Lk. Christenson et Rl. Stouffer, PROLIFERATION OF MICROVASCULAR ENDOTHELIAL-CELLS IN THE PRIMATE CORPUS-LUTEUM DURING THE MENSTRUAL-CYCLE AND SIMULATED EARLY-PREGNANCY, Endocrinology, 137(1), 1996, pp. 367-374
The objective of this study was to evaluate endothelial us. steroidoge
nic cell proliferation throughout the lifespan of the primate corpus l
uteum during the menstrual cycle and simulated early pregnancy (CG tre
atment). Tissues were collected from rhesus monkeys (Macaca mulatta; n
= 3/day) on days 3-4, 7, 10, 12, and 14 of the luteal phase and at me
nses during spontaneous menstrual cycles and after 1, 3, 6, or 9 days
of hCG treatment beginning on day 9 of the luteal phase. Corpora lutea
were snap-frozen in mounting medium for immunocytochemical and histoc
hemical evaluation. The labeling index (percentage of positive to tota
l nuclei) for Ki-67 antigen, a cell proliferation marker, was determin
ed in conjunction with cell-specific markers. Immunolocalization of pl
atelet/endothelial cell adhesion molecule-1 and von Willebrand factor
in addition to histochemical staining for the Ulex europaeus agglutini
n-1 (i.e, lectin)-binding site were used to identify endothelial cells
. Histochemical detection of 3 beta-hydroxysteroid dehydrogenase activ
ity was used to identify steroidogenic cells. Progesterone secretion w
as high on days 3-10 of the luteal phase and then declined progressive
ly (P < 0.05) on days 12 and 14 and at menses; luteal weight followed
a similar pattern, declining 2 days (i.e. day 14) after progesterone s
ecretion. In contrast, after hCG treatment,luteal progesterone product
ion increased (P < 0.05) 3-fold, and luteal weight was maintained. The
cell proliferation index was greatest (44.5 +/- 1.9%) on days 3-4 of
the luteal phase and remained high on days 7 and 10 (34.6 +/- 0.3% and
27.1 +/- 3.4%), but this was followed by a sharp decline on day 12 (9
.6 +/- 2.3%), which was sustained on day 14 and at menses. After 1 day
of hCG treatment, cell proliferation was less than that observed on t
he equivalent day of the luteal phase (day 10), but thereafter, it was
similar on days 3, 6, and 9 of simulated early pregnancy to those in
the late luteal phase of the menstrual cycle (i.e. day 12 to menses).
Dual label immunocytochemistry indicated that more than 85% of cells s
taining positively for the Ki-67 antigen costained for platelet/endoth
elial cell adhesion molecule-1. No cells staining positively for both
3 beta-hydroxysteroid dehydrogenase activity and the Ki-67 antigen wer
e noted. Thus, the level of cell proliferation within the primate corp
us luteum varies during the luteal lifespan in the menstrual cycle, an
d endothelial cells comprised the vast majority of proliferative cells
, whereas steroidogenically active cells were not proliferating. Furth
er, the elevated progesterone secretion and sustained luteal weight th
at occurred during CG exposure simulating early pregnancy were not ass
ociated with an increase or maintenance of cellular proliferation.