Embryo Mortality with an Impaired Interferon-Tau Release Mounts a Massive T-Helper Immune Response in Lactating Holstein-Friesian cows

Embryo mortality (EM) contributes to infertility, but its exact mechanism is poorly understood. It was hypothesized that bovine EM pregnancies have impaired conceptus-derived interferon-tau (IFNT) release and action and are associated with altered transcriptome responses. The objective was to discover transcriptome response in EM tissues (endometrium [ENDO], corpus luteum [CL] and peripheral blood mononuclear cells [PBMC]) in lactating Holstein-Friesian cows. Two experiments (E1, E2) in day 16 pregnant (exposed to semen; E1:n=13, E2:n=15) or non-pregnant (NP; not exposed to semen; E1:n=7, E2:n=7) cows were completed. Uterine flushings (UF) and tissues were collected. Pregnant cows were also classified based on conceptus morphology and appearance for EM (E1:n=5, E2:n=6) or normal (N) conceptuses (E1:n=8, E2:n=9). Conceptuses and tissues were RNA sequenced and analyzed. The N conceptuses were longer (P<0.05) than EM conceptuses. The IFNT protein concentrations in UF were greater in N compared to EM and NP cows in E1 but not for E2. The ENDO conjugated ISG15 concentrations were greater in N (E1) than EM and NP cows but N (E2) were only greater than NP not EM cows. The major up-regulated canonical pathway in EM conceptuses was T helper 1 (Th1) and Th2. The ENDO had a massive increase in interferon stimulated genes in N and EM compared to NP cows. Estradiol-associated genes were up-regulated in EM compared to N ENDO for E2. The PBMC in E1 reflected up-regulation of genes associated Th1 immune responses in EM compared to N cows. Luteolytic pathways were upregulated in EM CL compared to N cows. This disruption of maternal recognition of pregnancy in EM pregnancies entails a massive T helper immune response within the conceptus, estradiol re-modelling of the ENDO, abnormal immune system in PBMC, luteolysis cascade in CL and, potentially, loss of pregnancy. Overall design: Comparison of the gene expression profiles within conceptus and maternal tissues (endometrium, corpus luteum and peripheral blood mononuclear cells) in normal pregnancies compared to pregnancies with embryo mortality occurring at the preimplantation stage (day 16).