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Circulating Thyroid Hormone Concentrations and Placental Thyroid Hormone Receptor Expression in Normal Human Pregnancy and Pregnancy Complicated by Intrauterine Growth Restriction (IUGR)

Departments of Fetal Medicine (M.D.K., D.A.S.), Medicine (J.V., N.G., J.A.F.), and Clinical Chemistry (P.M.S.C.), University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

Address all correspondence and requests for reprints to: Dr. M.R. Kilby, Department of Fetal Medicine, Birmingham Women’s Hospital, Edgbaston, Birmingham, B15 2TG, United Kingdom.

Thyroid hormones are critical to growth and development of the human fetus. Abnormal placental development, a major cause of intrauterine growth restriction (IUGR), is associated with a high perinatal mortality and morbidity. Thyroid status has been postulated to play a role in the pathogenesis of such morbidity. In the present study, we have investigated fetal thyroid function and placental expression of thyroid hormone receptor (TR) and ß variants during normal human pregnancy and in pregnancy associated with IUGR. Measurement of free thyroid hormones and TSH concentrations revealed significant rises in free T₄ and free T₃ between the second and third trimesters of normal pregnancy. Serum concentrations of free T₄ and free T₃ were lower in fetuses affected by IUGR, although serum TSH levels were not significantly different. Immunocytochemistry demonstrated the presence of TR 1, 2, and ß1 proteins within the nuclei of trophoblast and stromal placental cells. Immunostaining for these TR variants increased with increasing gestation in normal placenta. Comparison of IUGR placental samples with normal samples revealed greater immunostaining for TR 1, 2, and ß1 variants in IUGR. Examination of pretranslational expression of TR 1, 2,ß1, and ß2 variants by semiquantitative RT-PCR revealed increasing expression of TR 1, 2, and ß2 messenger RNAs with increasing gestation in normal pregnancy, which "mirrored" post-translational expression. However, and in contrast, there were no significant differences in expression of TR messenger RNAs in normal and IUGR placenta. The present findings of reduction in serum free thyroid hormones and increased expression of TR and ß proteins in association with IUGR highlight the potential importance of thyroid status in influencing long-term fetal outcome in this condition.

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