Induction of catechol-O-methyltransferase in the luminal epithelium of rat uterus by progesterone

We performed light microscopic immunocytochemical observations of the localization of catechol-O-methyltransferase (COMT) in rat uterus, using a rabbit anti-rat serum specific for the soluble form of rat liver COMT, biotinylated goat anti-rabbit immunoglobulin, and peroxidase conjugated with streptavidin. In the non-pregnant rat, COMT was minimal but detectable in the uterine luminal and glandular epithelium, with greater amounts present in uteri from rats in estrus than those in diestrus. In early pregnancy a robust accumulation of COMT was observed in the luminal epithelium. To more precisely define both the timing and the factors contributing to the appearance of COMT, uteri were examined on Days 1-5 in pregnant and pseudopregnant rats. Accumulation of COMT in the luminal epithelium was observed by Day 3 in uteri from pregnant and pseudopregnant rats and by Day 4 in lactating post-partum rats. No immunostaining of COMT was observed in uteri from non-lactating post-partum rats. Ovariectomy on Day 0 or 1 but not on Day 2 of pregnancy prevented the appearance of COMT on Day 4. Progesterone treatment immediately after ovariectomy on Day 0 or 1 of pregnancy restored the COMT.     

Prostaglandin translocation from the lumen of the rabbit uterus in vitro in relation to day of pregnancy or pseudopregnancy

Transport of 3H-labeled prostaglandins (PGs) E2 and F2 alpha from the uterine lumen across the uterine wall has been studied in rabbit uteri in vitro in incubations lasting up to 180 min, in relation to sexual state of the rabbit, incubation temperature, intraluminal PG concentration, addition of metabolic inhibitors and time of incubation. PG accumulation by the tissue increased rapidly up to 30 min and then remained relatively constant. By 30 min, radioactivity was found in the external incubation medium, and this increased linearly with time. The translocation of PGF2 alpha was significantly greater in pseudopregnant than in pregnant animals on Day 6, whereas that of PGE2 was significantly higher in pregnant than in pseudopregnant animals on Day 6.8. In pregnant animals, both PGF2 alpha and PGE2 were translocated to the exterior more rapidly on Day 6.8 than on Days 5 or 6. Transport of PGs was reduced by low temperature, unaffected by metabolic inhibitors and only that of PGE2 increased with increased (5 microM) intraluminal concentrations. During incubation, the tissue remained viable as judged by T/M ratios (dpm tissue/dpm medium) for 204 thallium. Transport of [14C] sucrose was much slower than that of [14C] urea, which was greater than the fastest rates exhibited by the PGs. In general, amounts of radioactivity found in antimesometrial, mesometrial and lateral portions of the uterine wall, or in implantation and interimplantation areas did not differ, but more was found in the endometrium than the myometrium. PGF2 alpha was translocated unmetabolized to the external medium, while only two-thirds of the PGE2 was translocated unchanged, and one-third converted to PGF2 alpha. It is concluded that the rabbit uterus shows some selectivity in handling PGs in relation to stage of pregnancy.     

Platelet-activating factor in the rabbit uterus during early pregnancy

Platelet-activating factor (PAF) concentrations were low in the non-pregnant, oestrous uterus (mean +/- s.e.m.: 2.2 +/- 1.2 pmol/g, n = 3). However, uterine PAF increased dramatically during pregnancy to a maximum of 37.8 +/- 4.90 pmol/g (n = 7) on Day 5. By Day 7, PAF concentrations in the uteri of pregnant rabbits had returned to levels similar to those found at oestrus. In contrast, uterine PAF in pseudopregnant rabbits peaked at 30.6 +/- 2.8 pmol/g (n = 8) on Day 4, declined to 20.5 +/- 2.4 pmol/g (n = 8) on Day 5 and then remained at that concentration through Day 7. Uterine PAF co-migrated with synthetic PAF (1-O-hexadecyl-2-acetyl-sn-glycero-phosphocholine) in both thin-layer and normal-phase high-performance liquid chromatography. PAF activity in the uterus during pregnancy and pseudopregnancy was found almost exclusively in the endometrium; little or no PAF was found in myometrium, uterine flushings or blastocysts. While no PAF was detected in blastocysts on Days 5 and 6 of pregnancy, the presence of the embryo appears to modulate biosynthesis and/or degradation of PAF by the uterus, since PAF decreased significantly in uterine tissue apposed to the implanting embryo (but not in similar areas between such attachment sites). Increased concentrations of PAF in the preimplantation rabbit uterus followed by a dramatic decrease on the day of blastocyst attachment suggest that this potent inflammatory autacoid may play a vital role in implantation.     

Betamimetic effects on the electro-mechanical characteristics of the pregnant and postpartum myometrium in vitro

Myometrial strips were studied in the two extremes of regulatory conditions by measuring isometric tension and resting potentials in vitro. The effects of isoproterenol (IP) and PGF2 alpha were studied on pregnant and postpartum rabbit uteri. Lower IP concentrations inhibited the activity of the pregnant uterus as compared to the postpartum myometrium. Both pregnant and postpartum myometrium could be hyperpolarized by IP, however, lower concentrations were needed during pregnancy. The inhibiting effect on mechanical activity of IP developed without any hyperpolarization at its lower concentration.     

Conceptus-mediated integrity of endometrial epithelial cells and maintenance of relaxin synthesis in pregnant rabbits: effects of unilateral oviduct ligation

A previous study indicated rabbit endometrial relaxin synthesis is stimulated by blastocyst (Lee VH, Fields PA, Biol Reprod 1990; 40:737-745). To evaluate this hypothesis, unilateral oviduct ligations were placed (A) at the oviduct isthmus on Day 1 post-copulation and (B), in a separate group of rabbits, at the infundibulum before copulation. Blastocysts migrate into and implant in the uterine horn contralateral to the ligated oviduct only (conceptus-bearing uterus). The uterine horn ipsilateral to the ligated oviduct will be referred to as the non-conceptus-bearing uterus. Uteri and ovaries were removed on Days 4-28 of pregnancy and were evaluated for relaxin using guinea pig anti-porcine relaxin serum and avidin-biotin light microscopy immunohistochemistry. Results were identical for both models. Blastocysts first attach to the antimesometrial uterine surface by Day 7 post-copulation. Implantation on the mesometrial surface occurs on Days 8-11. Relaxin was observed in antimesometrial endometrial glands of both conceptus and non-conceptus-bearing uteri on Days 4-7 of pregnancy. Beyond Day 7, relaxin was observed in antimesometrial and mesometrial endometrial glandular and luminal epithelial cells at implantation sites of the conceptus-bearing uterus only. Relaxin was not found between implantation sites. Endometrial epithelial cells of the non-conceptus-bearing uterus were regressing by Day 9. These data indicate a conceptus-mediated maintenance of endometrial epithelial cells. Furthermore, the data suggest a paracrine maintenance of epithelial cell integrity and relaxin synthesis since these parameters are preserved only in the conceptus-bearing uterus. Cell-cell communication between conceptus and endometrium appears to be specific since endometrium between implantation sites does not contain relaxin. Uterine tissue from pseudopregnant rabbits (Days 1-16) was evaluated. Relaxin was observed in the antimesometrial glands on Day 7 only. Like the endometrium in the ligation model, endometrial epithelial cells of the pseudopregnant rabbit uterus were regressing by Day 9. These results indicate that pregnancy is not required for, but may enhance, relaxin synthesis. In addition, endometrial epithelial cells regress in the absence of pregnancy. Regression of endometrial epithelial cells on Day 9 suggests that maternal recognition of pregnancy occurs during the preimplantation period (Days 4-8).     

Epidermal growth factor-like ligands and erbB genes in the peri-implantation rabbit uterus and blastocyst

Molecular cloning of the partial cDNA coding sequences of the four erbB receptors and the epidermal growth factor (EGF)-like ligands EGF, transforming growth factor alpha (TGF), and heparin-binding EGF (HB-EGF) has provided the basis for a comprehensive analysis of the spatiotemporal expression pattern of the EGF receptor/ligand system during the peri-implantation period in the rabbit. Employing nonradioactive in situ hybridization and immunolocalization, we observed differential expression of erbB1-erbB3 within the trophectoderm of the blastocyst. ErbB1 was strongly expressed in the cytotrophoblast but was downregulated upon syncytium formation. ErbB3 was a product of both the cyto- and syncytiotrophoblast. Despite the expression of erbB2 mRNA, the trophectoderm was devoid of immunoreactive ErbB2. ErbB4 gene activity was exclusively detected in the trophoblast at midpregnancy. The luminal and glandular epithelium and stroma of the nonpregnant, pseudopregnant, and pregnant rabbit uterus at Day 6 of gestation also expressed ErbB1-ErbB3. In the peri-implantation period, gene activities of erbB1-erbB3 were upregulated upon decidualization. At the site of implantation, uterine luminal epithelial cells apposing the preimplantation blastocyst displayed a distinct membrane immunolocalization of ErbB2, identifying the uterine epithelium as target for EGF, TGFalpha, and HB-EGF derived from both the embryonic trophectoderm and the uterine epithelium. In the luminal epithelium at the antimesometrial uterine site, HB-EGF gene activity was upregulated at the time of blastocyst attachment, but this upregulation was not reflected in an increase in immunoreactive HB-EGF. The detection of tyrosine phosphorylated ErbB2 in the rabbit placenta indicated the presence of a functional ErbB/EGF-like system in the pregnant rabbit uterus. This study provides strong evidence for a role of the ErbB/EGF-like system in embryo/maternal interactions during the peri-implantation period in the rabbit.     

Decidualization induces the expression and activation of an extracellular protease neuropsin in mouse uterus

Uterine decidualization is accompanied by the remodeling of the cell-matrix and cell-cell interactions around the endometrial stromal cells to allow an appropriate invasion of trophoblasts. This remodeling is thought to require the proteolysis of extracellular matrix proteins or cell adhesion molecules; however, the molecular mechanism remains poorly understood. In this study, decidualization induced the expression and activation of an extracellular serine protease neuropsin in the mouse uterus. Although nonpregnant uteri contained little neuropsin, the protein content and enzymatic activity increased markedly and peaked at the midgestational period in pregnant uteri. Neuropsin expression and activity was also upregulated in artificially induced deciduomata but not in nondecidualized pseudopregnant uteri. Neuropsin is the first extracellular protease to show the evident induction of expression and activity by decidualization and might contribute to the remodeling of extracellular components after decidualization.     

Occurrence of cytochrome P-450 with prostaglandin omega-hydroxylase activity in rabbit placental microsomes

The microsomes of placenta and uterus from pregnant rabbits have been found to catalyze the omega-hydroxylation of PGE1, PGE2, PGF2 alpha, and PGA1 as well as the omega- and (omega-1)-hydroxylation of palmitate and myristate in the presence of NADPH. These activities were greatly inhibited by carbon monoxide, indicating the involvement of cytochrome P-450. The apparent Km for PGE1 was 2.38 microM and 2.1 microM with the placental and uterus microsomes, respectively. Cytochrome P-450 has been solubilized with 1% cholate from the placental microsomes, and partially purified by chromatography on 6-amino-n-hexyl Sepharose 4B, DEAE-Sephadex A-50 and hydroxylapatite columns. The partially purified cytochrome P-450 efficiently catalyzed the omega-hydroxylation of various prostaglandins such as PGE1, PGE2, PGF2 alpha, PGD2, and PGA1 in a reconstituted system containing NADPH-cytochrome P-450 reductase, cytochrome b5, and phosphatidylcholine. The reconstituted system also hydroxylated palmitate and myristate at the omega- and (omega-1)-position, but could not hydroxylate laurate. These catalytic properties resemble those of a new form of cytochrome P-450 highly purified from the lung microsomes of progesterone-treated rabbits (Yamamoto, S., Kusunose, E., Ogita, K., Kaku, M., Ichihara, K., and Kusunose, M. (1984) J. Biochem. 96, 593-603). This type of cytochrome P-450, viz., cytochrome P-450 with high prostaglandin omega-hydroxylase activity may play a role in the regulation of prostaglandin levels in pregnancy.     

Differential PGE2 and cAMP production by allogeneic and syngeneic pregnant mice uteri.

Prostaglandin E2 (PGE2) and cAMP production in allogeneic and syngeneic pregnant mice uteri, were measured in relation to the ratio of plasma estrogen/progesterone levels. PGE2 generation by allopregnant uteri varied with the days of pregnancy. The increment of the prostanoid coincided with the increase in plasma estrogen concentration, whereas the decrement of its production was in parallel with the increment of plasma progesterone. The syngeneic pregnant uterus was unable to increase the release of PGE2 above basal values during the whole pregnancy. The rise of PGE2 production by the allogeneic pregnant uterus was correlated with an increase in cAMP levels. It is proposed that the pregnant mouse uterus increases its ability to release PGE2 in response to an ovarian steroids.     

Rabbit relaxin: the influence of pregnancy and ovariectomy during pregnancy on the plasma profile.

A porcine relaxin radioimmunoassay was developed to evaluate the profile of immunoreactive relaxin in rabbit plasma. Relaxin was nondetectable in pseudopregnant (Days 1, 4, 5-8, 12, and 16), nonpregnant, and male rabbits. However, in pregnant rabbits, relaxin was detected during the peri-implantation period (Days 4-9). Peak concentrations were reached on Day 15 and were maintained until parturition (Day 32). Relaxin concentrations abruptly decreased on Day 1 postpartum to low but detectable concentrations that were unchanged during the first week postpartum. In contrast, progesterone concentrations peaked earlier (Day 13), decreased after Day 25, and were not detectable on Day 1 postpartum. The effect of ovariectomy on the profile of plasma relaxin was evaluated. Four pregnant rabbits were ovariectomized (Day 13) and treated with medroxyprogesterone acetate to maintain pregnancy. As in normal pregnant rabbits, relaxin was observed initially during the peri-implantation period (Days 4-9) and increased to peak concentrations by Day 16. These concentrations were maintained until parturition and abruptly decreased on Day 1 postpartum to low yet detectable concentrations during the first week postpartum. The concentrations of relaxin in the plasma of ovariectomized medroxyprogesterone-treated rabbits were not different from those in three sham controls. These results indicate that the ovary is not a significant source of relaxin in pregnant rabbits. The unique observation of the presence of relaxin during the peri-implantation period suggests that this hormone has a role in preparing the rabbit uterus for implantation. The continued presence of relaxin during the first week postpartum may represent residual hormone, or it may suggest a physiological role during the early postpartum period.     

Evaluation of the role of leukotrienes on ovum implantation in mice

Prostaglandins are considered to be one of the important mediators of ovum implantation. Various lipoxygenase products also have been implicated along with PGs for this process. A specific rather than preferential inhibitor of 5-lipoxygenase is used to investigate the role of leukotrienes in the event of implantation and decidualization process in mice. AA861, a selective inhibitor of 5-lipoxygenase is used in different dose levels like 50,100 and 500 μg in (A) intact pregnant mice (on D1-D4 and D2-D4 and D4); (B) delayed mice on (D3-D8); (C) pseudopregnant traumatized mice (on D1-D4). All the experimental animals of group A were killed on D6. Estrogen injected delayed animals of group  were killed 48 h after the induction of implantation. Implantation sites were counted as blue spot and compared with those of control animals. Traumatized animals of group C were killed 24 h after the mechanical traumatization and uterine weights were compared with those of vehicle treated controls. Results show that AA861 could not inhibit ovum implantation in either intact or ovariectomized delayed animals. It also did not show any adverse effect on tubal transport or development of embryos. AA861 did not have any inhibitory role on decidualization of pseudopregnant uteri also. This experiment shows that a selective inhibitor of 5-lipoxygenase enzyme may not impair the implantation in mice indicating a doubt about the involvement of 5-lipoxygenase products in implantation.     

Changes in phospholipase A2 in myometrium of the guinea pig uterus during pregnancy.

Phospholipase A2 activity has been measured in membrane and cytosolic fractions from non-pregnant and pregnant guinea pig myometrium has been studied. Enzyme activity was measured with 1-stearoyl-2- [3H]arachidonoyl-phosphatidylcholine exhibiting Michaelis-Menton kinetics with Km of 83.8 +/- 21.6 and 53.2 +/- 14.1 for membrane and cytosolic enzymes respectively. Fractionation of the myometrium from non-pregnant guinea pigs suggested that 35% of the activity was membrane associated compared with 20% (P < 0.01) in tissue from pregnant animals. In the presence of 1 mM calcium total activity rose from 3.03 +/- 0.41 to 1737 +/- 368 nmol/h per uterus between non-pregnant and late pregnancy. Calcium activated the membrane enzyme, but the effect was greater late in pregnancy with almost a 6-fold increase in activity at 1 mM calcium compared with a doubling in membrane from non-pregnant guinea pigs. The K0.5 for calcium activation was about 150 microM. Immunoblotting with anti-human-110 KDa phospholipase A2 showed in guinea pig uterus a 34 KDa form of the enzyme that, consistent with changes in activity, showed a fifteen-fold increase in quantity between non-pregnant and late pregnancy. The data are consistent with dramatic increases in the capacity for arachidonic acid release and prostaglandin production in the guinea pig myometrium late in pregnancy.     

Pseudopregnancy and the decidual response in the obese Zucker rat: a reexamination

The ability to induce the pseudopregnant (psp) state and the decidual response (DR) in the obese Zucker rat was reexamined. Lean and obese rats were cervically stimulated on the evening of proestrus or morning of estrus. This procedure lengthened the period of vaginal diestrus in both groups to approximately 13 days. The percentage of obese rats (70.0%) that became psp was not significantly different from that of lean rats (72.2%). To test sensitivity to a decidual stimulus, sesame oil was injected into the lumen of uteri of psp rats on Day 4 of vaginal diestrus. Treated uterine horns of all rats decidualized. The mean percentage increases in weights of Day 9 decidualized horns were not significantly different between obese and lean rats (752 +/- 85% SE and 875 +/- 133%, respectively). These data contradict previous reports that obese rats do not become psp following cervical stimulation, and that their uteri do not develop a typical DR. Although it is recognized that the reproductive capacity of the obese female Zucker rat is severely limited, this study describes aspects of reproductive function that are less abnormal than previously reported. The ability of the obese Zucker rat to become psp following cervical stimulation suggests that the progestational state of pregnancy might be induced reflexly. Furthermore, the ability of its uterus to respond to a decidual stimulus suggests that the obese Zucker rat may be able to support implantation.     

Prostaglandin-induced luteolysis in pregnant and pseudopregnant rabbits and the resultant effects on the myometrial activity.

The effect of prostaglandin (PG)-induced luteolysis on the myometrial activity in 20--21-day-pregnant and 11--12-day-pseudopregnant rabbits was studied by intrauterine pressure (IUP) recording during PG infusions. The same dose of PG (10 micrograms/h during 8h) was also given to 7 non-pregnant (untreated) does that were used as controls. Peripheral plasma concentration of progesterone and oestradiol-17 beta were measured at 2-h intervals during the infusion. Plasma progesterone level decreased significantly within 2 h or the start of infusion in pregnant and pseudopregnant does and continued to decrease; at the end of 8 h, the concentrations were 31 and 41%, respectively, of the pre-infusion levels. The amplitude of uterine contractions increased significantly after 4 h in pseudopregnant does, increased slightly but insignificantly in the pregnant does and showed no significant change in the non-pregnant does during PG infusion. The amplitudes developed in the pregnant and pseudopregnant does were significantly different. The direct effect of progesterone (1--3 micrograms/h during 4 h) was also studied in 7 non-pregnant rabbits. After 2 h the amplitude of contractions had decreased markedly and the pattern of activity had become irregular. The results support the concept of a myometrial inhibitory factor other than progesterone in rabbit pregnancy and suggest that this factor(s) originates in conceptus.     

Changes of the uterine size during pregnancy in cynomolgus monkeys (Macaca fascicularis) (author's transl)]

This paper describes changes in the uterine size during the normal course of pregnancy in cynomolgus monkeys. Twenty-four females which had conceived by 3-day individual mating with a male were laparotomized 4,5,6,7,8,9,10,15 and 20 weeks after conception. The width, thickness and length of uterus were measured by a pair of callipers. Them, the uterine volume was estimated by the formula, V = 4/3 piab2 (a, b: uterine length x 1/2, uterine width x 1/2). The increase in the uterine width (y) during pregnancy could be expressed as a linear equation: y = 0.35x + 1.48 (x: weeks after conception). The thickness of pregnant uteri could be represented by a a linear equation: y = 0.36x + 1.40. From the 4th to the 20th week of pregnancy, the uterine length increased along a straight line expressed as a linear equation: y = 0.58x + 1.14. Except for nonpregnant uteri, the change in the uterine volume after pregnancy could be expressed as a linear logarithmic equation: log y = 2.319 log x -0.315. These 24 pregnant monkeys had followed the normal course of gestation until the time of laparotomy without any abnormality in their fetuses of their placentas, indicating that the values obtained throughout this study are of practical use for taking care of pregnant cynomolgus monkeys.     

Inhibition of the beta-catenin signaling pathway in blastocyst and uterus during the window of implantation in mice

Beta-catenin, the mammalian homolog of Drosophila armadillo protein, was first identified as a cadherin-associated protein at cell-cell junctions. Another function of beta-catenin is the transduction of cytosolic signals to the nucleus in a variety of cellular contexts, which usually are elicited by the active form of beta-catenin. The aim of the present study was to examine the potential role of active beta-catenin in the mouse embryo and uterus during embryo implantation. Active beta-catenin was detected differentially in mouse embryos and uteri during the peri-implantation period. Aberrant activation of beta-catenin by LiCl, a well-known glycogen synthase kinase-3 inhibitor, significantly inhibited blastocyst hatching and subsequent adhesion and outgrowth on fibronectin. Results obtained from pseudopregnant and implantation-delayed mice imply an important role for implanting blastocysts in the temporal and spatial changes of active beta-catenin in the uterus during the window of implantation. Collectively, these results suggest that the beta-catenin signaling pathway is inhibited in both blastocyst and uterus during the window of implantation, which may represent a new mechanism to synchronize the development of preimplantation embryos and differentiation of the uterus during this process.     

Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus

The aim of this study was to analyze the function and expression of tachykinins, tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the tachykinin NK1 receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of late pregnant mice. Endpoint and real-time quantitative RT-PCR were used to analyze the expression of the genes that encode the tachykinins SP/NKA, NKB, and hemokinin-1 (HK-1) (Tac1, Tac2, and Tac4); and the genes that encode tachykinin NK1 (Tacr1), NK2 (Tacr2), and NK3 (Tacr3) receptors in uteri from pregnant and nonpregnant mice. The data show that the mRNAs of tachykinins (particularly NKB and HK-1), tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy. The tachykinin NK1 receptor is the predominant tachykinin receptor in the nonpregnant and early pregnant mouse and may mediate tachykinin-induced uterine contractions in the nonpregnant mouse. The tachykinin NK2 receptor is predominant in the late pregnant mouse and is the main receptor mediating uterotonic responses to tachykinins at late pregnancy. The tachykinin NK3 receptor is expressed in considerable amounts only in uteri from nonpregnant diestrous animals, and its physiological significance remains to be clarified.     

Leukotrienes and myometrial activity of the term pregnant uterus

Biopsies from different segments of the pregnant human uterus were superfused in organ chambers and contractile activity was registered. Leukotriene C4(LTC4) caused inhibition of spontaneous but not noradrenaline induced contractile activity in strips from the cervix. This effect occurred both in early pregnancy and at term. However, the lower and the upper uterine segment of the term pregnant uterus did not respond to LTC4. The results represent a documentation of the segmental differentiation in the uterine response to eicosanoids.     

金色中仓鼠胚胎植入小鼠子宫后PTEN、FAK、Shc信号分子的异常表达

除了马属动物外,种间妊娠的胚胎总在妊娠的一定时期流产。以往的研究多集中在宏观结构和解剖学差别的研究上,对于这种现象产生的分子机制却少有报道。为了从信号分子角度阐明种间妊娠维持失败的可能原因,我们通过免疫组化和明胶酶谱法比较了科间和同种妊娠部位整合素αvβ3、FAK、p-ERK、IGFⅡ、IGFBP-1、Shc、PTEN和MMP-2、-9表达的差异。科间妊娠是将金色中仓鼠(Mesocricetus auratus)的胚胎移植入假孕小鼠(Mus musculus)子宫并取妊娠D4、D8、D12的子宫为实验材料,相应时间同种小鼠胚胎移植小鼠妊娠后的子宫和假孕小鼠子宫分别为阳性和阴性对照。免疫组化结果表明D8时,科间妊娠孕体integrinαvβ3、IGF-Ⅱ、IGFBP-1、PTEN、Shc、FAK的表达强度均与正常同种妊娠有差异。而妊娠D8时同种、科间妊娠子宫p-ERK的表达部位与表达量无明显差异。明胶酶谱显示,科间妊娠时MMP-2,-9的分泌模式与同种妊娠明显不同。这些结果表明,上述信号通路分子的差异表达有可能是造成科间妊娠时母胎界面异常的组织学表现的一个原因。     

Differential PGE2 and cAMP production by allogeneic and syngeneic pregnant mice uteri

Prostaglandin E₂ (PGE₂) and cAMP production in allogeneic and syngeneic pregnant mice uteri, were measured in relation to the ratio of plasma estrogen/progesterone levels. PGE₂ generation by allopregnant uteri varied with the days of pregnancy. The increment of the prostanoid coincided with the increase in plasma estrogen concentration, whereas the decrement of its production was in parallel with the increment of plasma progesterone. The syngeneic pregnant uterus was unable to increase the release of PGE₂ above basal values during the whole pregnancy. The rise of PGE₂ production by the allogeneic pregnant uterus was correlated with an increase in cAMP levels. It is proposed that the pregnant mouse uterus increases its ability to release PGE₂ in response to an ovarian steroids.