TY  - JOUR
A1  - Prell, Andreas
A1  - Sen, Mustafa Orkun
A1  - Potabattula, Ramya
A1  - Bernhardt, Laura
A1  - Dittrich, Marcus
A1  - Hahn, Thomas
A1  - Schorsch, Martin
A1  - Zacchini, Federica
A1  - Ptak, Grazyna Ewa
A1  - Niemann, Heiner
A1  - Haaf, Thomas
T1  - Species-specific paternal age effects and sperm methylation levels of developmentally important genes
JF  - Cells
N2  - A growing number of sperm methylome analyses have identified genomic loci that are susceptible to paternal age effects in a variety of mammalian species, including human, bovine, and mouse. However, there is little overlap between different data sets. Here, we studied whether or not paternal age effects on the sperm epigenome have been conserved in mammalian evolution and compared methylation patterns of orthologous regulatory regions (mainly gene promoters) containing both conserved and non-conserved CpG sites in 94 human, 36 bovine, and 94 mouse sperm samples, using bisulfite pyrosequencing. We discovered three (NFKB2, RASGEF1C, and RPL6) age-related differentially methylated regions (ageDMRs) in humans, four (CHD7, HDAC11, PAK1, and PTK2B) in bovines, and three (Def6, Nrxn2, and Tbx19) in mice. Remarkably, the identified sperm ageDMRs were all species-specific. Most ageDMRs were in genomic regions with medium methylation levels and large methylation variation. Orthologous regions in species not showing this age effect were either hypermethylated (>80%) or hypomethylated (<20%). In humans and mice, ageDMRs lost methylation, whereas bovine ageDMRs gained methylation with age. Our results are in line with the hypothesis that sperm ageDMRs are in regions under epigenomic evolution and may be part of an epigenetic mechanism(s) for lineage-specific environmental adaptations and provide a solid basis for studies on downstream effects in the genes analyzed here.
KW  - age-related differentially methylated regions (ageDMRs)
KW  - bisulfite pyrosequencing
KW  - mammalian male germline
KW  - paternal age effect
KW  - species-specific epigenetic marks
KW  - sperm DNA methylation
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262301
SN  - 2073-4409
VL  - 11
IS  - 4
ER  - 
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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150261
VL  - 9
IS  - 12
ER  -