Natsumi Funeshima1, Ryotaro Miura2, Taiga Katoh1, Hikari Yaginuma3, Takeshi Kitou3, Itaru Yoshimura4, Kunitoshi Konda5, Seizo Hamano6, Koumei Shirasuna7. 1. Department of Animal Science, Tokyo University of Agriculture, Atsugi, Kanagawa, 243-0034, Japan. 2. Department of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, 180-8602, Japan. 3. Animal Bio-Technology Center, Livestock Improvement Association of Japan Inc., Shinagawa, Tokyo, 135-0041, Japan. 4. Fuji Animal Research Farm, Nippon Veterinary and Life Science University, Kawaguchiko, Yamanashi, 401-3338, Japan. 5. Kanagawa Prefectural Livestock Industry Technology Center, Ebina, Kanagawa, 243-0417, Japan. 6. Maebashi Institute of Animal Science, Livestock Improvement Association of Japan Inc., Maebashi, Gunma, 371-0121, Japan. 7. Department of Animal Science, Tokyo University of Agriculture, Atsugi, Kanagawa, 243-0034, Japan. ks205312@nodai.ac.jp.
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.
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.
Entities:
Keywords:
Bile acids; Indoleamine 2,3-dioxygenase; Interferon tau; Repeat breeding
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