Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows

The objective of this study was to identify alterations in the vaginal discharge (VD) metabolome and potential biomarkers to predict metritis development and a cure in dairy cows. This prospective cohort study was conducted on two dairies located in CA and TX. Vaginal discharge was evaluated and col...

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Main Authors: Eduardo B. de Oliveira, Hugo F. Monteiro, Jessica M. V. Pereira, Deniece R. Williams, Richard V. Pereira, Noelia Silva Del Rio, Paulo R. Menta, Vinicius S. Machado, Fabio S. Lima
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/13/11/1156
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author Eduardo B. de Oliveira
Hugo F. Monteiro
Jessica M. V. Pereira
Deniece R. Williams
Richard V. Pereira
Noelia Silva Del Rio
Paulo R. Menta
Vinicius S. Machado
Fabio S. Lima
author_facet Eduardo B. de Oliveira
Hugo F. Monteiro
Jessica M. V. Pereira
Deniece R. Williams
Richard V. Pereira
Noelia Silva Del Rio
Paulo R. Menta
Vinicius S. Machado
Fabio S. Lima
author_sort Eduardo B. de Oliveira
collection DOAJ
description The objective of this study was to identify alterations in the vaginal discharge (VD) metabolome and potential biomarkers to predict metritis development and a cure in dairy cows. This prospective cohort study was conducted on two dairies located in CA and TX. Vaginal discharge was evaluated and collected using the Metricheck<sup>®</sup> device. Cows were examined for metritis at 4, 7, and 9 days in milk (DIM). Cows with a fetid, watery, and reddish-brown uterine discharge were classified as having metritis and randomized to receive ceftiofur (<i>n</i> = 10) or remain untreated (<i>n</i> = 7). A cure was defined as the absence of a fetid, watery, reddish-brown uterine discharge at 14 d after enrollment. Vaginal discharge samples were collected from 86 cows within 6 h after parturition, at 4 and 7 DIM, at metritis diagnosis, and at 4 and 7 days after metritis diagnosis. Cows with metritis (MET; <i>n</i> = 17) were paired with counterparts without metritis (HTH) of a similar DIM and parity (<i>n</i> = 34). The uterine metabolome was evaluated using untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Metabolomic data were analyzed using the MetaboAnalyst 5.0. Data were log-transformed and auto-scaled for normalization. Univariate analyses, including the fold-change, were performed to identify the metabolites linked to metritis development and its cure and principal component analysis and partial least squares discriminant analysis were performed to explain metabolite variance between animals developing or not developing metritis and being cured or not being cured of metritis. Comparing HTH with MET cows at calving, 12 metabolites were upregulated, and one was downregulated. At four and seven DIM, 51 and 74 metabolites, respectively, were altered between MET and HTH cows. After metritis development, three and five metabolites were upregulated in cows that were cured and in cows that received treatment and were cured, respectively. In all scenarios, the metabolites lignoceric, malic, and maleic acids, ornithine, and hypotaurine, which are associated with arginine/aminoacyl-tRNA biosynthesis and taurine/purine metabolism, were upregulated in HTH cows. Metritis was associated with changes in the uterine metabolome. Cows not being cured of metritis had changes in the uterus metabolome independent of receiving ceftiofur or remaining untreated. Metabolome analysis may be an important tool to understand the vaginal discharge changes during postpartum and the dynamics of metritis development and cures and help to identify biomarkers to predict metritis being cured.
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spelling doaj.art-c46604b3e88347de811b553e36ae31482023-11-24T14:55:32ZengMDPI AGMetabolites2218-19892023-11-011311115610.3390/metabo13111156Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein CowsEduardo B. de Oliveira0Hugo F. Monteiro1Jessica M. V. Pereira2Deniece R. Williams3Richard V. Pereira4Noelia Silva Del Rio5Paulo R. Menta6Vinicius S. Machado7Fabio S. Lima8Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95106, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95106, USAVeterinary Medicine Teaching and Research Center, Tulare, CA 93274, USAVeterinary Medicine Teaching and Research Center, Tulare, CA 93274, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95106, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95106, USADepartment of Veterinary Sciences, Texas Tech University, Lubbock, TX 79409, USADepartment of Veterinary Sciences, Texas Tech University, Lubbock, TX 79409, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95106, USAThe objective of this study was to identify alterations in the vaginal discharge (VD) metabolome and potential biomarkers to predict metritis development and a cure in dairy cows. This prospective cohort study was conducted on two dairies located in CA and TX. Vaginal discharge was evaluated and collected using the Metricheck<sup>®</sup> device. Cows were examined for metritis at 4, 7, and 9 days in milk (DIM). Cows with a fetid, watery, and reddish-brown uterine discharge were classified as having metritis and randomized to receive ceftiofur (<i>n</i> = 10) or remain untreated (<i>n</i> = 7). A cure was defined as the absence of a fetid, watery, reddish-brown uterine discharge at 14 d after enrollment. Vaginal discharge samples were collected from 86 cows within 6 h after parturition, at 4 and 7 DIM, at metritis diagnosis, and at 4 and 7 days after metritis diagnosis. Cows with metritis (MET; <i>n</i> = 17) were paired with counterparts without metritis (HTH) of a similar DIM and parity (<i>n</i> = 34). The uterine metabolome was evaluated using untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Metabolomic data were analyzed using the MetaboAnalyst 5.0. Data were log-transformed and auto-scaled for normalization. Univariate analyses, including the fold-change, were performed to identify the metabolites linked to metritis development and its cure and principal component analysis and partial least squares discriminant analysis were performed to explain metabolite variance between animals developing or not developing metritis and being cured or not being cured of metritis. Comparing HTH with MET cows at calving, 12 metabolites were upregulated, and one was downregulated. At four and seven DIM, 51 and 74 metabolites, respectively, were altered between MET and HTH cows. After metritis development, three and five metabolites were upregulated in cows that were cured and in cows that received treatment and were cured, respectively. In all scenarios, the metabolites lignoceric, malic, and maleic acids, ornithine, and hypotaurine, which are associated with arginine/aminoacyl-tRNA biosynthesis and taurine/purine metabolism, were upregulated in HTH cows. Metritis was associated with changes in the uterine metabolome. Cows not being cured of metritis had changes in the uterus metabolome independent of receiving ceftiofur or remaining untreated. Metabolome analysis may be an important tool to understand the vaginal discharge changes during postpartum and the dynamics of metritis development and cures and help to identify biomarkers to predict metritis being cured.https://www.mdpi.com/2218-1989/13/11/1156metabolomicsuterine healthmetritismaleic acidornithine
spellingShingle Eduardo B. de Oliveira
Hugo F. Monteiro
Jessica M. V. Pereira
Deniece R. Williams
Richard V. Pereira
Noelia Silva Del Rio
Paulo R. Menta
Vinicius S. Machado
Fabio S. Lima
Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows
Metabolites
metabolomics
uterine health
metritis
maleic acid
ornithine
title Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows
title_full Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows
title_fullStr Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows
title_full_unstemmed Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows
title_short Changes in Uterine Metabolome Associated with Metritis Development and Cure in Lactating Holstein Cows
title_sort changes in uterine metabolome associated with metritis development and cure in lactating holstein cows
topic metabolomics
uterine health
metritis
maleic acid
ornithine
url https://www.mdpi.com/2218-1989/13/11/1156
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