Search

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.

Microdeletions of the long arm of the Y chromosome (Yq) are a common cause of male infertility. Since large structural rearrangements of the Y chromosome are commonly associated with a 45,XO/46,XY chromosomal mosaicism, we studied whether submicroscopic Yq deletions could also be associated with the development of 45,XO cell lines. We studied blood samples from 14 infertile men carrying a Yq microdeletion as revealed by polymerase chain reaction (PCR). Patients were divided into two groups: group 1 (n = 6), in which karyotype analysis demonstrated a 45,X/46,XY mosaicism, and group 2 (n = 8) with apparently a normal 46,XY karyotype. 45,XO cells were identified by fluorescence in-situ hybridization (FISH) using X and Y centromeric probes. Lymphocytes from 11 fertile men were studied as controls. In addition, sperm cells were studied in three oligozoospermic patients in group 2. Our results showed that large and submicroscopic Yq deletions were associated with significantly increased percentages of 45,XO cells in lymphocytes and of sperm cells nullisomic for gonosomes, especially for the Y chromosome. Moreover, two isodicentric Y chromosomes, classified as normal by cytogenetic methods, were detected. Therefore, Yq microdeletions may be associated with Y chromosomal instability leading to the formation of 45,XO cell lines.