title: Bovine ovarian cells have (pro)renin receptors and prorenin induces resumption of meiosis in vitro.
abstract: The discovery of a receptor that binds prorenin and renin in human endothelial and mesangial cells highlights the possible effect of renin-independent prorenin in the resumption of meiosis in oocytes that was postulated in the 1980s.This study aimed to identify the (pro)renin receptor in the ovary and to assess the effect of prorenin on meiotic resumption. The (pro)renin receptor protein was detected in bovine cumulus-oocyte complexes, theca cells, granulosa cells, and in the corpus luteum. Abundant (pro)renin receptor messenger ribonucleic acid (mRNA) was detected in the oocytes and cumulus cells, while prorenin mRNA was identified in the cumulus cells only. Prorenin at concentrations of 10(-10), 10(-9), and 10(-8)M incubated with oocytes co-cultured with follicular hemisections for 15h caused the resumption of oocyte meiosis. Aliskiren, which inhibits free renin and receptor-bound renin/prorenin, at concentrations of 10(-7), 10(-5), and 10(-3)M blocked this effect (P<0.05). To determine the involvement of angiotensin II in prorenin-induced meiosis resumption, cumulus-oocyte complexes and follicular hemisections were treated with prorenin and with angiotensin II or saralasin (angiotensin II antagonist). Prorenin induced the resumption of meiosis independently of angiotensin II. Furthermore, cumulus-oocyte complexes cultured with forskolin (200μM) and treated with prorenin and aliskiren did not exhibit a prorenin-induced resumption of meiosis (P<0.05). Only the oocytes' cyclic adenosine monophosphate levels seemed to be regulated by prorenin and/or forskolin treatment after incubation for 6h. To the best of our knowledge, this is the first study to identify the (pro)renin receptor in ovarian cells and to demonstrate the independent role of prorenin in the resumption of oocyte meiosis in cattle.
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil.
authors.forename: Andressa Minussi Pereira
authors.initials: AM
authors.lastname: Dau
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil.
authors.forename: Eduardo Pradebon
authors.initials: EP
authors.lastname: da Silva
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil.
authors.forename: Paulo Roberto Antunes
authors.initials: PR
authors.lastname: da Rosa
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil.
authors.forename: Felipe Tusi
authors.initials: FT
authors.lastname: Bastiani
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Gutierrez
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil.
authors.forename: Gustavo Freitas
authors.initials: GF
authors.lastname: Ilha
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil; Department of Medical Clinic, Faculty of Medicine, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Santa Maria, RS, Brazil.
authors.forename: Fabio Vasconcellos
authors.initials: FV
authors.lastname: Comim
authors.affiliation: Laboratory of Biotechnology and Animal Reproduction, BioRep, Federal University of Santa Maria, Roraima Avenue 1000, 97105-900, Veterinary Hospital, Santa Maria, RS, Brazil. Electronic address: bayard@ufsm.br.
authors.forename: Paulo Bayard Dias
authors.initials: PB
authors.lastname: Gonçalves
mesh_terms: D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005260:Female; D005650:Fumarates / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D009712:Nucleotides, Cyclic / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology; D013799:Theca Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000804:Angiotensin II; D005576:Colforsin; D005650:Fumarates; D009712:Nucleotides, Cyclic; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012083:Renin; D012504:Saralasin; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors; C584311:cyclic guanosine monophosphate-adenosine monophosphate; C446481:aliskiren
keywords: Aliskiren; Angiotensin II; Cumulus cell; Oocyte; Prorenin; Saralasin