title: Mouse oocytes suppress miR-322-5p expression in ovarian granulosa cells.
abstract: This study tested the hypothesis that oocyte-derived paracrine factors (ODPFs) regulate miRNA expression in mouse granulosa cells. Expression of mmu-miR-322-5p (miR-322) was higher in mural granulosa cells (MGCs) than in cumulus cells of the Graafian follicles. The expression levels of miR-322 decreased when cumulus cells or MGCs were co-cultured with oocytes denuded of their cumulus cells. Inhibition of SMAD2/3 signaling by SB431542 increased miR-322 expression by cumulus-oocyte complexes (COCs). Moreover, the cumulus cells but not the MGCs in Bmp15(-/-)/Gdf9(+/-) (double-mutant) mice exhibited higher miR-322 expression than those of wild-type mice. Taken together, these results show that ODPFs suppress the expression of miR-322 in cumulus cells. Gene ontology analysis of putative miR-322 targets whose expression was detected in MGCs with RNA-sequencing suggested that multiple biological processes are affected by miR-322 in MGCs. These results demonstrate that ODPFs regulate miRNA expression in granulosa cells and that this regulation may participate in the differential control of cumulus cell versus MGC functions. Therefore, the ODPF-mediated regulation of cumulus cells takes place at both transcriptional and post-transcriptional levels.
authors.affiliation: Laboratory of Applied Genetics, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sumitomo
authors.forename: Chihiro
authors.initials: C
authors.lastname: Emori
authors.forename: Yuta
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Mizuki
authors.initials: M
authors.lastname: Ueno
authors.forename: Kurenai
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Shiroguchi
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujii
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Naito
authors.forename: Koji
authors.initials: K
authors.lastname: Sugiura
mesh_terms: D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D054885:Cumulus Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; C582672:MIRN322 microRNA, mouse; D035683:MicroRNAs