Day‐7 embryos generate an anti‐inflammatory immune response in peripheral blood immune cells in superovulated cows

Abstract

Problem Recently, we demonstrated both in vitro and in vivo that an immunological crosstalk between Day‐7 embryo and immune cells exists locally in the uterus in cows. The peripheral immune response to early embryos at Day‐7 of pregnancy in cows remains largely unknown. Thus, we aimed to investigate the response of peripheral blood immune cells in the presence of multiple Day‐7 embryos in the uterus in donor cows of embryo transfer program. Method of study Superovulated cows were either inseminated (n = 13) at 12‐18 hours post‐estrus or remained without inseminations (n = 6). Blood was collected following insemination (Day‐1) and immediately after uterine flushing (Day‐7). Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood for analysis of gene expression. Results Interferon‐stimulated genes (ISGs: ISG15 and OAS1) were increased in both PMNs and PBMCs, with up‐regulation of PTGES and anti‐inflammatory cytokines (TGFB1 and IL10) expressions at Day‐7 of post‐inseminations in cows, when compared to those at Day‐7 in non‐inseminated cows. Conclusion The findings indicate that the presence of multiple embryos in the uterus generates an anti‐inflammatory immune response in peripheral blood immune cells at Day‐7 of pregnancy in cows, which might help to accept semi‐allogenic embryo in the uterus.

Day 7 Embryos Change the Proteomics and Exosomal Micro-RNAs Content of Bovine Uterine Fluid: Involvement of Innate Immune Functions

“…This hypothesis was supported by our previous study, demonstrating that the peripheral blood neutrophils could respond to the IFNT-signal much earlier (D5) than peripheral blood mononuclear cells (D8; Shirasuna et al, 2012 ). Additionally, we reported that superovulated D7 embryos generated an anti-inflammatory immune response in peripheral blood neutrophils through the upregulation of transcripts for anti-inflammatory cytokines (TGFB1 and IL10; Talukder et al, 2019 ). Moreover, it was found that insemination induces rapid and transient infiltrations of neutrophils into the uterine lumen for removal of bacteria, excess/dead sperm, and tissue debris, which enhances uterine clearance and subsequent embryo receptivity ( Katila, 2012 ).…”

“…This model could amplify embryo-derived signals in the uterus that can not be easily detected using the single-embryo model. Indeed, we previously found that interferon-stimulated genes were upregulated in circulating immune cells in the superovulation cow model ( Talukder et al, 2019 ). Furthermore, we used the Japanese Black cows that were prepared exclusively for embryo donors and have only one-time experience of pregnancy and lactation, so their responsiveness to hormone treatment was expected to be highly homogeneous.…”

ISGylation Inhibits an LPS-Induced Inflammatory Response via the TLR4/NF-κB Signaling Pathway in Goat Endometrial Epithelial Cells

“…In ruminants, IFN-τ is an important maternal gestation-recognition signaling factor secreted by embryonic trophoblast cells [ 51 ], that is highly expressed during embryo implantation and stimulates significant upregulation of ISG15 [ 52 ]. The establishment of pregnancy requires transient regulation of innate and adaptive maternal immunity [ 53 ].…”

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

“…Studies have found significant antiviral activity in the uterine vein's blood 15 and 16 days after conception (Bott et al, 2010;Romero et al, 2015). IFNT enters the uterine vein and, as a result, stimulates the expression of multiple ISGs and immune response genes in blood cells to help maintain pregnancy (Green et al, 2010;Shirasuna et al, 2012;Talukder et al, 2019). Collectively, in addition to the modulatory effects on embryo development, endometrial and luteal environments, IFNT also coordinates the maternal immune response during the MRP (Hansen et al, 2017).…”

“…PMNs produce numerous anti-and pro-inflammatory cytokines (Mantovani et al, 2011) that are essential in pregnancy. In pregnant cows, PMNs showed an anti-inflammatory response with greater expression of TGFB, IL10, and forkhead box P3 (FOXP3) (Talukder et al, 2019). Pro-inflammatory cytokines data have shown biases in different studies; however, expression patterns seem to increase according to the development of pregnancy (Figure 1) (Fiorenza et al, 2021;Manjari et al, 2016;Sheikh et al, 2019;Shirasuna et al, 2012).…”