Innate immunity and metabolism in the bovine ovarian follicle

Horlock, Anthony; HORLOCK, ANTHONY

doi:10.23889/SUthesis.59754

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Innate immunity and metabolism in the bovine ovarian follicle / Anthony Horlock; ANTHONY HORLOCK

Swansea University Authors: Anthony Horlock, ANTHONY HORLOCK

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DOI (Published version): 10.23889/SUthesis.59754

Abstract

Postpartum uterine disease in dairy cows is associated with reduced fertility. One of the first and most prevalent bacteria associated with uterine disease is Escherichia coli. The bacterial endotoxin, lipopolysaccharide (LPS), accumulates in the ovarian follicular fluid of animals with uterine dise...

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Published:	Swansea 2022
Institution:	Swansea University
Degree level:	Doctoral
Degree name:	Ph.D
Supervisor:	Sheldon, Martin I. ; Clift, Martin J.D. ; Bromfield, John J.
URI:	https://cronfa.swan.ac.uk/Record/cronfa59754
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first_indexed	2022-04-01T11:00:19Z
last_indexed	2022-04-02T03:19:55Z
id	cronfa59754
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spelling	2022-04-01T12:45:03.5968345 v2 59754 2022-04-01 Innate immunity and metabolism in the bovine ovarian follicle 4191b316c42c893bec2cada92597ad44 0000-0001-9580-552X Anthony Horlock Anthony Horlock true false 7fd9d848635f07e35a71926d25363ef1 ANTHONY HORLOCK ANTHONY HORLOCK true false 2022-04-01 BMS Postpartum uterine disease in dairy cows is associated with reduced fertility. One of the first and most prevalent bacteria associated with uterine disease is Escherichia coli. The bacterial endotoxin, lipopolysaccharide (LPS), accumulates in the ovarian follicular fluid of animals with uterine disease. The granulosa cells of the ovarian follicle respond to LPS by secreting pro-inflammatory cytokines, such as interleukin (IL)-1a, IL-1b and IL-8, and oocyte health is perturbed. Dairy cows also experience metabolic energy stress in the postpartum period, which is associated with an increased risk of developing uterine disease and ovarian dysfunction. This thesis explored the crosstalk between innate immunity and metabolic energy stress in bovine granulosa cells and cumulus-oocyte complex. Firstly, we found that glycolysis, AMP-activated protein kinase and the mechanistic target of rapamycin, regulate the innate immune responses to LPS in granulosa cells isolated from bovine ovarian follicles. Activation of AMP-activated protein kinase decreased the LPS-induced secretion of IL-1a, IL-1b, and IL8, and was associated with shortened duration of ERK1/2 and JNK phosphorylation. Next, we found that decreasing the availability of cholesterol or inhibiting cholesterol biosynthesis using short-interfering RNA impaired the LPS-induced secretion of IL-1a and IL-1b by granulosa cells. Furthermore, metabolic energy stress or inhibiting cholesterol biosynthesis in the bovine cumulus-oocyte complex modulated the innate immune responses to LPS, and perturbed meiotic progression during in vitro maturation. Finally, we explored an in vivo model of uterine disease in heifers, using RNAseq to investigate alterations to the transcriptome of the reproductive tract. We found that uterine disease altered the transcriptome of the endometrium, oviduct, granulosa cells and oocyte, several months after bacterial infusion; these changes were most evident in the granulosa cells and oocyte of the ovarian follicle. The findings from this thesis imply that there is crosstalk between innate immunity and metabolism in the bovine ovarian follicle. E-Thesis Swansea Innate immunity, metabolism, bovine, granulosa cells, oocyte 4 3 2022 2022-03-04 10.23889/SUthesis.59754 ORCiD identifier: https://orcid.org/0000-0001-9580-552X COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Sheldon, Martin I. ; Clift, Martin J.D. ; Bromfield, John J. Doctoral Ph.D National Institutes of Health; Grant number: R01HD084316 2022-04-01T12:45:03.5968345 2022-04-01T11:56:00.2129221 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Anthony Horlock 0000-0001-9580-552X 1 ANTHONY HORLOCK 2 59754__23757__a2d5233720e84e66b90f0417b470e36e.pdf Horlock_Anthony_D_PhD_Thesis_Final_Redacted_Signature.pdf 2022-04-01T12:05:33.1121896 Output 8576323 application/pdf E-Thesis – open access true Copyright: The author, Anthony D. Horlock, 2022. true eng
title	Innate immunity and metabolism in the bovine ovarian follicle
spellingShingle	Innate immunity and metabolism in the bovine ovarian follicle Anthony Horlock ANTHONY HORLOCK
title_short	Innate immunity and metabolism in the bovine ovarian follicle
title_full	Innate immunity and metabolism in the bovine ovarian follicle
title_fullStr	Innate immunity and metabolism in the bovine ovarian follicle
title_full_unstemmed	Innate immunity and metabolism in the bovine ovarian follicle
title_sort	Innate immunity and metabolism in the bovine ovarian follicle
author_id_str_mv	4191b316c42c893bec2cada92597ad44 7fd9d848635f07e35a71926d25363ef1
author_id_fullname_str_mv	4191b316c42c893bec2cada92597ad44_*_Anthony Horlock 7fd9d848635f07e35a71926d25363ef1_*_ANTHONY HORLOCK
author	Anthony Horlock ANTHONY HORLOCK
author2	Anthony Horlock ANTHONY HORLOCK
format	E-Thesis
publishDate	2022
institution	Swansea University
doi_str_mv	10.23889/SUthesis.59754
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str	1
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description	Postpartum uterine disease in dairy cows is associated with reduced fertility. One of the first and most prevalent bacteria associated with uterine disease is Escherichia coli. The bacterial endotoxin, lipopolysaccharide (LPS), accumulates in the ovarian follicular fluid of animals with uterine disease. The granulosa cells of the ovarian follicle respond to LPS by secreting pro-inflammatory cytokines, such as interleukin (IL)-1a, IL-1b and IL-8, and oocyte health is perturbed. Dairy cows also experience metabolic energy stress in the postpartum period, which is associated with an increased risk of developing uterine disease and ovarian dysfunction. This thesis explored the crosstalk between innate immunity and metabolic energy stress in bovine granulosa cells and cumulus-oocyte complex. Firstly, we found that glycolysis, AMP-activated protein kinase and the mechanistic target of rapamycin, regulate the innate immune responses to LPS in granulosa cells isolated from bovine ovarian follicles. Activation of AMP-activated protein kinase decreased the LPS-induced secretion of IL-1a, IL-1b, and IL8, and was associated with shortened duration of ERK1/2 and JNK phosphorylation. Next, we found that decreasing the availability of cholesterol or inhibiting cholesterol biosynthesis using short-interfering RNA impaired the LPS-induced secretion of IL-1a and IL-1b by granulosa cells. Furthermore, metabolic energy stress or inhibiting cholesterol biosynthesis in the bovine cumulus-oocyte complex modulated the innate immune responses to LPS, and perturbed meiotic progression during in vitro maturation. Finally, we explored an in vivo model of uterine disease in heifers, using RNAseq to investigate alterations to the transcriptome of the reproductive tract. We found that uterine disease altered the transcriptome of the endometrium, oviduct, granulosa cells and oocyte, several months after bacterial infusion; these changes were most evident in the granulosa cells and oocyte of the ovarian follicle. The findings from this thesis imply that there is crosstalk between innate immunity and metabolism in the bovine ovarian follicle.
published_date	2022-03-04T04:17:18Z
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score	11.037056

Innate immunity and metabolism in the bovine ovarian follicle / Anthony Horlock; ANTHONY HORLOCK

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