Effects of isolated positive maternal thyroglobulin antibodies on brain development of offspring in an experimental autoimmune thyroiditis model.

Abstract

Autoimmune thyroiditis (AIT) is a very common endocrine disorder in pregnancy. However, the effect of maternal positive thyroglobulin antibodies (TgAb) on brain development of offspring remains unclear. This study used an experimental autoimmune thyroiditis model in CBA/J mice and determined whether isolated positive maternal TgAb directly affected learning and memory abilities of offspring. An experimental autoimmune thyroiditis model was established in CBA/J mice through immunization with murine thyroglobulin (mTg). Measuring thyroid function and serum TgAb titer confirmed the presence of isolated positive maternal TgAb. Offspring serum TgAb titer, MCT8, Reelin, RC3, and BNDF mRNA expression in the brain, and brain histology were measured on postnatal days 0, 10, and 40 (PND0, PND10, PND40), and nerve cell migration (BrdU labeling) at PND40. Morris water maze, long-term potentiation (LTP), and LTP-related factor ERK1/2 levels were measured at PND40 to determine offspring spatial learning and memory development. Maternal serum TgAb titers increased and remained elevated through pregnancy compared to controls. Thyrotropin and thyroid hormone levels were normal. The T group offspring (Tg immunized) had higher TgAb titers than the control (C) group. However, antibody titers time-dependently decreased. MCT8, Reelin, RC3, and BDNF mRNA expression in the whole brain were similar in the T and C groups on PND0, PND10, and PND40. Neuronal distribution and BrdU from the cerebral cortex and hippocampus were similar in the T and C group offspring. Morris water maze tests, excitatory postsynaptic field potentials, and ERK1/2 levels were also similar between the T and C groups. Isolated positive maternal TgAb did not clearly influence the learning ability and memory of offspring, or nerve cell migration, despite a transient increase in TgAb in immunized mice.