Impact of Amphiregulin on Oocyte Maturation and Embryo Quality: Insights from Clinical and Molecular Perspectives

Abstract

Introduction

Identifying non-invasive biomarkers which can predict the outcome of intracytoplasmic sperm injection (ICSI) is crucial, particularly in Germany where the challenges are intensified by the Embryo Protection Act. Recent research has highlighted biomarkers within the epidermal growth factor (EGF) family as central to follicular processes, although their predictive utility remains a subject of debate in the literature. Therefore, the primary objective of this study was to investigate the significance of amphiregulin concentrations in follicular fluid and gene expression in mural granulosa cells on oocyte maturation, fertilization, and embryo quality.

Patients and Methods

A total of 33 women were recruited at the University Clinic of Saarland Fertility Center (Homburg, Germany). Follicular fluid aspiration consisted of single/individual aspiration of follicles, enabling a 1 : 1 correlation with retrieved oocytes. Follicular fluid and mural granulosa cell samples from 108 oocytes were analyzed. Amphiregulin levels were determined with enzyme-linked immunosorbent assay, while gene expression was analyzed with the StepOnePlus Real-Time PCR System using TaqMan Fast Advanced Master Mix assays.

Results

Results showed that amphiregulin concentrations affect oocyte maturation, fertilization, and embryo quality, while luteinizing hormone concentrations influence oocyte maturation, with significant differences identified between fertilized/unfertilized and good/poor embryo groups. Amphiregulin expression significantly impacts oocyte maturation, with downregulation observed in immature oocytes, while luteinizing hormone/chorionic gonadotropin receptor expression showed no significant differences between groups and did not influence maturation, fertilization, or embryo quality.

Conclusion

These findings are very important for advancing infertility treatment, especially in Germany. The results for amphiregulin may provide prognostic insights which could be useful when selecting viable oocytes and embryos. This research underscores the importance of non-invasive biomarkers for optimizing ICSI outcomes and potentially enhancing the success rates of assisted reproductive technology.

Zusammenfassung

Einleitung

Die Identifikation von nicht invasiven Biomarkern, die das Outcome nach intrazytoplasmatischer Spermieninjektion (ICSI) prognostizieren könnten, ist sehr wichtig, besonders in Deutschland, wo die Herausforderung durch das Embryonenschutzgesetz noch intensiviert wird. Die jüngste Forschung hat die Bedeutung einiger Biomarker innerhalb der Familie der epidermalen Wachstumsfaktoren als zentral für follikuläre Prozesse hervorgehoben, aber ihr prädiktiver Nutzen ist in der Literatur noch umstritten. Das Hauptziel dieser Studie war es daher, die Wirkung von Amphiregulin-Konzentrationen in der Follikelflüssigkeit und der Genexpression in muralen Granulosazellen auf Eizellreifung, Fertilisation und Embryoqualität zu untersuchen.

Patientinnen und Methoden

Insgesamt wurden 33 Frauen in der Klinik für Reproduktionsmedizin des Universitätsklinikums des Saarlandes (Homburg, Deutschland) für die Studie rekrutiert. Die Aspiration der Follikelflüssigkeit bestand aus einer einzelnen/individuellen Aspiration von Follikeln, was eine 1 : 1 Korrelation mit den entnommenen Eizellen erlaubte. Die Follikelflüssigkeit- und muralen Granulosazell-Proben von 108 Eizellen wurden analysiert. Der jeweilige Amphiregulin-Spiegel wurde mit ELISA (Enzyme-Linked ImmunoSorbent Assay) bestimmt, und die Genexpression mithilfe des StepOnePlus Real-Time PCR Systems und TaqMan Fast Advanced Master Mix Assays analysiert.

Ergebnisse

Die Ergebnisse zeigten, dass Amphiregulin-Konzentrationen die Eizellreifung, Fertilisation und Embryoqualität beeinflussen, während die Konzentrationen von luteinisierendem Hormon die Eizellreifung beeinflussen. Es fanden sich signifikante Unterschiede in den Konzentrationen zwischen fertilisierten/nicht fertilisierten Gruppen und den Gruppen mit guter/schlechter Embryonenqualität. Die Expression von Amphiregulin hatte eine signifikante Wirkung auf die Eizellreifung. Eine Downregulation von Amphiregulin wurde bei unreifen Eizellen beobachtet, wohingegen die Expression von luteinisierendem Hormon/Choriongonadotropinrezeptor sich nicht signifikant zwischen den Gruppen unterschied und keinen Einfluss auf die Eizellreifung, Fertilisation oder Embryonenqualität hatte.

Schlussfolgerung

Diese Ergebnisse liefern wichtige Hinweise für eine weitere Verbesserung von Fertilitätsbehandlungen, besonders in Deutschland. Die Ergebnisse könnten prognostische Erkenntnisse liefern, die bei der Selektion von lebensfähigen Eizellen und Embryonen nützlich wären. Diese Studie unterstreicht die Bedeutung von nicht invasiven Biomarkern bei der Optimierung von ICSI-Outcomes und könnte potenziell die Erfolgsraten der assistierten Reproduktionstechnologie verbessern.

Keywords

amphiregulin - follicular fluid - gene expression - mural granulosa cells - embryo quality

Schlüsselwörter

Amphiregulin - Follikelflüssigkeit - Genexpression - murale Granulosazellen - Embryoqualität

Publication History

Received: 19 April 2024

Accepted after revision: 11 August 2024

Article published online:
17 September 2024

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