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Sperm imprinting integrity in seminoma patients?
Céline Bruno1,2, Oxana Blagoskonov3, Julie Barberet1,2
1Université Bourgogne Franche-Comté-Equipe Génétique des Anomalies du Développement (GAD) INSERM UMR1231, 2 Rue Angélique Ducoudray, F-21000, Dijon, France.
Clinical Epigenetics
|October 21, 2018
Summary
Seminoma patients with normal sperm parameters show intact sperm imprinting. However, oligozoospermia (low sperm count) is linked to significant imprinting defects, suggesting distinct origins for testicular cancer and subfertility.
Area of Science:
- Reproductive Biology
- Epigenetics
- Oncology
Background:
- Testicular germ cell tumors (TGCT), like seminoma, are linked to male reproductive issues and testicular dysgenesis syndrome.
- GCNIS, a precursor to TGCT, shares similarities with fetal gonocytes, exhibiting global DNA hypomethylation, particularly on imprinting sequences.
- Perturbations in embryonal programming during fetal development may underlie both TGCT and related reproductive disorders.
Purpose of the Study:
- To investigate, for the first time, the sperm DNA methylation patterns in seminoma patients.
- To evaluate the imprinting status of sperm DNA in relation to seminoma and sperm parameters (normozoospermia vs. oligozoospermia).
Main Methods:
- Analyzed DNA methylation levels of seven differentially methylated regions (DMRs) in imprinted genes using pyrosequencing.
- Included 92 cryopreserved sperm samples: 31 before seminoma treatment (23 normozoospermic, 8 oligozoospermic) and 61 controls (31 normozoospermic, 30 oligozoospermic).
- Adjusted all comparative analyses for patient age.
Main Results:
- Seminoma patients with normozoospermia (SN) showed no significant difference in sperm imprinting compared to normozoospermic controls (N), except for the SNURF sequence, which lost significance after accounting for sperm parameters.
- Oligozoospermia (O) was significantly associated with imprinting defects in H19/IGF2-CTCF6, MEG3/DLK1, IGF2-DMR2, and SNURF regions compared to normozoospermic controls (N).
Conclusions:
- Sperm imprinting defects are highly prevalent in cases of oligozoospermia.
- Seminoma patients with normal spermatogenesis exhibit intact sperm imprinting, suggesting a low probability of a common imprinting defect causing both TGCT and subfertility.
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