Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring
IntroductionGestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility o...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1269121/full |
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| author | Juan Carlos Rivera Juan Carlos Rivera Ma. Cecilia Opazo Ma. Cecilia Opazo Rosario Hernández-Armengol Rosario Hernández-Armengol Oscar Álvarez Oscar Álvarez María José Mendoza-León María José Mendoza-León Esteban Caamaño Esteban Caamaño Sebastian Gatica Sebastian Gatica Karen Bohmwald Karen Bohmwald Susan M. Bueno Susan M. Bueno Pablo A. González Pablo A. González Michel Neunlist Helene Boudin Alexis M. Kalergis Alexis M. Kalergis Alexis M. Kalergis Claudia A. Riedel Claudia A. Riedel |
| author_facet | Juan Carlos Rivera Juan Carlos Rivera Ma. Cecilia Opazo Ma. Cecilia Opazo Rosario Hernández-Armengol Rosario Hernández-Armengol Oscar Álvarez Oscar Álvarez María José Mendoza-León María José Mendoza-León Esteban Caamaño Esteban Caamaño Sebastian Gatica Sebastian Gatica Karen Bohmwald Karen Bohmwald Susan M. Bueno Susan M. Bueno Pablo A. González Pablo A. González Michel Neunlist Helene Boudin Alexis M. Kalergis Alexis M. Kalergis Alexis M. Kalergis Claudia A. Riedel Claudia A. Riedel |
| author_sort | Juan Carlos Rivera |
| collection | DOAJ |
| description | IntroductionGestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring).MethodsGestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10–E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment.ResultsThe HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring.DiscussionGestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring. |
| first_indexed | 2024-03-08T17:05:42Z |
| format | Article |
| id | doaj.art-3162145ecbb74ac28950372693d26860 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-08T17:05:42Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-3162145ecbb74ac28950372693d268602024-01-04T04:52:17ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-01-011410.3389/fendo.2023.12691211269121Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspringJuan Carlos Rivera0Juan Carlos Rivera1Ma. Cecilia Opazo2Ma. Cecilia Opazo3Rosario Hernández-Armengol4Rosario Hernández-Armengol5Oscar Álvarez6Oscar Álvarez7María José Mendoza-León8María José Mendoza-León9Esteban Caamaño10Esteban Caamaño11Sebastian Gatica12Sebastian Gatica13Karen Bohmwald14Karen Bohmwald15Susan M. Bueno16Susan M. Bueno17Pablo A. González18Pablo A. González19Michel Neunlist20Helene Boudin21Alexis M. Kalergis22Alexis M. Kalergis23Alexis M. Kalergis24Claudia A. Riedel25Claudia A. Riedel26Laboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Medicina Veterinaria y Agronomía, Instituto de Ciencias Naturales, Universidad de las Américas, Santiago, ChileLaboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileLaboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileLaboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileLaboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileLaboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileInstituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileUniversité de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, IMAD, Nantes, FranceUniversité de Nantes, Inserm, TENS, The Enteric Nervous System in Gut and Brain Disorders, IMAD, Nantes, FranceMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileFacultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileLaboratorio de Endocrino-inmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileIntroductionGestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring).MethodsGestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10–E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment.ResultsThe HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring.DiscussionGestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.https://www.frontiersin.org/articles/10.3389/fendo.2023.1269121/fullgestational hypothyroxinemiaulcerative colitiscolon inflammationimmune cellsautoimmunityradical oxygen species |
| spellingShingle | Juan Carlos Rivera Juan Carlos Rivera Ma. Cecilia Opazo Ma. Cecilia Opazo Rosario Hernández-Armengol Rosario Hernández-Armengol Oscar Álvarez Oscar Álvarez María José Mendoza-León María José Mendoza-León Esteban Caamaño Esteban Caamaño Sebastian Gatica Sebastian Gatica Karen Bohmwald Karen Bohmwald Susan M. Bueno Susan M. Bueno Pablo A. González Pablo A. González Michel Neunlist Helene Boudin Alexis M. Kalergis Alexis M. Kalergis Alexis M. Kalergis Claudia A. Riedel Claudia A. Riedel Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring Frontiers in Endocrinology gestational hypothyroxinemia ulcerative colitis colon inflammation immune cells autoimmunity radical oxygen species |
| title | Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring |
| title_full | Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring |
| title_fullStr | Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring |
| title_full_unstemmed | Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring |
| title_short | Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring |
| title_sort | transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis like disorder in the male offspring |
| topic | gestational hypothyroxinemia ulcerative colitis colon inflammation immune cells autoimmunity radical oxygen species |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1269121/full |
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