Thyroid Hormone Imbalance in Pregnant Rats and its Impact on Neurodevelopment in Pups: A Minireview on Histopathological Endpoints

Market authorization of a pesticide or biocide in Europe requires the hazard assessment of endocrine-disrupting properties, including the thyroid modality. Substances inducing thyroid histopathological and/or thyroid hormone effects in rodent studies need to be further investigated to rule out whether the substance can be considered as an endocrine disruptor for the thyroid pathway, including neurodevelopmental impact in pups and its relevance in humans. Histopathological assessment for identifying reliable biomarkers for assessing neurodevelopmental effects is an important aspect of this testing scheme in rats. Periventricular heterotopia in the corpus callosum and persistence of the external granular layer in the cerebellum have been proposed as potential histopathological biomarkers in the brain. The correlation in the cochlea for hearing impairment seen in rat pups derived from hypothyroid dams is another potential biomarker. Herein, we provide a brief overview of the histopathological endpoints. The technical challenges in correctly identifying these changes during brain development and their significance in detecting the impact of maternal hypothyroidism in rodents are discussed. This mini review is part of a scientific presentation by Dr Gangadharan during the developmental neurotoxicity (DNT) session at the 21st ESTP’s Annual Congress (2024).