Molecular characterization of exosomes and their microRNA cargo in human follicular fluid Bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation

Highly represented exosomal microRNAs in human follicular fluid control pathways that are essential for follicular maturation. Identified microRNAs may be very useful as noninvasive biomarkers of oocyte quality.

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Authors

Manuela Santonocito, Ph.D., Marilena Vento, Ph.D., Maria Rosa Guglielmino, Ph.D., Rosalia Battaglia, M.Sc., Jessica Wahlgren, Ph.D., Marco Ragusa, Ph.D., Davide Barbagallo, Ph.D., Placido Borzì, M.D., Simona Rizzari, M.Sc., Marco Maugeri, Ph.D., Paolo Scollo, M.D., Carla Tatone, Ph.D., Hadi Valadi, Ph.D., Michele Purrello, M.D., Ph.D., Cinzia Di Pietro, Ph.D.

Volume 102, Issue 6, Pages 1751-1761

Abstract

Objective:

To characterize well-represented microRNAs in human follicular fluid (FF) and to ascertain whether they are cargo of FF exosomes and whether they are involved in the regulation of follicle maturation.

Design:

FF exosomes were characterized by nanosight, flow cytometry, and exosome-specific surface markers. Expression microRNA profiles from total and exosomal FF were compared with those from plasma of the same women.

Setting:

University laboratory and an IVF center.

Patient(s):

Fifteen healthy women who had undergone intracytoplasmic sperm injection.

Intervention(s):

None.

Main Outcome Measure(s):

TaqMan low-density array to investigate the expression profile of 384 microRNAs; DataAssist and geNorm for endogenous control identification; significance analysis of microarrays to identify differentially expressed microRNAs; nanosight, flow-cytometry, and bioanalyzer for exosome characterization; bioinformatic tools for microRNAs target prediction, gene ontology, and pathway analysis.

Result(s):

We identified 37 microRNAs upregulated in FF as compared with plasma from the same women. Thirty-two were carried by microvesicles that showed the well-characterized exosomal markers CD63 and CD81. These FF microRNAs are involved in critically important pathways for follicle growth and oocyte maturation. Specifically, nine of them target and negatively regulate mRNAs expressed in the follicular microenvironment encoding inhibitors of follicle maturation and meiosis resumption.

Conclusion(s):

This study identified a series of exosomal microRNAs that are highly represented in human FF and are involved in follicular maturation. They could represent noninvasive biomarkers of oocyte quality in assisted reproductive technology.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)02064-0/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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