Iron deficiency without anemia causes maternal hypothyroxinemia in pregnant rats

Because of increased total red blood cell mass and the demands of the fetus, iron requirements are greater during pregnancy than at most other times. Previous experiments in nonpregnant women have shown that iron deficiency (ID) can reduce circulating thyroxine and triiodothyronine levels; therefore, we hypothesized that ID before pregnancy can reduce thyroid hormone levels in maternal circulation and in the thyroid gland during pregnancy. In the present study, 2 types of rat models with ID were established using diets with different iron concentrations. Levels of thyroid hormone, hemoglobin, serum iron, liver iron, serum ferritin, serum transferrin receptor, and serum thyroid-stimulating hormone as well as thyroid peroxidase activity were measured throughout pregnancy, and thyroid structure was analyzed. Both mild ID with anemia and ID without anemia resulted in maternal hypothyroxinemia from midgestation to the end of the pregnancy. Thyroid peroxidase activity significantly decreased, even before the reduction of liver iron concentrations in ID groups. Iron deficiency reduced the size of follicular cavities but did not destroy the follicular structure. Linear regressions were performed to compare total levels of maternal serum thyroxine to indices of iron status for individual dams. This is the first rat study to report our results stating that ID can cause maternal hypothyroxinemia during early pregnancy.