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

Natsumi Funeshima,Taiga Katoh,Takeshi Kitou,Koumei Shirasuna,Kunitoshi Konda,Itaru Yoshimura,Hikari Yaginuma,Ryotaro Miura,Seizo Hamano

doi:10.1186/s12917-021-02755-7

Abstract

BackgroundRepeat 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.ResultsMetabolomic 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.ConclusionsThese findings provide valuable information towards the identification of critical biomarkers for repeat breeding syndrome in cattle.

Highlights

Repeat breeding is a critical reproductive disorder in cattle
Expressed metabolites identified in blood plasma samples from healthy and repeat breeder cows We analyzed the metabolomics profiles of plasma obtained from 4 healthy cows and 5 repeat breeder cows using both CE-TOF/MS and liquid chromatography (LC)-TOF/MS, and identified 318 differentially expressed metabolites based on their m/z values, migration time (MT) and retention time (RT)
After filtering for metabolites with at least a 2-fold differences, our final list of 8 lesser-detected metabolites included litocholic acid (LA), gycochenodeoxycholic acid (GCDC A), glycolithocholic acid (GLA), taurodeoxycholic acid (TDCA), deoxycholic acid (DCA), taurochenodeoxycholic acid (TCDCA), chenodeoxycholic acid (CDCA), and glycodeoxycholic acid (GDCA) in repeat breeder cows. These data suggest that the level of plasma bile acids in repeat breeder cows are significantly lower than in healthy cows

Summary

Introduction

The problem of repeat breeder cattle remains largely unmanageable due to a lack of informative biomarkers. We utilized metabolomic profiling in an attempt to identify metabolites in the blood plasma and uterine luminal fluids. The ability to identify repeat breeder cattle is one of the keys to efficient early therapy and farm management, repeat breeding syndrome remains largely unmanageable due to the lack of informative specific factors. Metabolomics analysis has been utilized to provide assessments of the quality of embryos and oocytes to identify interactions between mother and embryo, and to determine differences in fertility and infertility using plasma, uterine luminal fluid, and seminal plasma [5, 6, 8, 9]. There are no published studies that have reported metabolomics-based differences between healthy and repeat breeder cows

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