Rosie M Martinez1, Andrea A Baccarelli2, Liming Liang3, Laura Dioni4, Abdallah Mansur5, Michal Adir5, Valentina Bollati4, Catherine Racowsky6, Russ Hauser7, Ronit Machtinger8. 1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Laboratory of Precision Environmental Biosciences, Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, New York. 2. Laboratory of Precision Environmental Biosciences, Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, New York. 3. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Epidemiology, Epigenetics, and Toxicology Laboratory, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 5. Department of Obstetrics and Gynecology, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel. 6. Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 7. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 8. Department of Obstetrics and Gynecology, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Ramat-Gan, Israel. Electronic address: ronit.machtinger@sheba.health.gov.il.
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.
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.
Authors: Ahmed Gad; José María Sánchez; John A Browne; Lucie Nemcova; Jozef Laurincik; Radek Prochazka; Pat Lonergan Journal: Sci Rep Date: 2020-11-05 Impact factor: 4.379