Treatment with levothyroxine in pregnant rats with subclinical hypothyroidism improves cell migration in the developing brain of the progeny.
OBJECTIVE
This study aims to investigate whether maternal subclinical hypothyroidism (SCH) influences the developing brain, and the effect of treatment with levothyroxine (L-T4) in early maternal SCH on the progeny's developing brain.


METHODS
Seventy-five thyroidectomized female Wistar rats were divided randomly into groups of hypothyroidism (CH), SCH, SCH treated with L-T4 from embryonic day (E) 10, E13, and E17 till post-natal day 21. There were 15 sham operated controls.


RESULTS
Pups from SCH or CH group had significantly lower body weight than euthyroid group. Pups from E10, E13 or E17 groups had normal body weight compared to control pups at P3 and P7. The levels of TSH and total T4 (TT4) of all pups were normal. The mean latencies were longer in pups from CH, SCH, and E17 group than controls. The latencies from E10 and E13 pups were comparable to those from control pups. There were changes in the cytoarchitecture of the barrel cortex and of the hippocampus in CH, SCH, and E17 pups. The barrel cortex of E10 or E13 pups was similar to that of control pups. The distribution of bromodeoxyuridinelabeled cells was more widespread in CH, SCH, and E17 pups than in control, E10, and E13 progeny.


CONCLUSIONS
Maternal SCH disturbs learning and memory performances in pups, and affects cytoarchitecture and cell migration in the developing brain of the progeny. Treatment with L-T4 in early maternal SCH before E13 improves cell migration in the developing brain, as well as learning and memory function of the progeny.
Department of Endocrinology and Metabolism, the First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang, 110001 China.
L
L
Lu
X
X
Yu
W
W
Teng
Z
Z
Shan
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000196:embryology; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D007037:Hypothyroidism / Q000188:drug therapy*; D007124:Immunoenzyme Techniques; D007858:Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000627:therapeutic use*
D013974:Thyroxine