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Epigenetic heterogeneity of developmentally important genes in human sperm: Implications for assisted reproduction outcome

Please always quote using this URN: urn:nbn:de:bvb:20-opus-150261
  • 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 notThe 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.show moreshow less

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Metadaten
Author: Juliane Kuhtz, Eberhard Schneider, Nady El Hajj, Lena Zimmermann, Olga Fust, Bartosz Linek, Rudolf Seufert, Thomas Hahn, Martin Schorsch, Thomas Haaf
URN:urn:nbn:de:bvb:20-opus-150261
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Humangenetik
Language:English
Parent Title (English):Epigenetics
Year of Completion:2014
Volume:9
Issue:12
Pagenumber:1648-1658
Source:Epigenetics (2014) 9:12, 1648-165. DOI: 10.4161/15592294.2014.988063
DOI:https://doi.org/10.4161/15592294.2014.988063
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/PMC4622742
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ART outcome; GTL2; ICSI; IMSI; deep bisulfite sequencing; epigenetic heterogeneity; sperm DNA methylation
Release Date:2019/01/24
Licence (German):License LogoCC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell