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Influence of estradiol on oxidative stress in the castrated rat uterus.

OBJECTIVE: We set out to study how the concentration of estradiol influences oxidative stress (malondialdehyde) and the superoxide dismutase and catalase antioxidant systems in the castrated female Wistar rat uterus. METHODS: We used 28 castrated female Wistar rats: 7 were left to evolve freely and the rest were divided into three groups of 7 animals receiving respective doses of 4, 8, and 16 microg/day of estradiol (E2) for 15 days. At the end of the study period, we determined the plasma concentrations of E2 and the concentrations of malondialdehyde (MDA) and superoxide dismutase and catalase activities in the uterus. RESULTS: There was a significant correlation (P < 0.000028) between the uterine malondialdehyde levels and the logarithm (base 10) of the plasma E2 concentrations and also between malondialdehyde and the uterine catalase activity (P < 0.002). The regression plane that best fitted the correlation among the three variables was MDA = 10.21 + 12.88 x Log [E2] - 0.49 x catalase activity. We found no significant relationships with the superoxide dismutase activity. CONCLUSIONS: There was a linear correlation between the base-10 logarithm of the estradiol plasma concentration and the phenomenon of uterine lipid peroxidation as measured by the MDA concentration in the uterus. This phenomenon was in part modulated by the inverse linear relationship between the antioxidant activity of the uterine catalase and the concentration of uterine MDA.

Animals↗

Autoradiographic study on the localization of estradiol-17beta in neonatal mouse uterus and cervix.

The uptake of 3H-estradiol-17beta in the neonatal mouse uterus and cervix has been studied by an autoradiographic method. When the radioactive hormone is administered in vivo and in vitro, grains are found to be concentrated above the nuclei both in the uterine and cervical epithelium and stroma. Grain counts revealed that the nuclear concentration of grains is higher at 4 h than at 2 h after isotope injection. The cervical epithelium has a higher nuclear concentration than the uterine epithelium both in vivo and in vitro. In the stroma, this situation is reversed except after in vitro treatment of the tissues. In the cervix, more of the hormone seems to be located within the nucleus while in the uterus a higher proportion of the grains are found in the vicinity of the nuclear periphery. Although the nuclear concentration of grains is higher at 4 h than at 2 h, the number of grains above the sections is lower at 4 h. Both in vivo and in vitro, the number of grains is higher above the stromal than above the epithelial compartments of the uterus and cervix. Five days old animals showed the same labeling pattern. The differences in uptake and distribution of 3H-estradiol are discussed in relation to other known differences in the hormone responsiveness in these tissues.

Animals↗

The effect of oestradiol on the DNA synthesis in neonatal mouse uterus and cervix.

(3H)-Thymidine autoradiography was used to study the DNA synthesis in the stroma and epithelium in the uterus proper and the uterine cervix of neonatal mice treated with oestradiol. It was found that in the epithelium of the uterus proper the DNA synthesis is stimulated between 6 and 12 h after injection of oestradiol and decreases again at 18 h. In the stroma of the uterus proper the DNA synthesis is increased 18 h after oestradiol injection. In the epithelium and stroma of the uterine cervix the DNA synthesis decreases from 5 h and is strongly depressed 18 h after oestradiol treatment.

Animals↗

Relationship between cellular DNA synthesis, PCNA expression and sex steroid hormone receptor status in the developing mouse ovary, uterus and oviduct.

The proliferative activities of the different cellular compartments of the developing mouse ovary, uterus, and oviduct were studied by radioautographic assessment of DNA synthesis with [3H]-thymidine labeling and by immunohistochemical staining of proliferating cell nuclear antigen (PCNA). The distributions of estrogen and progesterone receptors (ER and PR) were studied by immunohistochemical staining. The values of the PCNA positive staining indices were a little higher than that of the radioautographic labeling indices. However, linear relations were shown for the two indices. The proliferative activities were high from postnatal day 1-7 and decreased from day 14 in the different cellular compartments of the ovary. The proliferative activities were high on days 1, 3 and decreased from day 7 in the uterus and oviduct. Staining of ER and PR was very weak in the surface epithelium, stroma and large follicles of the ovary. Positive staining for ER occurred from day 14 in the uterine epithelium and from day 7 in oviductal epithelium. Positive staining for PR was observed from day 1 in both the uterine and oviductal epithelium. However, the positivity of both ER and PR occurred from postnatal day 1 in the stromal cells of the uterus and oviduct. These results suggest that the appearance of the steroid receptors differ between the different cellular compartment of the reproductive organs. The proliferative activities have an inverse relation with the expression of the steroid hormone receptors in the female reproductive organs during developmental stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of kinins on paw oedema and uterus in rats.

Bradykinin (BK) produced a dose-related increase in the paw volume of the rat. Responses to BK at all doses used were not affected by pretreating the rats with diphenhydramine, 1 mg kg-1, or indomethacin, 2.5 and 5 mg kg-1. Indomethacin, 10 mg kg-1 produced a small but significant reduction in the responses to BK. Captopril 1 mg kg-1 enhanced responses to low but not to high doses of BK. The rank order of potency of various kinin analogues to increase paw volume was found to be methionyl-lysyl-BK (met-lys-BK) greater than BK greater than lysyl-BK (Kallidin) much greater than des-Arg9-BK. The B1-receptor antagonist des-Arg9-Leu8-BK did not affect responses to BK on paw volume. Two modified kinin fragments S2302 (H-D-Pro-Phe-Arg-p-Nitroaniline) and S2441 (H-D-Pro-Phe-Arg-NH-heptyl) produced dose-related increases in paw volume both having approximately half the potency of BK. These responses were not antagonised by diphenhydramine, 1 mg kg-1 which reduced significantly the response to histamine. On the isolated rat uterus the rank order of potency of various kinins was BK greater than Kallidin greater than met-lys-BK greater than des-Arg9-BK. The two modified kinin fragments S2302 and S2441 (but not des-Arg9-Leu8-BK) antagonised BK induced contractions of the rat uterus. From the rank order of potency studies the receptor mediating contraction of the rat uterus in vitro and increase in rat paw volume to BK appear to be of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An immunohistochemical study of the catecholamine synthesizing enzymes and neuropeptides in the female guinea-pig uterus and vagina.

The uterus and vagina of the guinea pig have been examined, region by region, for acetylcholinesterase, tyrosine hydroxylase, dopamine beta-hydroxylase and aromatic amino acid decarboxylase activity, as well as for the neuropeptides, neuropeptide Y, vasoactive intestinal peptide, substance P, enkephalin and somatostatin. No acetylcholinesterase activity was localized in the uterus, though it was present in associated paracervical ganglion tissues. Of the catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase activity was found virtually throughout the reproductive tract, whereas aromatic amino acid decarboxylase activity was restricted in its distribution. Neuropeptide distribution was quite varied. Neuropeptide Y was found throughout the endometrium/submucosa but only in the muscularis of the vagina and not in the myometrium. Substance P was localized in the vagina and uterine horn, though not the body of the uterus. Vasoactive intestinal peptide was present in all regions of the endometrium/submucosa, but not in the myometrium of the uterine horn. Enkephalin and somatostatin were not localized in any part of the reproductive tract examined, apart from paracervical ganglion tissues. The types and significance of the nerves supplying the reproductive tract are discussed.

Acetylcholinesterase↗

Cholinergic nerves in mouse uterus.

The topographical distribution of cholinergic nerve fibres in the uterus was studied in normal as well as chemically sympathectomized mice. Our analysis was performed using both transverse sections and whole mounts, in order to analyse the distribution of cholinergic nerves within the various layers of the uterus and to study the morphology of nerve plexuses that supply the organ. Cholinergic nerve fibres were found chiefly around the uterine artery and its primary ramifications. Nerve fibres coming from arterial plexuses are distributed to the myometrium and more infrequently to the endometrium. Groups of acetylcholinesterase positive ganglion cells were located in the cervix. The distribution pattern of the cholinergic innervation of mouse uterus shows important topographical differences. In the tubal end of uterine horn the innervation is poor and cholinergic nerve fibres are organized in a sparse plexus. The number and the density of uterine nerves increase gradually proceeding toward the cervix. The cervix shows the richest innervation. The findings that observed nerve fibres are unaltered by chemical sympathectomy and are revealed using short incubation times suggest their parasympathetic nature.

Acetylcholinesterase↗

The normal uterus on magnetic resonance imaging and variations associated with the hormonal state.

Magnetic Resonance Imaging of the pelvis has lead to a new radioanatomical description of the uterus. Variations in the anatomical zones of the uterus were noted with different sequences used in MRI. There was also structural and signal variation depending on hormonal impregnation. Twenty seven MRIs of pelvices were carried out on 16 female volunteers. Eight of them were on oestroprogesterone as the method of contraception (Group I) and had a single MRI. Six were not taking contraceptives (Group II) and had different MRI's during the same cycle. Two women already had already gone through the menopause (Group III). Results showed differences in the size of the uterus (uterine height, length of the uterine body and cervix, diameter of the cervix) between groups I and II but no cyclic changes were observed within group II. The myometrium was found to be thicker in group I and in the luteal phase of group II females in comparison to the follicular phase in the same group. The endometrial cavity was seen in 40% of cases on T1 weighted sequences; on T2 weighted sequences it was seen in all the cases. It was thicker during the second phase in group II than in group I and III. The myometrial signal compared to that of the bladder content (urine) showed a significant increase between early and late echoes on T2 weighted sequences in group I and during the second phase of the menstrual cycle in group II. No variations, or at times a decrease in signal, were observed during the first phase of the cycle in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of stress stimuli on glycogen level in the rat uterus.

Effect of prolonged exercise, acute cold exposure, and 24-h fasting on the glycogen level in the uterus of rats spayed and than treated with peanut oil or estradiol was investigated. It has been found that exercise increases significantly though transitorily the glycogen level in the uterus of the oil-treated group. Cold exposure resulted in significant reduction of the uterine glycogen level only in the oil-treated group. Fasting did not change the glycogen level in the uterus in the both groups. Five hours of swimming and fasting decreased significantly the blood glucose level.

Animals↗

Distribution of progestin-binding cells in estrogen-treated and untreated neonatal mouse uterus and oviduct: autoradiographic study with [125I]progestin.

Progestin-binding sites in uteri and oviducts of estrogen-treated and untreated 8-day-old mice were studied by thaw-mount autoradiography with [125I]progestin. In the untreated uteri, nuclear concentration of radiolabelled progestin was observed in all tissues of the uterus, with strongest nuclear labelling in luminal and glandular epithelia and in stroma. In the estrogen-treated uteri, the degree of labelling was markedly augmented in stroma and muscle, but much reduced in the luminal and glandular epithelia, compared to untreated uteri. In untreated oviducts, nuclear labelling was observed in stroma and muscle in all regions and in epithelium in the isthmic and uterine regions. The epithelium in infundibular and ampullar regions was only scarcely labelled. The estrogen-treatment augmented the labelling in stroma and muscle of the oviduct as in the uterus, but the labelling in epithelium was not affected. These results indicate that estrogen-treatment induces progesterone receptor differentially among tissue compartments both in the uterus and oviduct.

Animals↗

Effects of Jiantaiye on estrogen receptor and mRNA expressions in uterus of mice with embryo implantation dysfunction.

OBJECTIVE: To explore the effect of Jiantaiye (JTY) on the expression of estrogen receptor (ER) and ER mRNA in uterus of mice with embryo implantation dysfunction. METHODS: Embryo implantation dysfunction mouse models were induced with mifepristone and treated with JTY. All animals were sacrificed on day 8 of pregnancy. The endometrial ER and ER mRNA expressions were assessed by immunnohistochemical SP method and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Area ratio and absorbency of ER in the JTY treated group's gland and stroma were higher than those of the model group, quite similar to those of the normal control's, and ER mRNA expression in treated group's uterus was significantly higher than that in the models, but it was not significantly different from the normal control. CONCLUSION: JTY improves the endometrial development by increasing ER and ER mRNA expressions of uterus of mice with embryo implantation dysfunction.

Animals↗

An electron microscopic study of the post-partum involution of the rat uterus. With a note on apparent crinophagy of collagen.

During pregnancy the increase in mass of the rat uterus has been accounted for mainly by hypertrophy rather than hyperplasia of the smooth muscle cells and by an increase in collagen content. Following parturition the rat uterus regains its non-pregnant weight within little more than a week. Autophagy is a likely mechanism for the reduction in size of the smooth muscle cells. However, many previous investigations have failed to demonstrate an extensive lysosomal apparatus in uterine smooth muscle cells, a morphologically detectable prerequisite for augmented autophagy. The superfluous collagen has been assumed to be digested by macrophages. In the present electron microscopical study the involution of the rat uterus was followed at various time points post-partum. The results indicated that three pathways were involved namely, autophagocytosis, heterophagocytosis and crinophagy. Autophagocytosis was noted in smooth muscle cells--apparently a means to reduce their size. In some instances extensive autophagy appeared to lead to cell death. Macrophages and also to some extent fibroblasts have the ability to endocytose collagen and cell debris including split off portions of smooth muscle cell cytoplasm. The evidence obtained suggested that at the time of parturition the (pro)collagen synthesized but not yet secreted was retained within the fibroblasts and degraded by means of crinophagy.

Animals↗

Involvement of smooth muscle cells in collagen degradation in the postpartum uterus.

Ultrastructural study of gravid and postpartum involuting human uteri revealed a number of cells containing collagen fibrils in their cytoplasm. In gravid uteri these cells could be identified as macrophages and fibroblasts; in the postpartum uteri smooth muscle cells (SMC) were also found, containing cytoplasmic collagenous vacuoles. The morphology of intracellular collagen in SMC was similar to that observed in macrophages: fragments of banded collagen fibrils with a diameter corresponding to that of extracellular collagen were located within structures considered to be phagosomes. Limiting membranes were always smooth, most often in apposition to the fibrils that were single or packed in small groups; some cytoplasmic vacuoles contained banded elongated profiles barely discernable as collagen. The collagen fibrils within SMC of the involuting human uterus are regarded as a morphological manifestation of heterogenic enclosure of collagen fibrils and their intracellular degradation. It seems that in the postpartum uterus, where a substantial amount of collagen needs to be removed rapidly, both macrophages and SMC are involved in the process of collagen phagocytosis and degradation. These data suggest that SMC may be involved in the cellular mechanism for collagen breakdown in remodelling SMC-containing tissues like the uterus and the vascular wall.

Collagen↗

Differential expression of gangliosides in the ovary and uterus of streptozotocin-induced and db/db diabetic mice.

Gangliosides are widely distributed in mammalian cells and play important roles in various functions such as cell differentiation and growth control. In addition, diabetes and obesity cause abnormal development of reproductive processes in a variety of species. However, the mechanisms underlying these effects, and how they are related, are not fully understood. This study examined whether the differential expression of gangliosides is implicated in the abnormal follicular development and uterine architecture of streptozotocin (STZ)-induced and db/db diabetic mice. Based upon the mobility on high-performance thin-layer chromatography, mouse ovary consisted of at least five different ganglioside components, mainly gangliosides GM3, GM1, GD1a and GT1b, and diabetic ovary exhibited a significant reduction in ganglioside expression with apparent changes in the major gangliosides. A prominent immunofluorescence microscopy showed a dramatic loss of ganglioside GD1a expression in the primary, secondary and Graafian follicles of STZ-induced and db/db diabetic mice. A significant decrease in ganglioside GD3 expression was also observed in the ovary of db/db mice. In the uterus of STZ-induced diabetic mice, expression of gangliosides GD1a and GT1b was obviously reduced, but gangliosides GM1, GM2 and GD3 expression was increased. In contrast, the uterus of db/db mice showed a significant increase in gangliosides GM1, GD1a and GD3 expression. Taken together, a complex pattern of ganglioside expression was seen in the ovary and uterus of normoglycemic ICR and db/+ mice, and the correspoding tissues in diabetic mice are characterized by appreciable changes of the major ganglioside expression. These results suggest that alterations in ganglioside expression caused by diabetes mellitus may be implicated in abnormal ovarian development and uterine structure.

Animals↗

Epidermal growth factor influenced by opioid peptides in immature rat uterus.

The aim of the present experiment was to investigate the effect of [D-Met2,Pro5] enkephalinamide (ENK) implantation on the development of the uterus during 8-33 days of age and the involvement of epidermal growth factor (EGF) in the effect. Administration of ENK was attained by osmotic minipumps (5 microg/h) implanted intraperitoneally. ENK resulted in a decrease in the EGF content of the uterus, which was already significant after 48 h of the implantation. The DNA content 24 and 48 h after the treatment decreased, no change at 72 h was found, however the protein/DNA ratio on the effect of ENK treatment was significantly decreased at this time in all examined age groups. High affinity and lower capacity competitive naloxone binding sites were demonstrated in the membrane fraction of the uteri. Seventy-two h after ENK treatment the binding capacity of these sites significantly dropped. The present results suggest a novel multiple interaction between estrogen and two probably paracrine hormones, EGF and opioid peptide, in the regulation of growth and development of the uterus.

Animals↗

Estrogen and progesterone receptors in human uterus and oviduct.

The binding of 3H-estradiol and 3H-R5020 (dimethyl-19-norpregna-4,9-diene-3,20-dione) to estrogen (ER) and progesterone (PR) receptors in human uterus and oviduct were studied. The binding of the ligands to their respective receptors were of high specificity and affinity. The equilibrium dissociation constants for ER and PR were 0.07 +/- 0.025 nM respective 0.76 +/- 0.22 nM in the oviduct and 0.065 +/- 0.015 nM respective 0.82 +/- 0.25 nM in the uterus (mean +/- SE) (n = 12). Sucrose density gradient centrifugation revealed in both tissues specific binding in the area sedimenting at 8 S whereas the slower sedimenting 4 S and 5 S peaks contained both specific and non-specific binding. The oviductal cytosol contained a similar proteolytical activity that has been described in human uterine and breast cancer tissue. The protease, which can be inhibited by diisopropylfluorophosphate, converts the 8 S receptor from into a 4.2 S proteolytic fragment. The KCl-extracted uterine and oviductal estrogen and progesterone receptors sedimented at 5.2 S in both low salt (0.01 M KCl) and high salt (0.4 M KCl) sucrose gradients. It is well known that the suppression of the estrogen receptor system by progesterone correlates with suppressed function in the oviduct but with increased growth and secretory activity in the uterus. In the light of the present data it is concluded, that the difference in the hormonal response in the two tissues is most likely not due to differences in the binding characteristics of the estrogen or progesterone receptors.

Adult↗

Uterus necrosis after radiochemotherapy in two patients with advanced cervical cancer.

BACKGROUND: Simultaneous platinum-based radiochemotherapy is the standard of care for patients with advanced or node-positive cancer of the uterine cervix. A large body of literature concerning therapy-related acute and late morbidity is available. Chemoradiation-associated necrosis of the uterus has not been described so far. CASE REPORT: Two patients are reported who were treated by combined chemoradiation between 2004 and 2005 for histologically confirmed cervical cancer following laparoscopic staging. Both patients were diagnosed with squamous cell cancer of the cervix FIGO stage IIB (T2b pN1 pM1 LYM G2) and FIGO IIIA (T3a pN1 M0 G2), respectively. External-beam radiotherapy was applied in a 3-D-planned four-field technique, covering pelvic lymph nodes and primary tumor. Patient #1 received additional paraaortic irradiation. Patient #2 underwent 5 x 5 Gy brachytherapy covering the tumor. Simultaneously, cisplatin was given to both patients. Following chemoradiation, both patients developed pelvic pain and an elevation of C-reactive protein (CRP) in the presence of a normal leukocyte count. Both patients underwent relaparoscopy, and necrosis of the uterus combined with partial necrosis of the bladder was diagnosed in patient #1. Patient #1 underwent total supralevatoric exenteration and patient #2 laparoscopically assisted hysterectomy with bilateral salpingo-oophorectomy. CONCLUSION: In patients with persisting or incident pelvic pain, questionable findings in imaging techniques and/or elevated inflammation parameters following completion of chemoradiation for cervical cancer, differential diagnosis should include radiogenic necrosis of the uterus and other pelvic organs. Laparoscopy is an ideal technique to exclude or confirm this diagnosis.

Adult↗

Physiological 18F-FDG uptake in the ovaries and uterus of healthy female volunteers.

PURPOSE: Good knowledge of physiological 18F-fluorodeoxglucose (18F-FDG) uptake in the healthy population is of great importance for the correct interpretation of 18F-FDG positron emission tomography (PET) images of pathological processes. The purpose of this study was to investigate the physiological 18F-FDG uptake in the ovaries and uterus of healthy female volunteers. METHODS: One hundred and 33 healthy females, 78 of whom were premenopausal (age 37.2+/-6.9 years) and 55 postmenopausal (age 55.0+/-2.7 years), were examined using whole-body 18F-FDG PET and pelvic magnetic resonance (MR) imaging. Focal 18F-FDG uptake in the ovaries and uterus was evaluated visually and using standardised uptake value (SUVs). Anatomical and morphological information was obtained from MR images. RESULTS: Distinct ovarian 18F-FDG uptake with an SUV of 3.9+/-0.7 was observed in 26 premenopausal women out of 32 examined during the late follicular to early luteal phase of the menstrual cycle. Eighteen of the 32 women also showed focal 18F-FDG uptake in the endometrium, with an SUV of 3.3+/-0.3. On the other hand, all nine women in the first 3 days of the menstrual cycle demonstrated intense 18F-FDG uptake in the endometrium, with an SUV of 4.6+/-1.0. No physiological 18F-FDG uptake was observed in the ovaries or uterus of any postmenopausal women. CONCLUSION: In women of reproductive age, 18F-FDG imaging should preferably be done within a week before or a few days after the menstrual flow phase to avoid any misinterpretation of pelvic 18F-FDG PET images.

Adult↗