Effect of temozolomide on male gametes: an epigenetic risk to the offspring?

• Published in: Journal of assisted reproduction and genetics Vol. 30; no. 6; pp. 827 - 833
• Main Authors: Berthaut, I., Montjean, D., Dessolle, L., Morcel, K., Deluen, F., Poirot, C., Bashamboo, A., Mcelreavey, K., Ravel, C.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-06-2013; Springer Nature B.V
• Subjects: Adult; Alkylating agents; Brain cancer; Chromosomes; Cryopreservation; Dacarbazine - administration & dosage; Dacarbazine - adverse effects; Dacarbazine - analogs & derivatives; DNA methylation; DNA Methylation - drug effects; DNA Modification Methylases - metabolism; DNA Repair Enzymes - metabolism; Epigenesis, Genetic - genetics; Epigenetics; Female; Germ Cells - drug effects; Glioma - complications; Glioma - drug therapy; Gynecology; Human Genetics; Humans; Infertility; Male; Medicine; Medicine & Public Health; Morphology; Motility; Pregnancy; Proteins - metabolism; Reproductive Medicine; RNA, Long Noncoding - metabolism; Sperm; Spermatogenesis; Spermatogenesis - drug effects; Spermatozoa - cytology; Spermatozoa - drug effects; Tumor Suppressor Proteins - metabolism; France; Paris France; Epigenetics; Temozolomide; Fertility; Spermatogenesis; Glioblastoma
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-013-9999-8

Introduction
Temozolomide is an oral alkylating agent with proven efficacy in recurrent high-grade glioma. The antitumour activity of this molecule is attributed to the inhibition of replication through DNA methylation. However, this methylation may also perturb other DNA-dependent processes, such as spermatogenesis. The ability to father a child may be affected by having this treatment. Here we report a pregnancy and a baby born after 6 cures of temozolomide.
Methods
The quality of gametes of the father has been studied through these cures and after the cessation of treatment. Sperm parameters, chromosomal content and epigenetic profiles of
H19
,
MEST
and
MGMT
have been analysed.
Results
Sperm counts decrease significantly and hypomethylation of the
H19
locus increase with time even staying in the normal range.
Conclusion
This is the first report of an epigenetic modification in sperm after temozolomide treatment suggesting a potential risk for the offspring. A sperm cryopreservation before the initiation of temozolomide treatment should be recommended.