In primates, progesterone (P) upregulates endometrial keratinocyte growth factor (KGF), especially in the stromal cells of the basalis zone and around spiral arteries (Koji et al, J. Cell Biol., 1994). When P levels decline at the end of the luteal phase, KGF mRNA drops ~9-fold, the upper endometrial zones undergo menstrual breakdown and the basalis undergoes apoptotic cell death. We replaced KGF by systemic administration during P-withdrawal in order to evaluate its effects on menses, apoptosis and spiral artery growth. Juvenile rhesus monkeys were ovariectomized and treated sequentially with estradiol and P implants to induce menstrual cycles. In the test cycle, KGF (5 mg/kg or 1.5 mg/kg) or PBS was administered daily IV for 5 days, beginning 1 day before the P implant was withdrawn. On day 4 of P withdrawal, the uterus was removed. KGF substantially inhibited apoptosis in the basalis zone (mean apoptotic index = 0.58 vs 4.32 for KGF vs PBS treatments, respectively). Spiral artery dimensions, measured as arterial profiles/unit area in histological sections, were 5-fold greater in KGF-treated (ratio = 0.12) compared to saline-treated (ratio = 0.024) animals. There was no evidence that KGF enhanced proliferation or inhibited menstrual breakdown in the upper functionalis zone. In summary, replacement of KGF during P-withdrawal protected basalis cells against apoptosis and maintained the spiral arteries in a hypertrophied state without inhibiting menses. During the luteal phase, KGF may function to mediate the trophic effects of P on both the spiral arteries and the glands of the basalis in the rhesus macaque endometrium.
Showing the most recent 10 out of 492 publications
