Study summary · research use only
Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This mouse study investigated mechanisms by which ghrelin (Ghrl) misbalance during peri-implantation impairs embryo implantation and pregnancy, focusing on uterine nitric oxide synthase (NOS) activity, nitric oxide synthesis, and the uterine immune profile. Misbalance was induced by injecting 4nmol/animal/day of Ghrl (hyperghrelinemia) or 6nmol/animal/day of a Ghrl antagonist ((D-Lys3)GHRP-6) from day 3 to 8 of pregnancy, with control animals given vehicle; uteri were examined at pregnancy day 8. The abstract reports that antagonist treatment increased the percentage of reabsorbed embryos and uterine eNOS, iNOS, and nitrotyrosine expression, increased inflammatory cytokines IL-6, IL-17, and MMP9, decreased IL-10, increased NK cells and CD11b+ dendritic cells, and decreased T cells. Hyperghrelinemia showed similar increases in eNOS, iNOS, and nitrotyrosine, and a decrease in T cells, compared with control.
Abstract
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. 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). 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+ dendritic cells; and decreased T cells percentages. Similarly, hyperghrelinemia showed a significant increase vs. C on eNOS, iNOS and nytrotirosineuterine expression and a decrease in T cells percentages. 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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