Lösliches HLA‐G als Qualitätsparameter in der assistierten Reproduktion – ein Artefakt als Basis für eine (lebens-)wichtige Entscheidung?

Zusammenfassung

Auf der Suche nach Qualitätsparametern als Ergänzung zur morphologischen Beurteilung des humanen Präimplantationsembryos, aber auch der Oozyten, wurde in den letzten Jahren zunehmend lösliches (solubles) HLA‐G (sHLA‐G) diskutiert. Während mancherorts die sHLA‐G-Bestimmung in Kulturmedien früher menschlicher Teilungsstadien schon im klinischen Bereich angeboten wurde und kommerzielle Testsysteme erhältlich sind, zeigt die vorhandene wissenschaftliche Literatur deutlich, dass der Einsatz von sHLA‐G für diese Zwecke bedenklich ist. Wir demonstrieren in unserer Übersichtsarbeit einerseits, dass sich bei genauerer Betrachtung technische Unzulänglichkeiten bei den derzeit publizierten Nachweismethoden offenbaren. Andererseits diskutieren wir deutliche Hinweise aus der Grundlagenforschung, wonach das Konzept vom „aktiv sezernierten solublen HLA‐G“ selbst im klaren Widerspruch zu etablierten molekularen Mechanismen zum Abbau schadhafter, potenziell toxischer Messenger-RNA-Moleküle steht. Aufgrund des „nonsense mediated RNA-decay“ (NMD) wäre gar nicht mit einer messbaren sHLA‐G-Menge im Kulturüberstand einzelner Eizellen oder Präimplantationsembryonen zu rechnen. Es ist nicht zuletzt im Sinne der Glaubwürdigkeit der biomedizinischen Forschung und zur Vermeidung von „Wissenschaftsblasen“ wichtig, dass vor einer Anwendung neuer Marker die nötigen wissenschaftlichen und technischen Grundlagen kritisch geprüft werden – insbesondere, wenn es um (lebens-)wichtige Entscheidungen wie die Auswahl menschlicher Embryonen für den Transfer in den Uterus geht.

Abstract

Soluble HLA‐G has been proposed as a useful parameter for embryo and probably oocyte viability in ART. But while some clinicians already offer sHLA‐G analysis of cultured human embryos to infertile patients using commercially available test systems, there is considerable doubt about the validity of this marker. We present a review of the available data in the literature, which reveals serious technical problems with the detection methods and a critical lack of standardisation and reproducibility. Moreover, the concept of “active secretion of HLA‐G” is clearly contradictory to well established concepts of RNA decay. Considering what is known of nonsense mediated RNA decay (NMD), measurable amounts of sHLA‐G should not be expected in supernatants of human oocytes and preimplantation embryos at all. To avoid creating “scientific bubbles”, the scientific and technical basis needs to be critically investigated before a “new marker” is introduced in clinics. In our opinion, the decision which oocytes to fertilise and cultivate or which embryos to transfer into the uterus are too important to be based on a probable artefact.

Schlüsselwörter

lösliches (solubles) HLA‐G - assistierte Reproduktion - IVF - Blastozystenqualität - „nonsense mediated RNA‐decay“

Key words

soluble HLA‐G - assisted reproductive technology - IVF - embryo quality - nonsense mediated RNA decay

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