A number of histologic and histochemical techniques have been used to study 42 human fetal thyroids from fresh specimens ranging in crown-rump length from 22 to 201 mm. Three periods of differentiation (colloid production) were defined. The first or precolloid stage was found in fetuses of 22 to 65 mm and consisted of strands of compact epithelial cells separated by loose connective tissue which contained only a few vessels. The early colloid production period from 65 to 80 mm was characterized by the appearance of small accumulations of colloid in the center of the follicles. The blood vessels between follicles increased during this period. In the last period during maturation of the colloid cavities, the spaces between the epithelium were more reduced and almost completely filled with blood vessels. No change in the average cell height was found during differentiation.
With differentiation, the nuclei of epithelium became less compact and RNAase-removable cytoplasmic material increased. Also of interest was the marked decrease in glycogen at the time of colloid production.
The staining characteristics of the early colloid showed little change during the period studied. The colloid was stained by the following reagents: periodic-acid Schiff, mercury organge, toluidine, ninhydrin-Schiff, Millon's and Sakaguchi's. The larger colloid spaces took slightly more toluidine stain than the smaller ones.
The enzyme reaction for alkaline phosphatase was found only in the vascular system, and acid phosphatase was found in the cytoplasm of epithelium and, especially in the differentiated specimens, it was concentrated at the apex of the cell. Lactic and succinic dehydrogenase activity did not seem to change with maturation and was located in the cytoplasm around the nucleus and toward the apex of the cell.
Thin rays of colloid-like material were observed to radiate out between cells from early colloid cavities. Based on unpublished electron microscopic data, organ cultures of human thyroid and observations from the developing chick, these spaces probably represent intercellular dilatations which have been filled with colloid from the central cavity. These spaces may be a secondary or safety mechanism which allows the circumference of the follicle to increase in size.