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Functional morphology of the vascular plexuses associated with the cetacean uterus.

The cetacean reproductive system is surrounded by thermogenic locomotory muscle and insulating blubber. This arrangement suggests elevated temperatures at the uterus that could induce detrimental effects on fetal development. We present anatomical evidence for a complex countercurrent heat exchange system that could function to regulate the thermal environment of the uterus and a developing fetus. Cooled venous blood from the surfaces of the dorsal fin and flukes enters the abdominal cavity via the lumbo-caudal venous plexus. This plexus is juxtaposed to the arterial and venous plexuses associated with the uterus. The morphology of the lumbo-caudal venous plexus suggests that it acts as a "heat sink" for the adjacent tissues. Heat may be transferred to the cool, lumbo-caudal venous plexus from the warm blood in the arterial and venous plexuses supplying the uterus. Heat may also be transferred from adjacent locomotory muscles to the cool lumbo-caudal venous plexus. The countercurrent heat exchanger created by the juxtaposition of the lumbo-caudal venous plexus with the uterovarian arterial plexus is similar in design to that of the countercurrent heat exchanger described for male cetaceans. The functional implications of introducing cool superficial blood into the abdominal cavity of a diving, and locomoting female cetacean are discussed.

Animals↗

Sonographic investigation of the uterus during artificial uterine cavity distention.

The improvement of sonographic examination of the uterus during artificial uterine cavity distention was studied in 30 consecutive patients in whom a hysteroscopy was indicated. In 10 of 21 patients with a normal sonographic appearence of the uterus, after filling the uterine cavity with Hyskon, various pathologic conditions became visible. In 5 of 9 patients with abnormal sonographic appearance of the uterus, the procedure enabled a more precise diagnosis concerning localization of abnormal echoes in the uterus. The advantage of this method was clearly demonstrated in cases of central echogenic structures, congenital uterine anomalies, myoma's, synechiae, and corpora aliena.

Dextrans↗

Identification of estrogen-regulated genes in the mouse uterus using a delayed-implantation model.

Gonadal steroid hormones are known to modulate the implantation of the blastocyst, but how the controlling genetics are regulated remains largely unknown. Using a delayed-implantation model, we examined estrogen-regulated genes (ERGs) in the mouse uterus using the differential-display reverse transcription-polymerase chain reaction (DD RT-PCR). Pregnant mice were ovariectomized and injected daily with progesterone (P, 1 mg/mouse), followed by a single injection of estrogen (E, 200 ng/mouse); 24 or 48 hr later, total RNA was extracted from the uterus. Reverse Northern analysis verified the expression patterns of 36 clones out of thousands of RNA species. Only five clones had mRNA levels that were modified, whereas other mRNAs were unchanged or not detectable. Sequence analysis of these, using the Basic Local Alignment Search Tool (BLAST) service, revealed that four of these clones were novel; one clone, designated ERG10, was found to be the mouse homologue of that deleted in oral cancer DOC-1. DOC-1 mRNA was detected all tissues examined, but only in the uterus and cervix was markedly increased 12 hr after E administration, it returned to basal level by 48 hr. One of the novel genes, designated ERG8, had three different forms of mRNAs and was expressed ubiquitously in all examined tissues. In the uterus, the mRNA level of ERG8 also increased 12 hr after E administration. These results suggest that during the implantation process, E differentially regulates several genes depending on cell type. Uterine-specific induction of newly found genes, such as ERG8 and 10, by E appears to be important for the early implantation process.

Animals↗

Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy.

Leukemia inhibitory factor (LIF) has been shown to play an important role in the implantation of mouse blastocysts. The present study was designed to investigate the changes of LIF protein, LIF receptor, and gp130 in the mouse uterus during the early pregnancy. LIF protein and LIF receptor were at high levels in the mouse uterus near the time of ovulation and on day 4 of pregnancy. gp130 was highest on days 3 and 4 of pregnancy. Both LIF receptor and gp130 showed strong staining in the stroma of the day 5 uterus, at a time when LIF protein was low. The presence of LIF receptor and gp130 in the luminal epithelium on day 4 and in the stroma on day 5 may indicate the site of the high affinity LIF receptor. The coexistence of a high level of LIF protein, LIF receptor, and gp130 in the day 4 uterus is consistent with the previously observed high level of uterine LIF mRNA on the same day and the importance of LIF for the blastocyst implantation in mouse.

Animals↗

Synchronous expansion of intermediate TCR cells in the liver and uterus during pregnancy.

The immunophysiology of pregnancy was investigated in relation to how extra- and intrathymic pathways of T cell differentiation are modulated during pregnancy. Pregnancy was produced in syngeneic and allogeneic combinations in mice. In both cases, a prominent decrease in the number of thymocytes and a mild increase in the number of hepatic mononuclear cells (MNC) were induced during the periparturient period. The most striking change was the increase in the number of intermediate TCR cells with extrathymic T cell properties in the liver. When MNC yielded by the uterus were examined, an expansion of intermediate TCR cells was also observed in this organ during pregnancy. The major populations in the pregnant uterus were NK cells and intermediate TCR cells, the latter of which contained double-negative CD4-8- cells and consisted of both alpha beta and gamma delta T cells. All of these properties coincided with those of extrathymic T cells in the liver. Reflecting extrathymic T cell differentiation, MNC in the liver and pregnant uterus expressed mRNA of RAG-1 and RAG-2. To determine the role of hormonal regulation in this phenomenon, the effects of various pregnancy-associated hormones on thymocytes and hepatic MNC were examined in nonpregnant mice. Of the hormones tested, estrogen was found to induce a response similar to that seen in pregnant mice. These results suggest that a local immune response in the uterus during pregnancy is a phenomenon occurring synchronously with systemic immune systems.

Animals↗

Expression and regulation of chemokine genes in the mouse uterus during pregnancy.

Leukocytes accumulate in the pregnant mouse uterus following mating, during implantation and during placental development. Changes in leukocyte number are primarily due to recruitment from the blood, not local proliferation, but the underlying recruitment mechanisms are poorly understood. Mating-induced granulocyte and macrophage recruitment is due in part to pro-inflammatory and chemotactic factors present in seminal plasma. Accumulation of macrophages later in pregnancy appears to be caused in part by ovarian hormone-stimulated CSF-1 production and in part by other as yet unidentified uterine chemotactic factors. The current study was performed to assess chemokine production in the uterus during pregnancy. Northern blotting was used to demonstrate NSI/KC (KC), macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein one alpha (MIP1alpha) and regulated inactivation, normal T expressed and secreted protein (RANTES) mRNA in the uterus. Oestrogen and progesterone induced intrauterine production of all four chemokines and may have done so through the autocrine/paracrine activities of IL-1. The data suggest that C-C chemokines play a role in accumulation of macrophages in the uterus during pregnancy.

Animals↗

Expression of the arylhydrocarbon receptor and the arylhydrocarbon receptor nuclear translocator during early gestation in the rabbit uterus.

The arylhydrocarbon receptor (AhR) and the arylhydrocarbon receptor nuclear translocator (ARNT) are members of the PAS gene family mediating toxic effects of xenobiotics such as dioxin and polychlorinated biphenyls. We have analyzed the expression and cellular distribution of rabbit AhR and ARNT mRNA and protein level in the nonpregnant uterus and the pregnant and pseudopregnant uterus at Days 6 to 12 of gestation. In the preimplantation uterus at Day 6 of gestation and in the interimplantation and pseudopregnant uterus at Days 7, 8, 9, and 12 of gestation, low levels of AhR transcripts were detected in the glandular uterine epithelium. Upon attachment of the blastocyst at Day 7 of gestation, a strong expression of AhR and ARNT mRNA was observed in the luminal and glandular epithelium of the antimesometrial uterine compartment. In contrast, AhR and ARNT expression was low in the luminal epithelium of the paraplacental and the mesometrial placental fold. AhR mRNA was also detected in the trophoblast cells. During early placentation at Day 9 of gestation, expression of AhR and ARNT was first observed in the perivascular decidualized stromal cells and, at Day 12, extended to the decidualized stromal cells of the placental bed. Within the placenta, the syncytiotrophoblast expressed only low levels of AhR and ARNT mRNA and no protein. The specific expression patterns of AhR and ARNT during early gestation suggest functional roles for both transcription factors during feto-maternal interactions in the rabbit.

Animals↗

Induction of proliferative lesions of the uterus, testes, and liver in swiss mice given repeated injections of sodium arsenate: possible estrogenic mode of action.

Inorganic arsenic (As) is a human carcinogen but has not been unequivocally proven carcinogenic in rodents. For instance, one older study indicates that repeated iv injections of sodium arsenate might induce lymphomas in Swiss mice (58% incidence) (Osswald and Goerttler, Verh. Dtsch. Ges. Pathol. 55, 289-293, 1971), but it was considered inadequate for critical evaluation of carcinogenic potential largely because of issues in experimental design. Therefore, we studied repeated iv sodium arsenate injection and neoplastic response in male and female Swiss mice. Groups (n = 25) of mice received sodium arsenate (0.5 mg/kg, iv) or saline (control) once/week for 20 weeks and were observed for a total of 96 weeks when the study ended. Differences in survival and body weights were unremarkable. In females, arsenate induced marked increases in the incidence and severity of cystic hyperplasia of the uterus compared against controls. Arsenate also was associated with a rare adenocarcinoma of the uterus. Hyperplastic uterine epithelium from arsenate-exposed animals showed strong positive immunostaining for the proliferating cell nuclear antigen (PCNA). There was also an upregulation of estrogen receptor (ER) immunoreactive protein in the early lesions of uterine luminal and glandular hyperplasia, although a progressive decrease in its expression was seen in the severe hyperplastic or neoplastic epithelium. In common with the preneoplastic and neoplastic gynecological lesions in humans, the levels of immunoreactive inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine-containing proteins were greater in the uterine hyperplastic epidermis and their intensity was positively correlated with the severity of the lesions. Arsenate-induced uterine hyperplastic lesions also showed a strong upregulation of cyclin D1, an estrogen-associated gene product essential for progression through the G1 phase of the cell cycle. In other tissues, arsenate increased testicular interstitial cell hyperplasia incidence and severity over control but without affecting the incidence of tubular degeneration. Arsenate also induced increases in hepatic proliferative lesions (HPL; foci of alteration + neoplasia), but only in females. Significant skin changes (incidence of hyperkeratotic lesions) and renal lesions (severity of nephropathy) also occurred in arsenate-treated females. Thus, repeated arsenate exposure, though not outright tumorigenic in the present study, was associated with proliferative, preneoplastic lesions of the uterus, testes, and liver. Estrogen treatment has been associated with proliferative lesions and tumors of the uterus, female liver, and testes in other studies, supporting a hypothesis that arsenate might somehow act through an estrogenic mode of action.

Animals↗

The myostimulating effect of tissue kallikrein on rat uterus.

The mechanism of the myostimulating activity of rat tissue kallikrein on rat uterus was re-examined using uterus from kininogen-deficient rats and HOE 140 (D-Arg[Hyp3, Thi5, D-Tic7, Oic8]bradykinin), a specific bradykinin receptor-B2 antagonist. The uterus from kininogen-deficient rats was 50 times less sensitive to rat kallikrein than that from normal rats. HOE 140 (6 to 60 nM) inhibited the contracting effects of bradykinin and of rat kallikrein. Porcine kallikrein had no effect on rat uterus. Bradykinin and rat kallikrein induced a relaxation of rat duodenum. The duodenum from kininogen-deficient rats was 100 times less sensitive to rat kallikrein than the duodenum from normal rats. HOE 140 (0.6 to 3 nM) inhibited the relaxing effects of bradykinin and of kallikrein. Preincubation of rat kallikrein with aprotinin (Trasylol) abolished the effects of kallikrein on smooth muscles. HOE 140 inhibited the amidolytic activity of tissue kallikrein with a Ki value of 220 microM. HOE 140, at micromolar concentrations, suppressed the kininogenase activity of tissue kallikrein. Plasma of deficient rats contained 0.7% of the normal levels of kininogens. After washing the blood vessels with saline, kininogens were present in uterine homogenates but not in duodenal homogenates from both rat strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The innervation of the uterus in Salamandra salamandra (L.) (Amphibia, Urodela). A morphological and biochemical study.

The innervation of the uterus in the ovoviviparous urodele Salamandra salamandra was studied. In whole mount preparations of the thin-walled uterus of pregnant females, a dense adrenergic network was demonstrated using a modified glyoxylic acid fluorescence technique. Based on vesicle type and cytochemical reactivity after chromate/dichromate fixation for electron microscopy at least two types of neural process were distinguished and classified as adrenergic and cholinergic. Both types are preferentially situated above or between the smooth muscles of the uterine tissue. Adjacent to the muscles in the walls of arterioles mainly adrenergic fibers are seen. Using high performance liquid chromatography with electrochemical detection in tissue homogenates of uterus a considerable amount of noradrenaline could be identified. The significance of the dense innervation is discussed with respect to the function of the uterus during pregnancy and birth.

Adrenergic Fibers↗

Expression of myosin heavy and light chains changes during pregnancy in the rat uterus.

We investigated the in vivo expression of myosin heavy chains (MHC) and myosin light chains (MLC) in the rat uterus during pregnancy and post partum (p. p.). According to their antigenic reactivity, we observed two smooth-muscle-specific MHC (SM-MHC) of 204 kDa and 200 kDa (SM1 and SM2 respectively) and one non-muscle-specific MHC band of 198 kDa (NM-MHC). Adult virgin female rats expressed SM1 and NM-MHC (65/35) but no SM2. During the first pregnancy NM-MHC expression decreased in favour of the SM1 form, the SM1/NM-MHC ratio being 82/12 after 20 days of pregnancy. SM2 is newly expressed in the first p. p. state, the SM1/SM2/NM-MHC ratio being 58/28/14 between 3 and 33 days p. p. During the second pregnancy, starting 34 days p. p., both SM2 and NM-MHC expression decreased, the SM1/SM2/NM-MHC ratio being 85/0/15 after 20 days of pregnancy. Two protein bands of approximately 154 kDa and 145 kDa (sodium dodecylsulphate electrophoresis), designated SMP1 and SMP2 respectively, with the same immunoreactivity as the SM-MHC were observed in vivo in the pregnant but not in the non-pregnant uterus. In addition, a Ca(2+)-independent protease, which uses MHC as substrate, is expressed in the pregnant but not in the non-pregnant rat uterus. Two isoforms of the 17-kDa MLC (LC17a and LC17b) exist in the rat uterus. Expression of the LC17a isoform increased during the first pregnancy from 46% in virgin rats to 65% in uteri of rats 20 days pregnant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multistage functional system amplifying and spreading the effect of estradiol in rat uterus.

Estradiol is demonstrated to induce histidine decarboxylase, and histamine is shown to activate adenylate cyclase in rat uterus. Histamine and cyclic 3',5'-AMP mimic the effects of estradiol in that they enhance RNA synthesis, induce glycolytic enzymes and uterus imbibition. The data suggest that estradiol enhances by induction of histidine decarboxylase the formation of histamine, the latter activates adenylate cyclase providing accumulation of cyclic 3',5'-AMP, which, probably, induces glycolytic enzymes through phosphorylation of chromatin proteins, and mediates other estradiol effects. The chain of successively acting enzymes and mediators constitutes, obviously, a cascade amplifying estradiol action. Since histamine is known to act as an intercellular mediator, attempts were made to find out the distribution of estradiol histamine and cyclic 3',5'-AMP among uterus cells. Autoradiography has shown that [3H]-estradiol is bound by the nuclei of myometrium cells, [3H]-histamine was found above the cytoplasm of these cells, E13H]-cyclic 3',5'-AMP is selectively bound by the cells of capillary endothelium of the uterus. The estradiol mediators seem to spread effect of hormone on cells of different types which form together a kind of multicellular functional system.

Adenylyl Cyclases↗

Immunohistochemical detection of factor XIII subunit a in histiocytes of human uterus.

As spontaneous abortion is a frequent finding in females with Factor XIII (FXIII) deficiency it has been presumed that this clotting factor is essential to normal pregnancy. FXIII subunit a (FXIII A) has been demonstrated in the homogenate of human uterus, but no information on its cellular distribution has been published, so far. In the present study first FXIII A was detected in paraformaldehyde-fixed, paraffin-embedded sections of human uterus by immunoperoxidase technique. Cells containing FXIII A were localized between collagen fibrils stained by Picrosirius Red F3B in the connective tissue. To characterize them the immunofluorescent detection of FXIII A was combined by the visualization of different marker antigens of monocytes and macrophages recognized by Leu-M3, RFD7, anti-HLA-DR and DAKO-anti-macrophage monoclonal antibodies on frozen sections. The coexpression of FXIII A with monocyte and macrophage differentiation marker antigens clearly proves that cells containing FXIII A in the uterus are monocyte-derived tissue macrophages. The results well agree with our previous findings demonstrating FXIII A in human monocytes and different types of macrophages. On the basis of these results, the presence of FXIII A does not seem to be a specificity of the uterus but a characteristic of monocyte/macrophage cell line including tissue macrophages, in general.

Adult↗

Ultrastructural and kinetic studies on uteroglobin secretion in the uterus and oviduct of the pseudopregnant rabbit.

The intracellular localization of uteroglobin, a progesterone-induced protein, was studied in uterus and oviduct by means of immunoelectron microscopy with the protein A-gold technique. In the uterus, uteroglobin was synthesized in the columnar epithelium of the endometrium where most of the cells were immunoreactive. The protein was localized mainly in small secretory granules which were seen in the process of release into the uterine lumen. The luminal microvilli were also heavily stained. In the oviduct, the secretory cells contained large immunoreactive granules at the apical zone, some of which were observed while discharging into the lumen. Within these secretory granules, uteroglobin accumulated particularly in lens-shaped patches at the periphery of the granules. In vitro kinetic studies on the secretion of newly synthesized uteroglobin indicated that the ability to store uteroglobin is greater in the oviduct than in the uterus; however, the rate of uteroglobin secretion is greater in the uterus than in the oviduct. Thus, there appears to be a good correlation between the microscopic and the functional observations.

Animals↗

[Contents and distribution of Fe, Cu, Zn, Ni, and Mn in fetuses, amniotic fluid, placenta, and uterus of rats].

Fetuses, amniotic fluid, placenta, and uterus were taken from five gravid rats shortly prior to delivery, and the contents of Fe, Cu, Zn, Ni, and Mn were analyzed. Fe, Cu, Zn, and Mn exhibited a similar concentration in dry matter (DM) in all tested reproductive organs, whereby Fe-contents were five to ten times higher than Zn-contents and those five to ten times higher than Cu-contents, which amounted to 10-20 ppm. The Mn-contents range about a factor of ten below. Ni-concentration in DM of fetuses, placenta and uterus is below 1 ppm, whereas in contrast to this, Ni-concentration of 14 ppm in DM of amniotic fluid is 34 times higher than in fetuses and placenta. Uterus contained twice as much Ni as fetuses. Concerning the total content of the individual trace elements, Ni reacts also different as compared to Fe, Cu, Zn, and Mn. Its amniotic content exceeds the fetal content by 40%. Total excretion of Fe, Cu, Zn, Mn, and also DM is distributed differently as compared to Ni. Fetuses contain 60%-70% of these trace elements, placenta 15%-25%, uterus 6%-16%, and amniotic fluid only 1%-2%. Ni, however, is excreted mostly via amniotic fluid by about 35% of total excretion and only by about 25% via fetuses. These findings, concerning Ni, are discussed in detail.

Amniotic Fluid↗

Electrical activity of the bovine uterus prior to and post parturition.

Recordings of electrical activity of six different areas of the uterus were obtained from two pregnant cows before and after delivery of their calves. Periods of activity occurred as spike bursts of potentials which occupied 52% of the recording time before delivery and 92% at the expulsive phase. The mean duration of the bursts was nearly doubled in the last ten hours prior to parturition without changes in their frequency. After delivery, the activity of the uterus occupied 29% of the recording time and consisted of long-lasting periods of spike bursts whose frequency was nearly halved. The alternation of periods of activity and quiescence represents the basic motility pattern of the pregnant uterus. Periods of quiescence are shortened at the time of expulsion and become predominant in the empty uterus, a phenomenon paralleled by changes in the temporal organisation of the number of spike bursts with the periods of activity.

Action Potentials↗

Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant and pregnant rat uterus. Comparison with vascular tissue.

To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy, we determined the density of myometrial CGRP-encoded nerve fibre terminals and examined, in an organ bath, the relaxant effect of the peptide on uterine strips near parturition. Comparisons were made with the uterus and aorta of nonpregnant rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in nonpregnant rats and scarce at the parturient stage. In the aorta there was no variation in the density of CGRP fibres with gestation. In nonpregnant rats only, CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked uterine contractions (EC50 40 nM, Emax 80%). The effect was antagonized by CGRP[8-37] (pKB 6.47) but was not affected by either blockers of nitricoxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50, 2 nM, Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Amylin neither relaxed the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the uterus was limited on day 21 and was totally absent on day 22 of gestation. We conclude that the primary relaxant effect of CGRP on the uterus occurs at the level of myometrial smooth muscle cells. In the myometrium, gestation decreases CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not observed in vascular tissues like aorta.

Animals↗

Pyrimidine nucleoside phosphorylase activity in normal tissues of the uterus and ovary and in benign and malignant lesions of these organs.

BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) is identical to the protein, platelet-derived endothelial cell growth factor (PD-ECGF), which has angiogenic activity. The physiological roles of PyNPase activity in the uterus and ovary are not known. In this study, we measured PyNPase activity in normal tissues of the uterus, ovary, and lymph nodes, and in benign and malignant lesions of these organs, and we considered the clinical implications of PyNPase activity in the uterus and ovary. METHODS: Tissue samples were obtained from 163 patients (whose diseases are listed below) during surgery. PyNPase activity was measured spectrophotometrically, by monitoring the formation of 5-fluorouridine. RESULTS: Mean PyNPase activity in tissues from the lesions of patients with cervical cancer (n = 20), uterine endometrial cancer (n = 26), leiomyoma (n = 23), ovarian cancer (n = 46), ovarian endometriosis (n = 21), and benign epithelial ovarian tumor (n = 27) was significantly greater than that in the corresponding normal tissues. The PyNPase activity in the normal endometrium was significantly higher in the secretory phase than in the proliferative phase. The activity in normal or metastatic lymph nodes was significantly greater than that in normal tissues of the uterus and ovary. Mean PyNPase activity in cancerous cervical tissues was significantly greater than that in cancerous endometrial tissues or cancerous ovarian tissues. There were no significant differences in PyNPase activity in cervical cancer, endometrial cancer, and ovarian cancer tissues according to tumor stage. The enzyme activity appeared to be greater in histopathological G3 grade endometrial cancer than in G1 and G2 endometrial cancer. The enzyme activity in mucinous adenocarcinoma of the ovary was significantly lower than that in serous, endometrioid, and clear cell adenocarcinomas. All patients with cervical squamous cell carcinomas with PyNPase activity greater than 500 nmol/min per mg protein exhibited lymph node metastasis. CONCLUSION: Increased PyNPase activity consistently reflected neoplastic growth, and varying levels of activity were seen in different histologic cell types. This enzyme activity may be involved in cervical squamous cell carcinomas, in normal and metastatic lymph nodes, and in the normal, secretory phase in the endometrium.

Adenocarcinoma, Mucinous↗