Chronic inflammation decreases arcuate kisspeptin expression in male sheep

• 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
• ISSN: 0739-7240; 1879-0054; 1879-0054
• DOI: 10.1016/j.domaniend.2024.106868

•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]