Innate immune response to conceptus signaling in early pregnancy in cattle

Abstract

New technologies that could reliably detect pregnancy status before day 21 after insemination would allow the opportunity to rebreed cattle at the next estrus event and to improve reproductive performance and profitability of dairy and beef operations. Thus, quantification of interferon-Ä stimulated genes (ISG) in peripheral blood leukocytes and Doppler ultrasonography of corpus luteum (CL) have been tested by our group as early pregnancy diagnostic methods. Although the assessment of luteolysis using Doppler ultrasonography is an excellent predictor of pregnancy, it is not efficient in monitoring conceptus viability and predicting early embryonic mortality in cattle with an active CL. Also, the proportion of false-negative results is still no adequate for the use of ISG expression as a method with accuracy and feasibility for detection of pregnancy before day 20. Therefore, the better understanding of the basic events involved in modulation of the immune system during early pregnancy is the first step for the discovery of novel biomarkers and endpoints for prediction of pregnancy earlier than the traditional methodologies. Therefore, our main goal with the present study is to understand the maternal response to conceptus signaling between days 15 to 20 of gestation, in order to comprehend the modulation of the immune system associated with early embryonic loss and to identify, at an early stage, the gestational status in bovine females. For this, the profiles of specific cytokines, ISGs and novel potential pregnancy marker systems involved in the uterine and peripheral response will be determined in vivo in (1) uterine cytology samples from heifers with success or gestational failure after embryo transfer; (2) in heifers slaughtered on days 15 and 20 of gestation; and (3) using an in vitro immune cell culture system associated with uterine flushing treatments. Also a validated multiplex platform to determine Th1/Th2 cytokines in culture media and plasma will be used. We anticipate that understanding the local and circulating maternal response to the concept during days 15 and 20 of pregnancy using both in vivo and in vitro models has the potential to result in the discovery of new pregnancy indicators that can be determined on circulation or in immune cells. The new knowledge and the innovative methods here proposed will serve as basis for development of new technologies for beef and dairy systems. The practicability is guaranteed by the combined work of specialists in each analytical step and by the infrastructure of the institutions involved. (AU)