Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20704 |
Resumo: | Dairy cows milk production has increased over the past decades as a result of intense genetic selection. However, the advances in genetic selection of dairy herds did not come with an improvement of reproductive parameters. Negative energy balance (NEB) during postpartum period is important risk factor in the establishment of reproductive failure in high producing dairy cows. During NEB, nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) levels are increased in the serum and follicular fluid and affect follicular microenvironment and endometrium in cattle. Furthermore, the exact NEFAs and BHBA mechanism of action is not yet established and may occur via nuclear receptors. Therefore, the aim of present study was to investigate NEFAs and BHBA action on folliculogenesis and endometrium, as well as to investigate if peroxisome proliferator activated receptor gamma (PPARG) is involved in their regulation in cattle. In the first study, the aim was to investigate if the PPARG participates in the regulation of dominant follicle development and ovulation. Findings from this study revealed that the relative mRNA abundance of PPARG was similar between dominant and subordinate follicles around follicle deviation, decreased after the LH surge, and increased before ovulation. Intrafollicular injection of Troglitazone (TGZ; a PPARG agonist) inhibited follicular growth and decreased CYP19A1 mRNA abundance in granulosa cells. These findings indicate that PPARG is involved in the regulation of steroidogenesis, follicle growth and ovulation in cattle. In a second study, the aim was to investigate if intrafolicular injection of three most important NEFAs (oleic, stearic and palmitic acids) affects dominant follicle development and mRNA expression of candidate genes in granulosa cells. NEFAs injection reduced follicular growth at 24 and 48 h, demonstrating that the high concentrations of NEFAs are detrimental to follicle development. The mRNA expression of genes related to steroidogenesis energetic metabolism and apoptosis examined were not affected by intrafollicular injection of NEFAs. However, NEFAs affected the follicle growth rate of dominant follicle but the mechanism of action still needs further study. In the final study, we evaluated the effects of NEFAs and BHBA in endometrium cells. Findings from this study showed that in vitro treatment with NEFAs and NEFAs plus BHBA increased lipid accumulation, stimulated reactive oxygen species (ROS), altered the morphology and the mRNA expression of genes related to oxidative stress, apoptosis and glucose transport in the endometrium cells. Also, palmitic acid (PA) was able to modulate the try-methylation of histone 3 lysine 4 (H3K4me3) and the mRNA expression of DNA methyltransferase 1 (DNMT1). Altogether, data present in these studies provided evidence that NEFAs and BHBA are detrimental to follicle development and endometrium cells in cattle. |
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2021-04-27T11:35:18Z2021-04-27T11:35:18Z2020-02-10http://repositorio.ufsm.br/handle/1/20704Dairy cows milk production has increased over the past decades as a result of intense genetic selection. However, the advances in genetic selection of dairy herds did not come with an improvement of reproductive parameters. Negative energy balance (NEB) during postpartum period is important risk factor in the establishment of reproductive failure in high producing dairy cows. During NEB, nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) levels are increased in the serum and follicular fluid and affect follicular microenvironment and endometrium in cattle. Furthermore, the exact NEFAs and BHBA mechanism of action is not yet established and may occur via nuclear receptors. Therefore, the aim of present study was to investigate NEFAs and BHBA action on folliculogenesis and endometrium, as well as to investigate if peroxisome proliferator activated receptor gamma (PPARG) is involved in their regulation in cattle. In the first study, the aim was to investigate if the PPARG participates in the regulation of dominant follicle development and ovulation. Findings from this study revealed that the relative mRNA abundance of PPARG was similar between dominant and subordinate follicles around follicle deviation, decreased after the LH surge, and increased before ovulation. Intrafollicular injection of Troglitazone (TGZ; a PPARG agonist) inhibited follicular growth and decreased CYP19A1 mRNA abundance in granulosa cells. These findings indicate that PPARG is involved in the regulation of steroidogenesis, follicle growth and ovulation in cattle. In a second study, the aim was to investigate if intrafolicular injection of three most important NEFAs (oleic, stearic and palmitic acids) affects dominant follicle development and mRNA expression of candidate genes in granulosa cells. NEFAs injection reduced follicular growth at 24 and 48 h, demonstrating that the high concentrations of NEFAs are detrimental to follicle development. The mRNA expression of genes related to steroidogenesis energetic metabolism and apoptosis examined were not affected by intrafollicular injection of NEFAs. However, NEFAs affected the follicle growth rate of dominant follicle but the mechanism of action still needs further study. In the final study, we evaluated the effects of NEFAs and BHBA in endometrium cells. Findings from this study showed that in vitro treatment with NEFAs and NEFAs plus BHBA increased lipid accumulation, stimulated reactive oxygen species (ROS), altered the morphology and the mRNA expression of genes related to oxidative stress, apoptosis and glucose transport in the endometrium cells. Also, palmitic acid (PA) was able to modulate the try-methylation of histone 3 lysine 4 (H3K4me3) and the mRNA expression of DNA methyltransferase 1 (DNMT1). Altogether, data present in these studies provided evidence that NEFAs and BHBA are detrimental to follicle development and endometrium cells in cattle.Um dos principais problemas abordados na pecuária de leite nas últimas décadas tem sido a redução da fertilidade em vacas de alta produção. O balanço energético negativo (BEN) durante o período pós-parto é um fator de risco para que ocorram alterações reprodutivas. Durante esse período, as concentrações séricas dos ácidos graxos não esterificados (NEFAs) e do beta-hidroxibutirato (BHBA) estão aumentadas. Essas alterações têm reflexo no microambiente folicular e endométrio bovino. Além disso, o exato mecanismo de ação dos NEFAs e BHBA nos tecidos-alvo ainda não está estabelecido, podendo ocorrer via receptores nucleares. Portanto, o objetivo do presente trabalho foi investigar a ação dos NEFAs e do BHBA na foliculogênese e no endométrio bovino, bem como investigar se os efeitos ocorrem via receptor ativado por proliferador de peroxissomo gama (PPARG). Primeiramente, investigou-se a participação do PPARG na regulação do desenvolvimento do folículo dominante e ovulação. Os resultados deste estudo revelaram que a abundância de RNAm do PPARG foi similar entre os folículos dominante e subordinado em torno da divergência folicular, diminuindo após o pico de LH e aumentando antes da ovulação. Além disso, a ativação do PPARG com Troglitazone (TGZ; agonista do PPARG) inibiu o crescimento folicular e diminuiu a expressão de RNAm da CYP19A1 nas células da granulosa bovina. Portanto, PPARG é envolvido na regulação da esteroidogênese, crescimento folicular e ovulação em bovinos. O segundo estudo teve como objetivo investigar se a injeção intrafolicular com os três principais NEFAs (ácido oleico, esteárico e palmítico) afeta o desenvolvimento do folículo dominante e a expressão de RNAm de genes candidatos nas células da granulosa. Observou-se que a injeção intrafolicular com os NEFAs reduziram o crescimento folicular 24 e 48 h após o tratamento, demonstrando que altas concentrações dos NEFAs são prejudiciais para o desenvolvimento folicular. No entanto, a expressão de genes relacionados a esteroidogênese, metabolismo e apoptose não foram afetados. Da mesma forma, a expressão de RNAm do PPARG não foi alterada após o tratamento. Portanto, os NEFAs afetam a taxa de crescimento folicular do folículo dominante, mas o mecanismo de ação ainda necessita mais estudos. O terceiro estudo teve como objetivo avaliar os efeitos dos NEFAs e BHBA nas células endometriais bovinas. Os resultados obtidos revelaram que os tratamentos in vitro com NEFAs e NEFAs+BHBA induziram um acúmulo de lipídeos nas células, estimularam a produção de espécies reativas ao oxigênio (ROS), alteraram a morfologia das células e aumentaram a expressão de RNAm dos genes relacionados ao estresse oxidativo, apoptose e transporte de glicose. O estudo também evidenciou que o ácido palmítico (AP) afeta a regulação epigenética nas células endometriais, alterando a trimetilação da lisina 4 da histona 3 (H3K4me3) e a expressão de RNAm da DNA metiltransferase 1 (DNMT1). Em conjunto, os dados apresentados evidenciam os efeitos deletérios do aumento dos NEFAs e BHBA no desenvolvimento folicular e nas células endometriais bovinas.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de Santa MariaCentro de Ciências RuraisPrograma de Pós-Graduação em Medicina VeterináriaUFSMBrasilMedicina VeterináriaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessBovinoCélulas da granulosaCélulas endometriaisEpigenéticaDivergência folicularBovineGranulosa cellsEndometrium cellsEpigeneticsFollicle deviationCNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIAÁcidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriaisNonesterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) in the foliculogenesis and epigenetics regulation of the endometrial cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisGonçalves, Paulo Bayard Diashttp://lattes.cnpq.br/5837260966665885Mesquita, Fernando SilveiraSantos, Joabel Tonellotto dosOliveira, Dimas Estrasulas deLeivas, Fábio Gallashttp://lattes.cnpq.br/7452840783938989Ferst, Juliana Germano500500000007600600600600600600600fcd33ccc-f08d-428c-b7da-9d3757cf0a96fee2ab57-7b3d-44aa-979c-66c2d4b54bc24cd5e569-cc1a-47c5-8ad0-c8161879aedd271e0d1f-d49c-4b2e-a76d-bb0b373e96917902b582-128d-4a7f-932c-84aa3eb059d4acbd5b7a-313d-4f5b-ace0-b945078d5f4creponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGMV_2020_FERST_JULIANA.pdfTES_PPGMV_2020_FERST_JULIANA.pdfTeseapplication/pdf18549451http://repositorio.ufsm.br/bitstream/1/20704/1/TES_PPGMV_2020_FERST_JULIANA.pdf0c0b3d7d58b6d349a1b20152b6a9e1c5MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
dc.title.alternative.eng.fl_str_mv |
Nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) in the foliculogenesis and epigenetics regulation of the endometrial cells |
title |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
spellingShingle |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais Ferst, Juliana Germano Bovino Células da granulosa Células endometriais Epigenética Divergência folicular Bovine Granulosa cells Endometrium cells Epigenetics Follicle deviation CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
title_full |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
title_fullStr |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
title_full_unstemmed |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
title_sort |
Ácidos graxos não esterificados (NEFAs) e beta-hidroxibutirato (BHBA) na regulação da foliculogênese e epigenética das células endometriais |
author |
Ferst, Juliana Germano |
author_facet |
Ferst, Juliana Germano |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Gonçalves, Paulo Bayard Dias |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5837260966665885 |
dc.contributor.referee1.fl_str_mv |
Mesquita, Fernando Silveira |
dc.contributor.referee2.fl_str_mv |
Santos, Joabel Tonellotto dos |
dc.contributor.referee3.fl_str_mv |
Oliveira, Dimas Estrasulas de |
dc.contributor.referee4.fl_str_mv |
Leivas, Fábio Gallas |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7452840783938989 |
dc.contributor.author.fl_str_mv |
Ferst, Juliana Germano |
contributor_str_mv |
Gonçalves, Paulo Bayard Dias Mesquita, Fernando Silveira Santos, Joabel Tonellotto dos Oliveira, Dimas Estrasulas de Leivas, Fábio Gallas |
dc.subject.por.fl_str_mv |
Bovino Células da granulosa Células endometriais Epigenética Divergência folicular |
topic |
Bovino Células da granulosa Células endometriais Epigenética Divergência folicular Bovine Granulosa cells Endometrium cells Epigenetics Follicle deviation CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
dc.subject.eng.fl_str_mv |
Bovine Granulosa cells Endometrium cells Epigenetics Follicle deviation |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
Dairy cows milk production has increased over the past decades as a result of intense genetic selection. However, the advances in genetic selection of dairy herds did not come with an improvement of reproductive parameters. Negative energy balance (NEB) during postpartum period is important risk factor in the establishment of reproductive failure in high producing dairy cows. During NEB, nonesterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) levels are increased in the serum and follicular fluid and affect follicular microenvironment and endometrium in cattle. Furthermore, the exact NEFAs and BHBA mechanism of action is not yet established and may occur via nuclear receptors. Therefore, the aim of present study was to investigate NEFAs and BHBA action on folliculogenesis and endometrium, as well as to investigate if peroxisome proliferator activated receptor gamma (PPARG) is involved in their regulation in cattle. In the first study, the aim was to investigate if the PPARG participates in the regulation of dominant follicle development and ovulation. Findings from this study revealed that the relative mRNA abundance of PPARG was similar between dominant and subordinate follicles around follicle deviation, decreased after the LH surge, and increased before ovulation. Intrafollicular injection of Troglitazone (TGZ; a PPARG agonist) inhibited follicular growth and decreased CYP19A1 mRNA abundance in granulosa cells. These findings indicate that PPARG is involved in the regulation of steroidogenesis, follicle growth and ovulation in cattle. In a second study, the aim was to investigate if intrafolicular injection of three most important NEFAs (oleic, stearic and palmitic acids) affects dominant follicle development and mRNA expression of candidate genes in granulosa cells. NEFAs injection reduced follicular growth at 24 and 48 h, demonstrating that the high concentrations of NEFAs are detrimental to follicle development. The mRNA expression of genes related to steroidogenesis energetic metabolism and apoptosis examined were not affected by intrafollicular injection of NEFAs. However, NEFAs affected the follicle growth rate of dominant follicle but the mechanism of action still needs further study. In the final study, we evaluated the effects of NEFAs and BHBA in endometrium cells. Findings from this study showed that in vitro treatment with NEFAs and NEFAs plus BHBA increased lipid accumulation, stimulated reactive oxygen species (ROS), altered the morphology and the mRNA expression of genes related to oxidative stress, apoptosis and glucose transport in the endometrium cells. Also, palmitic acid (PA) was able to modulate the try-methylation of histone 3 lysine 4 (H3K4me3) and the mRNA expression of DNA methyltransferase 1 (DNMT1). Altogether, data present in these studies provided evidence that NEFAs and BHBA are detrimental to follicle development and endometrium cells in cattle. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-02-10 |
dc.date.accessioned.fl_str_mv |
2021-04-27T11:35:18Z |
dc.date.available.fl_str_mv |
2021-04-27T11:35:18Z |
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.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20704 |
url |
http://repositorio.ufsm.br/handle/1/20704 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
500500000007 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Rurais |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Medicina Veterinária |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Medicina Veterinária |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Rurais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Repositório Institucional Manancial UFSM |
collection |
Repositório Institucional Manancial UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/20704/1/TES_PPGMV_2020_FERST_JULIANA.pdf http://repositorio.ufsm.br/bitstream/1/20704/2/license_rdf http://repositorio.ufsm.br/bitstream/1/20704/3/license.txt http://repositorio.ufsm.br/bitstream/1/20704/4/TES_PPGMV_2020_FERST_JULIANA.pdf.txt http://repositorio.ufsm.br/bitstream/1/20704/5/TES_PPGMV_2020_FERST_JULIANA.pdf.jpg |
bitstream.checksum.fl_str_mv |
0c0b3d7d58b6d349a1b20152b6a9e1c5 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df d193bdd9e41e05b9dd09796f20ed8e2c 41ca1ecd206734ed5bc0c5c0283768ae |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
ouvidoria@ufsm.br |
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1808854704554246144 |