt S. Autologous ectopic grafting of cryopreserved testicular tissue preserves the fertility of prepubescent monkeys that receive sterilizing cytotoxic therapy. Cancer Res 2012 Oct 15;72(20):5174-8.
- Rodriguez-Sosa JR, Costa GM, Rathi R, França LR, Dobrinski I. Endocrine modulation of the recipient environment affects development of bovine testis tissue ectopically grafted in mice. Reproduction 2012 Jul;144(1):37-51.
- Arregui L, Rathi R, Modelski M, Zeng W, Roldan ER, Dobrinski I. Suppression of spermatogenesis before grafting increases survival and supports resurgence of spermatogenesis in adult mouse testis. Fertil Steril 2012 Jun;97(6):1422-9.
- Tang L, Rodriguez-Sosa JR, Dobrinski I. Germ cell transplantation and testis tissue xenografting in mice. J Vis Exp 2012 Feb 6;(60).
- Lo KC, Domes T. Can we grow sperm? A translational perspective on the current animal and human spermatogenesis models. Asian J Androl 2011 Sep;13(5):677-82.
- Gourdon JC, Travis AJ. Spermatogenesis in ferret testis xenografts: a new model. Comp Med 2011 Apr;61(2):145-9.
- Fortier LA, Travis AJ. Stem cells in veterinary medicine. Stem Cell Res Ther 2011 Feb 23;2(1):9.
- Zeng W, Baumann C, Schmidtmann A, Honaramooz A, Tang L, Bondareva A, Dores C, Fan T, Xi S, Geiman T, Rathi R, de Rooij D, De La Fuente R, Muegge K, Dobrinski I. Lymphoid-specific helicase (HELLS) is essential for meiotic progression in mouse spermatocytes. Biol Reprod 2011 Jun;84(6):1235-41.
- Honaramooz A, Yang Y. Recent advances in application of male germ cell transplantation in farm animals. Vet Med Int 2010 Oct 4;2011.
- Mota PC, Ramalho-Santos J, Schlatt S. Xenografting as a tool to preserve endangered species: outcomes and challenges in model systems. Vet Med Int 2010 Sep 2;2011.
- Abbasi S, Honaramooz A. The number of grafted fragments affects the outcome of testis tissue xenografting from piglets into recipient mice. Vet Med Int 2010 Aug 4;2011.
- Dobrinski I. De novo morphogenesis of functional testis tissue after ectopic transplantation of isolated cells. Organogenesis 2007 Oct;3(2):79-82.
- Honaramooz A, Cui XS, Kim NH, Dobrinski I. Porcine embryos produced after intracytoplasmic sperm injection using xenogeneic pig sperm from neonatal testis tissue grafted in mice. Reprod Fertil Dev 2008;20(7):802-7.
- Rathi R, Zeng W, Megee S, Conley A, Meyers S, Dobrinski I. Maturation of testicular tissue from infant monkeys after xenografting into mice. Endocrinology 2008 Oct;149(10):5288-96.
- Arregui L, Rathi R, Zeng W, Honaramooz A, Gomendio M, Roldan ER, Dobrinski I. Xenografting of adult mammalian testis tissue. Anim Reprod Sci 2008 Jun;106(1-2):65-76.
- Anvari A, Movahedin M, Ganji F. Comparing transplantation sites of mouse immature testicular tissue fragments embedded in chitosan scaffold to maintain tissue integrity: Epididymal fat pad or under the back skin. Iran J Basic Med Sci 2025;28(12):1706-1714.
- Damyanova KB, Nixon B, Johnston SD, Gambini A, Benitez PP, Lord T. Spermatogonial stem cell technologies: applications from human medicine to wildlife conservation†. Biol Reprod 2024 Oct 14;111(4):757-779.
- Asgenbaatar N, Yi M, Wang X, Ulaangerel T, Shen Y, Wen X, Du M, Dong X, Mengkh Y, Dugarjav M, Bou G. Optimizing the preparation of paraffin sections from stallion testes. Histol Histopathol 2025 Mar;40(3):335-342.
- Sung ZY, Liao YQ, Hou JH, Lai HH, Weng SM, Jao HW, Lu BJ, Chen CH. Advancements in fertility preservation strategies for pediatric male cancer patients: a review of cryopreservation and transplantation of immature testicular tissue. Reprod Biol Endocrinol 2024 Apr 18;22(1):47.
- Anvari A, Movahedin M, Hamzeh M. Optimizing Immature Testicular Tissue and Cell Transplantation Results: Comparing Transplantation Sites and Scaffolds. Int J Fertil Steril 2023 Nov 1;18(1):12-19.
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