Repetitive Maturation of Oocytes From Non-Stimulated Xenografted Ovarian Tissue From a Prepubertal Patient Indicating the Independence of Human Ovarian Tissue

Abstract

Introduction Modern anti-cancer strategies have distinctly increased survival rates; nevertheless, often accompanied by sterility. Currently, the only option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue and re-transplant frozen-thawed tissue to restore fertility after treatment. Our aim was to report the occurrence of repetitive antral follicle formation and oocyte maturation in a prepubescent ovarian tissue xenograft without exogenous hormone stimulation.

Material and Methods Frozen-thawed ovarian tissue from a 6-year-old patient suffering from nephroblastoma was xenotransplanted in oophorectomized severe combined immunodeficiency (SCID) mice to evaluate follicle development.

Ergebnisse Repetitive follicle development to the antral stage occurred in the same xenograft of prepubertal ovarian tissue without exogenous hormone administration; 37 days after retrieving a maturing oocyte (this first retrieval has been previously published), another, completely mature oocyte was harvested from the xenograft. Subsequent histological evaluation of the grafted tissue showed primordial follicles, nearly all stages of developing follicles, as well as large atretic ones. Many clusters with dormant primordial follicles were also present.

Conclusion Xenotransplanted prepubertal ovarian tissue has the potential for repetitive oocyte retrieval cycles without administering exogenous hormones. The results indicate that the human ovarian tissue might be able to synchronize the hypothalamus-hypophysis-axes of the mouse to the physiological human cycle; this should be investigated in future studies.

Zusammenfassung

Einleitung Moderne Krebsbekämpfungsstrategien haben zu einer deutlichen Steigerung der Überlebensraten geführt, was jedoch oft mit Sterilität einhergeht. Um die Fertilität präpubertärer Mädchen zu erhalten, besteht die einzige Option zurzeit aus der Kryokonservierung von Ovargewebe, gefolgt von einer Retransplantation des gefrorenen Eierstockgewebes nach Abschluss der onkologischen Behandlung, um die Fertilität wiederherzustellen. Unser Ziel war es, einen Nachweis zu führen über eine wiederholte Bildung antraler Follikel und Oozytenreifung in einem Xenotransplantat von präpubertärem Eierstockgewebe ohne exogene hormonelle Stimulation.

Material und Methoden Eingefrorenes Eierstockgewebe, das einem an einem Nephroblastom erkrankten 6-jährigen Mädchen entnommen wurde, wurde in oophorektomierten Mäusen mit SCID (schwerem kombinierten Immundefekt) xenotransplantiert, die anschließende Follikelreifung wurde evaluiert.

Ergebnisse Es folgte eine wiederholte Follikelbildung bis zum antralen Stadium in ebendiesem Xenotransplantat von präpubertärem Ovargewebe ohne exogene hormonelle Stimulation; 37 Tage nach der Entnahme einer heranreifenden Eizelle (weitergehende Daten zu dieser ersten Oozytenentnahme wurden bereits veröffentlicht), konnte eine weitere ausgereifte Eizelle dem Xenotransplantat entnommen werden. Eine anschließende histologische Untersuchung des transplantierten Gewebes zeigte sowohl Primordialfollikel und Follikel fast aller Entwicklungsstufen wie auch große atretische Follikel. Es waren also mehrere Ansammlungen ruhender Primordialfollikel vorhanden.

Schlussfolgerung Xenotransplantiertes präpubertäres Ovargewebe hat das Potenzial, wiederholt zyklisch Eizellen zur Entnahme zu generieren, auch ohne die zusätzliche Gabe exogener Hormone. Dieses Ergebnis zeigt, dass menschliches Eierstockgewebe möglicherweise in der Lage sein könnte, die Hypothalamus-Hypophysen-Achse der Maus mit den menschlichen physiologischen Zyklen zu synchronisieren. Dieser Frage sollte in zukünftigen Studien nachgegangen werden.

Key words

fertility preservation - ovarian tissue cryopreservation - prepubertal ovarian tissue - xenotransplantation - metaphase II oocyte

Schlüsselwörter

Fertilitätserhalt - Kryokonservierung von Eierstockgewebe - präpubertäres Ovargewebe - Xenotransplantation - Metaphase-II-Oozyte

^* These authors contributed equally to this work.

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