Detrimental effects of uterine disease and lipopolysaccharide on luteal angiogenesis

Mohammed, Zeravan A.; Robinson, Robert S; Harris, Rachel; McLaughlin, Yasmin; Turnbull, Kaitlin E.M.; Mann, George E.; Woad, Kathryn Jane

Abstract

© 2020 Society for Endocrinology Reproductive tract inflammatory disease (RTID) commonly occurs after the traumatic events of parturition and adversely affects follicular function. This study is the first to describe the cellular and steroidogenic characteristics of corpora lutea from cattle with RTID and the effects of pathogen-associated molecular patterns (PAMPs) on luteal angiogenesis and function in vitro. Luteal weight (P < 0.05) and progesterone content (P < 0.05) were reduced (1.2-fold) in cows with RTID, accompanied by reduced CYP11A (P < 0.05), HSD3B (P < 0.01) and STAR (P < 0.01) protein expression. Immunohistochemistry revealed that luteal vascularity (VWF) and pericyte (ACTA2) coverage were >3-fold lower in RTID cows (P < 0.05). To link these observations to bacterial infection and determine specificity of action, a physiologically relevant luteal angiogenesis culture system examined the effects of PAMPs on endothelial cell (EC) network formation and progesterone production, in the presence of pro-angiogenic factors. Luteal EC networks were reduced ≤95% (P < 0.05) by lipopolysaccharide (LPS, toll-like receptor (TLR) 4 agonist) but not by TLR2 agonists lipoteichoic acid or peptidoglycan. Conversely, progesterone production and steroidogenic protein expression were unaffected by PAMPs (P > 0.05). Moreover, the adverse effect of LPS on luteal EC networks was dose-dependent and effective from 1 ng/mL (P < 0.05), while few EC networks were present above 10 ng/mL LPS (P < 0.001). LPS reduced proliferation (P < 0.05) and increased apoptosis of EC (P < 0.001). The specific TLR4 inhibitor TAK242 reversed the effects of LPS on EC networks. In conclusion, luteal vasculature is adversely sensitive to LPS acting via TLR4, therefore ovarian exposure to LPS from any Gram-negative bacterial infection will profoundly influence subsequent reproductive potential.

Citation

Mohammed, Z. A., Robinson, R. S., Harris, R., McLaughlin, Y., Turnbull, K. E., Mann, G. E., & Woad, K. J. (2020). Detrimental effects of uterine disease and lipopolysaccharide on luteal angiogenesis. Journal of Endocrinology, 245(1), 79-92. https://doi.org/10.1530/JOE-19-0443

• Journal Article Type: Article
• Acceptance Date: Jan 27, 2020
• Online Publication Date: Jan 27, 2020
• Publication Date: Apr 1, 2020
• Deposit Date: Feb 3, 2020
• Publicly Available Date: Jan 28, 2021
• Journal: Journal of Endocrinology
• Print ISSN: 0022-0795
• Electronic ISSN: 1479-6805
• Publisher: BioScientifica
• Peer Reviewed: Peer Reviewed
• Volume: 245
• Issue: 1
• Pages: 79-92
• DOI: https://doi.org/10.1530/JOE-19-0443
• Keywords: Corpus luteum, angiogenesis, lipopolysaccharide, bovine, pathogen
• Public URL: https://nottingham-repository.worktribe.com/output/3862208
• Publisher URL: https://joe.bioscientifica.com/view/journals/joe/aop/joe-19-0443/joe-19-0443.xml
• Additional Information: This manuscript has been accepted for publication in Journal of Endo crinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at https://joe.bioscientifica.com/view/journals/joe/aop/joe-19-0443/joe-19-0443.xml