Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Berger, N; Rieder, A; Brugger, K; Amtmann, B; Kollmann, M; Oreskovic, I; Trajanoski, S; Hiden, U; Fluhr, H.
Novel link between plasma bilirubin and anti-inflammatory miRNA profiles in follicular fluid of IVF patients
AM J PHYSIOL-ENDOC M. 2025; 328(6): E1001-E1012. Doi: 10.1152/ajpendo.00479.2024
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Leading authors Med Uni Graz

Berger Natascha

Hiden Ursula

Co-authors Med Uni Graz

Amtmann Bettina

Brugger Katharina Charlotte

Fluhr Herbert

Kollmann Martina

Rieder Anna

Trajanoski Slave

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Abstract:

Maternal metabolic factors are increasingly recognized as critical preconceptional determinants of fertility outcomes. To investigate how metabolic health influences female fertility, we investigated the molecular composition of follicular fluid (FF), with a focus on microRNA (miRNA) expression. Blood and FF samples from 15 women undergoing controlled ovarian stimulation were examined in a pilot study. Clinical traits (glucometabolic markers, lipid profiles, liver function markers, inflammatory cytokines, and hormonal parameters) and oocyte outcomes were measured and recorded. Elevated plasma bilirubin levels were associated with a distinct miRNA profile in FF, characterized by an enrichment of anti-inflammatory miRNAs, including miR-146a-5p, miR-146b-5p, miR-487b-3p, and miR-21-5p. Bioinformatic analysis revealed that these miRNAs directly target key inflammatory mediators, including interleukin-6, cyclooxygenase 2, Toll-like receptor 4, interleukin 1 receptor-associated kinase 1, and nuclear factor kappa beta 1, suggesting a regulatory role in intrafollicular inflammation. Furthermore, patients with a fertilization rate of <= 50% exhibited higher transcript levels of miRNAs associated with elevated plasma bilirubin. Our findings provide a novel perspective on the growing body of evidence supporting bilirubin's regulatory properties, including antioxidative and anti-inflammatory effects, and highlight the relationship between plasma bilirubin and FF miRNA expression. The observed associations between bilirubin levels, follicular fluid miRNA composition, and oocyte quality underscore the critical influence of metabolic factors on reproductive outcomes. This exploratory work provides a foundation for further studies to investigate the functional role of plasma bilirubin in follicular physiology and its potential as a biomarker to optimize fertility treatments.

Find related publications in this database (Keywords)

bilirubin

fertility

follicular fluid

IVF

miRNA

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