IMPACT OF PROPYLTHIOURACIL-INDUCED HYPOTHYROIDISM DURING PREGNANCY ON POST-NATAL LOCOMOTOR DEVELOPMENT IN RAT PUPS
DOI:
https://doi.org/10.69656/pjp.v22i2.1895Keywords:
Antenatal care, Impaired locomotion, Maternal hypothyroidism, Motor cortex, NeurogenesisAbstract
Background: The foetus depends on maternal thyroid hormones for neurogenesis during early days of pregnancy. The objective of this study was to determine the impact of maternal hypothyroidism on cortical lamination, resulting in impaired locomotion in rat pups. Methods: This study was conducted in the Anatomy Department of Islamic International Medical College over 9 weeks. Twenty-four female and 12 male Sprague-Dawley rats were divided into two equal groups. Control group received a standard diet and drinking water, while the hypothyroid group was given 4.5 mg propylthiouracil/rat/ day via drinking water. Treatment began one week before mating and continued for three weeks after delivery. Pups were born after three weeks and nursed freely for 21 days. On day 22, locomotor testing was performed before dissection. Brains were extracted, and motor cortex was examined. Data from inclined plane test and microglial counts were analysed with t-test, while Chi-square test was applied for forelimb placing and cortical lamination assessment. Results: The control group exhibited typical locomotion, as evidenced by their performance in locomotor tests, which reflected a healthy pattern of neurogenesis. In contrast, the hypothyroid groups demonstrated a significant decline in their ability to stay on an inclined plane and a delayed response in forelimb placement, indicating atypical neurogenesis evidenced by an elevated number of microglia and disrupted cortical lamination. Conclusion: Experimentally induced maternal hypothyroidism in Sprague Dawley rats had a detrimental impact on the locomotion of pups associated with abnormal neurogenesis.
Pak J Physiol 2026;22(2):77–82, DOI: https://doi.org/10.69656/pjp.v22i2.1895
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References
Mendes D, Alves C, Silverio N, Marques FB. Prevalence of undiagnosed hypothyroidism in Europe: A Systematic Review and Meta-Analysis. Eur Thyroid J 2019;8(3):130–43.
Moog NK, Entringer S, Heim C, Wadhwa PD, Kathmann N, Buss C. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience 2017;342(4):68–100.
Batistuzzo A, Ribeiro MO. Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition. Arch Endocrinol Metab 2020;64(1):89–95.
Kourosh-Arami M, Hosseini N, Komaki A. Brain is modulated by neuronal plasticity during postnatal development. J Physiol Sci 2021;71(1):134–89.
Shen C, Liang D, Wang X, Shao W, Geng K, Wang X, et al. Predictive performance and verification of physiologically based pharmacokinetic model of propylthiouracil. Front Pharmacol 2022;13:1013432.
Ghanbari M, Ghasemi A. Maternal hypothyroidism: An overview of current experimental models. Life Sci 2017;187:1–8.
Ahmed RG, El-Gareib A. Incerpi S. Lactating PTU Exposure: II-Alters Thyroid-Axis and Prooxidant-Antioxidant Balance in Neonatal Cerebellum (March 12, 2014). Int Res J Nat Sci 2014;2(1):1–20.
Abdel-Hafez AMM, Mohamed NA. Effect of selenium in ameliorating the effect of induced perinatal hypothyroidism on postnatal rat cerebellar cortex development: A histological and immunohistochemical study. Egypt J Histol 2013;36(3):660–80.
Anifantaki F, Pervanidou P, Lambrinoudaki I, Panoulis K, Vlahos N, Eleftheriades M. Maternal prenatal stress, thyroid function and neurodevelopment of the offspring: A mini review of the literature. Front Neurosci 2021;15:692446.
Ghasemi F, Bagheri H, Barreto GE, Read MI, Sahebkar A. Effects of curcumin on microglial cells. Neurotox Res 2019;36(1):12–26.
Gui J, Xu W, Zhang J. Association between thyroid dysfunction and perinatal outcomes in women with gestational hypertension: a retrospective study. BMC Pregnancy Childbirth [Internet]. 2020;20(1):119.
Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother 2013;4(4):303–6.
Fahad T, Ali S, Qureshi T, Khan NF. Maternal hypothyroidism-induced impaired development of neurons in rat offspring: Insights for antenatal care. Life Sci 2024;5(1):68–74.
Hidayat M, Chaudhry S, Salman S, Lone KP. Melatonin prevents apoptosis in brains of neonates induced by maternal hypothyroidism. J Ayub Med Coll Abbottabad 2019;31(4):580–5.
El-Kholy WB, Omar MA, El-Habiby MM, Al-Gholam MAS. The effect of induction of maternal hypothyroidism on postnatal cerebellar cortex development in albino rat offspring and the role of thyroxin replacement therapy: Histological, immunohistochemical and genetic study. Egypt J Histol 2021;44(2):545–62.
Dhouib IB, Annabi A, Doghri R, Rejeb I, Dallagi Y, Bdiri Y, et al. Neuroprotective effects of curcumin against acetamiprid-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: biochemical, histological, and behavioral changes. Environ Sci Pollut Res 2017;24(35):27515–24.
Irvine KA, Ferguson AR, Mitchell KD, Beattie SB, Lin A, Stuck ED, et al. The Irvine, Beatties, and Bresnahan (IBB) forelimb recovery scale: an assessment of reliability and validity. Front Neuroanat 2014;5:116.
Maynard RL, Downes N, (Eds). Anatomy and histology of the laboratory rat in toxicology and biomedical research. Academic Press. UK: Academic press; 2019.p. 204–8.
Shaughnessy KLO, Thomas SE, Spring SR, Ford JL, Ford RL, Gilbert ME. A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development. Sci Rep 2019;9(1):4662.
Mann P, Vahle JL, Keenan CM, Baker JF, Bradley AE, Goodman DG, et al. International harmonization of toxicologic pathology nomenclature: An overview and review of basic principles. Toxicol Pathol 2012;40(4 Suppl):75–135.
Talat A, Khan AA, Nasreen S, Wass JA. Thyroid screening during early pregnancy and the need for trimester specific reference ranges: a cross-sectional study in Lahore, Pakistan. Cureus 2019;11(9):e5661.
Barez-Lopez S, Grijota-Martınez C, Auso E, Fernandez-de Frutos M, Montero-Pedrazuela A, Guadano-Ferraz A. Adult mice lacking Mct8 and Dio2 proteins present alterations in peripheral thyroid hormone levels and severe brain and motor skill impairments. Thyroid 2019;29(11):1669–82.
Khairinisa MA, Takatsuru Y, Amano I, Kokubo M, Haijima A, Miyazaki W, et al. Perinatal propylthiouracil-induced hypothyroidism impaired motor coordination in adult female offspring. Pharmacol Clin Pharm Res 2019;4(3):71–5.
Dandekar MP, Yin X, Peng T, Devaraj S, Morales R, Mcpherson DD, et al. Repetitive xenon treatment improves post-stroke sensorimotor and neuropsychiatric dysfunction. J Affect Disord 2022;301:315–30.
Qureshi T, Ali S, Fahad T. Synergistic effect of coenzyme Q10 and L-Carnitine on Gliosis and Anhedonia, in a rat model of multiple sclerosis : An immunohistochemical study. Clin Psychopharmacol Neurosc 2024;22(3):484–92.
Chagas LDS, Sandre PC, Ribeiro E Ribeiro NCA, Marcondes H, Oliveira Silva P, Savino W, et al. Environmental signals on microglial function during brain development, neuroplasticity, and disease. Int J Mol Sci 2020;21(6):2111.
Chamas L, Seugnet I, Poirier R, Clerget-froidevaux MS, Enderlin V. A fine regulation of the hippocampal thyroid signalling protects hypothyroid mice against glial cell activation. Int J Mol Sci 2022;23(19):11938.
Wang Y, Tian A, Zhang F, Yu J, Ling J. Inflammatory immune process and depression-like behavior in hypothyroid rats: A [18F] DPA-714 micro positron emission tomography study. Pharmaceuticals (Basel) 2023;16(2):279.
O’Shaughnessy KL, Gilbert ME. Thyroid disrupting chemicals and developmental neurotoxicity—New tools and approaches to evaluate hormone action. Mol Cell Endocrinol 2020;518:110663.
Montero-pedrazuela A, Grijota-martı C, Auso E, Bárez-López S, Guadaño-Ferraz A. Endocrine aspects of development. Thyroid hormone actions in neurological processes during brain development. In: Marton CR, Preedy VR, Rajendram R, (Eds). Diagnostic Management and Modeling in Neurodevelopmental Disorder. UK: Academic Press; 2021.p. 85–97.
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Copyright (c) 2026 Tayyaba Fahad, Shabana Ali, Tayyaba Qureshi, Arifa Haroon, Sadia Farooq, Maria Yasmeen
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