Effects of maternal subclinical hypothyroidism on neurodevelopment of offspring- an animal-based study

Abstract

Background and Objective: Maternal subclinical hypothyroidism (SCH) during pregnancy is associated with adverse maternal and neonatal outcomes, including cognitive and neuropsychiatric effects. This study aimed to assess the impact of maternal SCH on young rats, examining behavioral and gross brain structure changes, and evaluating reversibility after levothyroxine treatment. Methods: This experimental animal study was conducted at the Aga Khan University for a duration of 10 months. The study was approved by the Ethical committee for Animal Care and Use. Fourteen female Sprague Dawley rats were grouped into Treated (induced with SCH, treated with levothyroxine), Untreated (induced with SCH, no treatment), and Control (administered saline). Pups' body weight was monitored, and histological procedures were conducted at postnatal days 7, 14, and 21. Behavioral tests (elevated plus maze, forced swim, and tail suspension) assessed anxiety and depression. The data was analysed using SPSS (version 25.0). The mean, median, and standard deviation were calculated for each quantitative parameter. A one-way ANOVA was performed to identify any variation in mean thyroid levels between groups, and an independent sample t-test was utilized to confirm mean differences in anxiety levels. Results: On postnatal day 7, untreated pups showed lower body weight compared to treated and control groups. This trend continued on days 14 and 21. By day 21, an elevated plus maze (EPM) test indicated anxiety-like behaviour in untreated pups, while they also exhibited more signs of depression in tests like the forced swim test (FST) and tail suspension test (TST). Brain structure, including the prefrontal cortex, remained intact in offspring affected by maternal thyroid dysfunction, with no significant changes observed in brain morphology across the groups. Conclusion: Despite unchanged brain structure, untreated rat pups exhibited significant behavioral differences indicative of depression. This underscores the importance of understanding the behavioral impacts of maternal SCH even in the absence of gross anatomical alterations.