Innate immune response to conceptus signaling in early pregnancy in cattle

• Grant number: 22/14936-7
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2023
• End date: September 30, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Guilherme Pugliesi
• Grantee: Guilherme Pugliesi
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Adroaldo Jose Zanella ; Akio Miyamoto ; Angela Maria Gonella-Diaza ; Claudia Maria Bertan Membrive ; Juliano Coelho da Silveira ; Mario Binelli ; Rodrigo Silva Goulart
• Associated scholarship(s): 24/19428-5 - Modulation of the expression of angiogenic and antiluteolytic factors in the corpus luteum on day 20 of gestation, BP.IC; 24/19432-2 - Th1 and Th2 cytokine profile in uterine fluid at the beginning of pregnancy in Nelore heifers, BP.TT; 24/17467-3 - Modulation of the maternal immune system by the bovine conceptus in early pregnancy, BP.IC; + associated scholarships 24/16341-6 - In vivo modulation of the immune system by conceptus signaling between days 15 and 20 of gestation in cattle, BP.MS; 24/12016-3 - Modulation of genes stimulated by interferon-tau secreted by the bovine conceptus into immune cells, BP.IC; 24/12763-3 - Endometrial and circulating immune cell modulation of Th1 and Th2 cytokines by the bovine conceptus along early pregnancy., BP.IC; 24/12924-7 - Local and systemic profile of interferon-stimulated genes (ISGs) and interferon-tau concentrations during early pregnancy in cattle, BP.IC; 23/07459-0 - Use of cytobrush for determination of citokynes on endometrium during early pregnancy, BP.TT - associated scholarships

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)