Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer
Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.
Materials and Methods:
We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values.
A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6 months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation.
The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation.
- 1 : Male gonadal toxicity. Pediatr Blood Cancer2009; 53: 261. Google Scholar
- 2 : Subfertility in children and young people treated for solid and haematological malignancies. Br J Haematol2005; 131: 143. Google Scholar
- 3 : Options for fertility preservation in prepubertal boys. Hum Reprod Update2010; 16: 312. Google Scholar
- 4 : Testicular tissue cryopreservation in prepubertal male children: an analysis of parental decision-making. Pediatr Blood Cancer2014; 61: 1673. Google Scholar
- 5 : Long-term survival of human spermatogonial stem cells in mouse testes. Fertil Steril2002; 78: 1225. Google Scholar
- 6 : An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Hum Reprod2010; 25: 37. Google Scholar
- 7 : Development of cryptorchid testes. Eur J Pediatr1987; 146: S8. Google Scholar
- 8 : Abnormal germ cell development in cryptorchidism. Horm Res2001; 55: 11. Google Scholar
- 9 : Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc Natl Acad Sci U S A2009; 106: 21672. Google Scholar
- 10 : Occurrence of primary spermatocytes in the infant and child testis. Andrologia1984; 16: 532. Google Scholar
- 11 : Testicular histology related to fertility outcome and postpubertal hormone status in cryptorchidism. Klin Padiatr2008; 220: 302. Google Scholar
- 12 : Disruption of spermatogenesis by the cancer disease process. J Natl Cancer Inst Monogr2005; 34: 9. Google Scholar
- 13 : Role of cytokines in testicular function. Endocrine1999; 10: 201. Google Scholar
- 14 : Childhood adversity and immune and inflammatory biomarkers associated with cardiovascular risk in youth: a systematic review. Brain Behav Immun2012; 26: 239. Google Scholar