Effect of maternal subclinical hypothyroidism during pregnancy on brain development in rat offspring

Abstract

Objective To explore whether maternal subclinical hypothyroidism gives rise to poor performance in the offspring and whether this is associated with the expression of several genes that are under the control of thyroid hormones. Methods Sixty female rats were divided into three groups （ each group n = 20）： （ 1 ）maternal subclinical hypothyroidism （ total thyroidectomy with T4 infusion）, （2） maternal hypothyroidism （ total thyroidectomy without T4 infusion）, and （3） control （sham operated）. All rats were mated 10 days after the start of infusion. The infusion continued until 10 days postpartum. Pups were sacrificed at postnatal day 3, 7, and 21. The hippocampus was collected and tested for brain-derived neurotrophic factor （BDNF） and Rap1 protein expression by Western blotting and for BDNF and neural cell adhesion molecule （ NCAM ） mRNA expression by real-time polymerase chain reaction. On day 41-49, rat pups explored the Morris water maze. Time spent in the quadrant previously containing the plat form was recorded. Results The present study found decreases in BDNF mRNA （on day 3 ） and protein levels （on day 3 and 7 ） in hippocampi of pups from subclinical hypothyroidism dams （P〈0.05）. No change was observed in the levels of NCAM mRNA, whereas at day 21, expression of Rap1 protein was higher than that of control offspring. In addition, pups of subclinical hypothyroidism dams showed a trend toward depression in short-term memory （P〉0.05）, and long-term memory testing revealed a trend toward subclinical hypothyroidism group pups being less able to remember a fixed platform position than controls, spending less time in the proper quadrant （ P〈0. 05 ）. Conclusion The long-term memory deficits of pups born to maternal subclinical hypothyroidism dams are likely related with decrease in BDNF expression as well as increase in Rap1 expression in hippocampi. Key words: Subclinical hypothyroidism; Pregnancy; Brain development