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Clin Epigenetics. 2018 Oct 19;10(1):125. doi: 10.1186/s13148-018-0559-z.

Sperm imprinting integrity in seminoma patients?

Author information

1
Université Bourgogne Franche-Comté-Equipe Génétique des Anomalies du Développement (GAD) INSERM UMR1231, 2 Rue Angélique Ducoudray, F-21000, Dijon, France.
2
CHU Dijon Bourgogne, Laboratoire de Biologie de la Reproduction-CECOS, 14 rue Gaffarel, F-21000, Dijon, France.
3
CHRU Besançon, Service de Biologie et de Médecine de la Reproduction-CECOS, 3 Boulevard Fleming, F-25030, Besançon, France.
4
CHU Dijon Bourgogne, Centre d'Investigation Clinique, Module Epidémiologie Clinique/Essais Cliniques (CIC-EC), 7 boulevard Jeanne d'Arc, F-21000, Dijon, France.
5
Université Bourgogne Franche-Comté-INSERM, CIC1432, Module Épidémiologie Clinique, 7 boulevard Jeanne d'Arc, F-21000, Dijon, France.
6
CHU Dijon Bourgogne, Service de Pathologie, 14 rue Gaffarel, F-21000, Dijon, France.
7
CHU Dijon Bourgogne, Service de Gynécologie-Obstétrique, 14 rue Gaffarel, F-21000, Dijon, France.
8
Université Bourgogne Franche-Comté-Equipe Génétique des Anomalies du Développement (GAD) INSERM UMR1231, 2 Rue Angélique Ducoudray, F-21000, Dijon, France. patricia.fauque@chu-dijon.fr.
9
CHU Dijon Bourgogne, Laboratoire de Biologie de la Reproduction-CECOS, 14 rue Gaffarel, F-21000, Dijon, France. patricia.fauque@chu-dijon.fr.

Abstract

BACKGROUND:

Testicular germ cell tumor such as seminoma is strongly associated with male reproductive problems commonly associated with the alteration of sperm parameters as described in testicular dysgenesis syndrome. Interestingly, numerous studies have reported that the precursor of germ cell cancer, germ cell neoplasia in situ (GCNIS), present similarities to fetal gonocytes, specifically characterized by global DNA hypomethylation particularly on imprinting sequences. These disorders may have a common origin derived from perturbations of embryonal programming during fetal development. Presently, there is no available information concerning the sperm DNA methylation patterns of testicular cancer patients. For the first time, we evaluated the sperm imprinting of seminoma patients. A total of 92 cryopreserved sperm samples were included, 31 before seminoma treatment (S): 23 normozoospermic (SN) and 8 oligozoospermic (SO) and 61 sperm controls samples: 31 normozoospermic (N) and 30 oligozoospermic (O). DNA methylation levels of seven differentially methylated regions (DMRs) of imprinted genes [H19/IGF2: IG-DMR (CTCF3 and CTCF6 of H19 gene); IGF2-DMRs (DMR0 and DMR2); MEG3/DLK1:IG-DMR; SNURF:TSS-DMR; KCNQ1OT1:TSS-DMR] were assessed by pyrosequencing. All comparative analyses were adjusted for age.

RESULTS:

Comparisons of sperm DNA methylation levels between seminoma (S) and normozoospermic (N) samples showed a significant difference for the SNURF sequence (p = 0.017), but after taking into account the sperm parameters, no difference was observed. However, we confirmed a significant association between oligozoospermia (O) and imprinting defects for H19/IGF2-CTCF6 (p = 0.001), MEG3/DLK1 (p = 0.017), IGF2-DMR2 (p = 0.022), and SNURF (p = 0.032) in comparison with control groups (N).

CONCLUSIONS:

This study highlights the high risk of sperm imprinting defects in cases of oligozoospermia and shows for the first time that seminoma patients with normal spermatogenesis present sperm imprinting integrity. These data suggest a low probability of the involvement of a common imprinting defect in fetal cells leading to both TGCT and subfertility.

KEYWORDS:

Imprinted genes; Oligozoospermia; Seminoma; Sperm DNA methylation; Testicular dysgenesis syndrome (TDS); Testicular germ cell tumor (TGCT)

PMID:
30340650
PMCID:
PMC6194738
DOI:
10.1186/s13148-018-0559-z
[Indexed for MEDLINE]
Free PMC Article

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