Article: Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress.
2023 Volume 14, Page(s) 1288779
Abstract: Introduction: In a previous study we found that ghrelin (Ghrl) misbalance during the peri-implantation period significantly impaired fetus development. In this study we aimed to evaluate the putative mechanisms underlying these effects, including embryo ...
Abstract | Introduction: In a previous study we found that ghrelin (Ghrl) misbalance during the peri-implantation period significantly impaired fetus development. In this study we aimed to evaluate the putative mechanisms underlying these effects, including embryo implantation success, uterine nitric oxide synthase (NOS) activity, nitric oxide synthesis and the inflammatory/immune uterine profile. Methods: Ghrelin misbalance was induced by injecting 4nmol/animal/day of Ghrl (hyperghrelinemia) or 6nmol/animal/day of a Ghrl antagonist (Ant: (D-Lys3)GHRP-6) from day 3 to 8 of pregnancy. Control animals (C) were injected with de vehicle. Females were euthanized at pregnancy day 8 and their uteri excised in order to evaluate: the percentage of reabsorbed embryos (microscopically), eNOS, iNOS and nytrotirosine expression (by immunohistochemistry), nitrite synthesis (by Griess technique), VEGF, IL-10, IL-17, IL-6, MMP9 and GM-CSF expression (by qPCR) and leukocyte infiltration by flow cytometry (evaluating T cells, NK cells, granulocytes, dendritic cells and macrophages). Results: Ant-treatment significantly increased the percentage of reabsorbed embryos and the uterine expression of eNOS, iNOS and nytrotirosine. (D-Lys3)GHRP-6-treatment increased also the expression of the inflammatory cytokines IL-6, IL-17 and MMP9, and decreased that of IL-10 (anti-inflammatory). Moreover, Ant-treatment increased also the NK cells population and that of CD11b Conclusion: Ghrl misbalance during the peri-implantation period induces pro-inflammatory changes and nitrosative stress in the gravid uterus, impairing significantly embryo implantation and/or development. |
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MeSH term(s) | Female ; Pregnancy ; Mice ; Animals ; Interleukin-10 ; Interleukin-17 ; Matrix Metalloproteinase 9 ; Ghrelin/pharmacology ; Nitrosative Stress ; Interleukin-6 ; Embryo Implantation ; Uterus |
Chemical Substances | Interleukin-10 (130068-27-8) ; Interleukin-17 ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Ghrelin ; Interleukin-6 |
Language | English |
Publishing date | 2023-12-01 |
Publishing country | Switzerland |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2592084-4 |
ISSN | 1664-2392 |
ISSN | 1664-2392 |
DOI | 10.3389/fendo.2023.1288779 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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