The Inability of Dibutyryl Adenosine 3',5'-Monophosphate to Induce the Decidual Reaction in Intact Pseudopregnant Mice

Abstract

The technique for assessing the ability of a compound to initiate the decidual response is simple and conclusive. It involves introducing the compound in solution into the uterine lumen of an intact rat or mouse during the`sensitive period' of pseudopregnancy (Finn & Keen, 1963;Hetherington, 1968). This technique was used to compare the ability of arachis oil, phosphate-buffered saline (PBS; Dulbecco & Vogt, 1954) and dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP\p=m-\dcAMP) to initiate the decidual response after injection into the uterine lumen of the mouse at various times on the 4th day of pseudopregnancy.Pseudopregnancy was induced in A2G mice from a closed colony in the Department, by mating them with vasectomized males of the same strain, vaginal plugs being taken to indicate the 1st day of pseudopregnancy. Animals were allocated to fifteen groups, each comprising four to seven mice. On the 4th day at 09.30, 12.30 or 15.30 hours, a single intraluminal injection (by way of the uterotubal junction) of 0\m=.\02 ml arachis oil, PBS or a solution of dcAMP (Sigma) in PBS was given. Three concentrations of dcAMP were used: 1\m=.\25 mm, 2\ m=. \ 5 mM and 3\ m=. \ 75 mm. At autopsy on the 7th day, the horns were excised, divided at the cervix and weighed separately before being fixed in Bouin's solution for subsequent histological examination.

Deciduogenic effect of prostaglandins in the pseudopregnant rabbit

“…Intraluminal injections of histamine failed to trigger a DCR in hormonally primed immature rabbits (Elton, 1966) and our results were inconclusive. As reported for mice (Webb, 1975), dcAMP was ineffective in inducing a DCR in rabbits.…”

Cyclic AMP and the preparation of the mouse uterus for implantation

“…Histamine is known to be re¬ leased during early oestrogen action (Spaziani & Szego, 1958;Shelesnyak, 1959a;McKercher, Van Orden, Bhatnagar & Burke, 1973) and uterine histamine levels fall at the time of implantation (Shelesnyak, 1959b). These observations led Shelesnyak, Marcus & Lindner (1970) to suggest a role for histamine as the mediator of the decidual stimulus, but both histamine (see Finn, 1971) and cyclic AMP (Webb, 1975b) have now been shown not to be involved in evoking the response. On the other hand, the present results are compatible with a role for histamine in sensitization of the uterus in preparation for the decidual response, an idea supported by the observations of Ferrando & Nalbandov (1968) who showed that implantation could not take place in the absence of uterine mast cells which are the only known source of uterine histamine (McKercher et ai, 1973).…”

Hormone involvement in the establishment of pregnancy

“…A rapid but transient increase in cyclic AMP and cyclic GMP in uterine tissue following oil-induced decidualization indicated their involvement in the early events leading to decidual cell formation (Ledford, Rankin & Baggett, 1975;Rankin, Ledford & Baggett, 1977). In the rat, mouse and rabbit, however, neither intraperitoneal injection nor intraluminal application of cyclic AMP or dibutyryl cyclic AMP (dbcAMP) were effective in inducing deciduoma or the implantation of diapausal blastocysts (Leroy, Vansande, Shetgen & Brasseur, 1974;Webb, 1975a;Holmes & Bergstrom, 1976;Hoffman et al, 1977;Rankin et al, 1977;Wu & Chang, 1977). Fisher & Gunaga (1975) have reported that blastocyst development was retarded when cyclic AMP accumulation was induced following incubation with theophyUine to inhibit the intracellular breakdown of cyclic AMP.…”