Thyroid Hormone in the Pathogenesis of Congenital Intestinal Dysganglionosis

Abstract

Introduction The objective of this study is to investigate the role of thyroid hormone (TH) in the pathogenesis of intestinal dysganglionosis (ID). Methods A zebrafish model of congenital hypothyroidism (CH) was created by exposing the larvae to the 6-propyl-2-thiouracil (PTU). The enteric neurons were labeled with anti-HuC/D antibodies. The number of enteric neurons was counted. The larval intestine was dissociated and stained with anti-p75 and anti-α4 integrin antibodies. Mitosis and apoptosis of the p75+ α4 integrin+ enteric neural crest cells (ENCCs) were studied using flow cytometry. Intestinal motility was studied by analyzing the transit of fluorescent tracers. Results PTU (25 mg/L) significantly reduced TH production at 6- and 9-days post fertilization without changing the body length, body weight, and intestinal length of the larvae. Furthermore, PTU inhibited mitosis of ENCCs and reduced the number of enteric neurons throughout the larval zebrafish intestine. Importantly, PTU inhibited intestinal transit of fluorescent tracers. Finally, thyroxine supplementation restored ENCC mitosis, increased the number of enteric neurons, and recovered intestinal motility in the PTU-treated larvae. Conclusions PTU inhibited TH production, reduced the number of enteric neurons, impaired intestinal motility, and impeded ENCC mitosis in zebrafish, suggesting a possible role of CH in the pathogenesis of ID.

Hypothyroidism impairs development of the gastrointestinal tract in the ovine fetus

“…Thyroid hormones are important for the development of both central and peripheral nervous systems (Williams, 2008;Prezioso et al, 2018), and have been shown to regulate proliferation and differentiation of progenitor cells of the enteric nervous system taken from neonatal mice and studied in vitro (Mohr et al, 2013). Furthermore, in zebrafish larvae, pharmacological hypothyroidism suppresses intestinal transit in association with a reduction in proliferating and total number of enteric neurones; these changes are restored to normal by T4 supplementation (Wang et al, 2020). Further experiments are needed to establish the extent to which the development of the enteric nervous system and control of gastrointestinal motility is influenced by hypothyroidism in the ovine fetus before birth with consequences for the maturation of the gastrointestinal tract.…”

Systematic analysis of proximal midgut‐ and anorectal‐originating contractions in larval zebrafish using event feature detection and supervised machine learning algorithms

“…Dishes were supplemented with 0.033 mg mL −1 methylene blue and 0.013 mg mL −1 1‐phenyl‐2‐thiourea (PTU) to prevent melanin synthesis. The low PTU concentration was chosen because concentrations above 0.025 mg mL −1 alter gut function 39 . After 12 h postfertilization, methylene blue was omitted from the E3 media.…”

“…The low PTU concentration was chosen because concentrations above 0.025 mg mL −1 alter gut function. 39 After 12 h postfertilization, methylene blue was omitted from the E3 media. Egg incubator was maintained at 28.5°C (14 h/10 h light/dark cycle).…”

Exposure to Polystyrene Nanoplastics Led to Learning and Memory Deficits in Zebrafish by Inducing Oxidative Damage and Aggravating Brain Aging

“…After corresponding exposure, the zebrafish were anesthetized in 0.02% Tricaine (E10521, Sigma‐Aldrich) and sacrificed in ice water before obtaining the tissue specimen. [ 44 ]…”

“…After corresponding exposure, the zebrafish were anesthetized in 0.02% Tricaine (E10521, Sigma-Aldrich) and sacrificed in ice water before obtaining the tissue specimen. [44] Exposure Experiments: In total, four experimental groups were set up in triplicate, namely, a male control group, a male PS-NPs exposure group, a female control group, and a female PS-NPs exposure group. In brief, after the acclimation, 840 zebrafish individuals (420 males and females, respectively) were randomly assigned to corresponding control and NP-exposure groups (4 experimental groups × 3 replicates/group × 70 zebrafish/replicate).…”