Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring
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Frontiers Media
Materias (Palabras claves):
Fecha de publicación:
2024
Resumen:
Introduction: Gestational 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).
Methods: Gestational 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.
Results: The 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
Frontiers in Endocrinology frontiersin.org01
OPEN ACCESS
EDITED BY
Federico Gatto,
San Martino Hospital (IRCCS), Italy
REVIEWED BY
Irenice Coronado-Arra´ zola,
Universidad Mayor de San Simo´ n, Bolivia
Carmen Cabanelas Pazos Moura,
Federal University of Rio de Janeiro, Brazil
*CORRESPONDENCE
Claudia A. Riedel
[email protected]
†These authors have contributed equally to
this work
RECEIVED 29 July 2023
ACCEPTED 06 November 2023
PUBLISHED 04 January 2024
CITATION
Rivera JC, Opazo MC,
Herna´ ndez-Armengol R, Álvarez O,
Mendoza-León MJ, Caamaño E, Gatica S,
Bohmwald K, Bueno SM, Gonza´ lez PA,
Neunlist M, Boudin H, Kalergis AM and
Riedel CA (2024) Transient gestational
hypothyroxinemia accelerates and
enhances ulcerative colitis-like disorder in
the male offspring.
Front. Endocrinol. 14:1269121.
doi: 10.3389/fendo.2023.1269121
COPYRIGHT
© 2024 Rivera, Opazo,
Herna´ ndez-Armengol, Álvarez,
Mendoza-León, Caamaño, Gatica,
Bohmwald, Bueno, Gonza´ lez, Neunlist,
Boudin, Kalergis and Riedel. This is an open-
access article distributed under the terms of
the Creative Commons Attribution License
(CC BY). The use, distribution or
reproduction in other forums is permitted,
provided the original author(s) and the
copyright owner(s) are credited and that
the original publication in this journal is
cited, in accordance with accepted
academic practice. No use, distribution or
reproduction is permitted which does not
comply with these terms.
TYPE Original Research
PUBLISHED 04 January 2024
DOI 10.3389/fendo.2023.1269121
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.
Discussion: Gestational 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.
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