Human Reproduction, Vol 13, 1047-1056, Copyright © 1998 by Oxford University Press
NR Nayak, D Ghosh and J Sengupta
Early luteal phase administration of a potent anti-progestin like
mifepristone (RU486) inhibits blastocyst implantation and the establishment
of pregnancy without marked changes in menstrual cyclicity and ovarian
steroid hormone profiles; however, the underlying mechanism is not very
clear. In the present study, a hypothesis that prostaglandins (PG) are
involved in the anti-gestatory action of luteal phase mifepristone was
tested. Endometrial changes in rhesus monkeys were examined following
luteal phase administration of mifepristone, a prostaglandin synthesis
inhibitor (diclofenac) and a prostaglandin analogue (misoprostol) either
alone or in combination. Twenty-five monkeys were randomly assigned to six
groups: group 1 (n = 4), normal control group; group 2 (n = 4),
mifepristone (2 mg, daily, s.c.) treated group; group 3 (n = 4), diclofenac
(25 mg, daily, i.m.) treated group; group 4 (n = 4), misoprostol (100
microg, daily, oral) treated group; group 5 (n = 5), mifepristone and
diclofenac (same dosages as for groups 2 and 3) treated group; group 6 (n =
4), mifepristone and misoprostol (same dosages as for groups 2 and 4)
treated group. All treatments were given to monkeys on days 16-18 of mated
cycles and endometrial tissue samples were collected on day 20. With
diclofenac alone (group 3), marginal changes were observed in glandular,
stromal and vascular compartments, and there were few apoptotic bodies in
gland cells; partial inhibition and delay in implantation was earlier
reported. Significantly higher oestrogen receptor expression in glandular
epithelial cells as compared with all other treatment groups was found
after treatment with misoprostol alone (group 4) and was associated with
normal fecundity. The anti-nidatory action of luteal phase antiprogestin
treatment alone or in combination with diclofenac or misoprostol was
associated with altered endometrial histometric features characterized by
glandular apoptosis, regression in secretory functions, decreased oedema,
extravasation and a higher degree of stromal leukocytic infiltration. In
these three groups (groups 2, 5 and 6) receptors for oestrogen and
progesterone receptors were significantly higher in stromal cells, and
lower in vascular cells, while glandular cells showed significantly higher
progesterone receptors compared with the control group. The anti-nidatory
activity of mifepristone and associated endometrial changes could not be
accentuated or attenuated with co-administration of PGE or diclofenac, nor
could these be mimicked by these agents alone.
ARTICLES
Effects of luteal phase administration of mifepristone (RU486) and prostaglandin analogue or inhibitor on endometrium in the rhesus monkey
Department of Physiology, All India Institute of Medical Sciences, New Delhi.
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