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

Abstract

Objective: To study whether increased body mass index is associated with altered expression of extracellular vesicle microRNAs (EVlinked 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. (Fertil Steril Ò 2019;112:387-96. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Similar miRNomic signatures characterize the follicular fluids collected after follicular and luteal phase stimulations in the same ovarian cycle

“…It is an antioncogenic miRNA, reported to regulate estradiol concentrations and significantly associated with PCOS from the analysis of both cumulus cells and FFs [22,55]. An association with a higher concentration of miR-320a in the FFs was also reported for increasing body mass indexes in non-PCOS women [33]. Moreover, an important role for this miRNA has been outlined in the regulation of (i) metalloproteases [56], (ii) oxidative stress-response by acting on the glycolytic pathway [57], and (iii) X chromosome inactivation [58,59].…”

“…To this end, FFs were screened for their content in growth factors, proteins, metabolites, reactive oxygen species, and nucleic acids [16][17][18][19][20]. More recently, microRNAs (miRNAs) have been investigated from human FFs collected after oocyte retrieval [21][22][23][24][25][26][27][28][29][30][31][32][33]. These small (~20-22 nucleotides) single strand non-coding RNA molecules figure among the main transcriptional/post-transcriptional regulators of gene expression, especially due to their pleiotropy.…”

Exosomes as a Potential Tool for Supporting Canine Oocyte Development

“…In contrast, these miRNAs were found in follicular fluid where the oocyte maturation occurs in the cow [33]. These findings are considered particularly interesting for the canine reproduction system because various miRNAs in EVs showed potential roles for gamete maturation, fertilization, and embryo development from the previous literature [34,[127][128][129][130][131]. Therefore, it can be assumed that these miRNAs are present in the oviduct cells as canine oocyte maturation occurs in the oviductal canal.…”

Plasma extracellular vesicle miRNAs as potential biomarkers of superstimulatory response in cattle

“…In the last few years, EV-miRNAs have been considered as potential biomarkers for diagnosis and prediction of different physiological and pathological conditions in mammals. For instance, the expression pattern of EV-miRNAs from follicular fluid has been reported to be influenced by energy balance status in postpartum dairy cows 47 and by body mass index in humans 48 . In relation to ovarian stimulation, distinct miRNA profiles have been identified in serum as predictive molecular markers for ovarian response to stimulation in humans 49 .…”