title: Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development.
abstract: Maternal hypothyroxinemia in early pregnancy is often associated with irreversible effects on neuropsychomotor development. To evaluate fetal tissue exposure to maternal thyroid hormones up to midgestation, we measured total T(4) and free T(4) (FT(4)), T(3), rT(3), TSH, and possible binding proteins in first trimester coelomic and amniotic fluids and in amniotic fluid and fetal serum up to 17 wk. Samples were obtained before interruption of maternal-fetal connections. The concentrations in fetal compartments of T(4) and T(3) are more than 100-fold lower than those in maternal serum, and their biological relevance for fetal development might be questioned. We found, however, that in all fetal fluids the concentrations of T(4) available to developing tissues, namely FT(4), reach values that are at least one third of those biologically active in their euthyroid mothers. FT(4) levels in fetal fluids are determined by both their T(4)-binding protein composition and the T(4) or FT(4) in maternal serum. The binding capacity is determined ontogenically, is independent of maternal thyroid status, and is far in excess of the T(4) in fetal fluids. Thus, the availability of FT(4) for embryonic and fetal tissues would decrease in hypothyroxinemic women, even if they were euthyroid. A decrease in the availability of FT(4), a major precursor of intracellular nuclear receptor-bound T(3), may result in adverse effects on the timely sequence of developmental events in the human fetus. These findings ought to influence our present approach to maternal hypothyroxinemia in early pregnancy regardless of whether TSH is increased or whether overt or subclinical hypothyroidism is detected.
authors.affiliation: Unidad de Endocrinología Molecular, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Calvo
authors.forename: Eric
authors.initials: E
authors.lastname: Jauniaux
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gulbis
authors.forename: Myriam
authors.initials: M
authors.lastname: Asunción
authors.forename: Christine
authors.initials: C
authors.lastname: Gervy
authors.forename: Bernard
authors.initials: B
authors.lastname: Contempré
authors.forename: Gabriella
authors.initials: G
authors.lastname: Morreale de Escobar
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005314:Embryonic and Fetal Development; D005260:Female; D005312:Fetal Blood; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D009994:Osmolar Concentration; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D013961:Thyroid Gland / Q000502:physiology; D013974:Thyroxine / Q000097:blood / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism
chemical_list: D014284:Triiodothyronine; D013974:Thyroxine