Efeito do estresse térmico em leucócitos bovinos durante o reconhecimento materno da gestação

Abstract

Heat stress represents one of the major causes of productive and reproductive losses in a milk production system. Heat stress induces hyperthermia, alters folliculogenesis, reduces the expression of estrus signals, causes decreased oocyte quality and loss or development of lowquality embryos; it also induces oxidative stress, which is a precursor of endoplasmic reticulum (ER) stress. The effects of heat stress become even more pronounced in the first days of the embryo's life, compromising the production of interferon tau (IFNT), a protein necessary for maternal recognition of pregnancy. In addition to pregnancy recognition, IFNT is responsible for inducing the expression of interferon-stimulated genes (ISGs). Studies have demonstrated the expression of ISGs in blood cells after IFNT signaling in early pregnancy in ruminants. The presence of IFNT stimulates the expression of ISGs in in vitro culture of mononuclear (PBMCs) and polymorphonuclear (PMNs) cells. In addition, it is known that IFNT modulates the immune system and, during maternal recognition of pregnancy, recruits immune cells to the corpus luteum (CL), demonstrating its systemic action in the maintenance of pregnancy. However, the mechanism by which IFNT modulates its systemic expression during the occurrence of heat stress in cattle is still unclear. Therefore, our hypothesis was that heat stress alters the type 1 interferons (IFNs) pathway and ISGs in leukocytes of dairy cows during the maternal recognition period of pregnancy, alters the innate immune response genes in dairy cows in early pregnancy from an anti-inflammatory state to a pro-inflammatory state and induces the occurrence of oxidative stress, consequently stress of ER and Heat Shock Proteins (HSPs) in the peripheral blood of cows with early pregnancy. First, we investigated the effect of heat stress on the modulation of the type 1 IFNs pathway in leukocytes from pregnant cows and parameters of oxidative stress. The results showed that heat stress in pregnant cows not only impairs the expression of ISGs, but also interferes with the activation of the type 1 IFN pathway, preventing the correct signaling for maternal recognition of pregnancy in PMNs. In addition, heat stress causes oxidative stress in dairy cows. Subsequently, we evaluated whether heat stress modulates the immune response in pregnant cows. According to the results, heat stress modifies the expression of anti- and pro-inflammatory genes in pregnant cows. Finally, we verified the effects of heat stress on the parameters of ER stress and HSPs during the period of maternal recognition of pregnancy in cattle. The results of this study support the hypothesis that oxidative stress caused by heat stress triggers ER stress in PBMCs. From the data obtained with this thesis, it was possible to determine that heat stress negatively influences endocrine signaling in bovine leukocytes during maternal recognition of pregnancy.