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Open AccessArticle

Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

1
Medical Research Council (MRC) Centre for Reproductive Health, The University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
2
School of Environmental and Life Sciences, University of Newcastle, Callaghan 2308, Australia
3
Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium
4
Department of Oncology and Haematology, Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK
5
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet and Karolinska University Hospital, Solna SE-17164, Sweden
6
Department of Diabetes and Endocrinology, Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 266; https://doi.org/10.3390/jcm9010266
Received: 6 December 2019 / Revised: 10 January 2020 / Accepted: 13 January 2020 / Published: 18 January 2020
(This article belongs to the Special Issue Approach to Male Infertility and Induction of Spermatogenesis)
The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application. View Full-Text
Keywords: Sertoli cell; Leydig cell; steroidogenesis; hCG; human fetal testis; xenotransplantation; fertility preservation; oncofertility Sertoli cell; Leydig cell; steroidogenesis; hCG; human fetal testis; xenotransplantation; fertility preservation; oncofertility
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MDPI and ACS Style

Hutka, M.; Smith, L.B.; Goossens, E.; Wallace, W.H.B.; Stukenborg, J.-B.; Mitchell, R.T. Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation. J. Clin. Med. 2020, 9, 266. https://doi.org/10.3390/jcm9010266

AMA Style

Hutka M, Smith LB, Goossens E, Wallace WHB, Stukenborg J-B, Mitchell RT. Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation. Journal of Clinical Medicine. 2020; 9(1):266. https://doi.org/10.3390/jcm9010266

Chicago/Turabian Style

Hutka, Marsida; Smith, Lee B.; Goossens, Ellen; Wallace, W. H.B.; Stukenborg, Jan-Bernd; Mitchell, Rod T. 2020. "Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation" J. Clin. Med. 9, no. 1: 266. https://doi.org/10.3390/jcm9010266

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