Regulação da divergência folicular in vivo: uma abordagem molecular
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/4074 |
Resumo: | The role of local factors in follicular selection in mammals is not fully understood. The aim of the present study was to identify local factors, receptors and intracellular signaling pathways involved in bovine dominant follicle selection and subordinate follicles atresia. In the first study, the pattern of mRNA expression and function of FGF10 and its receptor FGFR2b was evaluated during bovine follicle deviation. FGF10 and FGFR2b were significantly more expressed in theca and granulosa cells retrieved from subordinate follicles, respectively. Intrafollicular FGF10 treatment in the larger follicle dose-dependently inhibited follicle growth and significantly reduced estradiol secretion. In granulosa cells, FGF10 treatment decreased CYP19A1 and cyclin D2 mRNA expression whereas FGFR2b tended to be more expressed after treatment. In theca cells, a significant increase in FGF10 expression was observed in FGF10-treated follicles. In a second study, BMPRs, BMP15 and GDF9 expression was evaluated in cows ovariectomized when the size of the largest and second largest follicle did not have a significant difference (D2), had slight difference (D3) or marked difference (D4). At day 2 of follicular wave, it was observed a significant increase in BMPR1A expression whereas BMPR-2 and - 1B tended to be more expressed in future subordinate follicles. At day 3, when dominant and subordinate follicles are reliably identified, BMPR-2 and 1B were more expressed in subordinate follicles. At day 4, BMPR1B (mRNA and protein) was significantly more expressed in granulosa cells from atretic follicles. The increased BMPR1B expression during atresia was confirmed in granulosa cells from follicles induced to atresia with FGF10 or estradiol receptor antagonist treatment. Similar levels of BMP15 and GDF9 proteins were observed in follicular fluid from dominant and subordinate follicles. In a third study, we aimed to identify intracellular signaling pathways differentially activated in granulosa cells during deviation. Phosphorylated MAPK was more abundant in the future dominant follicle, but did not differ between follicles at the expected moment and after follicular deviation. Subordinate follicles phosphorylated STAT3 levels tended to increase at day 3 and were significantly greater at day 4 in comparison to dominant follicles. In conclusion, present results suggest that decreased FGF10 and FGFR2b expression allows dominant follicle growth and differentiation whereas increased FGF10 signaling in the subordinate follicle induces atresia. The patterns of BMPR- 2, -1B and -1A indicate that these receptors play roles during follicle deviation. Phosphorylated MAPK abundance is an early marker of follicle dominance, but is not differentially regulated during and after deviation. The functional status of STAT3 suggests that this pathway is involved in granulosa cell death. |
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2017-05-292017-05-292012-08-17GASPERIN, Bernardo Garziera. Regulation of follicular deviation in vivo: a molecular approach. 2012. 123 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/4074The role of local factors in follicular selection in mammals is not fully understood. The aim of the present study was to identify local factors, receptors and intracellular signaling pathways involved in bovine dominant follicle selection and subordinate follicles atresia. In the first study, the pattern of mRNA expression and function of FGF10 and its receptor FGFR2b was evaluated during bovine follicle deviation. FGF10 and FGFR2b were significantly more expressed in theca and granulosa cells retrieved from subordinate follicles, respectively. Intrafollicular FGF10 treatment in the larger follicle dose-dependently inhibited follicle growth and significantly reduced estradiol secretion. In granulosa cells, FGF10 treatment decreased CYP19A1 and cyclin D2 mRNA expression whereas FGFR2b tended to be more expressed after treatment. In theca cells, a significant increase in FGF10 expression was observed in FGF10-treated follicles. In a second study, BMPRs, BMP15 and GDF9 expression was evaluated in cows ovariectomized when the size of the largest and second largest follicle did not have a significant difference (D2), had slight difference (D3) or marked difference (D4). At day 2 of follicular wave, it was observed a significant increase in BMPR1A expression whereas BMPR-2 and - 1B tended to be more expressed in future subordinate follicles. At day 3, when dominant and subordinate follicles are reliably identified, BMPR-2 and 1B were more expressed in subordinate follicles. At day 4, BMPR1B (mRNA and protein) was significantly more expressed in granulosa cells from atretic follicles. The increased BMPR1B expression during atresia was confirmed in granulosa cells from follicles induced to atresia with FGF10 or estradiol receptor antagonist treatment. Similar levels of BMP15 and GDF9 proteins were observed in follicular fluid from dominant and subordinate follicles. In a third study, we aimed to identify intracellular signaling pathways differentially activated in granulosa cells during deviation. Phosphorylated MAPK was more abundant in the future dominant follicle, but did not differ between follicles at the expected moment and after follicular deviation. Subordinate follicles phosphorylated STAT3 levels tended to increase at day 3 and were significantly greater at day 4 in comparison to dominant follicles. In conclusion, present results suggest that decreased FGF10 and FGFR2b expression allows dominant follicle growth and differentiation whereas increased FGF10 signaling in the subordinate follicle induces atresia. The patterns of BMPR- 2, -1B and -1A indicate that these receptors play roles during follicle deviation. Phosphorylated MAPK abundance is an early marker of follicle dominance, but is not differentially regulated during and after deviation. The functional status of STAT3 suggests that this pathway is involved in granulosa cell death.O controle local da seleção folicular em mamíferos ainda é pouco compreendido. O objetivo do presente estudo foi identificar fatores locais, receptores e rotas de sinalização envolvidas na seleção do folículo dominante e atresia dos subordinados em bovinos. Em um primeiro estudo, avaliou-se a regulação e função do FGF10 e do seu receptor FGFR2b durante a divergência folicular. A expressão de FGF10 e FGFR2b foi significativamente maior nas células da teca e granulosa, respectivamente, provenientes dos folículos subordinados. A injeção intrafolicular de FGF10 inibiu o crescimento folicular de maneira dose dependente e reduziu significativamente a síntese de estradiol. Nas células da granulosa, a injeção de FGF10 diminuiu a expressão de RNAm de CYP19A1 e ciclina D2, enquanto que uma tendência de aumento da expressão do receptor FGFR2b foi observada. Nas células da teca, um aumento significativo na expressão de FGF10 foi observado nos folículos tratados com FGF10. Em um segundo estudo, o padrão de expressão dos receptores de BMPs e das proteínas BMP15 e GDF9 foram avaliados em vacas ovariectomizadas em diferenes dias em relação ao inicio da onda folicular, comparando os dois maiores folículos antes (dia 2), durante (dia 3) ou após a divergência folícular (dia 4). No dia 2 da onda folicular, foi observada maior expressão do receptor BMPR-1A e tendências a maior expressão dos receptores BMPR-2 e -1B nos futuros folículos subordinados. No dia 3, quando os folículos dominantes e subordinados são identificados, a expressão de BMPR-1B e -2 foi maior nos folículos subordinados. No dia 4, o receptor BMPR1B (RNAm e proteína) foi significativamente mais expresso nas células da granulosa de folículos atrésicos. O aumento da expressão do BMPR1B durante a atresia folicular foi confirmado nas células da granulosa de folículos induzidos à atresia através do tratamento com FGF10 ou inibidor dos receptores de estradiol. A abundância de BMP15 e GDF9 no fluído folicular não diferiu entre folículos dominantes e subordinados. Em um terceiro estudo, buscou-se identificar rotas de sinalização diferentemente ativas nas células da granulosa durante a divergência. Os níveis de MAPK fosforilada foram significativamente superiores nos futuros folículos dominantes (dia 2), mas não diferiram entre os dois maiores folículos durante ou após a divergência. Folículos subordinados apresentaram maiores níveis de STAT3 fosforilada em relação aos seus respectivos dominantes em todos os pares de folículos coletados, sendo observado um aumento significativo em folículos atrésicos coletados no dia 4. Em conclusão, os resultados sugerem que a expressão reduzida de FGF10 e do receptor FGFR2b possibilitam o crescimento e diferenciação do folículo dominante, enquanto que o aumento da sinalização do FGF10 no folículo subordinado está associado com a atresia. O perfil de expressão dos receptores BMPR-2, -1B e -1A indica que os mesmos apresentam funções na regulação da divergência folicular em bovinos. A fosforilação da MAPK é um marcador inicial de dominância folicular, mas não é diferentemente regulada durante e após a divergência, enquanto que o padrão de ativação da STAT3 sugere que essa via está envolvida na morte das células da granulosa.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Medicina VeterináriaUFSMBRMedicina VeterináriaFGF10BMPRsGDF9BMP15MAPKSTAT3FGF10BMPRsGDF9BMP15MAPKSTAT3CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIARegulação da divergência folicular in vivo: uma abordagem molecularRegulation of follicular deviation in vivo: a molecular approachinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisGonçalves, Paulo Bayard Diashttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781845H4Schoenau, Williamhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4786464J0Comim, Fabio Vasconcelloshttp://lattes.cnpq.br/5119233991388822Costa, Luís Fabiano Santos dahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794804D6Mesquita, Fernando Silveirahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4706920D8http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4757171E8Gasperin, Bernardo Garziera500500000007400300300300300300300fcd33ccc-f08d-428c-b7da-9d3757cf0a96030d815b-50d4-446b-9ff4-cea7cd8987f11c8df021-4c5c-4d5a-b661-07a806ffe3911251088f-87d7-4b52-baa6-8e5739b3bf79c4134c6a-7f66-40a5-a3c6-408ee424689c524361ed-01c9-4c08-b4d9-53739d37ebd2info:eu-repo/semantics/openAccessreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALGASPERIN, BERNARDO GARZIERA.pdfTese de Doutoradoapplication/pdf5884222http://repositorio.ufsm.br/bitstream/1/4074/1/GASPERIN%2c%20BERNARDO%20GARZIERA.pdf3239b24a1001b88ba1b3b153ed9a22adMD51TEXTGASPERIN, BERNARDO GARZIERA.pdf.txtGASPERIN, BERNARDO GARZIERA.pdf.txtExtracted texttext/plain210326http://repositorio.ufsm.br/bitstream/1/4074/2/GASPERIN%2c%20BERNARDO%20GARZIERA.pdf.txt0d235dbeb769940675cf5ab0ace01722MD52THUMBNAILGASPERIN, BERNARDO GARZIERA.pdf.jpgGASPERIN, BERNARDO GARZIERA.pdf.jpgIM Thumbnailimage/jpeg4560http://repositorio.ufsm.br/bitstream/1/4074/3/GASPERIN%2c%20BERNARDO%20GARZIERA.pdf.jpg06d510b3375013be6fe350563298543aMD531/40742017-12-02 13:29:15.371oai:repositorio.ufsm.br:1/4074Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132017-12-02T15:29:15Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Regulação da divergência folicular in vivo: uma abordagem molecular |
dc.title.alternative.eng.fl_str_mv |
Regulation of follicular deviation in vivo: a molecular approach |
title |
Regulação da divergência folicular in vivo: uma abordagem molecular |
spellingShingle |
Regulação da divergência folicular in vivo: uma abordagem molecular Gasperin, Bernardo Garziera FGF10 BMPRs GDF9 BMP15 MAPK STAT3 FGF10 BMPRs GDF9 BMP15 MAPK STAT3 CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
Regulação da divergência folicular in vivo: uma abordagem molecular |
title_full |
Regulação da divergência folicular in vivo: uma abordagem molecular |
title_fullStr |
Regulação da divergência folicular in vivo: uma abordagem molecular |
title_full_unstemmed |
Regulação da divergência folicular in vivo: uma abordagem molecular |
title_sort |
Regulação da divergência folicular in vivo: uma abordagem molecular |
author |
Gasperin, Bernardo Garziera |
author_facet |
Gasperin, Bernardo Garziera |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Gonçalves, Paulo Bayard Dias |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781845H4 |
dc.contributor.referee1.fl_str_mv |
Schoenau, William |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4786464J0 |
dc.contributor.referee2.fl_str_mv |
Comim, Fabio Vasconcellos |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/5119233991388822 |
dc.contributor.referee3.fl_str_mv |
Costa, Luís Fabiano Santos da |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794804D6 |
dc.contributor.referee4.fl_str_mv |
Mesquita, Fernando Silveira |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4706920D8 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4757171E8 |
dc.contributor.author.fl_str_mv |
Gasperin, Bernardo Garziera |
contributor_str_mv |
Gonçalves, Paulo Bayard Dias Schoenau, William Comim, Fabio Vasconcellos Costa, Luís Fabiano Santos da Mesquita, Fernando Silveira |
dc.subject.por.fl_str_mv |
FGF10 BMPRs GDF9 BMP15 MAPK STAT3 |
topic |
FGF10 BMPRs GDF9 BMP15 MAPK STAT3 FGF10 BMPRs GDF9 BMP15 MAPK STAT3 CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
dc.subject.eng.fl_str_mv |
FGF10 BMPRs GDF9 BMP15 MAPK STAT3 |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
The role of local factors in follicular selection in mammals is not fully understood. The aim of the present study was to identify local factors, receptors and intracellular signaling pathways involved in bovine dominant follicle selection and subordinate follicles atresia. In the first study, the pattern of mRNA expression and function of FGF10 and its receptor FGFR2b was evaluated during bovine follicle deviation. FGF10 and FGFR2b were significantly more expressed in theca and granulosa cells retrieved from subordinate follicles, respectively. Intrafollicular FGF10 treatment in the larger follicle dose-dependently inhibited follicle growth and significantly reduced estradiol secretion. In granulosa cells, FGF10 treatment decreased CYP19A1 and cyclin D2 mRNA expression whereas FGFR2b tended to be more expressed after treatment. In theca cells, a significant increase in FGF10 expression was observed in FGF10-treated follicles. In a second study, BMPRs, BMP15 and GDF9 expression was evaluated in cows ovariectomized when the size of the largest and second largest follicle did not have a significant difference (D2), had slight difference (D3) or marked difference (D4). At day 2 of follicular wave, it was observed a significant increase in BMPR1A expression whereas BMPR-2 and - 1B tended to be more expressed in future subordinate follicles. At day 3, when dominant and subordinate follicles are reliably identified, BMPR-2 and 1B were more expressed in subordinate follicles. At day 4, BMPR1B (mRNA and protein) was significantly more expressed in granulosa cells from atretic follicles. The increased BMPR1B expression during atresia was confirmed in granulosa cells from follicles induced to atresia with FGF10 or estradiol receptor antagonist treatment. Similar levels of BMP15 and GDF9 proteins were observed in follicular fluid from dominant and subordinate follicles. In a third study, we aimed to identify intracellular signaling pathways differentially activated in granulosa cells during deviation. Phosphorylated MAPK was more abundant in the future dominant follicle, but did not differ between follicles at the expected moment and after follicular deviation. Subordinate follicles phosphorylated STAT3 levels tended to increase at day 3 and were significantly greater at day 4 in comparison to dominant follicles. In conclusion, present results suggest that decreased FGF10 and FGFR2b expression allows dominant follicle growth and differentiation whereas increased FGF10 signaling in the subordinate follicle induces atresia. The patterns of BMPR- 2, -1B and -1A indicate that these receptors play roles during follicle deviation. Phosphorylated MAPK abundance is an early marker of follicle dominance, but is not differentially regulated during and after deviation. The functional status of STAT3 suggests that this pathway is involved in granulosa cell death. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-08-17 |
dc.date.accessioned.fl_str_mv |
2017-05-29 |
dc.date.available.fl_str_mv |
2017-05-29 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
GASPERIN, Bernardo Garziera. Regulation of follicular deviation in vivo: a molecular approach. 2012. 123 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4074 |
identifier_str_mv |
GASPERIN, Bernardo Garziera. Regulation of follicular deviation in vivo: a molecular approach. 2012. 123 f. Tese (Doutorado em Medicina Veterinária) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
url |
http://repositorio.ufsm.br/handle/1/4074 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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500500000007 |
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400 300 300 300 300 300 300 |
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openAccess |
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Universidade Federal de Santa Maria |
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Programa de Pós-Graduação em Medicina Veterinária |
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UFSM |
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BR |
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Medicina Veterinária |
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Universidade Federal de Santa Maria |
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