Journal
JOURNAL OF CLINICAL MEDICINE
Volume 9, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/jcm9010266
Keywords
Sertoli cell; Leydig cell; steroidogenesis; hCG; human fetal testis; xenotransplantation; fertility preservation; oncofertility
Categories
Funding
- ITN Marie Sklodowska-Curie programme 'Growsperm' [EU-FP7-PEOPLE-2013-ITN 603568]
- Wellcome Trust Intermediate Clinical Fellowship [098522]
- UK Research and Innovation (UKRI) Future Leaders Fellowship [MR/S017151/1]
- Children with Cancer UK [15-198]
- Swedish Childhood Cancer Foundation [TJ2016-0093]
- [MR/N022556/1]
- MRC [MR/N022556/1] Funding Source: UKRI
- UKRI [MR/S017151/1] Funding Source: UKRI
Ask authors/readers for more resources
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 similar to 12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3x/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barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months.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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available