Maria Jose Mendoza

Chile

Low thyroxine levels during pregnancy and the Intestinal outcome in the adult offspring

Mendoza-León María José1,2, González-Madrid Enrique1,2, Álvarez-Mardones Oscar1,2, Rangel-Ramírez Ma Andreina1,2, Bueno Susan M 2,3, Opazo Ma Cecilia4, Melo-González Felipe 1,2, Riedel Claudia A1,2

1 Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.
2 Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
3 Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
4 Facultad de Medicina Veterinaria y Agronomía, Instituto de Ciencias Naturales. Universidad de las Américas, Santiago, Chile

Abstract

Background

Gestational hypothyroxinemia (HTX) is a thyroid condition characterized by low plasmatic levels of tetraiodothyronine (T4) with normal levels of thyroid-stimulating hormone (TSH) and triiodothyronine (T3). We have shown that the offspring gestated in HTX (HTX-offspring) are more susceptible to developing autistic spectrum disorder and ulcerative colitis. Both conditions have been linked with disrupted mucosal immune homeostasis. The content of immunoglobulin A (SIgA) and the Paneth cell-derived antimicrobial peptides are immune factors that support intestinal homeostasis. However, the intestinal levels of these two molecules in the HTX offspring have not been characterized.

Methods

Gestational HTX was induced in pregnant C57BL/6 mice by the treatment with methimazole in the tap water. Control mice were only given tap water. Their respective adult offspring were euthanized at P55; to obtain ileum samples, that were analyzed to determine SIgA by ELISA, Paneth cell granules by electron microscopy, and genes that encode antimicrobial peptides by RT-qPCR.

Results

As a result, it was found that in the ileum, there was significantly increased expression of the transcripts that encode lysozyme, cryptidin-1, cryptidin-4, and Mmp7 in the male HTX offspring compared to control offspring. Paneth cell granules were abnormal compared to control offspring, and reduced levels of secretory IgA (sIgA) were found in the ileum content of the female and male HTX offspring compared to control offspring, with reduced expression of the transcripts for polymeric immunoglobulin receptor (pIgRs) in the female HTX offspring.

Conclusions

The findings suggest that gestational hypothyroxinemia alters innate immune system in the ileum of the adult offspring