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PubMed2000

Distribution and origin of secretoneurin-immunoreactive nerves in the female rat uterus.

Secretoneurin is a 33-amino acid peptide derived from secretogranin II. Secretoneurin immunoreactivity has been localized in the peripheral nervous system where it exerts potent chemotactic activity for monocytes and may play a role in inflammation. Secretoneurin could play a role in this process, although the presence and distribution of secretoneurin-immunoreactive neurons in the female reproductive system has not been documented. Thus, this study was undertaken to examine secretoneurin immunoreactivity in nerves of the rat uterus and uterine cervix. A moderate plexus of secretoneurin-immunoreactive nerve fibers was present in the myometrium and endometrium of the uterus as well as in the smooth muscle and endocervix of the cervix. Many of these fibers were associated with the vasculature as well as the myometrium. Secretoneurin immunoreactivity was present in small- to medium-sized neurons of dorsal root and nodose ganglia. Retrograde tracing with FluoroGold indicated that some of these sensory neurons project axons to the cervix and uterine horns. Secretoneurin-immunoreactive terminal-like structures were associated with neurons in the sacral parasympathetic nucleus of the lumbosacral spinal cord. In addition, some secretoneurin terminals were apposed to pelvic parasympathetic neurons in the paracervical ganglia that projected axons to the uterus and cervix. Double-immunostaining indicated co-existence of calcitonin gene-related peptide or substance P with secretoneurin in some sensory neurons, in some terminals of the pelvic ganglia, as well as nerve fibers in the uterine horn and cervix. Finally, fibers in the uterus and cervix were depleted of secretoneurin by capsaicin treatment. This study indicates that secretoneurin is present in the uterus in C-afferent nerve fibers whose cell bodies are located in sensory ganglia. Some of these fibers contain both secretoneurin and calcitonin gene-related peptide or substance P. These substances have functions in inflammatory reactions. Further, secretoneurin could influence postganglionic parasympathetic "uterine-related" neurons in the pelvic ganglia and preganglionic parasympathetic neurons in the lumbosacral spinal cord.

Animals↗
PubMedDate not supplied

Multiple mechanisms are involved in apoptotic cell death in the mouse uterus and vagina after ovariectomy.

Withdrawal of sex hormones by gonadectomy results in rapid involution of mouse reproductive organs. To study the regression mechanism in the uterus and vagina after ovariectomy, histologic and biochemical changes were examined. Apoptotic cells were detected by in situ 3'-DNA nick end labeling method and electron microscopy, while the number of cells showing incorporation of bromo-deoxyuridine (BrdU) decreased in the uterus and vagina after ovariectomy. DNA fragmentation in the uterus was observed even at estrus and the degree of fragmentation increased after ovariectomy. DNA fragmentation in the vagina occurred 1-5 days after ovariectomy. Semi-quantitative RT-PCR revealed that expression of Fas-ligand and tumor necrosis factor-alpha (TNF-alpha) mRNA in the uterus and vagina was increased by ovariectomy. These results suggest that apoptotic cell death is induced by ovariectomy through the mediation of both Fas and TNF-alpha in the mouse uterus and vagina; however, uterine and vaginal cells in CBA lpr(cg)/lpr(cg) mice lacking functional Fas showed apoptosis, indicating that Fas is not the sole regulator of apoptosis in female reproductive organs in mice.

Animals↗
PubMed1992

The connective tissue sheath of uterus and vagina in the human female fetus.

A morphological study concerning the development and arrangement of the connective tissue surrounding uterus and vagina was performed by investigating epoxy resin impregnated sections through the pelves of 9-37-week-old female fetuses, of newborn children and a three-year-old child. In order to study the histology of the connective tissue in detail paraffin, semithin and ultrathin sections were used. The organization of the pelvic connective tissue in female fetuses can best be studied in middle-aged fetuses (19-28 weeks of gestation). We here report that no supportive ligaments of the uterus are found in fetuses of that age group, but that the connective tissue covering uterus and vagina is part of the connective tissue sheaths of neighbouring structures. The fetal uterus is interposed between dense subperitoneal connective tissue circularly covering the vesico- and rectouterine pouch. Dorsally the subperitoneal tissue of the rectouterine pouch joins the circularly arranged connective tissue of the rectal adventitia. A triangularly-shaped plate of dense connective tissue is situated at each lateral border of the cervix uteri. Dorsally it is continuous with the circularly running fibres of the rectouterine pouch. Whereas the dorsal wall of the vagina is loosely connected with the rectal adventitia, fibrous connective tissue intimately fuses the muscular wall of the vagina with that of the neck of the bladder and of the urethra. No evidence is provided for the existence of smooth muscle cells and elastic material within the connective tissue covering the fetal uterus.

Child, Preschool↗
PubMed1996

Purification and characterization of glutathione S-transferases of rat uterus.

Glutathione S-transferases (GSTs) provide protection to cells against electrophilic xenobiotics as well as lipid hydroperoxides and 4-hydroxynonenal generated during lipid peroxidation. The catalytic properties of the alpha class GSTs are well suited for detoxification of electrophilic products of lipid peroxidation. An immunologically distinct subgroup of the alpha class GST isozymes having high activity towards 4-hydroxynonenal has been recently identified in several mammalian tissues [Zimniak et al. (1994) J. Biol. Chem. 269, 992-1000]. Since oxidative stress can exert deleterious effects during gestation, the present studies were performed to determine whether the rat homolog of this group of GSTs, rGST 8-8, is expressed in gravid rat uterus, where it may function as a defense mechanism against oxidative stress. GSTs were purified by GSH-affinity chromatography. Individual GST isozymes were separated by column isoelectric focusing and their immunologic identities were established using highly specific polyclonal antibodies in Western blot analysis. Their expression was quantified and kinetic properties were characterized. Rat uterus contained an alpha class GST (pI 9.8), a pi class GST (pI 8.1), two mu class GSTs (pI 6.7 and 6.2) and rGST 8-8. This result indicated that rGST subunits 1, 2, 3, 4, 7 and 8 are present in rat uterus. The relative abundance of rGST 8-8 in the gravid rat uterus was found to be about three-fold higher as compared with that previously seen in rat liver. Higher relative abundance of rGST8-8 in gravid rat uterus suggests that it may play a protective role against the deleterious effects of lipid peroxidation during gestation.

Amino Acid Sequence↗
PubMed2001

The role of activation of the renin-angiotensin system on the reflex regional vasoconstriction caused by distension of the uterus in anaesthetized pigs.

Distension of the uterus in anaesthetized pigs has been shown to cause a reflex regional vasoconstriction and an increase in plasma renin activity (PRA) through efferent sympathetic mechanisms which respectively involved alpha- and beta-adrenergic receptors. The present study was undertaken to determine the possible contribution of the activation of the renin-angiotensin system (RAS) to the observed regional vasoconstrictive responses to uterus distension. In pigs anaesthetized with alpha-chloralose, blood flow in the left circumflex or anterior descending coronary, superior mesenteric, left renal and left external iliac arteries was assessed using electromagnetic flowmeters. Distension of the uterus for periods of 30 min was performed by injecting 20 ml of warm Ringer solution into balloons positioned within the viscus before and after blockade of angiotensin II receptors with losartan. Changes in heart rate and renal blood flows were respectively prevented by atrial pacing and injection of phentolamine into the renal arteries. Changes in baroreceptors activity and in regional perfusion pressure were minimized by section of cervical vagus nerves and denervation of carotid sinuses and by an aortic constriction. PRA was assessed during the last minute of distension by radioimmunoassay of angiotensin 1. Before blockade of angiotensin II receptors, in six pigs, distension of the uterus decreased coronary blood flow by 19%, and in other six pigs, decreased mesenteric and iliac blood flows by 13.1% and 29.4% in the absence of changes in arterial perfusion pressure. After losartan, these decreases were significantly reduced to 11.7%, 8.2% and 18%. These results showed that the activation of the RAS significantly contributed to the alpha-adrenergic receptor-mediated regional vasoconstrictive responses reflexly elicited by distension of the uterus.

Anesthesia↗
PubMed1999

Effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer.

PURPOSE: Our objective was to study the effect of a sonographically diffusely enlarged uterus without distinct uterine masses on the outcome of in vitro fertilization-embryo transfer (IVF-ET). METHODS: Nineteen primary infertility patients undergoing IVF-ET who had a sonographically diffusely enlarged uterus without distinct uterine masses were enrolled. An age-controlled group of 144 primary infertility patients undergoing IVF-ET with a normal uterus and no history of uterine surgery was included. RESULTS: The age, day 3 follicle stimulating hormone, antral follicle count, ovarian response, endometrial thickness, number of retrieved and fertilized oocytes, number of transferred embryos, clinical pregnancy rate, and total delivery rate were not statistically different between the two groups (P < 0.05). Patients with a sonographically diffused enlarged uterus without distinct uterine masses had a higher spontaneous abortion rate (66.7%) than controls (P < 0.04; odds ratio = 7.5; 95% confidence interval, 1.16-48.56). CONCLUSIONS: A high spontaneous abortion rate was found in patients with a sonographically diffusely enlarged uterus without distinct uterine masses undergoing IVF-ET. Enhanced luteal support was required.

Abortion, Spontaneous↗
PubMed1998

A cDNA cloned from pregnant mouse uterus exhibits temporo-spatial expression and predicts a novel protein.

A cDNA was cloned from a pregnant mouse uterus cDNA library. On conceptual translation, the cDNA has one long open reading frame that predicts a novel protein of 606 amino acids. This protein is principally composed of two CUB domains and a ZP domain; motifs found in proteins implicated in egg-sperm recognition. Probes derived from the cDNA were used to conduct Northern hybridizations. The expression of this mRNA is temporal; message first appears in the uterus 6 days prior to birth, it increases each subsequent day to attain maximal levels at 3 days prior to birth and then abruptly decreases during the last 3 days of pregnancy. The expression of this mRNA is restricted; message is abundant in the uterus during late pregnancy, but it is not found in non-pregnant uterus or in a variety of adult or fetal tissues. The temporo-spatial expression of this pregnant uterus specific mRNA and the consolidation in the predicted protein of two motifs implicated in early pregnancy events suggests that the product of the gene represented by this mRNA may play an important role in events that transpire during late pregnancy.

Amino Acid Sequence↗
PubMed2006

[Massive adenomyosis in a patient with uterus septus completus].

Septate uterus is a malformation caused by the defective resorption of the Müllerian ducts. It may be incomplete, or -- less frequently -- complete. We present a case of a uterus septus completus with special emphasis on the endometrial changes. We describe a 46-year-old female patient (nullipara) with a known uterus septus suffering from hypermenorrhea. Sonography demonstrated a massively enlarged uterus with several nodes. Hysterectomy was performed and tissue specimens were routinely processed. Macroscopical examination revealed a 1 230 g-weight uterus septus completus. In particular, the myometrium was enlarged and exhibited a cystic cut surface with several nodes measuring up to 4.5 cm. Histologically, we found prominent adenomyosis with several leiomyomas. Patients with uterine malformations are known to suffer from endometrial dysfunction, most commonly due to endometriosis. However, massive adenomyosis in combination with leiomyomas, as presented in this case report, has not been described so far. These endometrial changes are important, since they significantly contribute to infertility.

Adenomyoma↗
PubMed2000

Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus.

Many of the effects of estrogens on the uterus are mediated by ERalpha, the predominant ER in the mature organ. Because of the poor reproductive capacity of ERbeta knockout (BERKO) female mice (small litter size, multiple-resorbed fetuses), the role of uterine ERbeta was explored. In the immature uterus, ERalpha and ERbeta are expressed at comparable levels in the epithelium and stroma, and 17beta-estradiol (E(2)) treatment decreases ERbeta in the stroma. The immature uterus of untreated BERKO mice exhibits elevated levels of progesterone receptor (PR) and the proliferation-associated protein, Ki-67. It also exhibits exaggerated responsiveness to E(2), as indicated by enlargement of the lumen, increase in volume and protein content of uterine secretion, induction of the luminal epithelial secretory protein, complement C3, and its regulatory cytokine IL-1beta, and induction of vascular endothelial growth factor and insulin-like growth factor 1 but not its receptor. As expected, E(2) increased PR in the stroma and decreased it in the luminal epithelium of wild-type mice. In the BERKO uterus, E(2) induced PR in the stroma but did not down-regulate it in the epithelium. Increased cell proliferation and exaggerated response to E(2) in BERKO suggest that ERbeta plays a role in modulation of the effects of ERalpha and in addition (or as a consequence of this) has an antiproliferative function in the immature uterus.

Animals↗
PubMed1994

Differential effect of estrogen on the production of cyclin B1, cdc2 p34 and c-fos protein in rat uterus.

The uterine content of c-fos protein, cyclin B1 (cell cycle protein) and cdc2 p34(cyclin-dependent kinase) in immature and mature rats was determined using the enhanced chemiluminescence(ECL) western blot method. Cyclin B1 was found predominantly in immature rat uterus and cdc2 p34 only in mature rat uterus. Several isoforms of c-fos oncogene protein were present in both mature and immature rat uteri. An additional immunoreactive c-fos protein with an estimated molecular weight of 28 kDa was found in mature rat uterus and was missing in immature uterus. Uteri from ovariectomized rats treated with estrogen and/or ICI 182,780, an antiestrogen, were analyzed by ECL western blot. cdc2 p34 and the c-fos 28 kDa protein were found in estradiol-treated rat uteri and were not detected in uteri of control and ICI 182,780-treated animals; whereas Cyclin B1 was absent in uteri from control and estradiol-treated ovariectomized animals. ICI 182,780 administered to estradiol-treated ovariectomized rats blocked the induction of cdc2 p34 and the c-fos 28 kDa protein in the uterus. The present results show that the production of the cell cycle factors, cyclin B1, cdc2 p34 and c-fos, during rat uterine growth are under different regulatory controls. cdc2 p34 and c-fos 28 kDa protein are under the control of estradiol; whereas cyclin B1 and the majority of the immunoreactive isoforms of c-fos are not influenced by this hormone.

Animals↗
PubMed1969

The effect of hypertonic solution on the wet weight and contractions of rat uterus and vas deferens.

The role of propagated activity in the responses to agonist drugs was studied for the rat uterus and vas deferens. Hypertonic solutions were used to inhibit propagation of activity by shrinking cells. Tissue weight was used to indicate cell volume. Hypertonic solutions after 10 min caused weight loss and reduced the size of contractions in response to submaximal doses of drugs, to KCl, and to external electrical stimulation. Contractions in response to KCl and drugs were diminished to a similar degree in the vas deferens, but in the uterus, drug contractions were depressed much more. Prolonged action of hypertonic solution also differed for the two tissues. In the uterus, weight changes correlated with changes in size of the drug-induced contractions. Uterine contractions reduced in hypertonic solution could be increased by using supramaximal doses of drug. When stimulation was applied to one end of the uterus in a three compartment bath, propagation of spontaneous drug- and KCl-induced contraction occurred, but it was prevented by placing hypertonic solution in the center compartment. An increase of the KCl to 44 mM in the hypertonic solution restored propagation. These experiments yielded no evidence of propagated responses in the rat vas deferens. It was concluded that propagated activity plays a role in drug-induced contractions in the rat uterus but not in the rat vas deferens. Hyperpolarization of shrunken cells might be involved in inhibition of propagation by hypertonic solutions.

Acetylcholine↗
PubMed1996

Activation of 4-hydroxytamoxifen and the tamoxifen derivative metabolite E by uterine peroxidase to form DNA adducts: comparison with DNA adducts formed in the uterus of Sprague-Dawley rats treated with tamoxifen.

Daily intraperitoneal treatment of female Sprague-Dawley rats with either 5, 10 or 20 mg/kg tamoxifen (TAM) for 1 week increased the level of peroxidase activity in the uterus 2- to 10-fold compared to the control level. Using uterine extracts prepared from control and TAM treated animals, we investigated the activation of 4-hydroxytamoxifen (4-HO-TAM) and (E,Z)-1,2-diphenyl-1-(4-hydroxyphenyl)-but-1-ene (cis/trans-metabolite E) to form DNA adducts. Activation of 4-HO-TAM by uterine extracts prepared from either control or TAM-treated rats produced one major (a) and two minor DNA (b and c) adducts. A similar activation of cis/trans-metabolite E produced two adducts (d and e). There was good correlation between levels of uterine peroxidase activity and levels of DNA adducts formed by 4-HO-TAM and cis/trans-metabolite E. Activation of 4-HO-TAM and cis/trans-metabolite E with horseradish peroxidase (HRP) produced the same adducts as observed by activation with uterine extract. Treatment of Sprague-Dawley rats with 5 and 10 mg/kg for 7 days produced eleven DNA adducts in the liver with no adducts detected in the uterus. However, treatment of rats with 20 mg/kg of TAM for 7 days produced the same adduct pattern in the liver and also one major adduct (1) in the uterus with a relative adduct level of 6.4 - 4.1 x 10(-9). Tamoxifen-DNA adduct 1 detected both in the liver and in the uterus of treated rats was similar to adducts produced by activation of 4-HO-TAM with either uterine extract or HRP. The results of these studies suggest a general model whereby the tamoxifen metabolite 4-HO-TAM is further activated in the uterus by peroxidase enzymes to form DNA adducts.

Alkenes↗
PubMed1997

Laparoscopic extirpation of an aplastic ectopic uterus in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome comprises the combined hypoplasia of the vagina and the uterus. In recent years, variable anomalies of the development of the Mullerian duct [as classified by the American Fertility Society (AFS)] have been operated on by the laparoscopic approach. We describe here a laparoscopic extirpation of an aplastic ectopic uterus in a patient found to have a hypoplastic vagina and ectopic uterus attached to the right pelvic wall. The uterus was linked to a normotopic right Fallopian tube and right ovary which were covered with endometriosis and adhesions. While the uterine vessels and the round ligament could be demonstrated on the right side, these structures were missing on the contralateral left side of the uterus. However, a normal tube and ovary were present on the left pelvic wall. Although not explicitly described in the AFS classification, this constellation most likely corresponds to the AFS classification stage Ie.

Abnormalities, Multiple↗
PubMed2001

Preferential vascular-based transfer from vagina to the corpus but not to the tubal part of the uterus in postmenopausal women.

BACKGROUND: Vaginal administration of progesterone during infertility treatment has therapeutic advantages over oral administration. However, the reasons for this are poorly defined. To demonstrate a preferential vagina-to-uterus distribution of substances, we investigated cold distribution from vagina to the uterus and rectum. METHOD: In 10 postmenopausal women, thermoprobes were inserted into the uterine cavity and in the rectum at <9 cm or at >9 cm from the anus; temperatures were subsequently measured during 10 min flushing of vagina with cold saline. RESULTS: After 10 min, temperature decreased as follows: uterus, tubal angle: -0.22 +/- 0.07 degrees C, 10 (mean +/- SEM, n); uterus, middle cavity: -1.26 +/- 0.34 degrees C, 9; rectum, <9 cm insertion: -3.69 +/- 0.68 degrees C, 3; rectum, >9 cm insertion: -0.51 +/- 0.19 degrees C, 6. CONCLUSIONS: Despite obviously different distances to the vagina of the uterine and the low rectal probes (<9 cm) the temperature decrease occurred at the same time. Cold transfer from vagina to the uterus and rectum is probably not the result of simple diffusion but of a vascular counter-current transfer. Differential cooling of corpus and tubal angles suggests a different arterial supply; while uterine corpus is supplied from the uterine artery, the tubal angles seem to be mainly supplied from the ovarian artery via the tubal arcade.

Arteries↗
PubMed2005

Is there an association between septate uterus and endometriosis?

BACKGROUND: The question of whether Müllerian anomalies are significantly more often combined with endometriosis is a controversially discussed problem. Some publications described this association in patients with obstructive but not non-obstructive Müllerian anomalies or controls without Müllerian anomalies. The aim of this study was to evaluate the incidence of endometriosis in patients with a septate uterus as a non-obstructive form of Müllerian anomalies. METHODS: In a retrospective study, we evaluated 120 patients (29.4 +/- 4.7 years; mean +/- SD) with a septate uterus. The control group consisted of 486 consecutive infertile patients (30.8 +/- 6.3 years) with a normal hysteroscopy and laparoscopy. RESULTS: The incidence of dysmenorrhoea was comparable in both groups, but the incidence of endometriosis was significantly higher in patients with a septate uterus (25.8 versus 15.2%, P = 0.006). CONCLUSION: Our results suggest a higher incidence of endometriosis in patients with a septate uterus. If it can be confirmed by others, the initial finding of a septate uterus in infertile patients should be followed by a combined hysteroscopy and laparoscopy.

Adult↗
PubMed2005

Rejection patterns in allogeneic uterus transplantation in the mouse.

BACKGROUND: Transplantation of the uterus in the mouse has been developed as a model system for research towards human uterine transplantation. Previous studies in a mouse model have demonstrated that a syngeneic uterus transplant can give rise to normal offspring. The aim of this study was to characterize the time course of rejection in a fully allogeneic mouse uterus transplantation model. METHODS: Uteri of BALB/c mice were transplanted to a heterotopic position in C57BL/6 recipients, whose native uteri were left in situ. The blood flow of the uteri, their gross appearance and general histology and the density of T-lymphocytes were examined on postoperative days 2-28. RESULTS: Macroscopic signs of rejection were apparent from day 5. At the light microscopy level, minimal inflammatory changes were seen from day 5 and massive inflammation was seen from day 10 to day 15. At day 28, necrosis and fibrosis were seen. The density of T-lymphocytes (CD3(+)) was increased in the grafted uterus from day 2 in the myometrium and from day 5 in the endometrium. Blood flow in the grafted uteri was reduced from day 15. CONCLUSION: A murine model to study rejection of allogeneic uterus transplants was characterized. Signs of rejection were seen from day 2 to day 5 and severe rejection was seen from day 10 to day 15. The data will be useful in future studies on immunosuppressants in this model.

Animals↗
PubMed2004

Matrix metalloproteinases and their tissue inhibitors in the developing neonatal mouse uterus.

Postnatal development of the mouse uterus involves differentiation and development of the endometrial glands as well as the myometrium. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in extracellular matrix breakdown and morphogenesis of many epitheliomesenchymal organs. As a first step to understanding their roles in postnatal mouse uterine development, MMPs and TIMPs found to be expressed in the neonatal mouse uterus by microarray analysis were localized by in situ hybridization. The MMP-2 mRNA was detected only in the uterine stroma, whereas the MMP-10 mRNA was present only in the uterine epithelium from Postnatal Day (PND) 3 to PND 9. All other MMPs (MMP-11, MMP-14, and MMP-23) as well as TIMP-1, TIMP-2, and TIMP-3 were detected in both epithelial and stromal cells of the endometrium, but not in the myometrium. Uterine extracts were then analyzed by gelatin and casein gel zymography to detect active gelatinases and stromelysins, respectively. Five major gelatinase bands of activity were detected and inhibited by the MMP inhibitors, EDTA or 1,10-phenanthroline, but not by PMSF, a serine protease inhibitor. Western blot analysis confirmed the presence of MMP-2 and MMP-9 proteins in the uterus. Immunoreactive MMP-9 protein was detected only in the endometrial stroma, whereas immunoreactive MMP-2 protein was detected in both the stroma and epithelium of the uterus. Casein zymography detected three major bands of activity ( approximately 54, 63, and 80 kDa) that were inhibited by the serine protease inhibitor, PMSF, but not by the MMP inhibitors, EDTA or 1,10-phenanthroline, suggesting that they were serine proteases. These results support the hypothesis that MMPs and TIMPs regulate postnatal development of the mouse uterus.

Aging↗
PubMed1997

Potential sites of prostaglandin actions in the periimplantation mouse uterus: differential expression and regulation of prostaglandin receptor genes.

Prostaglandins (PGs), especially PGE2 and PGF2alpha, are considered important for blastocyst spacing, implantation, and decidualization in the rodent uterus. However, information regarding uterine sites of PG actions in these processes is lacking. PGE2 or PGF2alpha interacts with specific G protein-coupled membrane receptors. PGE2 receptors are classified into four subtypes, EP1, EP2, EP3, and EP4. While EP1 is coupled to Ca2+ mobilization, activation of EP2 and EP4 triggers stimulation of adenylyl cyclase. In contrast, activation of EP3 inhibits adenylyl cyclase. PGF2alpha receptor (FP) is coupled to stimulation of phospholipase C-inositol trisphosphate (IP3) pathway and Ca2+ mobilization. This investigation demonstrates that PGE2 and PGF2alpha receptor genes are expressed in a temporal and cell-specific manner in the periimplantation mouse uterus. In the mouse, the attachment reaction occurs in the evening (2200-2300 h) of Day 4 of pregnancy and is preceded by embryo spacing, uterine edema, and luminal closure resulting in an intimate apposition of the blastocyst with the uterine luminal epithelium. Expression of EP3 and FP primarily in the circular muscle of the myometrium on Days 3-5 of pregnancy suggests that the circular muscle, not the longitudinal muscle, is the primary target for PG-mediated uterine contractions required for embryo transport, spacing, and/or accommodation in the uterus. In contrast, expression of EP3 in a subpopulation of cells in the stromal bed at the mesometrial side, and of EP4 in the epithelium and stroma on these days, suggests that PGE2 effects on uterine preparation for implantation (such as epithelial cell differentiation, stromal cell proliferation, uterine edema, luminal closure, and increased localized endometrial vascular permeability at the sites of blastocyst attachment) are mediated by these receptor subtypes. Similar expression patterns of EP3 and EP4 in the Day 4 pseudopregnant mouse uterus or in the ovariectomized uterus under combined treatment with estrogen and progesterone suggest that these genes are regulated by ovarian steroids rather than by the embryo during the preimplantation period (Days 1-4). In contrast, the expression of these genes during the postimplantation period (Days 5-8) is associated with the onset of decidualization.

Animals↗