Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress
IntroductionIn 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 synth...
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| Format: | Article |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1288779/full |
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| author | Eugenia Mercedes Luque Eugenia Mercedes Luque Cintia María Díaz-Luján Daniela Andrea Paira Daniela Andrea Paira Nicolás de Loredo Pedro Javier Torres Pedro Javier Torres Verónica Inés Cantarelli Verónica Inés Cantarelli Ricardo Fretes Ricardo Fretes Rubén Darío Motrich Rubén Darío Motrich Ana Carolina Martini Ana Carolina Martini |
| author_facet | Eugenia Mercedes Luque Eugenia Mercedes Luque Cintia María Díaz-Luján Daniela Andrea Paira Daniela Andrea Paira Nicolás de Loredo Pedro Javier Torres Pedro Javier Torres Verónica Inés Cantarelli Verónica Inés Cantarelli Ricardo Fretes Ricardo Fretes Rubén Darío Motrich Rubén Darío Motrich Ana Carolina Martini Ana Carolina Martini |
| author_sort | Eugenia Mercedes Luque |
| collection | DOAJ |
| description | IntroductionIn 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.MethodsGhrelin 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).ResultsAnt-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.ConclusionGhrl misbalance during the peri-implantation period induces pro-inflammatory changes and nitrosative stress in the gravid uterus, impairing significantly embryo implantation and/or development. |
| first_indexed | 2024-03-09T08:41:11Z |
| format | Article |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-09T08:41:11Z |
| publishDate | 2023-12-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-af13028625894c83912a092ee9ecda772023-12-02T16:59:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12887791288779Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stressEugenia Mercedes Luque0Eugenia Mercedes Luque1Cintia María Díaz-Luján2Daniela Andrea Paira3Daniela Andrea Paira4Nicolás de Loredo5Pedro Javier Torres6Pedro Javier Torres7Verónica Inés Cantarelli8Verónica Inés Cantarelli9Ricardo Fretes10Ricardo Fretes11Rubén Darío Motrich12Rubén Darío Motrich13Ana Carolina Martini14Ana Carolina Martini15Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaInstituto de Biología Celular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaInstituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaInstituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaInstituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaInstituto de Biología Celular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaDepartamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaInstituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET)/Universidad Nacional de Córdoba (UNC), Córdoba, ArgentinaIntroductionIn 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.MethodsGhrelin 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).ResultsAnt-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.ConclusionGhrl misbalance during the peri-implantation period induces pro-inflammatory changes and nitrosative stress in the gravid uterus, impairing significantly embryo implantation and/or development.https://www.frontiersin.org/articles/10.3389/fendo.2023.1288779/full(D-Lys3)GHRP-6NOSnitrosative stressILsMMP9NK cells |
| spellingShingle | Eugenia Mercedes Luque Eugenia Mercedes Luque Cintia María Díaz-Luján Daniela Andrea Paira Daniela Andrea Paira Nicolás de Loredo Pedro Javier Torres Pedro Javier Torres Verónica Inés Cantarelli Verónica Inés Cantarelli Ricardo Fretes Ricardo Fretes Rubén Darío Motrich Rubén Darío Motrich Ana Carolina Martini Ana Carolina Martini Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress Frontiers in Endocrinology (D-Lys3)GHRP-6 NOS nitrosative stress ILs MMP9 NK cells |
| title | Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress |
| title_full | Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress |
| title_fullStr | Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress |
| title_full_unstemmed | Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress |
| title_short | Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress |
| title_sort | ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress |
| topic | (D-Lys3)GHRP-6 NOS nitrosative stress ILs MMP9 NK cells |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1288779/full |
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