Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation
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 maturati...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-01-01
|
Series: | Journal of Clinical Medicine |
Subjects: | |
Online Access: | https://www.mdpi.com/2077-0383/9/1/266 |
id |
doaj-64c0b3f1e0084c97ae1939985ac0705d |
---|---|
record_format |
Article |
spelling |
doaj-64c0b3f1e0084c97ae1939985ac0705d2020-11-25T00:36:20ZengMDPI AGJournal of Clinical Medicine2077-03832020-01-019126610.3390/jcm9010266jcm9010266Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility PreservationMarsida Hutka0Lee B. Smith1Ellen Goossens2W. Hamish B. Wallace3Jan-Bernd Stukenborg4Rod T. Mitchell5Medical Research Council (MRC) Centre for Reproductive Health, The University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UKMedical Research Council (MRC) Centre for Reproductive Health, The University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UKBiology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumDepartment of Oncology and Haematology, Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UKNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet and Karolinska University Hospital, Solna SE-17164, SwedenMedical Research Council (MRC) Centre for Reproductive Health, The University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UKThe 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 (<i>n</i> = 9, 1 year-adult). Human fetal testis (<i>n</i> = 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.https://www.mdpi.com/2077-0383/9/1/266sertoli cellleydig cellsteroidogenesishcghuman fetal testisxenotransplantationfertility preservationoncofertility |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marsida Hutka Lee B. Smith Ellen Goossens W. Hamish B. Wallace Jan-Bernd Stukenborg Rod T. Mitchell |
spellingShingle |
Marsida Hutka Lee B. Smith Ellen Goossens W. Hamish B. Wallace Jan-Bernd Stukenborg Rod T. Mitchell Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation Journal of Clinical Medicine sertoli cell leydig cell steroidogenesis hcg human fetal testis xenotransplantation fertility preservation oncofertility |
author_facet |
Marsida Hutka Lee B. Smith Ellen Goossens W. Hamish B. Wallace Jan-Bernd Stukenborg Rod T. Mitchell |
author_sort |
Marsida Hutka |
title |
Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation |
title_short |
Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation |
title_full |
Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation |
title_fullStr |
Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation |
title_full_unstemmed |
Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation |
title_sort |
exogenous gonadotrophin stimulation induces partial maturation of human sertoli cells in a testicular xenotransplantation model for fertility preservation |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-01-01 |
description |
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 (<i>n</i> = 9, 1 year-adult). Human fetal testis (<i>n</i> = 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. |
topic |
sertoli cell leydig cell steroidogenesis hcg human fetal testis xenotransplantation fertility preservation oncofertility |
url |
https://www.mdpi.com/2077-0383/9/1/266 |
work_keys_str_mv |
AT marsidahutka exogenousgonadotrophinstimulationinducespartialmaturationofhumansertolicellsinatesticularxenotransplantationmodelforfertilitypreservation AT leebsmith exogenousgonadotrophinstimulationinducespartialmaturationofhumansertolicellsinatesticularxenotransplantationmodelforfertilitypreservation AT ellengoossens exogenousgonadotrophinstimulationinducespartialmaturationofhumansertolicellsinatesticularxenotransplantationmodelforfertilitypreservation AT whamishbwallace exogenousgonadotrophinstimulationinducespartialmaturationofhumansertolicellsinatesticularxenotransplantationmodelforfertilitypreservation AT janberndstukenborg exogenousgonadotrophinstimulationinducespartialmaturationofhumansertolicellsinatesticularxenotransplantationmodelforfertilitypreservation AT rodtmitchell exogenousgonadotrophinstimulationinducespartialmaturationofhumansertolicellsinatesticularxenotransplantationmodelforfertilitypreservation |
_version_ |
1725305912430690304 |