Effect of RU 486 on the endometrial response to deciduogenic stimulus in ovariectomized rhesus monkeys treated with oestrogen and progesterone.
Using the artificial plaque--decidual cell model in rhesus monkeys, the potential role of progesterone in the process of of epithelial and stromal cell responses was investigated by time-adjusted application of an antiprogestin, RU 486. Epithelial plaque formation is an immediate response of the endometrium to either trauma or invading trophoblast cells. To study this process, RU 486 (2.5 mg/kg body weight) or vehicle (ethanol/saline, 7:3, v/v, i.m.) was administered to the first group of monkeys immediately following traumatization (days 16 and 17 of treatment cycle). Histometric analysis revealed that treatment with RU 486 led to significant inhibition (P less than 0.001) in the recruitment of epithelial cells into plaque acini and consequent reduction (P less than 0.001) in the spread of the plaque reaction compared with control monkeys. In the second group of monkeys, experimental treatment was delayed until plaque formation had occurred (days 21 and 22 of cycle). RU 486 induced increased degeneration (P less than 0.01) in plaque cells. Thus the transformation and the maintenance of the epithelial plaque response appears to be progesterone-dependent. Glandular epithelium showed only marginal changes (P less than 0.05) in maximum cell height, amount of pseudostratification and secretory activity of glands as a consequence of RU 486 treatment; however, the antiprogestin induced a higher incidence of glandular apoptosis (P less than 0.01 for both groups). It has been suggested that the higher degree of apoptosis in the glandular epithelium could be a consequence of the progesterone receptor blocking action of RU 486. No distinctive change in endothelial cell ultrastructure was evident following RU 486 treatment; however, venular diameter was significantly increased (P less than 0.01, group I; P less than 0.001, group II) along with an apparent reduction in the extent of oedema. There was increased extravasation (P less than 0.01) and leukocytic infiltration (P less than 0.001, group I; P less than 0.05, group II) following RU 486 treatment. RU 486 induced vascular responses and increased diapedesis could presumably have resulted from its progesterone blocking action in vascular cells. RU 486 accelerated the incidence (P less than 0.01) of stromal decidualization (group I), as well as quantitatively accentuating (P less than 0.001) the decidual cell reaction (group II). It is possible that RU 486 may inhibit specific functions of decidual cells, despite morphologically consistent decidual transformation.
Ghosh
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Department of Physiology, All India Institute of Medical Sciences, New Delhi.
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Sengupta
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D000818:Animals; D003656:Decidua / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology; D004847:Epithelial Cells; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007962:Leukocytes / Q000166:cytology; D008253:Macaca mulatta; D008854:Microscopy, Electron; D015735:Mifepristone / Q000494:pharmacology*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*
D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol