Body mass index in relation to extracellular vesicle–linked microRNAs in human follicular fluid

Rosie M. Martinez, Andrea A. Baccarelli, Liming Liang, L. Dioni, Abdallah Mansur, Michal Adir, Valentina Bollati, Catherine Racowsky, Russ Hauser, R. Machtinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Objective: To study whether increased body mass index is associated with altered expression of extracellular vesicle microRNAs (EV-linked miRNAs) in human follicular fluid. Design: Cross-sectional study. Setting: Tertiary-care university-affiliated center. Patient(s): One hundred thirty-three women undergoing in vitro fertilization (IVF) were recruited from January 2014 to August 2016. Interventions(s): None. Main Outcome Measure(s): EV-linked miRNAs were isolated from follicular fluid and their expression profiles were measured with the use of the Taqman Open Array Human miRNA panel. EV-linked miRNAs were globally normalized and inverse-normal transformed. Associations between body mass index (BMI) and EV-linked miRNA outcomes were analyzed by means of multivariate linear regression and principal component analysis. Result(s): Eighteen EV-linked miRNAs were associated with an increase in BMI after adjusting for age, ethnicity, smoking status, and batch effects. Hsa-miR-328 remained significant after false discovery rate adjustments. Principal component analyses identified the first principal component to account for 40% of the variation in our EV-linked miRNA dataset, and adjusted linear regression found that the first principal component was significantly associated with BMI after multiple testing adjustments. Using Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we predicted gene targets of EV-linked miRNA in silico and identified PI3K-Akt signaling, ECM-receptor interaction, focal adhesion, FoxO signaling, and oocyte meiosis pathways. Conclusion(s): These results show that a 1-unit increase in BMI is associated with altered follicular fluid expression of EV-linked miRNAs that may influence follicular and oocyte developmental pathways. Our findings provide potential insight into a mechanistic explanation for the reduced fertility rates associated with increased BMI.

Original languageEnglish
Pages (from-to)387-396.e3
JournalFertility and Sterility
Volume112
Issue number2
DOIs
StatePublished - Aug 2019

Funding

FundersFunder number
Education and Research Center for Occupational Safety and Health CDC
Education and Research Center for Occupational Safety and Health CDC/NIOSHT42/OH008416
Environment and Health Fund, Israel1301
National Institutes of Environmental Health SciencesR21-ES024236
National Institutes of HealthT42OH008416
Centers for Disease Control and Prevention
National Institute of Environmental Health Sciences
National Institute for Occupational Safety and Health
Israel Science Foundation1936/12
Environment and Health Fund

    Keywords

    • BMI
    • IVF
    • extracellular vesicles
    • microRNAs

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