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Imprintingstörungen in der Reproduktionsmedizin

Imprinting defects in reproductive medicine

Zusammenfassung

Stochastische, Umwelt- und/oder genetisch bedingte Fehler (Epimutationen) bei der Genomreprogrammierung in den Keimzellen und unmittelbar nach der Befruchtung sind eine wichtige Quelle für phänotypische Variation und Krankheitssuszeptibilität. Tierexperimente belegen eindrucksvoll, dass assistierte Reproduktionstechniken (ART) mit sensitiven Phasen der epigenetischen Reprogrammierung interferieren. Epidemiologische Studien beim Menschen berichten über ein erhöhtes Risiko für Beckwith-Wiedemann- und Angelman-Syndrom, aber das absolute Risiko für ein ART-Kind mit Imprintingkrankheit bleibt gering. Zumindest einige Gene zeigen statistisch signifikante Methylierungsunterschiede innerhalb der normalen Methylierungsvariabilität zwischen ART und Nicht-ART-Schwangerschaften. Das heißt, entweder ART selbst oder mit der elterlichen Infertilität assoziierte Faktoren haben Einfluss auf das Epigenom der nächsten Generation. Fehlerhafte Methylierungsmuster in geprägten Genen zeigen eine signifikante Assoziation mit abnormalen Spermaparametern. Dies unterstützt die Vermutung, dass Epimutationen von der Keimbahn in den Embryo transferiert werden können.

Abstract

Stochastic, environmentally and/or genetically induced errors (epimutations) during genome reprogramming in germ cells and shortly after fertilization are an important source of phenotypic variation and disease susceptibility. Animal experiments provide convincing evidence that assisted reproductive technologies (ART) interfere with sensitive time windows for epigenetic reprogramming. Epidemiological studies in humans suggest an increased risk for Beckwith-Wiedemann and Angelman syndrome; however, the absolute risk of receiving an ART child with imprinting disorder remains small. At least some genes display statistically significant methylation differences within the normal range of methylation variation between ART and non-ART pregnancies. Thus, either ART themselves or factors associated with parental infertility affect the epigenome of the next generation. Faulty methylation patterns in imprinted genes show a significant association with abnormal semen parameters. This supports the idea that epimutations can be transferred from the germline into the embryo.

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Correspondence to T. Haaf.

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Haaf, T. Imprintingstörungen in der Reproduktionsmedizin. medgen 22, 424–428 (2010). https://doi.org/10.1007/s11825-010-0248-6

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Schlüsselwörter

  • In-vitro-Fertilisation
  • DNA-Methylierung
  • Embryogenese
  • Epigenetische Prozesse
  • Genomische Prägung

Keywords

  • In vitro Fertilization
  • DNA methylation
  • Embryogenesis
  • Epigenetic processes
  • Genomic imprinting