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LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function

Jhamat, Naveed and Niazi, Adnan and Guo, Yongzhi and Chanrot, Metasu and Ivanova, Elena and Kelsey, Gavin and Bongcam-Rudloff, Erik and Andersson, Göran and Humblot, Patrice (2020). LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function. BMC Genomics. 21
[Research article]

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Abstract

BackgroundLipopolysaccharide (LPS) endotoxin stimulates pro-inflammatory pathways and is a key player in the pathological mechanisms involved in the development of endometritis. This study aimed to investigate LPS-induced DNA methylation changes in bovine endometrial epithelial cells (bEECs), which may affect endometrial function. Following in vitro culture, bEECs from three cows were either untreated (0) or exposed to 2 and 8 mu g/mL LPS for 24h.ResultsDNA samples extracted at 0h and 24h were sequenced using reduced representation bisulfite sequencing (RRBS). When comparing DNA methylation results at 24h to time 0h, a larger proportion of hypomethylated regions were identified in the LPS-treated groups, whereas the trend was opposite in controls. When comparing LPS groups to controls at 24h, a total of 1291 differentially methylated regions (DMRs) were identified (55% hypomethylated and 45% hypermethylated). Integration of DNA methylation data obtained here with our previously published gene expression data obtained from the same samples showed a negative correlation (r=-0.41 for gene promoter, r=-0.22 for gene body regions, p<0.05). Differential methylation analysis revealed that effects of LPS treatment were associated with methylation changes for genes involved in regulation of immune and inflammatory responses, cell adhesion, and external stimuli. Gene ontology and pathway analyses showed that most of the differentially methylated genes (DMGs) were associated with cell proliferation and apoptotic processes; and pathways such as calcium-, oxytocin- and MAPK-signaling pathways with recognized roles in innate immunity. Several DMGs were related to systemic inflammation and tissue re-modelling including HDAC4, IRAK1, AKT1, MAP3K6, Wnt7A and ADAMTS17.ConclusionsThe present results show that LPS altered the DNA methylation patterns of bovine endometrial epithelial cells. This information, combined with our previously reported changes in gene expression related to endometrial function, confirm that LPS activates pro-inflammatory mechanisms leading to perturbed immune balance and cell adhesion processes in the endometrium.

Authors/Creators:Jhamat, Naveed and Niazi, Adnan and Guo, Yongzhi and Chanrot, Metasu and Ivanova, Elena and Kelsey, Gavin and Bongcam-Rudloff, Erik and Andersson, Göran and Humblot, Patrice
Title:LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function
Series Name/Journal:BMC Genomics
Year of publishing :2020
Volume:21
Number of Pages:12
Publisher:BMC
ISSN:1471-2164
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 404 Agricultural Biotechnology > Genetics and Breeding
Keywords:LPS, Bovine endometrial epithelial cells, RRBS, Endometritis, Inflammation, Implantation
URN:NBN:urn:nbn:se:slu:epsilon-p-106776
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-106776
Additional ID:
Type of IDID
DOI10.1186/s12864-020-06777-7
Web of Science (WoS)000540263800003
ID Code:21940
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:03 Feb 2021 03:23
Metadata Last Modified:03 Feb 2021 06:01

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