Chronic inflammation decreases arcuate kisspeptin expression in male sheep

•Suppression of LH secretion following a single, acute dose of lipopolysaccharide (LPS).•Suppression of LH secretion following 7 days of a rising LPS dose.•Chronic administration of LPS decreases the expression of kisspeptin. Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune res...

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Published in:	Domestic animal endocrinology Vol. 89; p. 106868
Main Authors:	Renwick, AN, Whitlock, BK, Nestor, CC, Daniel, JA, Strickland, L, Lear, AS, Adkins, M, Griffin, C, Esteller-Vico, A
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-10-2024
Subjects:	Animals Arcuate Nucleus of Hypothalamus - metabolism Chronic Disease Gene Expression Regulation - drug effects Inflammation Inflammation - veterinary Kisspeptin Kisspeptins - genetics Kisspeptins - metabolism Lipopolysaccharide Lipopolysaccharides - pharmacology Luteinizing hormone Luteinizing Hormone - blood Male Sheep Sheep Diseases - chemically induced Sheep Diseases - metabolism Kisspeptin Lipopolysaccharide Luteinizing hormone Sheep Inflammation
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Summary:	•Suppression of LH secretion following a single, acute dose of lipopolysaccharide (LPS).•Suppression of LH secretion following 7 days of a rising LPS dose.•Chronic administration of LPS decreases the expression of kisspeptin. Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune response and impairs reproduction through suppression of gonadotropin releasing hormone (GnRH), subsequently luteinizing hormone (LH) secretion. While there is evidence that acute inflammation inhibits kisspeptin, little is known about the impact of chronic inflammation on this key reproductive neuropeptide in livestock species. Thus, we sought to examine a central mechanism whereby LPS suppresses LH secretion in sheep. Twenty wethers were randomly assigned to one of five treatment groups: control (CON; n=4), single acute IV LPS dose (SAD; n=4), daily acute IV LPS dose (DAD; n=4), daily increasing IV LPS dose (DID; n=4), and chronic subcutaneous LPS dose (CSD; n=4). On Days 1 and 7, blood samples were collected every 12 minutes for 360 minutes using jugular venipuncture. Following blood collection on Day 7, all animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and hypothalamic blocks were removed and processed for immunohistochemistry. On Day 1, LH pulse frequency was significantly lower (p=0.02) in SAD (0.25 ± 0.1 pulses/hour), DAD (0.25 ± 0.1 pulses/hour), DID (0.35 ± 0.1 pulses/hour), and CSD (0.40 ± 0.1 pulses/hour) compared to CON (0.70 ±0.1 pulses/hour). On Day 7, only DID animals (0.35 ± 0.1 pulses/hour) had significantly lower (p=0.049) LH pulse frequency compared to controls (0.85 ± 0.1 pulse/hour). Furthermore, only DID animals (33.3 ± 10.9 cells/section/animal) had significantly fewer (p=0.001) kisspeptin-immunopositive cells compared to controls (82.6 ± 13.6 cells/section/animal). Taken together, we suggest that daily increasing doses of LPS is a powerful inhibitor of kisspeptin neurons in young male sheep and a physiologically relevant model to examine the impact of chronic inflammation on the reproductive axis in livestock. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0739-7240 1879-0054 1879-0054
DOI:	10.1016/j.domaniend.2024.106868