EFFECTS OF MATERNAL THYROID STATUS ON THYROID-HORMONES AND GROWTH IN CONGENITALLY HYPOTHYROID GOAT FETUSES DURING THE 2ND-HALF OF GESTATION

Congenital hypothyroidism in Dutch goats is due to a thyroglobulin (TG ) synthesis defect that is inherited in an autosomal recessive manner. Minute amounts of mutated TG messenger RNA are translated into glycos ylated TG fragments that contain the N-terminal hormonogenic site and are able to form T-4, albeit less efficiently. We analyzed the effects of maternal thyroid status on fetal plasma thyroid hormones and growt h during the second half of gestation (E90-E150). Maternal hypothyroid ism, present from midgestation, resulted in decreased brain and cerebe llum weights of affected goitrous fetuses, most evident at term gestat ion (E150). Brain and cerebellum weights of affected fetuses from unaf fected mothers were not decreased. T-4 and FT4 levels in affected fetu ses were dependent on the maternal phenotype, as was the degree of enl argement of the goiter at E150. Newborn unaffected lambs from affected mothers had plasma T-4 levels within the normal range. The present da ta show that in late gestation, fetal goats have to rely on their own thyroidal T-4 production. The results suggest that affected fetuses ar e able to maintain sufficiently high T-4 and T-3 levels to prevent sev ere adverse effects of thyroid hormone deficiency on the brain if mate rnal iodide supply is adequate, although a possible increased transfer of maternal T-4 to affected fetuses cannot be excluded. Under normal conditions, sufficient amounts of iodine are provided by the efficient iodine metabolism in euthyroid mothers. In affected mothers, much iod ine is wasted because the thyroid also iodinates proteins other than t he aberrant TG, resulting in insufficient iodine provision of the fetu s and, consequently, in severe hypothyroidism.