Radioautographic analysis of epithelial and stromal cell proliferation in the primate endometrial functionalis and basalis (rhesus monkey) has identified horizontal zonal patterns of mitotic activation and inhibition during natural menstrual cycles. At 1 h after a single i.v. injection of [3H]thymidine, mitotic activity in endometrial biopsies (hysterotomy) was determined on 9 days from the late proliferative to the late luteal phase (-2 days to + 14 days relative to the estrogen [E2]peak). Labeling indices (LIs) were determined within glandular segments of the 4 horizontal endometrial zones: Transient functionalis Zone I (luminal epithelium) and Zone II (uppermost gland); Germinal basalis: Zone III (middle gland) and Zone IV (basal gland). The size of the dividing epithelial populations (LI) differed zonally. During E2 dominance (-2 days to +3 days), the epithelial LIs of functionalis I (10 +/- 0.3%) and II (9.8 +/- 1.0%) were greater than those of basalis III (5.8 +/- 0.2%) and basalis IV (3.7 +/- 0.8%). During progesterone (P) dominance (+5 days to +14 days), epithelial mitosis was strongly inhibited in functionalis I (4.3 +/- 1.9%), functionalis II (0.8 +/- 0.2%), and basalis III (1.4 +/- 0.5%). Thus germinal basalis III was linked functionally with transient functionalis I and II by periovulatory uniformity in epithelial proliferation and postovulatory mitotic inhibition. A unique mitotic pattern set basalis IV apart from other zones by a steady rise in LI from 1% (-2 days) to 11% (+10 days). The LIs for stromal fibroblasts remained quite uniform in basalis IV but varied in other zones. Thus the postovulatory primate basalis was a distinct bipartite compartment in which the mitotic rate in basalis IV glandular epithelium increased steadily whereas that of basalis III was strongly inhibited. The remarkable enhancement of epithelial mitotic activity in basalis IV may reflect expansion of the stem-progenitor cell population for gestational growth or for post-menstrual regeneration.

The cellular and tissue basis of endometrial renewal in the rhesus monkey is being investigated by radioautographic localization of proliferating cell populations. Here we report our findings on epithelial cell proliferation during the midcycle estrogen surge. Endometrial biopsies were obtained by hysterotomy at approximately 1 h after a single intravascular injection of [3H] thymidine ([3H]T). Light and electron microscopic radioautography was performed on 7 specimens obtained from 4 monkeys in relation to the serum estradiol (E2) peak as follows: -2, -1, 0, +1, +2, and +3 days (+/- 1 day). Cell proliferation and differentiation were analyzed according to the 4 horizontal histologic endometrial zones (Bartelmez et al., 1951). Epithelial labeling indices were higher in the functionalis (Zone I, luminal epithelium, 9-12%; Zone II, uppermost gland segments, 7-14%) than in the basalis (Zone III, middle gland segments, 5-7%; and Zone IV, basal gland segments, 1-7%). Despite the large and rapid serum E2 fluctuations during the surge from -2 days to +3 days E2 peak, proliferating epithelial populations within Zones I, II and III remained quite uniform in size. In the basalis, the proliferative patterns of Zones III and IV were dissimilar. The labeling index of Zone III remained quite uniform (5-7%), whereas in Zone IV, it increased progressively from 1% (-2 days) to 7% (+3 days). These data establish the bipartite nature of the basalis. Radioautographic evidence indicates that endometrial cell proliferation is tightly coupled to progressive cell differentiation in the functionalis and basalis. Thus intrinsic positional differences exist in the responsiveness of the primate endometrium to common hormonal stimulation during the E2 surge and the initial postovulatory rise of progesterone.