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A positive difference in nature of envelopes of thymus- and uterus-derived leukemia viruses of AKR mice.

Thymus-derived leukemia virus of AKR/J mice was inactivated by anti-theta antiserum. But it was not inactiviated by the antiserum which had been absorbed with intact thymus cells of AKR/J or RF/J mice, and by anti-uterus-derived leukemia virus antiserum. In contrast, uterus-derived leukemia virus of the strain was not inactivated by anti-theta antiserum, but was neutralized by anti-uterus-derived leukemia virus antiserum. The results suggest the possibility that some constitutents of the envelope of thymus-derived leukemia virus are derived from the plasma membrane of thymus cells of AKR mice at the time of budding and that such constituents are not associated with the enveloped of uterus-derived leukemia virus.

AKR murine leukemia virus↗

Expression of c-fos and c-myc genes in uterus and nonreproductive organs during the implantation period in the rat.

The c-fos and c-myc mRNA levels were investigated in the uterus and nonreproductive organs of rats during the implantation period (from day 5 to 7 of pregnancy). They were determined by densitometric analysis of slot blots and the mean values (n = 4) at a defined age of pregnancy were compared with those observed in nonpregnant control rats (NP group). No significant variations of c-fos level were observed in the liver and brain of pregnant rats. In the uterus, the c-fos level decreased, reached a minimum on day 6 (4-fold decrease compared with the NP group), and then increased. The c-fos level significantly increased in the kidney (2- and 2.5-fold on days 6 and 7), and in the lung (2.5-fold on day 7). The c-myc level did not significantly vary in the uterus, liver, and lung. It significantly increased in the kidney (3-fold on day 7) and in the brain (4.1-, 3.8-, and 6-fold, on days 5, 6, and 7). The changes in c-fos and (or) c-myc gene expression in the uterus and nonreproductive organs could be due to sexual steroids and (or) systemic factors from uterine cells or blastocysts.

Animals↗

Immunohistochemical localization of cyclooxygenase-2 in pregnant rat uterus by Sp-6 acupuncture.

As pregnancy advances, prostaglandins (PG) increase in the uterus, leading to elevated uterine contractility. Therefore, regulating the concentration of PG in the uterus can be a key factor for controlling the duration of labor. Since the synthesis of PGs in the uterus is catalyzed by cyclooxygenase-2 (COX-2), devising a tool to regulate the expression of COX-2 could provide a method for treating complicated labor. In this study, Sp-6 acupuncture treatment was evaluated for its potential in controlling uterine motility. Immunohistochemical methods showed the COX-2 enzyme was primarily found in the endometrium and myometrium of rat uterus. COX-2 expression in these two locations were intensified by pregnancy, but reduced by acupuncture at the Sp-6 acupoint. Uterine motility monitored during Sp-6 acupuncture was reduced by 28.15% (p < 0.05) and 19.88% (p < 0.05) in pregnant rats and non-pregnant rats, respectively. The significant reduction of uterine motility in pregnant rat suggests a role for Sp-6 acupuncture in regulating the expression of COX-2 during pregnancy. These results suggest that Sp-6 acupuncture could be used as a complementary method for controlling labor in human pregnancy.

Acupuncture Therapy↗

Kinematics of the uterus: cine mode MR imaging.

Cine mode magnetic resonance (MR) imaging has allowed evaluation of kinematics of the pelvis. Visualization of dynamic changes under strain facilitates evaluation of prolapses and adhesions between organs. The uterus, an organ of smooth muscle, has an inherent contractility that characterizes it as different from other visceral organs. This sustained contraction has occasionally been shown on static images as a finding masquerading as a leiomyoma or as adenomyosis. Cine mode MR imaging clearly shows the configuration of the myometrium during these dynamic changes, as well as its signal intensity during contractions. Uterine peristalsis, the subtle and rhythmic contractions of the inner myometrium, is also clearly identifiable on cine mode images as a wavy movement of the endometrium and/or inner myometrium. The direction and frequency of uterine peristalsis are different in each of the menstrual cycle phases and are thought to have important roles in uterine function, such as in fertility and menstrual blood discharge. Elucidation of these kinematics of the uterus will help in the evaluation of static MR images and study of the physiology of the uterus. Cine MR imaging is a novel technique for diagnosis and evaluation of the pelvic organs, especially the uterus.

Adult↗

Role of Ca in isoproterenol-induced increases in cAMP levels in rat uterus.

The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. In muscles depolarized with 47.5 mM K+ (with or without Na+), the ability of isoproterenol to increase cAMP levels and to produce relaxation was found to be inversely related to external calcium concentration. The pretreatment of the muscle with D600 or EGTA restored the cAMP response to isoproterenol in the depolarized uterus to a level observed in nondepolarized muscle. The study with Ro 20-1724, a phosphodiesterase (PDE) inhibitor indicated that the failure of isoproterenol to elevate cAMP levels in the depolarized uterus could not be related to the activation of PDE by Ca2+. The exposure of rat uterus to a zero-Ca2+ solution accentuated the increases in cAMP levels produced by isoproterenol. These results have raised the question of a possible regulatory role of Ca2+ in beta-adrenoceptor-induced increases in cAMP levels in uterine smooth muscle.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function.

Progesterone and its interaction with nuclear progesterone receptors (PR) PR-A and PR-B play a critical role in the regulation of female reproductive function in all mammals. However, our knowledge of the regulation and possible cellular function of PR protein isoforms in the fallopian tube and uterus in vivo is still very limited. In the present study, we revealed that equine chorionic gonadotropin (eCG) treatment resulted in a time-dependent increase in expression of both isoforms, reaching a maximal level at 48 h in the fallopian tube. Regulation of PR-A protein expression paralleled that of PR-B protein expression. However, in the uterus PR-B protein levels increased and peaked earlier than PR-A protein levels after eCG treatment. With prolonged exposure to eCG, PR-B protein levels decreased, whereas PR-A protein levels continued to increase. Furthermore, subsequent treatment with human (h)CG decreased the levels of PR protein isoforms in both tissues in parallel with increased endogenous serum progesterone levels. To further elucidate whether progesterone regulates PR protein isoforms, we demonstrated that a time-dependent treatment with progesterone (P(4)) decreased the expression of PR protein isoforms in both tissues, whereas decreases in p27, cyclin D(2), and proliferating cell nuclear antigen protein levels were observed only in the uterus. To define the potential PR-mediated effects on apoptosis, we demonstrated that the PR antagonist treatment increased the levels of PR protein isoforms, induced mitochondrial-associated apoptosis, and decreased in epidermal growth factor (EGF) and EGF receptor protein expression in both tissues. Interestingly, immunohistochemistry indicated that the induction of apoptosis by PR antagonists was predominant in the epithelium, whereas increase in PR protein expression was observed in stromal cells of both tissues. Taken together, these observations suggest that 1) the tissue-specific and hormonal regulation of PR isoform expression in mouse fallopian tube and uterus, where they are potentially involved in regulation of mitochondrial-mediated apoptosis depending on the cellular compartment; and 2) a possible interaction between functional PR protein and growth factor signaling may have a coordinated role for regulating apoptotic process in both tissues in vivo.

Animals↗

Influence of mechanical stretch on growth and protein turnover of rat uterus.

A new technique has been developed and used to distend the uterus of nonpregnant rats for up to 5 days. Continuous distension of the saline-filled uterus induced rapid and extensive growth of the whole uterus and the myometrium by a combination of hyperplasia and hypertrophy. In both cases, 1 day after this imposition of mechanical stretch significant increases (25-50%) in the protein, RNA, and DNA contents were found, with larger changes (100-250%) being progressively expressed up to 5 days. This stretch-induced growth primarily results from a stimulation of protein synthesis (measured both in vivo and in vitro), with little or no change being evident in the rate of protein breakdown. These findings have been discussed in relation to the role of stretch in the growth of the uterus during pregnancy and stretch-induced responses found in other types of muscle.

Algorithms↗

Neuronal responses to stimulation of the cervix, uterus, colon, and skin in the rat spinal cord.

1. Previous studies in the rat have shown that the hypogastric nerve conveys input from the cervix and uterus mainly to the T13-L3 segments of the spinal cord, whereas the pelvic nerve conveys input from the cervix and vaginal canal mainly to the L6-S2 segments. 2. To study the effects of this input, the dorsal horns of the T13-L1, L6-S2, and L4-L5 segments in 13 decerebrate, T10-spinalized, unanesthetized, and paralyzed adult female rats in estrus were searched for neurons responsive to gentle mechanical stimulation of the cervix. The 87 neurons found were then further tested for their responses to gentle mechanical stimulation of the skin and to distension of both uterine horns, distension of the colon, and shearing stimulation of the colon and vaginal canal. 3. Neurons responsive to cervix stimulation, primarily by excitation, were readily found in the ventral part of the dorsal horn in T13-L1 and throughout the dorsal horn in L6-S2. Cervix-responsive neurons were less readily found throughout the dorsal horn in L4-L5, where 25% were inhibited by the stimulation. All but one neuron had cutaneous receptive fields. 4. The 30 cervix-responsive neurons in T13-L1 had large bilateral cutaneous receptive fields covering the perineum and hind-limbs. Most (76%) also responded, primarily by excitation, to uterine distension, as well as to colonic stimulation (59%). More than half were activated by both types of stimulation. 5. The 33 cervix-responsive neurons in L6-S2 had cutaneous receptive fields in the same regions as those in T13-L1, but generally smaller, particularly for neurons in the dorsal part of the dorsal horn, many of whose receptive fields were confined to the perineum. The L6-S2 neurons also exhibited less convergent input from other visceral structures, particularly the uterus. Fewer neurons (42%) responded to uterine distension, mostly by being inhibited, whereas about the same proportion (51%) responded with excitation to colonic stimulation. Only 24% responded to both uterus and colon. 6. All 24 cervix-responsive neurons in medial L4-L5 had small cutaneous receptive fields on the toes, and the neurons received less convergent input from other visceral structures (25% from the uterus, 33% from the colon, 13% from both). 7. These results indicate the presence of an extensive system of neurons throughout the caudal spinal cord of the rat, concentrated in separated thoracolumbar and lumbosacral segments, that is concerned with input from the reproductive tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

IL-10 inhibits nitric oxide synthesis in murine uterus.

OBJECTIVES: Recent reports point to a role for the nitric oxide/nitric oxide synthase (NO/NOS) system in implantation. It has been suggested that inducible NOS expressed at peri-implantation would lead to enhanced NO production, which could promote the attachment of the blastocyst. Short-term administration of NO donors during the pre-implantation period reduced the pregnancy rate in a dose-dependent manner. Thus, it is thought that optimal levels of NO are critical for embryo implantation, so regulation of NOS must be crucial. Taking this into consideration, interleukin-10 (IL-10), synthesized and secreted by the embryo, could be modulating NOS during implantation. In this study we have investigated the in vitro effect of IL-10 on NOS in the uterus. METHODS: To determine the effect of IL-10, slices of uterus from estrogenized mice were pre-incubated for 60 min with different concentrations of IL-10 and NOS activity was measured. RESULTS: IL-10 (50 and 100 ng/ml in vitro) diminished NOS activity. The in vivo administration of lipopolysaccharide (LPS; 8 mg/kg) significantly increased the conversion of arginine into citrulline. This effect was abolished after 60 min of preincubation with IL-10 (100 ng/ml). The stimulatory effect of LPS and estrogen on NOS activity is exerted on the Ca-independent isoform and IL-10 in vitro abolished this increase. We observed that the uterus of pregnant mice on day 5 of gestation synthesized NO. This production was significantly inhibited by preincubation with IL-10 (100 ng/ml). CONCLUSIONS: This report demonstrates that IL-10 is capable of inhibiting NO synthesis in estrogenized, LPS-treated and pregnant rat uterus.

Animals↗

Identification and electrophysiological characteristics of isoforms of T-type calcium channel Ca(v)3.2 expressed in pregnant human uterus.

Electrophysiological characteristics were compared among four cloned human alpha1H isoforms transcripted by alternative splicings of exons 25B and 26 [Delta25B/+26 (native form; alpha1H-a), Delta25B/Delta?6 (alpha1H-b), +25B/Delta26, and +25B/+26] in the intracellular loop between domains III and IV (III-IV linker) of a human T-type calcium channel (Ca(v)3.2). The native isoform Delta25B/+26 predominated in ovary and non-pregnant uterus, while isoform Delta25B/Delta26 (alpha1H-b) predominated in pregnant uterus and testis. Expressions of the newly identified +25B/Delta26 and +25B/+26 isoforms were greater in the uterus at gestation than in the non-pregnant uterus. When expressed in Xenopus laevis oocytes, all isoforms produced transient inward currents with low voltage-dependent activation and inactivation characterized in typical T-type Ca2+ currents. Each isoform possessing exon 25B (+25B/?Delta26 or +25B/+26) showed current activation and inactivation at a more negative membrane potential than the respective isoform (Delta25B/Delta26 or Delta25B/+26) lacking it. Moreover, the current activation and inactivation rates were faster for the two isoforms possessing exon 25B than for the respective isoforms lacking it. By itself, exon 26 seemed not to affect any electrophysiological characteristics. Increasing the net positive charge (relative to the native form), as occurred in isoforms Delta25B/Delta26, +25B/Delta26, and +25B/+26, caused recovery from short-term inactivation to become faster. Our results show that molecular-structure variations within the III-IV linker influence the voltage-dependence and kinetics of both activation and inactivation. Although the role of T-type Ca2+ channels in uterine tissue remains unknown, changes in the uterine expression of these alpha1H isoforms may influence physiological functions during pregnancy.

Alternative Splicing↗

Intrinsic innervation of the uterus in guinea pig and rat.

The pattern of distribution of cholinergic and adrenergic nerves in the uterus of albino rats and guinea pigs was examined histochemically. In the albino rat, the uterus was found well-innervated by both adrenergic and cholinergic nerves with a clear regional variation. Dense innervation was demonstrated at the tubal and cervical ends of the uterus and in the cervix. Cholinergic nerves supplying the glands were more numerous than the adrenergic nerves which were relatively few. In the guinea-pigs, the uterus was richly innervated by adrenergic nerves with a clear regional variation. No cholinesterase-positive nerves or nerve cells were demonstrated.

Adrenergic Fibers↗

Effects of testosterone on morphology and on progestin and estrogen receptor levels in the mouse uterus and mammary gland.

The effects of androgen on the morphology and levels of cytosolic estrogen and progestin receptors (ER and PR) were studied in the mouse uterus and mammary gland. Testosterone neonatally and/or continuously in the adult lowers ER and PR levels particularly at early ages (40-60 days of age) in both the uterus and mammary gland. At older ages, less prominent changes in ER and PR levels are observed. Neonatal androgen treatment appears to exert both direct effects on the uterus and mammary gland and indirect effects (via the hypothalamo-hypophysio-ovarian axis). At all ages, neonatal testosterone in combination with continuous adult testosterone consistently depressed PR levels in both uterus and mammary gland, indicating that testosterone is a negative modulator of PR in these tissues.

Animals↗

Behavioural pattern of tumour cells in mouse uterus.

The behavioural pattern of transplantable mouse fibrosarcoma (MFS) cells infused into the pregnant, pseudopregnant and nonpregnant mouse uteri was studied histologically. In some nonpregnant and pseudopregnant uteri, the tumour cells, without colonizing inside the uterus, traverse the endometrium and within 5 days of treatment form tumour nodules outside the myometrium, indicating the presence of an initial and temporary tumour rejection mechanism in these uteri. In later stages MFS cells form large necrotic tumours in these uteri. In the pregnant uterus no tumour nodules are formed outside the myometrium even after 20 days of treatment. Furthermore, the size of the tumour formed in the endometrium of the pregnant uterus is quite small and the tumour cell growth rate is lower than that of the tumour cells in the nonpregnant and pseudopregnant uteri. These results indicate that, in the pregnant mouse uterus, fibrosarcoma cells display an altered pattern of invasion and decreased growth rate compared to those in nonpregnant and pseudopregnant uteri.

Animals↗

Prostacyclin produced by the pregnant uterus in the dog may act as a circulating vasodepressor substance.

Uterine production of PGI2 (prostacyclin) was quantitated in late pregnant dogs to evaluate if PGI2 could act as circulating vasodepressor substance in pregnancy. In five anesthetized, laparotomized dogs, the uterine venous plasma concentration of 6-keto PGF1 alpha (the in vitro hydrolysis product of PGI2) was 6.7 +/- 1.9 ng/ml and the arterial plasma concentration was 2.6 +/0 0.8 ng/ml. In four nonpregnant female dogs the arterial plasma concentration of 6-keto PGF1 alpha was consistently below 0.2 ng/ml. In eight pregnant dogs we also evaluated the ability of the pregnant uterus to inactivate PGI2 by comparing the hypotensive response to increasing doses of PGI2 infused into the uterine artery to the hypotensive response to increasing doses of PGI2 infused into the inferior vena cava. In addition, the effect of PGI2 infused into the uterine artery on uterine blood flow and intraamniotic fluid pressure was evaluated. The dose-response curves of intrauterine and intravenous PGI2 in causing systemic hypotension were identical suggesting that the pregnant uterus does not inactivate infused PGI2. Intrauterine PGI2 had no consistent effect on uterine hemodynamics although it did increase intraamniotic fluid pressure significantly. These data demonstrate that the pregnant uterus has the capacity to produce large quantities of PGI2 which is not inactivated in the uterus and therefore can appear in the arterial blood to exert a systemic vasodepressor effect.

Animals↗

Fluctuating gene expression and localized cellular distribution of vasoactive intestinal contractor (VIC) in mouse uterus.

To understand the physiological roles of vasoactive intestinal contractor (VIC) and endothelin-2 (ET-2) in the uterus, we examined the expression levels of VIC mRNA by real-time quantitative reverse transcription-linked polymerase chain reaction (RT-PCR) and characterized the cellular distribution of VIC peptide and mRNA by immunostaining and in situ hybridization in mouse uterus. In pregnant mouse uterus, VIC mRNA expression changed considerably between Days 10.5 and 12.5 of pregnancy. The expression levels were significantly (p<0.05) higher (approximately fivefold) in the later stage of pregnancy (Days 12.5-17.5) than in the earlier stage (Days 7.5-10.5). In nonpregnant uterus, VIC mRNA expression was significantly (p <0.05) higher (approximately threefold) in proestrus and estrus than in diestrus. Immunohistochemical studies demonstrated the presence of VIC peptide in endometrial epithelial cells, myometrial cells, and vascular smooth muscle cells during the estrous cycle and pregnancy and after parturition. Notably, myometrial cells showed dominant immunostaining in proestrus and estrus, in the later pregnancy stage, and in the early postpartum period, analogous to the expression pattern of VIC mRNA. In situ hybridization confirmed localization of VIC mRNA in myometrial cells. These findings suggest that VIC may play an important role in the function of myometrial cells.

Animals↗

The vascular cast of the human uterus: from anatomy to physiology.

The blood supply to the uterus originates mainly from the uterine artery. However, the uterine and ovarian arteries form anastomoses bilaterally. Controversy exists about the direction of the flow in the anastomoses and thus the origin of the arterial supply to the tube and tubal part of the uterus. A similar arcade is formed by the vaginal and uterine arteries. We have investigated the vascular border of supply between the uterine and ovarian arteries in postmenopausal women, which was positioned in the uterus 1-2 cm from the tube. A similar result was found in younger, ovulating women. However, the border between the territories irrigated by the uterine and ovarian arteries differs between the follicular and luteal phase; more uterine tissue is perfused from the ovarian artery when a large follicle is present. This constitutes the first description of a functionally determined shift in the territorial divide of two vascular systems and has numerous practical implications. The venous system copies the arterial one with one major exception: some of the uterine veins join the ovarian outlet. The close contact between veins and arteries facilitates transfer of substances, thus forming semilocal systems of regulation; for example, the ovary locally influences the function of the ipsilateral tube and part of the uterus. From a therapeutic point of view, it has been documented that application of progesterone to the vagina creates high uterine concentrations due to local vascular transfer.

Arteries↗

Movement of oxygen, glucose, and lactate across the uterus of the awake near-term guinea pig.

In this study the uterine movement of oxygen, glucose, and lactate was quantitated in the awake late pregnant guinea pig. Mean uterine uptake of oxygen per kg of uterus with conceptus was 581 mumol min-1, which is comparable to the value reported for the awake near-term rabbit, but 30% higher than the value reported for the awake near-term sheep. Experiment-related anemia in some animals was associated with a reduced uterine oxygen uptake. The arteriovenous oxygen difference across the uterus correlated positively with the arterial oxygen content and the hemoglobin concentration and negatively with uteroplacental blood flow. Uterine oxygen uptake showed a positive correlation with both the arterial hemoglobin and the uteroplacental blood flow. Uterine lactate output accounted for 20% of uterine glucose uptake, assuming maternally derived glucose to be the only source for uterine lactate output. After correction for this lactate output, the uterine glucose uptake was 96.5 mumol min-1 X kg-1 of pregnant uterus. This value is 30% higher than in the awake near-term rabbit and more than twice as high as that in the awake near-term sheep. Nevertheless, because of the high uterine demand for substrates, this uterine glucose uptake could only cover 45% of the caloric requirements of the pregnant uterus. The late pregnant guinea pig fetus may derive as much as 55% of its caloric uptake for fat deposition and protein accretion. Therefore, it is likely that the nonglucose uterine caloric uptake in the late pregnant guinea pig consists predominantly of fat precursors and amino acids.

Anemia↗

Interferon-stimulated gene-15 (Isg15) expression is up-regulated in the mouse uterus in response to the implanting conceptus.

An early response of the human and bovine endometrium to pregnancy is induction of an interferon (IFN)-stimulated gene (ISG) that encodes the ubiquitin-related protein, ISG15. Because the mode of implantation differs among species, we tested whether Isg15 mRNA was also expressed in the mouse uterus in response to the implanting conceptus. Isg15 mRNA was detected in the mouse uterus and increased after d 4.5 of pregnancy but did not change between d 3.5 and 9.5 of pseudopregnancy. Within the decidua, Isg15 mRNA was localized to the antimesometrial zone of the implantation sites. The level of Isg15 mRNA in artificially induced deciduomas was similar to the nonpregnant uterus and was approximately 10-fold lower than in the pregnant uterus. In vitro, murine decidual cells derived from artificially induced deciduomas could be induced to produce the Isg15 protein as well as Isg15-conjugated proteins when stimulated with type 1 IFN, though were less responsive to IFN-gamma. Isg15 is one of few gene products identified in murine implantation sites to require presence of the conceptus and not simply differentiation of the stroma. In vitro data support the inference that the pregnancy-specific inducer of uterine Isg15 is a type 1 IFN or a cytokine that signals through a similar pathway.

Animals↗