Subclinical hypothyroidism in pregnancy rats impaired offspring's spatial learning and memory and the cerebellar development

Subclinical hypothyroidism (SCH) is a very common preclinical condition during pregnancy. The adverse effect of maternal clinical hypothyroidism (CH) on the nervous system development of offspring is beyond doubt, but it is still controversial in SCH. The aim of this study was to investigate whether spatial learning and memory ability of offspring is inhibited in SCH rat model and its possible mechanism. 45 Wistar female rats were randomly divided into SCH, CH and control (CON) groups, which were induced by semi-thyroid electrocauterization, total thyroidectomy and sham operation, respectively. Rat pups were sacrificed at embryonic day 14 (E14), E18, postnatal day 1 (P1), P3, and P10, and pups' cerebellar tissues were collected. The proliferation, differentiation and migration of cerebellar cells were observed, and RNA level of the thyroid hormone receptor α (TRα) and TRβ in the cerebellum was detected by real-time PCR, respectively. Morris Water Maze (MWM) test was performed to detect the spatial learning and memory ability of pups at P40. Our data indicated that maternal SCH will significantly extend the offspring's escape latency time, and pups perform worse in the spatial probe test compared with the CON group. Except for E14, the proliferation of pups' cerebellar granule cells (GCs), and the migration of pups' Purkinje cells (PCs) in the SCH group was significantly inhibited compared with that in the CON group at other time points (P < 0.05 or P < 0.01), and the differentiation of cerebellar astrocytes (As) in SCH group was higher than that in CON group at P3 and P10. Except for E14, the expression of TRα mRNA in SCH group was significantly lower than that in CON group (P < 0.05 or P < 0.01). And the difference of the differentiation of As and the spatial learning and memory between SCH and CH groups was not statistically significant. Our findings suggested that SCH during pregnancy nuisances the offspring's spatial learning and memory. It may be related to the decrease of the expression of TRα in cerebellum, which may further inhibit the proliferation of GCs and the migration of PCs, and increase the differentiation of As.