Nr. Nayak et al., EFFECTS OF LUTEAL-PHASE ADMINISTRATION OF MIFEPRISTONE (RU486) AND PROSTAGLANDIN ANALOG OR INHIBITOR ON ENDOMETRIUM IN THE RHESUS-MONKEY, Human reproduction (Oxford. Print), 13(4), 1998, pp. 1047-1056
Early luteal phase administration of a potent anti-progestin like mife
pristone (RU486) inhibits blastocyst implantation and the establishmen
t of pregnancy without marked changes in menstrual cyclicity and ovari
an 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 mifepristo
ne was tested. Endometrial changes in rhesus monkeys were examined fol
lowing luteal phase administration of mifepristone, a prostaglandin sy
nthesis inhibitor (diclofenac) and a prostaglandin analogue (misoprost
ol) 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), m
isoprostol (100 mu g, daily, oral) treated group; group 5 (n = 5), mif
epristone 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 monkey
s on days 16-18 of mated cycles and endometrial tissue samples were co
llected on day 20, With diclofenac alone (group 3), marginal changes w
ere observed in glandular, stromal and vascular compartments, and ther
e were few apoptotic bodies in gland cells; partial inhibition and del
ay in implantation was earlier reported. Significantly higher oestroge
n receptor expression in glandular epithelial cells as compared with a
ll other treatment groups was found after treatment with misoprostol a
lone (group 4) and was associated with normal fecundity, The anti-nida
tory action of luteal phase antiprogestin treatment alone or in combin
ation with diclofenac or misoprostol was associated with altered endom
etrial histometric features characterized by glandular apoptosis, regr
ession in secretory functions, decreased oedema, extravasation and a h
igher degree of stromal leukocytic infiltration. In these three groups
(groups 2, 5 and 6) receptors for oestrogen and progesterone receptor
s were significantly higher in stromal cells, and lower in vascular ce
lls, while glandular cells showed significantly higher progesterone re
ceptors compared with the control group, The anti-nidatory activity of
mifepristone and associated endometrial changes could not be accentua
ted or attenuated with co-administration of PGE or diclofenac, nor cou
ld these be mimicked by these agents alone.