Recombinant human chorionic gonadotropin and gonadotropin-releasing hormone agonist differently affect the profile of extracellular vesicle microRNAs in human follicular fluid

R. Machtinger*, C. Racowsky, A. A. Baccarelli, V. Bollati, R. Orvieto, R. Hauser, Z. Barnett-Itzhaki

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To compare the expression profile of extracellular vesicle microRNAs (EV-miRNAs) derived from follicular fluid after a trigger with recombinant human chorionic gonadotropin (r-hCG) or with a gonadotropin-releasing hormone GnRH agonist (GnRH-a) for final oocyte maturation. Methods: A retrospective analysis of a prospective cohort. Women undergoing in vitro fertilization at a tertiary university-affiliated hospital were recruited between 2014 and 2016. EV-miRNAs were extracted from the follicular fluid of a single follicle, and their expression was assessed using TaqMan Open Array®. Genes regulated by EV-miRNAs were analyzed using miRWalk2.0 Targetscan database, DAVID Bioinformatics Resources, Kyoto-Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO). Results: Eighty-two women were included in the r-hCG trigger group and 9 in the GnRH-a group. Of 754 EV-miRNAs screened, 135 were detected in at least 50% of the samples and expressed in both groups and were further analyzed. After adjusting for multiple testing, 41 EV-miRNAs whose expression levels significantly differed between the two trigger groups were identified. Bioinformatics analysis of the genes regulated by these EV-miRNAs showed distinct pathways between the two triggers, including TGF-beta signaling, cell cycle, and Wnt signaling pathways. Most of these pathways regulate cascades associated with apoptosis, embryo development, implantation, decidualization, and placental development. Conclusions: Trigger with GnRH-a or r-hCG leads to distinct EV-miRNAs expression profiles and to downstream biological effects in ovarian follicles. These findings may provide an insight for the increased apoptosis and the lower implantation rates following GnRH-a trigger vs. r-hCG in cases lacking intensive luteal phase support.

Original languageEnglish
Pages (from-to)527-536
Number of pages10
JournalJournal of Assisted Reproduction and Genetics
Volume40
Issue number3
DOIs
StatePublished - Mar 2023

Funding

FundersFunder number
National Institute of Environmental Health SciencesR21 ES024236/ES/NIEHS NIH HHS

    Keywords

    • Extra-cellular vesicles
    • GnRH-agonist
    • Ovulation triggers
    • Recombinant chorionic gonadotropin
    • miRNA

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