Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Graft Recovery Rate and Graft Weight
2.2. Histological Evaluation and Localisation of Prepubertal Human Testis Grafts
2.3. Effect of Exogenous Gonadotrophins on Steroidogenesis in Prepubertal Human Testis Grafts
2.4. Effect of Exogenous Gonadotrophins on Sertoli Cell Maturation
2.4.1. Expression of AR and AMH in Prepubertal Human Testis Grafts
2.4.2. Expression of SOX9 and Ki67 in Prepubertal Human Testis Grafts
2.4.3. Expression of CX43 and CLDN11 in Prepubertal Human Testis Grafts
2.5. Effect of Exogenous Gonadotrophins on Germ Cell Survival in Prepubertal Human Testis Grafts
3. Discussion
4. Materials and Methods
4.1. Ethics Statement
4.2. Animals
4.3. Subcutaneous Grafting Procedure
4.4. Intratesticular Grafting Procedure
4.5. Treatment of Host Mice
4.6. Retrieval of Xenografts and Seminal Vesicles
4.7. Measurement of Plasma Testosterone Levels
4.8. Histology and Immunostaining
4.9. Image Acquisition and Analysis
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Age (yrs) | Diagnosis | Pre-Biopsy Chemotherapy | Biopsy Condition | Most Advanced Germ Cell Type |
---|---|---|---|---|
1 | Ependymoma | No | Fresh | Spermatogonia |
5 | Medulloblastoma | No | Fresh | Spermatogonia |
8 | Aplastic Anaemia | No | Cryopreserved | Spermatogonia |
13 | Myelodysplastic Syndrome | No | Cryopreserved | Spermatogonia |
13 | Acute Lymphoblastic Leukaemia | Yes * | Cryopreserved | Spermatocytes |
14 | Anaplastic Large Cell Lymphoma | Yes ** | Fresh | Spermatogonia |
Subcutaneous - Castrate | Subcutaneous - Intact | Intratesticular - Intact | ||||
---|---|---|---|---|---|---|
Treatment | Vehicle | hCG+FSH | Vehicle | hCG+FSH | Vehicle | hCG+FSH |
Testis Tissue | n = 6 | n = 6 | n = 3 | n = 3 | n = 4 | n = 4 |
Patient Age (Years) | 1, 5, 8, 13, 13, 14 | 1, 5, 8, 13, 13, 14 | 8, 13, 13 | 8, 13, 13 | 8, 13, 13, 14 | 8, 13, 13, 14 |
Recipient Mouse | n = 10 | n = 11 | n = 6 | n = 6 | n = 8 | n = 8 |
Graft Recovery Rate (%) | 15/43 (35) | 26/47 (55) | 4/18 (22) | 4/18 (22) | 9/16 (56) | 11/15 (73) |
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Hutka, M.; Kadam, P.; Van Saen, D.; Homer, N.Z.M.; Onofre, J.; Wallace, W.H.B.; Smith, L.B.; Stukenborg, J.-B.; Goossens, E.; Mitchell, R.T. Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment. Cancers 2020, 12, 2830. https://doi.org/10.3390/cancers12102830
Hutka M, Kadam P, Van Saen D, Homer NZM, Onofre J, Wallace WHB, Smith LB, Stukenborg J-B, Goossens E, Mitchell RT. Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment. Cancers. 2020; 12(10):2830. https://doi.org/10.3390/cancers12102830
Chicago/Turabian StyleHutka, Marsida, Prashant Kadam, Dorien Van Saen, Natalie Z. M. Homer, Jaime Onofre, W. Hamish B. Wallace, Lee B. Smith, Jan-Bernd Stukenborg, Ellen Goossens, and Rod T. Mitchell. 2020. "Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment" Cancers 12, no. 10: 2830. https://doi.org/10.3390/cancers12102830