Time course of the changes in uterine vascular permeability associated with the development of the decidual cell reaction in ovariectomized steroid-treated rats

Uterine vascular permeability and tissue blood volume during the development of the oil-induced decidual cell reaction (DCR) in ovariectomized steroid-treated rats were assessed by measuring the extravascular accumulation of 125I-labelled human serum albumin and the tissue content of 51Cr-labelled red cells 30 min after intravenous administration. Within 15 min of oil instillation into one uterine horn, the vascular permeability of the horn was significantly elevated. Permeability rose to a sharp peak (10 times control levels) 9 h after oil instillation, but dropped to 5 times control values by 12 h and continued a steady decline over the next 7 days. Although a marked increase in uterine weight was associated with the development of the DCR, there was no significant change in blood volume/g tissue until 4 days after oil instillation.     

The sensitivity of the uterus of the mouse and rat to intraluminal instillation

The tissue accumulation of 125I-labelled human serum albumin 30 min after intravenous injection was used as an index of uterine vascular permeability. In ovariectomized mice, all sham and experimental instillation procedures produced a 6-10-fold increase in vascular permeability. Some effects were also manifest in the contralateral, control horn. In ovariectomized rats, instillation of saline and arachis oil increased vascular permeability 3-7-fold. After 3 or more days of progesterone treatment following oestradiol priming, fluorocarbon and arachis oil instillation produced marked vascular responses, but these were not restricted to the transient period in which the uterus would respond with decidualization. An IUD prevented the response to arachis oil instillation. These results indicate that the uterus is very sensitive to any manipulation and are consistent with decidualization representing a specialization of a normal uterine inflammatory response.     

Tissue spaces during development and regression of the decidual cell reaction in ovariectomized, steroid-treated mice

Changes in the extracellular and blood spaces of the uterus were assessed from the distribution volumes of 51Cr-EDTA and 51Cr-labelled red blood cells during the development and regression of the artificially induced decidual cell reaction in ovariectomized, steroid-treated mice. The normally high values for uterine extracellular space (0.35-0.40 microliter/mg) fell to less than 0.20 microliter/mg in association with decidual growth. Uterine blood space increased from around 0.02 microliter/mg to 0.03-0.05 microliter/mg with decidual development. Induction of decidual regression by removal of s.c. progesterone implants caused a rapid decline in tissue blood volume to reach control values (0.01-0.02 microliter/mg) within 24 h and preceded any reduction in uterine weight. Uterine vascular permeability, as determined from the tissue accumulation of 125I-labelled human serum albumin, fell with a similar time course. Tissue extracellular space returned to the higher control values within 48 h of initiating decidual regression.     

A study of the early morphological changes initiated in the uterine luminal epithelium by substances (oil and carrageenan) which induce the decidual cell reaction in mice

Oil, carrageenan or saline were injected into the uteri of ovariectomized mice treated with hormones on schedules which would sensitize, partly sensitize or not sensitize the uterus to an intraluminal decidual stimulus. The uterine epithelium was examined histologically at various times over the succeeding 5 h. Saline did not produce any morphological change whereas almost immediately after the injection of oil or carrageenan epithelial cell death was apparent in the uterus, regardless of hormone treatment. Within 45 min the dead cells had been removed and the epithelium was re-established. Oil droplets were still present in the uterus after 5 h and these were able to stimulate a decidual reaction in partly sensitized animals when oestrogen was administered 18-44 h after the oil instillation, well after the re-establishment of the epithelium. It is suggested that the early transient cell death in the uterine epithelium is not responsible for triggering the decidual reaction but that it is the contact of the oil droplet with an intact epithelium which triggers the response when the hormonal conditions so allow.     

Estrogen induced changes in uterine sensitivity for the decidual cell reaction: Interactions between prostaglandin E2 and histamine or bradykinin

In rats receiving high doses of estrogen along with progesterone, the uterus is desensitized and does not respond to artificial stimuli with increased endometrial vascular permeability or decidualization. In addition, prostaglandin E₂ (PGE₂), the putative mediator of endometrial vascular permeability changes in sensitized uteri, is ineffective when given into the uterine lumen. The possibility that this inability of PGE₂ to increase endometrial vascular permeability may be related to the unavailability of hitamine of bradykinin was investigated. Rats were differentially sensitized for the decidual cell reaction by the daily injection of 2 mg progesterone with either 0.5 of 10 μg estrone for the 3 days preceding the unilateral intra-uterine injection of 50 μl phosphate buffered saline containing gelatin with or without 10 μg PGE₂ and with or without 1 mg histamine or 1 μg bradykinin. Prior to the intrauterine injection, all rats were treated with indomethacin to inhibit endogenous prostaglandin production. Endometrial vascular permeability changes were determined 8 h later by determining radioactivity levels in injected and non-injected uterine horns 15 min after the i.v. injection of ¹²⁵I-labelled bovine serum albumin. PGE₂ increased endometrial vascular permeability in rats receiving 0.5 μg estrone, but not in those receiving 10 μg. Histamine or bradykinin, alone or with PGE₂, did not affect endometrial vascular permeability in rats receiving either estrogen dose. The data suggest that the unresponsiveness of uteri from rats treated with high doses of estrogen is not simply due to the unavailability of bradykinin or histamine.     

Varying effects of an IUD on decidualization in mice.

Chronically implanted IUDs consisting of silk suture threads induced decidualization in regions of the uterus remote from the suture site in ovariectomized mice treated with a regimen of progesterone and oestrogen which sensitizes the uterus to a decidual stimulus. In these conditions the IUDs did not inhibit decidualization induced by instilled oil, although they did so in pregnant animals of the same strain. Varying the dose of progesterone and oestrogen did not produce conditions in which IUD's inhibited oil-induced decidualization in ovariectomized mice and progesterone treatment did not prevent IUDs inhibiting decidualization in pregnant animals. However, when ovariectomized mice, sensitized as before, were primed repeatedly with oestrogen to simulate continuing oestrous cycles after IUD insertion, the IUD's inhibited oil-induced decidualization. This involved the premature loss of instilled oil from the uterine lumen and was associated with heavy infiltration of leucocytes into the luminal epithelium. Numbers of leucocytes free in the uterine lumen did not appear to be critical. It appears that contact between the oil and the luminal epithelial surface must be sustained for some length of time to induce a decidual reaction; brief contact is not sufficient to trigger the response.     

Effects of cycloheximide on the uterine refractory state induced by 'nidatory' oestrogen in rats.

After priming with oestradiol, ovariectomized rats were given 6 days of progesterone treatment in which two doses of 50 ng oestradiol were given on Days 3 and 6. This basic treatment allows the oestradiol-induced (1st injection) disappearance of uterine sensitivity to decidual stimuli to occur. Cycloheximide could not mimic oestrogen action in the production of the uterine refractory state. However, a high dose (500 micrograms per animal) of this inhibitor given with the first injection of oestradiol allowed the uterus to remain in a neutral state and to respond to decidual induction after the second dose of oestradiol. By delaying the injection of cycloheximide after the first oestrogen treatment, protein synthesis requisite to the occurrence of uterine refractoriness would not take place within 12 h after the 'nidatory' oestrogen injection.     

Induction of mammary prolactin receptors and lactose synthesis after ovariectomy in the pregnant mouse.

The development of prolactin receptors in the mammary gland after ovariectomy was investigated in pregnant KA mice. Mice were ovariectomized on day 13 of pregnancy and used for the determination of the amount of specific binding of 125I-labelled prolactin to the mammary tissue, and the contents of lactose and nucleic acids in the mammary gland 0, 8, 24, and 72 hr after the operation. The specific binding of 125I-labelled prolactin, lactose and RNA contents in the mammary gland remained low until 8 hr, sharply increased 24 hr and decreased 72 hr after ovariectomy. When ovariectomized mice were treated with 0.2 mg progesterone, pregnancy was maintained and an increase (1.5-fold) in the amount of specific binding was observed with an increase of lactose content. Five mg progesterone completely inhibited lactose synthesis. Cortisol administered with progesterone did not show any specific change at the dose used (0.5 to 10 mg). Although the amount of specific binding was also increased after hysterectomy, this increase (2-fold) did not fully cover the increase after ovariectomy (3-fold). These results suggest that the recepter site for prolactin is induced before the initiation of lactose synthesis caused by ovariectomy during pregnancy.     

Uterine blood flow during the development and regression of the decidual cell reaction in ovariectomized, steroid-treated mice

Uterine blood flow was assessed in mice by measuring organ uptake of intravenously injected [14C]butanol. In ovariectomized mice, injection of 100 ng oestradiol-17 beta increased blood flow 5-fold over that of untreated controls. The injection of oestradiol-17 beta in progesterone-treated mice also increased uterine blood flow at the time of maximal sensitivity to a decidual stimulus, but not 4 days later. Absolute values of blood flow increased during development of the decidual cell reaction in proportion to the increase in uterine weight, reaching maximal values 96 h after decidual induction. When progesterone injections were stopped 72 h after decidual induction, a rapid decrease in absolute and relative blood flow values preceded the decrease in uterine weight. This decrease in uterine blood flow occurred within 12 h of removing a subcutaneous implant containing progesterone. These results are consistent with the view that increased uterine blood flow during decidual development may be necessary to support the rapid increase in uterine weight at implantation and the subsequent decrease in both relative and absolute uterine blood flow on withdrawal of progesterone may promote decidual regression in the mouse.     

Progesterone pretreatment has a direct effect on GnRH-induced preovulatory follicles to determine their ability to develop into normal corpora lutea in anoestrous ewes

In two experiments carried out during seasonal anoestrus, Romney Marsh ewes were treated with small-dose (250 ng) multiple injections of GnRH at 2-h intervals with and without progesterone pretreatment. In Exp. 1, 8/8 progesterone-primed ewes ovulated and produced functionally normal corpora lutea compared with 2/9 non-primed ewes. Follicles were recovered from similarly treated animals 18 or 28 h after the start of GnRH treatment (at least 14 h before the estimated time of the LH peak) and assessed in terms of diameter, granulosa cell number, oestradiol, testosterone and progesterone concentrations in the follicular fluid, oestradiol production in vitro and binding of 125I-labelled hCG to granulosa and theca. There were no significant differences in any of these measures in 'ovulatory' follicles recovered from the progesterone-pretreated compared to non-pretreated animals. In Exp. 2, follicles were removed from similar treatment groups just before and 2 h after the start of the LH surge. Unlike 'ovulatory' follicles recovered from the non-pretreated ewes, those recovered from progesterone-pretreated ewes responded to the LH surge by significantly increasing oestradiol secretion (P less than 0.01) and binding of 125I-labelled hCG (P less than 0.05) to granulosa cells. Overall there was also more (P less than 0.05) hCG binding to granulosa and theca cells from progesterone-pretreated animals. Non-ovulatory follicles recovered from progesterone-primed ewes had more (P less than 0.05) binding of 125I-labelled hCG to theca and a higher testosterone concentration in follicular fluid (P less than 0.05) than did those from non-primed ewes. These results suggest that inadequate luteal function after repeated injections of GnRH may be due to a poor response to the LH surge indicative of a deficiency in the final maturational stages of the follicle.     

Uterine vascular permeability, blood flow and extracellular fluid space during implantation in rats

Vascular permeability to plasma proteins in uterine implantation and non-implantation sites (i.e. dye sites and non-dye sites) was assessed quantitatively by a method which accounts for steady-state volumes of distribution. Extracellular fluid volume and uterine blood flow were also determined. On both the evening of Day 5 and the morning of Day 6, vascular permeability to 125I-labelled human serum albumin, extracellular fluid volume and blood flow were significantly increased in implantation sites compared to non-implantation sites. Vascular permeability in implantation sites was increased significantly between Days 5 and 6, whereas that in non-implantation sites was unchanged. This increase in vascular permeability between Days 5 and 6 was not accompanied by further increases in extracellular fluid volume and blood flow. This result shows a dissociation between vascular permeability and extracellular fluid volume immediately after the onset of implantation and raises important questions as to whether the rat uterus undergoes a truly oedematous response at implantation as has been generally accepted.     

Estrogen and uterine sensitization for the decidual cell reaction in the rat: role of prostaglandin E2 and adenosine 3':5'-cyclic monophosphate

The possibility that estrogen affects uterine sensitization for decidualization by altering the ability of E-series prostaglandins (PGs) to increase adenosine 3':5'-cyclic monophosphate (cAMP) concentrations was investigated. To determine if increased endometrial vascular permeability, a response which precedes decidualization, could be obtained in nonsensitized uteri by treatments designed to increase endometrial intracellular cAMP concentrations, cholera toxin, an activator of adenylate cyclase, was injected into the uterine lumen of immature rats pretreated with progesterone and either 0, 0.5 or 10 micrograms estrone with indomethacin to inhibit endogenous PG synthesis. Endometrial vascular permeability, determined using 125I-labeled bovine serum albumin, was assessed 8 h later. Cholera toxin produced a dose-dependent increase in endometrial vascular permeability in all groups; the uteri of rats pretreated with the optimal hormone regimen (0.5 micrograms estrone plus 2 mg progesterone) responded to a lower dose of the toxin. As determined by uterine weights and histologic examination 5 days after the intrauterine administration of cholera toxin or its vehicle, the toxin induced decidualization in rats pretreated with progesterone and 0 or 0.5 micrograms estrone, but not in those receiving 10 micrograms estrone. Cholera toxin had no detectable effect on uterine cAMP concentrations in animals sacrificed 15 min or 3 h after intrauterine treatment. The intrauterine injection of 8-Br-cAMP, with or without 3-isobutyl-1-methyl-xanthine, did not increase endometrial vascular permeability in indomethacin-treated animals pretreated with the different hormone regimens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uterine decidualization in hypophysectomized-ovariectomized rats: effects of pituitary hormones

Decidualization of the endometrial stroma occurs in rats in response to implanting blastocysts or after the application of an appropriately timed artificial stimulus. It is well established that decidualization is regulated by estrogens and progesterone (P). The present study investigated the role of pituitary hormones in this response. Decidualization produced by the bilateral intrauterine injection of 100 microliter sesame oil was compared in ovariectomized (OVX) and hypophysectomized (HYPOX)-OVX rats. All animals were treated with a sequence of 17 beta-estradiol (E2) and P that in OVX rats supported decidualization. As assessed by uterine weights 5 days after uterine stimulation, decidualization was much greater in OVX than in HYPOX-OVX rats (geometric mean uterine weights of 1539 and 376 mg, respectively). To determine the ability of pituitary hormones to restore decidualization in HYPOX-OVX rats, animals were treated with ovine prolactin (oPRL, 2 x 100 micrograms daily), bovine growth hormone (bGH, 2 x 125 micrograms daily), and thyroxine (1 microgram/day, replacement for thyrotropin) in addition to E2 and P. Combined treatment with bGH + thyroxine resulted in decidualization which was not significantly different from that obtained in OVX rats; the effects of bGH and thyroxine were additive. oPRL had no significant effect. Administration of bGH + thyroxine during the prestimulation period resulted in decidualization which did not differ significantly from that obtained when the hormones were administered both pre- and poststimulation; administration during the poststimulation period only, when growth and differentiation of decidual cells occurs, resulted in much less decidualization. Because an increase in endometrial vascular permeability is a prerequiste for decidualization, [125I]-labeled bovine serum albumin was used to assess permeability 8 h after uterine stimulation. Uterine concentrations of radioactivity indicated that endometrial vascular permeability was increased to the same extent in bGH + thyroxine-treated HYPOX-OVX rats as in OVX animals; this increase was significantly reduced in vehicle-treated HYPOX-OVX rats. Because prostaglandins (PGs) are involved in decidualization, the possibility that the reduced responses in vehicle-treated HYPOX-OVX rats were a consequence of a decreased capacity of the uterus to produce PGs in response to the deciduogenic stimulus was investigated. As indicated by uterine PGE and PGF concentrations 15 min after uterine stimulation, uterine PGE and PGF production was increased by the stimulus in both vehicle-treated and bGH + thyroxine-treated HYPOX-OVX rats.(ABSTRACT TRUNCATED AT 400 WORDS)     

Endometrial ultrastructure in the early uterine response to blastocysts and artificial deciduogenic stimuli in rats

Summary The early uterine response to transplanted, delayed and estrogenactivated blastocysts was studied ultrastructurally and compared with that induced by intrauterine instillations of deciduogenic agents (arachis oil, air). The uterine responses to delayed and activated blastocysts showed no ultrastructural or temporal differences. Already within 4 h after transfer to a sensitized uterus, the delayed blastocysts exhibited signs of activation, and both types of blastocysts had started to attach onto an undamaged epithelial lining. Signs of stromal cell differentiation into decidual cells were also seen as early as 4 h after transfer, while the Pontamine-blue reaction did not appear until after 8 h. The results therefore indicate that the transplanted blastocysts induced decidualization atraumatically and that the delayed blastocysts were either deciduogenic already before transfer or rapidly acquired deciduogenic properties after transfer.Artificial decidual induction with oil and air led to damage or death of a large number of cells in the uterine luminal epithelium. Within only 15 min after instillation pronounced signs of cell damage were seen, and later numerous cells were extruded from the epithelial lining. In the stroma ultrastructural signs of decidual cell differentiation and a Pontamine-blue reaction were observed as early as 4 h after induction. It is therefore suggested that oil and air induce decidualization via the epithelium by means of trauma.Supported by grants from the Swedish Medical Research Council (Project 12X-70)     

Lectins, calcium ionophore A23187 and peanut oil as deciduogenic agents in the uterus of pseudopregnant mice: effects of tranylcypromine, indomethacin, iproniazid and propranolol

Intraluminal injections of lectins, including concanavalin A (Con A), wheatgerm lectin, and soybean lectin, Con A-Sepharose 4B beads, calcium ionophore A23187 or peanut oil into the left uterine horns of mice on day 4 of pseudopregnancy induced the formation of deciduomata and significantly increased the weight and alkaline phosphatase activity of uterine tissue on day 7 of pseudopregnancy. In contrast, injections of these materials into the uterine horns of non-pseudopregnant mice that had not been previously mated failed to induce similar responses. Tranylcypromine blocked the decidual cell reaction artificially induced by lectins, calcium ionophore A23187 and peanut oil in pseudopregnant mice. However, uterine responses observed after individual and concurrent injections with indomethacin, iproniazid, propranolol or progesterone indicated that this deciduoma-blocking effect may not be solely related to the ability of tranylcypromine to inhibit prostacyclin biosynthesis but may also involve catecholamines and luteolytic prostaglandins which interfere with decidualization on day 4 and day 6 of pseudopregnancy, respectively. A role for prostaglandins and uterine beta-adrenergic receptors, however, was implicated in the induction of decidualization because both indomethacin and propranolol blocked the response to peanut oil. The results suggested that the embryonic signal responsible for the induction of the decidual cell reaction in mice may involve surface interactions between the embryo and uterine luminal epithelium resulting in a stimulation of the uterus via glycoprotein receptors. A role for calcium was implicated in this phenomenon.     

The effect of synthetic leukotrienes on tracheal microvascular permeability

The effect of synthetic leukotrienes (LT) C4, D4 and E4 on the permeability of the airway microvasculature to plasma albumin was quantitatively evaluated using an in situ guinea pig tracheal model. Vascular permeability was measured as extravascular albumin content by employing 125I-bovine serum albumin and, in order to correct for blood volume, 51Cr-erythrocytes were used. Intratracheal injection of synthetic LTC4, LTD4 and LTE4 (0.1-1000 ng) produced dose-dependent increases in tracheal extravascular albumin content. The leukotrienes were approximately 100-1000 fold more potent than histamine, although histamine did produce a greater maximal increase in extravascular albumin than the leukotrienes. Methacholine did not increase extravascular albumin content. The microvascular permeability effect of LTD4 was antagonized by FPL 55712 but not by mepyramine; conversely, the effect of histamine was antagonized by mepyramine and not by FPL 55712. Additionally, indomethacin did not alter the LTD4-induced increases in tracheal vascular permeability. These results suggest that the effect of LTD4 on tracheal microvascular permeability is directly mediated and is not the indirect result of cholinergic stimulation, histamine release or de novo synthesis of cyclooxygenase products.     

Regulatory effect of steroid hormones and fetal tissues on expression of oxytocin receptor in the endometrium of late pregnant ewes.

Oxytocin receptors play an important role in the establishment of pregnancy and parturition in ruminants. Previous studies in cyclic and early pregnant ewes have indicated that receptor concentrations are regulated by steroid hormones and fetal secretory products. This study investigated the effect of oestradiol and progesterone, or co-culture with placenta or corpus luteum on oxytocin receptor expression. Endometrial explants from late pregnant ewes were cultured for up to 96 h in various treatment combinations. After culture, tissues were subjected to in situ hybridization and autoradiography with 125I-labelled oxytocin receptor antagonist to localize and measure the expression of oxytocin receptor mRNA and protein. Results were quantified as absorbance units from autoradiographs. Oxytocin receptors were confined to the endometrial luminal epithelium and both mRNA and 125I-labelled oxytocin receptor antagonist binding were upregulated spontaneously in basic serum-free medium. Upregulation occurred earlier in the presence of oestradiol (0.1 mumol l-1) but the final receptor concentration was similar to that found in the basic medium. Continuous progesterone treatment (1 mumol l-1) and co-culture with corpus luteum both delayed the increase in oxytocin receptor mRNA, but a short initial (4 h) period in progesterone-free basic medium resulted in loss of the inhibitory effect. Co-culture with placental tissues had no effect. In conclusion, oxytocin receptor expression in the luminal epithelium increased immediately on removal from the maternal environment. This occurred regardless of treatment and did not require the presence of steroid hormones, but could be accelerated or delayed by oestradiol and progesterone, respectively. There may be an additional inhibitory factor present in the corpus luteum.     

Regulation of progesterone receptors and decidualization in uterine stroma of the estrogen receptor-alpha knockout mouse

Regulation of progesterone receptor (PR) in uterine stroma (endometrial stroma plus myometrium) by estrogen was investigated in estrogen receptor-alpha (ERalpha) knockout (alphaERKO) mice. 17 beta-Estradiol (E(2)) increased PR levels in uterine stroma of ovariectomized alphaERKO mice, and ICI 182 780 (ICI) inhibited this E(2)-induced PR expression. Estrogen receptor-beta(ER beta) was detected in both uterine epithelium and stroma of wild-type and alphaERKO mice by immunohistochemistry. In organ cultures of alphaERKO uterus, both E(2) and diethylstilbestrol induced stromal PR, and ICI inhibited this induction. These findings suggest that estrogen induces stromal PR via ERbeta in alphaERKO uterus. However, this process is not mediated exclusively by ERbeta+, because in ERbeta knockout mice, which express ERalpha, PR was up-regulated by E(2) in uterine stroma. In both wild-type and alphaERKO mice, progesterone and mechanical traumatization were essential and sufficient to induce decidual cells, even though E(2) and ERalpha were also required for increase in uterine weight. Progesterone receptor was strongly expressed in decidual cells in alphaERKO mice, and ICI did not inhibit decidualization or PR expression. This study suggests that up-regulation of PR in endometrial stroma is mediated through at least three mechanisms: 1) classical estrogen signaling through ERalpha, 2) estrogen signaling through ERbeta, and 3) as a result of mechanical stimulation plus progesterone, which induces stromal cells to differentiate into decidual cells. Each of these pathways can function independently of the others.     

Uterine DNA synthesis and cell proliferation during early decidualization induced by oil in mice

[3H]Thymidine autoradiography was used to study cell proliferation during decidualization induced by intraluminal oil in ovariectomized mice treated with oestrogen and progesterone. Development of the decidual reaction involves two distinct populations of stromal cells. Periluminal cells start to synthesize DNA 11--15 h after instillation and by 17--20 h, without dividing, differentiate into epithelioid decidual cells which continue to incorporate [3H]thymidine, presumably becoming polyploid. Cells peripheral to this zone also start to synthesize DNA between 11 and 15 h, but at 18.5 h many have divided before differentiating. None of these dividing cells had been arrested in G2. The periluminal and peripheral cells do not appear to differ in their proliferative antecedents.     

Effects of analogues of prostaglandin E2 and F2 alpha on the decidual cell reaction in the rat

The identity of the prostaglandins (PGs) involved in the decidual cell reaction is uncertain. In the present study we investigated the ability of analogues of PGE2 and PGF2 alpha, 16,16-dimethyl-prostaglandin E2, methyl ester (16,16Me2PGE2) and 15(S)-15-methyl-prostaglandin F2 alpha (15MePGF2 alpha) respectively, to bring about decidualization when infused into the uterine lumen of rats sensitized for the decidual cell reaction. As indicated by uterine weights 5 days after the commencement of the infusions into rats in which endogenous PG production had been inhibited by treatment with indomethacin, 16,16Me2PGE2 produced decidualization which was equivalent to that produced by PGE2. By contrast, the infusion of 15MePGF2 alpha inhibited decidualization, even when PGE2 was infused concomitantly. As indicated by uterine radioactivity concentrations after i.v. administration of 125I-labeled bovine serum albumin, the PGF2 alpha analogue also inhibited the endometrial vascular permeability increase which precedes decidualization. Compared to PGE2, 16,16Me2PGE2 was slightly less effective at displacing 3H-PGE2 from an endometrial membrane preparation; by contrast 15MePGF2 alpha was considerably less effective. These data suggest that PGE2 mediates the decidual cell reaction, and that the decidualization obtained in response to PGF2 alpha may involve its conversion within the uterus to PGE2.