RELATIONSHIP BETWEEN OESTROGEN, PROSTAGLANDIN F2α AND HISTAMINE IN DELAYED IMPLANTATION IN THE MOUSE

Abstract

Treatment of pregnant mice ovaricctomized on day 3 (23.00-2330 h) with progesterone (1 mg/day/mouse, from day 4 through 11 post coitum (p.c.)) and oestrogen (single injection of 0.05 \g=a\g on day 8 p. c.) induced implantation in all the animals. Implantation was inhibited in animals following three subcutaneous injections of indomethacin given on the morning and afternoon of day 8 and the morning of day 9 p. c. A single injection of histamine on day 8 p. c. partially compensated the effect of indomethacin. A complete reversal of the antifertility effect of indomethacin was achieved following intraperitoneal administration of histamine (2 \g=a\g at noon of day 8 p. c.) and PGF2\g=a\(20 \g=m\g on the morning and afternoon of day 8 p. c.). This study suggests that in the mouse uterus indomethacin impairs the physiological changes which are required for the decidual cell formation and implantation. It is likely that an injection of oestradiol in the progesterone treated ovariectomized mice triggers the release of PGF2\g=a\ and histamine and that these compounds are involved in the chain of events leading to implantation of the blastocysts.During the past few years, a considerable amount of evidence has suggested that prostaglandins are involved in various reproductive processes, including implantation. A sequence of hormonal changes occurs during normal implan¬ tation and any alteration of these events prevents implantation (Psychoyos

Prostaglandin E2 Is a Product of Induced Prostaglandin-endoperoxide Synthase 2 and Microsomal-type Prostaglandin E Synthase at the Implantation Site of the Hamster

“…of Ptgs by NSAIDs leads to either complete or partial delay in implantation (1)(2)(3)(4)(5)43). These observations were supported by an infertility phenotype of Ptgs2 null mice (13).…”

“…However, unlike mice that showed only mesometrial stromal expression of Ptgs2 on the day 6 implantation site, hamsters showed Ptgs2 expression in decidual cells (PDZ cells) immediately surrounding the implanting embryo. Expression of Ptgs2 in cells of the PDZ of days 5 and 6 and its expression in trophoblast cells of the growing embryo on later days of pregnancy suggest that Ptgs2 could not only be associated with inflammatory aspects of implantation 2 but also be involved in protection of the embryo proper by its immunomodulatory and cell-cell barrier formation properties (55,56). In rodents, implantation is followed by loss of uterine luminal epithelial cells and their barrier functions just around the implanted embryo (42).…”

“…In this context, we have preliminary evidence that preimplantation embryos of hamsters express the Cyp19 gene that encodes aromatase protein. 2 The differential expression of Ptgs1 and Ptgs2 at hamster implantation sites suggests that PGs produced at the implantation site are mainly the contributed products of Ptgs2. We reported previously (17) that PGI 2 rather than PGE 2 is the major prostanoid in the mouse implantation site.…”

“…PGE 2 Is the Most Abundant PG at the Implantation SitesThe reduced expression of Ptgs1 mRNA and the increased expression of Ptgs2 mRNA and protein at the implantation site, as compared with their expression patterns in uterine tissue away from the implantation site, prompted us to measure and compare the levels of PGs at the implantation site versus interimplantation site on day 5 of pregnancy. Fig.…”

“…This was demonstrated by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) prior to or during the time of implantation that resulted in either complete or a partial delay in implantation, depending on the species. NSAIDs inhibit implantation in mice (1,2) and rats (3,4) but not rabbits (5). However in rabbits, indomethacin did reduce the following: 1) the intensity of the uterine blue dye reaction at the implantation site, 2) the size of the decidual swellings, and 3) the number of implantation sites.…”