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

Abstract

Abstract Background: Subclinical hypothyroidism (SCH) is characterized by high thyroid stimulating hormone (TSH) levels (4.5 to 10 IU/L) and normal T3 and T4 hormones. It may occur with or without mild symptoms of hypothyroidism and autoimmunity. In pregnancy one of the common complications is SCH. Multiple adverse maternal and neonatal outcomes such as cognitive and neuropsychiatric effects are associated with SCH. Globally, 3-15% of the general population is affected by SCH. In Pakistan, the prevalence of SCH is ~ 8.1% in women during gestation. This study was conducted to see the effects of maternal SCH during pregnancy on young rats in terms of behavioural and gross brain structure changes and their reversibility after treatment with levothyroxine. Method: 14 Female Sprague Dawley rats (200–300g) were acclimatized and allowed to get impregnated. They were divided into 3 groups. 1. Treated (n=4): was induced with SCH by propylthiouracil (PTU) 5µg/kg/day at PD6 and treated with levothyroxine from gestational day 16 to postnatal day 40. 2. Untreated (n=5): was induced with SCH and left untreated. 3. Control (n=5) was administered with equal volumes of saline. Body weight of pups was recorded regularly. Histological procedures were performed at postnatal day 7, 14 and 21 to identify any neonatal neurological problems. Behavioural tests such as elevated plus maze, forced swim and tail suspension tests were performed to test anxiety and depression. Result: On postnatal day 7, pups from the untreated mothers showed a substantial decline in body weight compared to treated and control groups. These differences were more profound with age at P14 and P21. No major changes were seen in the gross brain structure of untreated rats as compared to treated rats. The most depressed behaviour was found in pups from untreated dams evident from significantly increased immobility time in FST and TST as compared to healthy ones. Conclusion: Despite the absence of any gross changes in the brain structure, minor but significant behavioural difference, indicative of depression, was observed in the pups of untreated rats.