Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle

Detalhes bibliográficos
Autor(a) principal: Martins, Thiago
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: eng
Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
Texto Completo: http://www.teses.usp.br/teses/disponiveis/10/10131/tde-17102018-145206/
Resumo: Inadequate uterine environment is one of the main causes of pregnancy failure in cattle. Progesterone (P4) supplementation during early diestrus may either induce a receptive uterine status or shorten luteal lifespan and reduce fertility. Regulation that leads to either outcome is currently unclear. In this thesis, four studies were conducted to test the main hypothesis that the pre-implantational conceptus plays a major role on preventing P4-luteolytic effects in Bos indicus beef cows, due the supplementary P4. In a fifth study the importance of the uterine luminal milieu on the establishment of pregnancy was evaluated. P4 was supplemented by injecting 150 mg of long acting injectable P4 (iP4) on 3 days post-ovulation. In the last study, uterine luminal flushings were performed on days 1, 4 and/or 7 post-estrus, aiming to deplete the uterine milieu. In this thesis, we evidenced that uterus played a key role on determining the iP4-luteolytic response. In this sense, first study revealed that higher uterine exposure to estradiol (E2) during pre-ovulatory period prevented P4-luteolytic effect, but did not increase overall pregnancy outcome. Further analysis, revealed that optimal uterine estradiol exposure is required for beneficial effects of iP4. Cows with large preovulatory follicle or with small follicle, but exposed to the exogenous estradiol presented higher pregnancy rates. Next, we demonstrated that iP4 hindered CL formation, but this had a minor impact on iP4-induced luteolysis. About half of iP4 supplemented cows presented early luteolysis, which occurred by day 15 post-ovulation. Role of the embryo to inhibit iP4-induced early luteolysis relied on its capability to establish pregnancy. In the third study, we demonstrated that iP4-inhibition of growth of the first-wave dominant follicle was related to early luteolytic onset, and this was independent of number of waves in the cycle (two vs. three). Three-wave cycles favored embryonic capacity to inhibit early luteolysis. In the fourth study, we failed to demonstrate that P4 supplementation supported embryonic survival. This was despite of the transfer of 5 embryos to each recipient cow to maximize embryonic signaling. In the last study we disturbed the composition of the uterine environment and negatively affected, but did not abolish, embryonic survival. Overall, from the results obtained in the course of this thesis, we conclude that variability in fertility rates after P4 supplementation, are in part attributable to the complexity of uterine function programming by sex steroids, rather than caused by the incidence of early luteolysis. Furthermore, we highlighted that a sub-optimal composition of the uterine environment is a major contributor to embryonic losses in beef cattle.
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spelling Luteolytic and embryotrophic effects of progesterone supplementation in beef cattleEfeitos luteolíticos e embriotróficos da suplementação de progesterona em bovinos de corteCorpus LuteumCorpus LuteumEmbriãoEmbryoEstradiolEstradiolFolículoFollicleÚteroUterusInadequate uterine environment is one of the main causes of pregnancy failure in cattle. Progesterone (P4) supplementation during early diestrus may either induce a receptive uterine status or shorten luteal lifespan and reduce fertility. Regulation that leads to either outcome is currently unclear. In this thesis, four studies were conducted to test the main hypothesis that the pre-implantational conceptus plays a major role on preventing P4-luteolytic effects in Bos indicus beef cows, due the supplementary P4. In a fifth study the importance of the uterine luminal milieu on the establishment of pregnancy was evaluated. P4 was supplemented by injecting 150 mg of long acting injectable P4 (iP4) on 3 days post-ovulation. In the last study, uterine luminal flushings were performed on days 1, 4 and/or 7 post-estrus, aiming to deplete the uterine milieu. In this thesis, we evidenced that uterus played a key role on determining the iP4-luteolytic response. In this sense, first study revealed that higher uterine exposure to estradiol (E2) during pre-ovulatory period prevented P4-luteolytic effect, but did not increase overall pregnancy outcome. Further analysis, revealed that optimal uterine estradiol exposure is required for beneficial effects of iP4. Cows with large preovulatory follicle or with small follicle, but exposed to the exogenous estradiol presented higher pregnancy rates. Next, we demonstrated that iP4 hindered CL formation, but this had a minor impact on iP4-induced luteolysis. About half of iP4 supplemented cows presented early luteolysis, which occurred by day 15 post-ovulation. Role of the embryo to inhibit iP4-induced early luteolysis relied on its capability to establish pregnancy. In the third study, we demonstrated that iP4-inhibition of growth of the first-wave dominant follicle was related to early luteolytic onset, and this was independent of number of waves in the cycle (two vs. three). Three-wave cycles favored embryonic capacity to inhibit early luteolysis. In the fourth study, we failed to demonstrate that P4 supplementation supported embryonic survival. This was despite of the transfer of 5 embryos to each recipient cow to maximize embryonic signaling. In the last study we disturbed the composition of the uterine environment and negatively affected, but did not abolish, embryonic survival. Overall, from the results obtained in the course of this thesis, we conclude that variability in fertility rates after P4 supplementation, are in part attributable to the complexity of uterine function programming by sex steroids, rather than caused by the incidence of early luteolysis. Furthermore, we highlighted that a sub-optimal composition of the uterine environment is a major contributor to embryonic losses in beef cattle.Um ambiente uterino deficiente é uma das principais causas de falha gestacional em bovinos. A suplementação com progesterona (P4) durante o diestro inicial estimula a receptividade uterina, mas também pode encurtar a fase luteal, prejudicando a fertilidade. Os fatores que levam a um dos dois resultados não são claros. Nesta tese, quatro estudos foram conduzidos para testar a hipótese principal de que o concepto pré-implantacional bloqueia o efeito luteolítico antecipado causado pela P4 suplementar. Em um quinto estudo, avaliou-se a importância do ambiente uterino no estabelecimento da gestação. A suplementação com P4 foi realizada pela administração de 150 mg de P4 injetável (iP4) de longa ação 3 dias após a ovulação. No último estudo, lavados uterinos foram coletados nos dias 1, 4 e/ou 7 após o estro, com o objetivo de depletar o ambiente uterino. Nestes estudos, o útero desempenhou um papel crucial na determinação da resposta luteolítica da iP4. O primeiro experimento demonstrou que a exposição uterina a maiores concentrações de estradiol (E2) durante o período pré-ovulatório bloqueou efeito luteolítico da iP4, mas não resultou em incremento na taxa de prenhez. Análises complementares revelaram que a suplementação de iP4 teve efeito positivo na fertilidade quando houve uma ótima exposição do útero ao E2 pré-ovulatório. Vacas com maiores folículos pré-ovulatórios ou com pequenos folículos, mas suplementadas com estradiol exógeno, apresentaram maiores taxas de prenhez. A exposição sub-ótima ou exagerada ao E2 foi deletéria ao efeito embriotrófico da P4. Em seguida, demonstramos que a iP4 prejudicou o desenvolvimento luteal, porém, esse não foi o principal fator relacionado com a antecipação da luteólise. Aproximadamente metade das vacas suplementadas com iP4 apresentaram luteólise precoce, que ocorreu no dia 15 após a ovulação. O efeito do embrião sobre o processo luteolítico antecipado foi dependente da sua capacidade de estabelecer a gestação. No terceiro estudo, verificamos que a redução do desenvolvimento do folículo dominante da primeira onda esteve associado à ocorrência de luteólise precoce, e isso foi independente do número de ondas no ciclo (dois vs. três). No entanto, ciclos de três ondas favoreceram a capacidade embrionária de inibir a luteólise precoce. No quarto estudo, nós não evidenciamos um efeito embriotófico da iP4 reduzindo a mortalidade embrionária, mesmo quando 5 embriões foram transferidos para cada receptora, com objetivo de maximizar a sinalização embrionária. No último estudo, a composição do ambiente uterino foi alterada por lavagens uterinas e isso afetou negativamente a prenhez, porém não aniquilou as chances de sobrevivência embrionária. A partir dos resultados obtidos nessa tese, concluímos que a variabilidade nas taxas de fertilidade após a suplementação com P4 é, em grande parte, determinada pela complexidade na programação da função uterina pelos hormônios ovarianos, em vez de ser causada pela incidência de luteólise precoce. Além disso, concluímos que uma composição sub-ótima do ambiente uterino é um dos principais contribuintes para as perdas embrionárias em bovinos de corte.Biblioteca Digitais de Teses e Dissertações da USPBinelli, MarioMartins, Thiago2018-07-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://www.teses.usp.br/teses/disponiveis/10/10131/tde-17102018-145206/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2019-04-09T23:21:59Zoai:teses.usp.br:tde-17102018-145206Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212019-04-09T23:21:59Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
Efeitos luteolíticos e embriotróficos da suplementação de progesterona em bovinos de corte
title Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
spellingShingle Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
Martins, Thiago
Corpus Luteum
Corpus Luteum
Embrião
Embryo
Estradiol
Estradiol
Folículo
Follicle
Útero
Uterus
title_short Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
title_full Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
title_fullStr Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
title_full_unstemmed Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
title_sort Luteolytic and embryotrophic effects of progesterone supplementation in beef cattle
author Martins, Thiago
author_facet Martins, Thiago
author_role author
dc.contributor.none.fl_str_mv Binelli, Mario
dc.contributor.author.fl_str_mv Martins, Thiago
dc.subject.por.fl_str_mv Corpus Luteum
Corpus Luteum
Embrião
Embryo
Estradiol
Estradiol
Folículo
Follicle
Útero
Uterus
topic Corpus Luteum
Corpus Luteum
Embrião
Embryo
Estradiol
Estradiol
Folículo
Follicle
Útero
Uterus
description Inadequate uterine environment is one of the main causes of pregnancy failure in cattle. Progesterone (P4) supplementation during early diestrus may either induce a receptive uterine status or shorten luteal lifespan and reduce fertility. Regulation that leads to either outcome is currently unclear. In this thesis, four studies were conducted to test the main hypothesis that the pre-implantational conceptus plays a major role on preventing P4-luteolytic effects in Bos indicus beef cows, due the supplementary P4. In a fifth study the importance of the uterine luminal milieu on the establishment of pregnancy was evaluated. P4 was supplemented by injecting 150 mg of long acting injectable P4 (iP4) on 3 days post-ovulation. In the last study, uterine luminal flushings were performed on days 1, 4 and/or 7 post-estrus, aiming to deplete the uterine milieu. In this thesis, we evidenced that uterus played a key role on determining the iP4-luteolytic response. In this sense, first study revealed that higher uterine exposure to estradiol (E2) during pre-ovulatory period prevented P4-luteolytic effect, but did not increase overall pregnancy outcome. Further analysis, revealed that optimal uterine estradiol exposure is required for beneficial effects of iP4. Cows with large preovulatory follicle or with small follicle, but exposed to the exogenous estradiol presented higher pregnancy rates. Next, we demonstrated that iP4 hindered CL formation, but this had a minor impact on iP4-induced luteolysis. About half of iP4 supplemented cows presented early luteolysis, which occurred by day 15 post-ovulation. Role of the embryo to inhibit iP4-induced early luteolysis relied on its capability to establish pregnancy. In the third study, we demonstrated that iP4-inhibition of growth of the first-wave dominant follicle was related to early luteolytic onset, and this was independent of number of waves in the cycle (two vs. three). Three-wave cycles favored embryonic capacity to inhibit early luteolysis. In the fourth study, we failed to demonstrate that P4 supplementation supported embryonic survival. This was despite of the transfer of 5 embryos to each recipient cow to maximize embryonic signaling. In the last study we disturbed the composition of the uterine environment and negatively affected, but did not abolish, embryonic survival. Overall, from the results obtained in the course of this thesis, we conclude that variability in fertility rates after P4 supplementation, are in part attributable to the complexity of uterine function programming by sex steroids, rather than caused by the incidence of early luteolysis. Furthermore, we highlighted that a sub-optimal composition of the uterine environment is a major contributor to embryonic losses in beef cattle.
publishDate 2018
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dc.publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
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reponame_str Biblioteca Digital de Teses e Dissertações da USP
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