An important issue for young men affected by testicular germ cell tumor (TGCT) is how TGCT and its treatment will affect, transiently or permanently, their future reproductive health. Previous studies have reported that xenobiotics can induce changes on human sperm epigenome and have the potential to promote epigenetic alterations in the offspring.
Here we report the first longitudinal DNA methylation profiling of frozen sperm from a TGCT patient before and up to two years after a BEP (bleomycin, etoposide, and cisplatin) chemotherapy.
A TGCT was diagnosed in a 30-year-old patient. A cryopreservation of spermatozoa was proposed before adjuvant BEP treatment. Semen samples were collected before and after chemotherapy at 6, 9, 12 and 24 months. The DNA methylation status was determined by RRBS to detect DNA differentially methylated regions (DMRs).
The analysis revealed that among the 74 DMRs showing modified methylation status 6 months after therapy, 17 remained altered 24 months after treatment. We next associated DMRs with differentially methylated genes (DMGs), which were subsequently intersected with loci known to be important or expressed during early development.
The consequences of cancer treatment on the sperm epigenome during the recovery periods are topical issues of increasing significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. The altered methylated status of these DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis, potentially leading to developmental disorders or miscarriages. This article is protected by copyright. All rights reserved.
Andrology. 2023 Jun 24 [Epub ahead of print]
Anne-Sophie Neyroud, Antoine D Rolland, Gwendoline Lecuyer, Bertrand Evrard, Nathan Alary, Nathalie Dejucq-Rainsford, Louis Bujan, Célia Ravel, Frédéric Chalmel
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, Rennes, France., DEFE (Dévelopement Embryonnaire, Fertilité, Environnement) UMR Inserm 1203 université Toulouse 3 et Montpellier, Toulouse, France.