The period of maximal endometrial sensitivity in the rat was characterized by high
alkaline phosphatase activity in uterine luminal and glandular epithelium and endometrial
stroma. The activity in endometrial stroma increased following decidualization. Pinopod
development on the endometrial surface was first observed during the presensitivity
period. Their number increased, apparently more so on the antimesometrial rather than
the mesometrial segment of the uterus, on the day of maximal sensitivity. Inhibition
in endometrial sensitivity by single anti-implantation (1.25 mg/kg, po) dose of centchroman
on day 1 post-coitum (p.c.), although it did not affect alkaline phosphatase activity
on days 2 and 3 p.c., caused complete inhibition in its activity in uterine luminal
and glandular epithelium and pinopod development on days 4 and 5-coinciding, respectively,
with time of entry of preimplantation embryos into the uterus and period of maximal
endometrial sensitivity in this species. Significant decrease in enzyme activity was
also evident in the entire endometrial stroma and myometrium, except blood capillaries,
on these days. In comparison, prevention of entry of native embryos into the uterus
by placing a ligature at the utero-tubal junction had no effect on pinopod development,
but caused marked decrease in enzyme activity in luminal and glandular epithelium
only during the immediate postimplantation period. The uterine lumen on the day of
maximal sensitivity in centchroman-treated rats appeared highly distended and was
lined with tall columnar epithelium, in comparison to low cuboidal epithelium in controls.
The findings demonstrate: (a) a correlation between uterine luminal epithelial alkaline
phosphatase activity and endometrial sensitivity; (b) complete inhibition in enzyme
activity in luminal and glandular epithelium following centchroman treatment might
be related to altered permeability characteristics of epithelial cells, which together
with the absence of pinopods and highly distended uterine lumen on the day of maximal
sensitivity, suggest inhibition of endocytosis/pinocytosis of luminal fluid, luminal
closure, apposition of blastocyst trophoblast to luminal epithelium, and secretory
activity of glandular epithelium; (c) pinopod development on the endometrial surface
was independent of presence of viable blastocysts in utero; and (d) complete absence
of pinopods suggests lack of endometrial sensitivity, but their presence might not
necessarily indicate a sensitized endometrium in the rat.