Studies on the progestational endometrium of the rabbit. II. Electron microscopy, day 0 to day 13 of gonadotrophin-induced pseudopregnancy.

The fine structure of the endometrial epithelium of the pseudo-pregnant rabbit from the day of induced ovulation (day 0) to the 13th day is here correlated with previously defined light microscopic phases. In Phase 1 (0-1 day), in which there is a presumed "priming" of the endometrium by ovarian steroidal hormones, no changes were observed. In Phase 2 (1-3 days), in addition to mitotic activity, the epithelium showed a disappearance of the mucification and lymphocytic migration typical of Phase 1 and also of the non-pregnant or "estrous" phase, and showed other nuclear and cytoplasmic changes which probably reflect endogenous growth and protein synthesis. In Phase 3 (4-6 days), two distinct populations of reacting cells were present: (1) surface and cryptal cells investing the now folded mucosal surface, and (2) glandular cells. The first group showed characteristic dome-like protrusions of the cytoplasm into the lumen, and also showed distinct cytoplasmic and nuclear changes which appear to be a prelude to the succeeding phase of fusion but are not necessarily secretory in type. The glandular cells, in contrast, showed cytoplasmic changes which appear to reflect active secretory activity (hypertrophy of the Golgi area, cytoplasmic vacuoles containing electron-opaque material, etc.). This phase coincides with the maximal secretion of uterine-specific proteins, and electron-opaque material is abundant within the endometrial lumen. In Phase 4 (6-8 days), the surface and cryptal epithelium undergoes a transformation into multinucleated cells, the result of a process of lysis of intervening plasma membranes, the precise mechanism of which (i.e., with or without initial membrane fusion) was not determined. Cell fusion proceeded earlier and more actively mesometrially than antimesometrially. The glandular cells showed evidence of reduced secretory activity, but did not at any stage undergo multinucleate-cell transformation. In Phase 5 (8-13 days) there was progressive fusion, and the number of nuclei per cytoplasmic sac appeared increased, presumably due to the continued action of progesterone which is maximal during this phase. Glandular cells showed further reduced secretory activity but remained columnar. Ciliation of the epithelium was sporadic in the pre-secretory phases and rare or absent in the secretory and fusion phases; it became widespread during the phase of decline after day 14, a period which will not be included in this study. The fine structure of the ciliated cells was the same at all stages; there was no evidence for their origin from a reserve population; it is possible that they arise by modification of the multinucleated cells. Cytoplasmic crystals and intramitochondrial densities or lamellae were observed during the secretory and fusion stages, the former only in the glands, the latter in the surface and cryptal epithelium. They appear to be associated with rising or maximal progesterone secretion.