Effect of single-dose, early luteal phase administration of mifepristone (RU486) on implantation stage endometrium in the rhesus monkey.
The characteristics of implantation stage endometrium following a single-dose, early luteal phase application of mifepristone (RU486) in proven conception cycles has been examined in the rhesus monkey in an attempt to understand the physiological basis of the anti-implantation activity of the drug. Endometrial samples were collected from monkeys subjected to vehicle (group 1, n = 14) and RU486 (2 mg/kg body weight; group 2, n = 12) on day 2 after the presumed day of ovulation of successfully mated cycles. The average diameter of glands (P < 0.05), number of vacuolated cells (P < 0.01), number of supranuclear vacuolated cells (P < 0.05) in glandular epithelium and amount of glandular secretion (P < 0.05) were significantly lower in RU486-treated endometrium compared with control tissue samples. Additionally, 18% of glandular epithelial cells showed apoptotic and degenerative features in RU486-treated tissue samples. These data, together with the observed significant decreases in precipitate area (P < 0.02) and in the optical absorbance of alkaline phosphatase reaction end-product (P < 0.05), confirm that retardation in glandular differentiation in the upper functionalis is a likely target of antiprogestin action in implantation stage endometrium. An increased frequency of mitosis in stromal cells (P < 0.05) and a greater degree of extravasation (P < 0.05) were also observed after RU486 exposure. Despite an apparent indication of constriction and regression in few RU486-exposed endometria compared with controls, morphometric analyses did not show any changes in capillary structure. Whether endometrial vasculature in progesterone-exposed uterus is a target of antiprogestin action during the peri-implantation stage remains to be determined. Further studies are required to explain the observed increase (P < 0.02) in the area of precipitate of von Willebrand (vW) factor with no change in vW factor-positive vessels, and the apparent increase in collagen IV immunostain in subepithelial and perivascular basement membrane in implantation stage endometrium after early luteal phase RU486 treatment in monkeys.
Ghosh
D
D
Department of Physiology, All India Institute of Medical Sciences, New Delhi, India.
Sengupta
J
J
Hendrickx
A G
AG
D000021:Abortifacient Agents, Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D007150:Immunohistochemistry; D008183:Luteal Phase; D008253:Macaca mulatta; D008297:Male; D008854:Microscopy, Electron; D015735:Mifepristone / Q000008:administration & dosage* / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
D000021:Abortifacient Agents, Steroidal; D014841:von Willebrand Factor; D015735:Mifepristone; D003094:Collagen; D000469:Alkaline Phosphatase