Characterization of microRNAs (miRNAs) in bovine antral follicles from Nelore cattle: involvement during ovarian follicle cells differentiation and regulation of LH receptor (LHr) expression

• Grant number: 13/11480-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: October 01, 2014 - September 30, 2018
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Anthony César de Souza Castilho
• Grantee: Anthony César de Souza Castilho
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Oeste Paulista (UNOESTE). Presidente Prudente , SP, Brazil
• Associated researchers: Ciro Moraes Barros ; Marcelo Fábio Gouveia Nogueira
• Associated grant(s): 15/04505-5 - Characterization of microRNAs (miRNAs) in bovine antral follicles from Nelore cows: involvement during ovarian follicle cells differentiation and regulation of LH receptor (LHR) expression, AP.EMU
• Associated scholarship(s): 18/06454-7 - Impact of pregnancy-associated plasma protein- a (PAPP-A) addition during in vitro oocyte maturation on the profile and lipid metabolism of bovine embryos, BP.IC; 17/19679-4 - Effect of Pregnancy-Associated Plasma Protein- A (PAPP-A) about profile and lipid metabolism of bovine oocytes matured in vitro, BP.IC; 16/22812-5 - Cumulus-oocyte complexes in vitro maturation from Holstein cows with pregnancy-associated plasm protein-A: effects on embryo production and quality, BP.MS; + associated scholarships 15/13862-6 - Effect of addition of pregnancy-associated plasma protein a (PAPPA) on cellular and molecular aspects of in vitro maturation from bovine oocyte, BP.IC; 15/10841-8 - Effect of addition of pregnancy-associated plasma protein a (Pappa) during in vitro maturation on bovine embryo production, BP.IC; 14/19469-1 - Characterization of microRNAs (miRNAs) in bovine antral follicles from Nelore cows: involvement during ovarian follicle cells differentiation and regulation of LH receptor (LHR) expression, BP.JP - associated scholarships

Abstract

Luteinizing hormone (LH) plays a key role in the control of physiological processes such as follicle development, ovulation and luteal maintenance in the ovary acting via, LHR. The LHR expression in bovine granulosa cells is crucial for the transition of FSH/LH-dependency in antral follicles. In cattle during the growth and differentiation of granulosa cells, there is an increase on LHR mRNA abundance. Among several factors that control the ovarian development, there is an involvement of microRNAs (miRNAs). MiRNAs are small no-coding RNA molecules composed by 19-25 base pairs that control the cellular translation. Studies have characterized the presence and dual actions of miRNAs in mammalian female reproductive tract, including, deleterious effects on female fertility, as the reduction in ovulatory capacity. Inversely, there is a pro-follicular effect, as inhibition of apoptosis in ovarian follicular by in vivo administration of miRNAs. In cattle, some studies have identified the profile of miRNAs expressed in adult and fetal ovaries and characterized the regulatory effect of miRNAs on mRNA targets involved in ovarian follicular differentiation, but not in the context aimed in this work. Thus, this project using four integrated experiments, aims to investigate and characterize the profile of miRNAs expressed in the theca and granulosa cells during follicle deviation in Nelore heifers, as well as its regulation by pro-survival factors for follicles (IGF1) and gonadotropins (FSH and eCG) used in pharmacological strategies for control of the estrous cycle in cattle. Additionally, we intend to evaluate in vitro actions of miRNAs on the differentiation and steroidogenesis of ovarian follicular cells (granulosa cells) with focus on regulation of LHR expression. Therefore, it is expected that the compilation of the results generated by this study may be identify new targets for enhanced reproductive efficiency in cattle different pharmacological on strategies for the manipulation of the estrus cycle, producing a "molecular signature" of miRNAs required for the development of the follicle dominant in Nellore females, stimulating, perhaps, the development of molecular therapies through the use of miRNAs (in situ) to post transcriptional regulation in the bovine ovary in females of low fertility. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS, P. H.; NUNES, S. G.; FRANCHI, F. F.; GIROTO, A. B.; FONTES, P. K.; PINHEIRO, V. G.; CASTILHO, A. C. S.. Expression of bta-miR-222 and LHCGR in bovine cultured granulosa cells: Impact of follicle deviation and regulation by FSH/insulin in vitro. Theriogenology, v. 182, p. 7-pg., 2022-02-04. (15/04505-5, 13/11480-3)

SANTOS, P. H.; FONTES, P. K.; FRANCHI, F. F.; NOGUEIRA, M. F. G.; BELAZ, K. R. A.; TATA, A.; EBERLIN, M. N.; SUDANO, M. J.; BARROS, C. M.; CASTILHO, A. C. S.. Lipid profiles of follicular fluid from cows submitted to ovarian superstimulation. Theriogenology, v. 94, p. 64-70, MAY 2017. (13/11480-3, 12/07206-0)

SANTOS, P. H.; SATRAPA, R. A.; FONTES, P. K.; FRANCHI, F. F.; RAZZA, E. M.; MANI, F.; NOGUEIRA, M. F. G.; BARROS, C. M.; CASTILHO, A. C. S.. Effect of superstimulation on the expression of microRNAs and genes involved in steroidogenesis and ovulation in Nelore cows. Theriogenology, v. 110, p. 192-200, APR 1 2018. (13/11480-3)

FAVERO, PAOLA FRANCINI; VIEIRA DE LIMA, VICTOR AUGUSTO; DOS SANTOS, PRISCILA HELENA; MARQUES ANDRADE, ANA PAULA; MENDES, LEONARDO OLIVEIRA; PACAGNELLI, FRANCIS LOPES; DE SOUZA CASTILHO, ANTHONY CESAR. Differential fractal dimension is associated with extracellular matrix remodeling in developing bovine corpus luteum. Biochemical and Biophysical Research Communications, v. 516, n. 3, p. 888-893, AUG 27 2019. (18/06674-7, 13/11480-3)

FRANCHI, FERNANDA FAGALI; SATRAPA, RAFAEL AUGUSTO; FONTES, PATRICIA KUBO; SANTOS, PRISCILA HELENA; RAZZA, EDUARDO MONTANARI; EMANUELLI, ISABELE PICADA; ERENO, RONALDO LUIZ; MARECO, EDSON ASSUNCAO; GOUVEIA NOGUEIRA, MARCELO FABIO; BARROS, CIRO MORAES; et al. Equine chorionic gonadotropin drives the transcriptional profile of immature cumulus-oocyte complexes and in vitro-produced blastocysts of superstimulated Nelore cows. Molecular Reproduction and Development, v. 86, n. 11, AUG 2019. (13/11480-3, 12/50533-2)

ALAN BRUNHOLI GIROTO; MARINA PLATZECK CHAVES; PRISCILA HELENA DOS SANTOS; PATRÍCIA KUBO FONTES; SARAH GOMES NUNES; THAINÁ SALLUM BACCO MANSSUR; LEONARDO OLIVEIRA MENDES; ANTHONY CÉSAR DE SOUZA CASTILHO. Expression of luteinizing hormone receptor during development of bovine fetal ovary. Animal Reproduction, v. 21, n. 1, 2024-04-15. (15/04505-5, 13/11480-3)

FRANCHI, FERNANDA FAGALI; HERNANDES, MARIANA PELICHO; COALHO FERREIRA, AMANDA LETICIA; VIEIRA DE LIMA, VICTOR AUGUSTO; MENDES, LEONARDO DE OLIVEIRA; DE AQUINO, ARIANA MUSA; SCARANO, WELLERSON RODRIGO; DE SOUZA CASTILHO, ANTHONY CESAR. Fractal analysis and histomolecular phenotyping provides insights into extracellular matrix remodeling in the developing bovine fetal ovary. Biochemical and Biophysical Research Communications, v. 523, n. 4, p. 823-828, MAR 19 2020. (15/04505-5, 13/11480-3)

GIROTO, ALAN B.; FONTES, PATRICIA K.; FRANCHI, FERNANDA F.; DOS SANTOS, PRISCILA H.; RAZZA, EDUARDO M.; NOGUEIRA, MARCELO F. G.; MAIOLI, MARCOS A.; NOGUEIRA, GUILHERME P.; NUNES, GIOVANA B.; MINGOTI, GISELE Z.; et al. Use of pregnancy-associated plasma protein-A during oocyte in vitro maturation increases IGF-1 and affects the transcriptional profile of cumulus cells and embryos from Nelore cows. Molecular Reproduction and Development, v. 86, n. 11, p. 1694-1704, NOV 2019. (16/22812-5, 15/04505-5, 12/50533-2, 13/11480-3)