Doctor of Philosophy / Department of Animal Sciences and Industry / Luis G. Mendonca / Reproduction is an important part of a dairy operation that directly affects milk production and profitability. Fertility of high-producing dairy cows is less than desired. Reproductive efficiency is further impaired during summer months and after cows develop postpartum uterine disease. Heat stress and uterine disease act as stressors that negatively influence fertility of dairy cattle through a variety of mechanisms. This dissertation further investigates the negative effects of heat stress and uterine disease on reproduction, as well as examines two potential markers for predicting risk of developing uterine disease. Study 1 investigated the treatment of lactating dairy cows with gonadotropin-releasing hormone (GnRH) before first insemination during heat stress. Two experiments were performed to compare ovarian responses, pregnancy per artificial insemination (AI), and patterns of insemination of two estrus detection-based presynchronization protocols before first AI during summer heat stress. Treatment of cows with GnRH during summer heat stress altered ovarian response and pattern of insemination, however, did not improve pregnancy per AI. Study 2 evaluated ovarian response to treatment with GnRH and the odds of bearing a corpus luteum or being inseminated in cows with or without purulent vaginal discharge (PVD). Furthermore, hazard of insemination after administration of prostaglandin F2α was evaluated in dairy cows with or without PVD. Ovarian response was altered in cows with PVD compared with cows without PVD. Odds of bearing a corpus luteum or being inseminated was not associated with PVD in primiparous cows, whereas it was associated with PVD in multiparous cows. Hazard of insemination after prostaglandin F2α was not associated with PVD. Study 3 investigated arginase and matrix metalloproteinase-8 (MMP-8) as potential markers for metritis. Activity of arginase 7 days before parturition has been identified as a potential marker for the risk of developing metritis in dairy cows. In contrast, MMP-8 was not associated with the risk of developing metritis, therefore, MMP-8 is not a good candidate as a marker for metritis. Further research is warranted in the areas of reproductive physiology, heat stress, and uterine disease because several unanswered questions still exist. Improving fertility during times of heat stress and after the occurrence of postpartum uterine disease will improve milk production, animal welfare, and profitability of dairy farms across the world.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Contaminação bacteriana que normalmente infecta o endométrio bovino no pós-parto prejudica a defesa imunológica quando há estresse metabólico, levando a endometrite e infertilidade. A resposta do endométrio contra bactérias depende da imunidade inata, com o reconhecimento de padrões moleculares associados a patógenos, estimulando a inflamação, caracterizadas por secreção de interleucinas (IL)-1p, IL-6 e IL-8. Entretanto, animais frequentemente falham em eliminar a infecção microbiana quando apresentam reduzidas concentrações de glicose e glutamina, que são fontes de energia para o endométrio no conhecido balanço energético negativo. A contínua inflamação e resposta imune inata contra infecção bacteriana no útero após o parto compromete o bem-estar animal. Neste estudo testou-se a hipótese de que as vias homeostáticas conferidas pela glicose, glutamina e biotina integram o metabolismo energético e a imunidade inata no tecido endometrial bovino. A ausência de glicose reduziu a secreção de IL-1P, IL-6 e IL-8 em culturas de órgãos endometriais desafiadas com a endotoxina lipopolissacarídeo (LPS). Depleção de glutamina também reduziu a atividade inflamatória do endométrio contra LPS. Entretanto, as atividades de glicose e glutamina dependem da presença de glicólise. A vitamina biotina demonstrou ter caráter anti- inflamatório, reduzindo a produção de citocinas pró-inflamatórias no endométrio. Em conclusão, o estresse energético metabólico afetou as respostas inflamatórias à infecções bacterianas no endométrio. Providenciamos dados que demonstram como o balanço energético negativo pode estar ligado a doença uterina no pós-parto. / Bacteria that usually infect the bovine endometrium at postpartum impairs immune defense when exist metabolic stress, leading to endometritis and infertility. The response of the endometrium to bacteria depends on innate immunity, with the recognition of pathogen-associated molecular patterns by stimulating inflammation, characterized by secretion of interleukins (IL) -1p, IL-6 and IL-8. However, animals often fail to eliminate the microbial infection when they have reduced levels of glucose and glutamine, which are sources of energy to the endometrium in the negative energy balance. Continuous inflammation and innate immune response to bacterial infection in the uterus after calving compromise animal welfare. In this study we tested the hypothesis that homeostatic pathways conferred by glucose , glutamine and biotin, link the energy metabolism and innate immunity in the bovine endometrial tissue. The deprivation of glucose reduced the secretion of IL-1P, IL-6 and IL-8 in cultures of endometrial organs challenged with the endotoxin lipopolysaccharide (LPS). Glutamine depletion also reduces the inflammatory activity of the endometrium to LPS. However, glucose and glutamine activities depend on the presence of glycolysis. The vitamin biotin demonstrates anti-inflammatory nature, reducing the production of proinflammatory cytokines in the endometrium. In conclusion, the energy metabolic stress disrupts inflammatory responses to bacterial infections in the endometrium. We provide data on how negative energy balance may be linked to postpartum uterine disease. / Tese (Doutorado)