Estrous cycle impacts microRNA content in extracellular vesicles that modulate bovine cumulus cell transcripts during in vitro maturation

Author(s):Show less -

Cavalcante Mendes de Avila, Ana Clara Faquineli ^[1] ; Bridi, Alessandra ^[1] ; Andrade, Gabriella Mamede ^[1] ; del Collado, Maite ^[1] ; Sangalli, Juliano Rodrigues ^[1] ; Nociti, Ricardo Perecin ^[1] ; da Silva Junior, Wilson Araujo ^[2] ; Bastien, Alexandre ^[3] ; Robert, Claude ^[3] ; Meirelles, Flavio Vieira ^[1] ; Perecin, Felipe ^[1] ; da Silveira, Juliano Coelho ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Pirassununga, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[3] Laval Univ, Res Ctr Reprod Biol, Inst Nutr & Funct Foods, Anim Sci Dept, Quebec City, PQ - Canada

• Document type: Journal article
• Source: BIOLOGY OF REPRODUCTION; v. 102, n. 2, p. 362-375, FEB 2020.
• Web of Science Citations: 11

Abstract

Extracellular vesicles (EVs) are nanoparticles secreted by ovarian follicle cells. Extracellular vesicles are an important form of intercellular communication, since they carry bioactive contents, such as microRNAs (miRNAs), mRNAs, and proteins. MicroRNAs are small noncoding RNA capable of modulating mRNA translation. Thus, EVs can play a role in follicle and oocyte development. However, it is not clear if EV contents vary with the estrous cycle stage. The aim of this study was to investigate the bovine miRNA content in EVs obtained from follicles at different estrous cycle stages, which are associated with different progesterone (P4) levels in the follicular fluid (FF). We collected FF from 3 to 6 mm follicles and evaluated the miRNA profile of the EVs and their effects on cumulus-oocyte complexes during in vitro maturation. We observed that EVs from low P4 group have a higher abundance of miRNAs predicted to modulate pathways, such as MAPK, RNA transport, Hippo, Cell cycle, FoxO, oocyte meiosis, and TGF-beta. Additionally, EVs were taken up by cumulus cells and, thus, affected the RNA global profile 9 h after EV supplementation. Cumulus cells supplemented with EVs from low P4 presented upregulated genes that could modulate biological processes, such as oocyte development, immune responses, and Notch signaling compared with genes of cumulus cells in the EV free media or with EVs from high P4 follicles. In conclusion, our results demonstrate that EV miRNA contents are distinct in follicles exposed to different estrous cycle stage. Supplementation with EVs impacts gene expression and biological processes in cumulus cells. Summary Sentence MicroRNA contents of small EVs obtained from bovine follicular fluid are modified depending on the estrous cycle stage and can modulate the RNA profile of cumulus cells during in vitro oocyte maturation. (AU)

• FAPESP's process: 17/02037-0 - Description of a new mechanism involved in cellular communication between female reproductive system cells and oocyte mediated by extracellular vesicles and their impacts on oocyte maturation, fertilization and bovine embryo cleavage
• Grantee: Ana Clara Faquineli Cavalcante Mendes de Ávila
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 18/14869-2 - The role of extracellular vesicles in the intercellular communication within the bovine cumulus-oocyte complex during in vitro maturation
• Grantee: Ana Clara Faquineli Cavalcante Mendes de Ávila
• Support type: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 14/22887-0 - Cell-secreted vesicles containing miRNAs modulate epigenetic changes during in vitro culture of bovine gametes and embryos
• Grantee: Juliano Coelho da Silveira
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 15/21829-9 - Multi-user equipment approved in grant 2014/22887-0: Nanosight LM10
• Grantee: Juliano Coelho da Silveira
• Support type: Multi-user Equipment Program