Cyclic AMP and the preparation of the mouse uterus for implantation

Abstract

Experiments are described that demonstrate the ability of dibutyryl cyclic AMP (dcAMP) to induced oestrogen-like changes in the uteri of ovariectomized mice treated with progesterone. A single intraluminal injection of 6-14 micrograms dcAMP in 0-02 ml phosphate-buffered saline promoted cell division in the uterine stroma and sensitized the endometrium so that a decidual reaction could be induced by a subsequent injection of arachis oil into the uterine lumen. Since dcAMP has already been shown to induce implantation of diapausing mouse blastocysts in the absence of oestrogen, it is suggested that cyclic AMP is involved in egg implantation in rodents.

Effect of Dibutyryl Cyclic Amp and Oestradiol on Incorporation of [3h]leucine Into the Proteins of Luminal Fluid of the Rat Uterus

“…Blastocyst implantation is temporally asso¬ ciated with the detection of the luminal proteins (Surani, 1975(Surani, , 1976(Surani, , 1977, and in their absence, blastocysts in the lumen enter into metabolic quiescence (Webb & Surani, 1975;Surani, 1977). The stimulation by dbcAMP of physiological and cytological responses such as embryo implantation, uterine cell mitotic activity and decidualization (Webb, 1975(Webb, , 1977 and the more specific changes in the uterine proteins demonstrated in this study after treatment of the uterus with dbcAMP, affirm that the nucleotide is able to have specific oestrogen-like effects on the uterus so that it is functionally competent for embryo implantation.…”

“…Uteri of ovariectomized rats treated repeatedly with cyclic AMP show both hyperplastic and hypertrophie growth (Rath & Prasad, 1974). Administration of dbcAMP, instead of oestradiol, to ovariectomized mice given progesterone alone induces normal growth of uterine cells (Webb, 1977).…”

“…An injection of dbcAMP, instead of oestradiol, to ovariectomized pregnant mice given progesterone alone induces embryo implantation (Webb, 1975). Blastocyst implantation provides a critical test for the action of the cyclic nucleotide, since a stringent sequence of progesterone and oestradiol action is required for uterine functional differentiation at this time (Psychoyos, 1973) and the apparently oestrogen-like effects of the nucleotide result in specific physiolo¬ gical events (Webb, 1975(Webb, , 1977. Oestradiol stimulates synthesis and secretion of uterine specific proteins in the lumen and these apparently regulate blastocyst cell metabolism before implantation (Surani, 1975(Surani, ,1976(Surani, ,1977.…”

Hormone involvement in the establishment of pregnancy

“…Ebert & Fox (1977) have observed a simUar effect using cyclic GMP in the rat. Webb (1977) has explained these findings by experi¬ ments using ovariectomized progesterone-treated mice in which intraluminal dbcAMP induced oestrogen-like changes in the luminal epithelium. Stromal mitosis was also observed, permitting subsequent oil induction of decidualization; this response is characteristic of oestrogen adminis¬ tration when the uterus is dominated by progesterone.…”

Control of cyclic AMP concentration in bovine endometrial stromal cells by arachidonic acid

“…Compounds activating adenylyl cyclase in the endometrium include prostaglandin (PG) E 2 , relaxin, activin, luteinizing hormone and corticotrophin-releasing hormone, all of which have been implicated in changes in endometrial function during early pregnancy (Tseng et al 1992, Tang & Gurpide 1993, Frank et al 1994, Ferrari et al 1995. Administration of dibutyryl cAMP to the uterine lumen in mice has been known for three decades to induce a decidual response and implantation (Webb 1977). Recently, it has been proposed that cAMP acts to support the action of progesterone, through synergy between the protein kinase A substrate, CREB and the progesterone receptor (Gellerson & Brosens 2003).…”