Metabolomic profiles of plasma and uterine luminal fluids from healthy and repeat breeder Holstein cows

Abstract

Background Repeat breeding is a critical reproductive disorder in cattle. The problem of repeat breeder cattle remains largely unmanageable due to a lack of informative biomarkers. Here, we utilized metabolomic profiling in an attempt to identify metabolites in the blood plasma and uterine luminal fluids. We collected blood and uterine fluid from repeat breeder and healthy cows on day 7 of the estrous cycle. Results Metabolomic analysis identified 17 plasma metabolites detected at concentrations that distinguished between the two groups, including decreased various bile acids among the repeat breeders. However, no metabolites that varied significantly were detected in the uterine luminal fluids between two groups. Among the plasma samples, kynurenine was identified as undergoing the most significant variation. Kynurenine is a metabolite produced from tryptophan via the actions of indoleamine 2,3-dioxygenase (IDO). As IDO is key for maternal immune tolerance and induced in response to interferon tau (IFNT, ruminant maternal recognition of pregnancy factor), we examined the responsiveness to IFNT on peripheral blood mononuclear cells (PBMC) isolated from healthy and repeat breeder cows. The mRNA expression of IFNT-response makers (ISG15 and MX2) were significantly increased by IFNT treatment in a dose-dependent manner in both groups. Although treatment with IFNT promoted the expression of IDO in PBMCs from both groups, it did so at a substantially reduced rate among the repeat breeder cows, suggesting that decreased levels of kynurenine may relate to the reduced IDO expression in repeat breeder cows. Conclusions These findings provide valuable information towards the identification of critical biomarkers for repeat breeding syndrome in cattle.

Serum biochemical profiles of repeat breeder holstein friesian cows

“…There is no relationship between TC and RB syndrome, which has already been investigated by some researchers (Guzel and Tanriverdi, 2014;Funeshima et al, 2021). Our results are consistent with those of previous studies.…”

Metabolomic evolution of the postpartum dairy cow uterus

“…These parallels across studies suggest links between metabolite concentration in blood and uterine fluid, similar to what has been demonstrated for a portion of the proteome (Faulkner et al, 2012). On the other hand, Funeshima et al (2021) found 17 plasma metabolites detected at concentrations that distinguished between healthy cows and repeat breeders at Day 7 of estrus, but no differences in the ULF metabolome between the two groups. While there are potential matrix differences, especially regarding the technical challenges of ULF collection, there can be value in systems biology integration of available data across body fluids and organs to highlight possible interactions between different pools, enzymes, and substrates in relation to bovine pregnancy success (Figure 2).…”

Embryo–Uterine Cross-Talk: Exploration of the Immunomodulatory Mechanism in Buffalo

“…During pregnancy, the immune complex may be the important factor regulating pregnancy maintenance, and deregulation of immune responses during conception may be responsible for pregnancy losses [ 7 ]. Therefore, synchronous signaling between the embryo and uterine endometrium during the pre-implantation period is crucial for the implantation of the embryo, placentation, and development of the normal embryo [ 8 ].…”