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

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

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.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

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Funding

This work was supported by the National Institutes of Environmental Health Sciences R21 ES024236/ES/NIEHS NIH HHS/United States.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of IVF, Sheba Medical Center, Ramat Gan 5262000, Israel

    R. Machtinger & R. Orvieto

  2. Sackler School of Medicine, Tel-Aviv University, 6997801, Tel Aviv, Israel

    R. Machtinger

  3. Department of Obstetrics, Gynecology and Reproductive Medicine, Hospital Foch, Suresnes, France

    C. Racowsky

  4. Laboratory of Precision Environmental Biosciences, Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY, 10032, USA

    A. A. Baccarelli

  5. EPIGET Lab, Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, 20122, Milan, Italy

    V. Bollati

  6. Occupational Health Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy

    V. Bollati

  7. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA

    R. Hauser

  8. Public Health Services, Ministry of Health, 9446724, Jerusalem, Israel

    Z. Barnett-Itzhaki

  9. Faculty of Engineering, Ruppin Academic Center, 4025000, Emek Hefer, Israel

    Z. Barnett-Itzhaki

  10. Ruppin Research Group in Environmental and Social Sustainability, Ruppin Academic Center, 4025000, Emek Hefer, Israel

    Z. Barnett-Itzhaki

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  1. R. Machtinger
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  2. C. Racowsky
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  3. A. A. Baccarelli
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  4. V. Bollati
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  5. R. Orvieto
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Correspondence to R. Machtinger.

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Machtinger, R., Racowsky, C., Baccarelli, A.A. et al. Recombinant human chorionic gonadotropin and gonadotropin-releasing hormone agonist differently affect the profile of extracellular vesicle microRNAs in human follicular fluid. J Assist Reprod Genet 40, 527–536 (2023). https://doi.org/10.1007/s10815-022-02703-w

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  • DOI: https://doi.org/10.1007/s10815-022-02703-w

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