TY  - JOUR
A1  - Kuhtz, Juliane
A1  - Schneider, Eberhard
A1  - El Hajj, Nady
A1  - Zimmermann, Lena
A1  - Fust, Olga
A1  - Linek, Bartosz
A1  - Seufert, Rudolf
A1  - Hahn, Thomas
A1  - Schorsch, Martin
A1  - Haaf, Thomas
T1  - Epigenetic heterogeneity of developmentally important genes in human sperm: Implications for assisted reproduction outcome
T2  - Epigenetics
N2  - The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated GTL2 gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1% GTL2 epimutations, whereas one (7%) of 14 normozoospermic and 7 (50%) of 14 OAT samples without pregnancy displayed 1–14% GTL2 epimutations.
KW  - ART outcome
KW  - deep bisulfite sequencing
KW  - epigenetic heterogeneity
KW  - GTL2
KW  - sperm DNA methylation
KW  - IMSI
KW  - ICSI
Y1  - 2014
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/15026
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-150261
VL  - 9
IS  - 12
ER  -