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  1. Home
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Browsing by Subject "Uterus"

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    A morphological study on the reproductive organs as a possible cause of developmental abnormalities in diabetic NOD mice
    (Murcia : F. Hernández, 1989) Tatewaki, Reiko; Otani, Hiroki; Tanaka, Osamu; Kitada, Jin-ichi
    The reproductive organs in non-obese diabetic (NOD) mice were histopathologically studied, in order to elucidate the relationships between developmental abnormalities, such as diminkhed rates of implantation and viable embryos, and structural changes in the reproductive organs. NOD mice with (NOD-DM) and without (NOD-N) diabetes mellitus and ICR mice were compared. The severity of histopathological changes in the pancreas and in the liver were used as parameters which indicated the severity of diabetes itself and of the secondary metabolic disorder. NOD-DM mice exhibited uterine weight loss, accumulation of lipids in luminal and glandular epithelium, atrophies of the endometrium and myometrium and a decrease in the number of muscle cell layers. They also showed a high concentration of lipid droplets in ovarian granulosa cells, atretic follicles and atrophy and lack of lipids in ovarian stroma cells. The severity of these structural changes in the reproductive organs corresponded to those of the changes in the pancreas and the liver. The structural alterations in the ovary suggested disorder in oocyte maturation. The structural changes in the uterus appeared to be related to the decrease in the ratios of implantation and of viable embryos at post-implantation stage. The present studies suggest that the impaired structural environment together with the metabolic environment caused the abnormal development seen, for example. in the oocyte maturation, and at the implantation and post-implantation stage of diabetic mice. It also caused alterations in their hormonal environment
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    Acute and chronic estrogen supplementation decreases uterine sympathetic innervation in ovariectomized adult virgin rats
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Zoubina, E. V.; Mize, A. L.; Alper, R. H.; Smith, P. G.
    Uterine innervation undergoes substantial reorganization associated with changes in reproductive status. Nerves innervating the uterus are decreased in pregnancy and puberty, and even the normal rodent estrous cycle is characterized by fluctuations in numbers of myometrial nerve fibers. During the follicular (proestrus/estrous) phase of the estrous cycle, intact nerves are rapidly depleted and then return over the next 2-3 days in the luteal (metestrus/diestrus) phase. We hypothesize that uterine nerve depletion is initiated by increased circulating estrogen in the follicular phase . However, studies have not shown whether estrogen can reduce uterine innervation and, if so, whether the time course is compatible with the rapid changes observed in the estrous cycle. These questions were addressed in the present study. Mature ovariectomized virgin rats received 17-B-estradiol as a single injection (10 .ug/kg s.c.) or chronically from timed-release pellets (0.1 .ug/pellet for 3 weeks sustained release). Total (protein gene-product 9.S-immunoreactive) and sympathetic (dopamine B-hydroxylase-immunoreactive) uterine innervation was assessed quantitatively. Both total and sympathetic innervation was abundant in uterine longitudinal smooth muscle of ovariectomized rats. However, following acute or chronic estrogen administration, total and sympathetic fiber numbers were markedly decreased. This was not due to altered uterine size, as reductions persisted after correcting for size differences. Our results indicate that sympathetic nerves are lost from uterine smooth muscle after estradiol treatment in a manner similar to that seen in the intact animal during estrus and pregnancy. This suggests that the rise in estradiol prior to estrus is sufficient to deplete uterine sympathetic innervation.
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    Aging and uterine serous carcinoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Hachisuga, Toru
    Uterine serous carcinoma (USC) is closely associated with advanced age in patients. The p53 signature (p53S) is considered the earliest indication for the presence of carcinogenesis of USC. Based on our previous studies, the presence of p53Ss have almost always been found in elderly women and are suspected of being responsible for the imbalance between the proliferation and apoptosis of endometrial epithelial cells with advanced age. We have summarized the current state of knowledge regarding the association between age and cancer and propose an age-related type of endometrial cancer instead of Type II estrogenindependent endometrial cancer.
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    Assessment of morphological changes and steroid receptors in the uteri of postmenopausal women
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Teresiński, Leszek; Sipak, Olimpia; Rył, Aleksandra; Masiuk, Marek; Rotter, Iwona; Ratajczak, Weronika; Łazowska, Malwina; Słomczyńska, Maria; Marchlewicz, Mariola; Karakiewicz, Beata; Kram, Andrzej; Laszczyńska, Maria
    Introduction. The morphology of the endometrium constantly changes in the reproductive period, depending on the levels of ovarian steroid hormones, and undergoes atrophic changes during menopause as a result of their insufficiency. The purpose of this study was to analyze morphological and morphometric changes in the mucous and muscle layers of the uterine wall in postmenopausal women, and to assess localization and number of cells showing the expression of steroid hormone receptors, namely estrogen receptor α (ER-α), progesterone receptor (PR), and androgen receptor (AR) in glandular epithelial cells and smooth muscle cells in particular groups of women. Material and methods. The study material consisted of uterine specimens sectioned across the full thickness of the uterine wall, and embedded in 164 paraffin blocks. The specimens came from women without menopausal hormone therapy (MHT) operated due to reproductive organ prolapse or uterine myomas. The material was divided into four groups depending on the time interval from menopause to surgery: group I - from 1 to 5 years after menopause, group II - from 6 to 10 years after menopause, group III - more than 11 years after menopause, and group IV - women over 70 years of age. The sections were stained by standard HE, Masson’s trichrome, and immunohistochemical methods (ERα, PR, AR). Quantitative assessment of the results was based on computer image analysis. Results. Analysis of morphological changes in the endometrium and myometrium revealed the presence of increasing regressive changes, such as various types of atrophy, fibrosis, and calcification, augmented over time from the last menstruation. Furthermore, endometrial polyps, foci of endometriosis, and leiomyomas were observed. Based on the results of morphometric measurements, a constant decrease in the endometrial and myometrial thickness was noticed in the studied groups (I-IV). Significant differences between the groups were observed in the number of ER-α positive cells in the myometrium, but not in the endometrial glandular epithelium. Statistically significant differences in the number of AR positive cells were detected in the endometrial epithelium and in the uterine muscle. The analysis the number of PR positive cells demonstrated differences between the groups in the endometrial stroma and the myometrium. Conclusion. The uterus of postmenopausal woman undergo major morphological changes (mainly atrophic lesions in the endometrium and myometrium), leading to a decline in their morphometric parameters over time from the last menstruation. Localization and number of cells showing the expression of steroid receptors: ER-α, PR, and AR in the uterus of postmenopausal women, depending on the time interval from the last menstruation.
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    Detection of transforming growth factor-a and epidermal growth factor receptor mRNA and immunohistochemical localization of the corresponding proteins in the canine uterus during the estrous cycle
    (Murcia : F. Hernández, 2005) Tamada, H.; Tominaga, M.; Kida, K.; Kawate, N.; Inaba, T.; Matsuyama, S.; Sawada, T.
    Uterine expression of the epidermal growth factor (EGF) family of growth factors has not been studied in the dog. The present study looks at the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-a (TGF-a), which is the potent EGF family member, and for EGF receptor (EGF-R) in the canine uterus during the estrous cycle. The reverse transcriptase-polymerase chain reaction together with sequencing of the products confirmed the presence of their mRNA transcripts in the endometrium throughout the estrous cycle. Immunohistochemical analysis found clear positive staining for TGF-a and EGF-R in the luminal and glandular epithelia at proestrus and estrus. Immunoreactivity decreased at the early stage of diestrus. In the mid stage of diestrus, clear staining for TGF-a was again found in the glands of the luminal region, and staining for EGF-R was observed in all glands. Very little staining was seen at anestrus for either TGF-a or EGF-R. These results suggest that TGF-a expressed in the uterus may be involved in regulating growth, differentiation and regression in the endometrial epithelial cells during the estrous cycle in the dog.
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    Differential expression of prostaglandin E receptor subtype EP2 in rat uterus during early pregnancy
    (Murcia : F. Hernández, 2005) Shi, J.J.; Ma, X.H.; Diao, H.L.; Ni, H.; Xu, L.B.; Zhu, H.; Yang, Z.M.
    PGE2 is essential for mammalian female reproduction. This study was to examine the expression of EP2 gene in the rat uterus during early pregnancy, delayed implantation and artificial decidualization by in situ hybridization and immunohistochemistry. There was no detectable EP2 mRNA expression in the uterus from days 1 to 4 of pregnancy (day 1 = day of vaginal sperm). A low level of EP2 immunostaining was observed in the luminal and glandular epithelium from days 1 to 4 of pregnancy. Both EP2 mRNA and protein expression were highly detected in the luminal epithelium at implantation sites on day 6 of pregnancy. EP2 expression decreased from day 7 of pregnancy and was undetectable on days 8 and 9 of pregnancy. After delayed implantation was terminated by estrogen treatment and the embryo implanted, both EP2 mRNA and protein expression were strongly observed in the luminal epithelium at the implantation site. There was no detectable EP2 expression in both control and decidualized uteri. In conclusion, these data suggest that EP2 expression at implantation site may play an important role during embryo implantation in rats.
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    Effects of neonatal diethylstilbestrol exposure on c-fos and c-jun protooncogene expression in the mouse uterus
    (Murcia : F. Hernández, 2001) Yamashita, S.; Takayanagi, A.; Shimizu, N.
    Quantitative and cell-type-specific expression of c-fos and c-jun genes after 17B-estradiol (E2) stimulation, was investigated in the uteri of neonatally diethylstilbestrol (DES)-exposed and ovariectomized adult mice (neoDES-mice), employing Northern blot analysis, immunohistochemistry and in situ hybridization. The c-fos mRNA level before E2 injection (at baseline) was about 2.2-fold higher in neoDES-mice than in vehicle-treated control mice. In controls, E2 treatment transiently increased c-fos mRNA levels, showing a peak value (15.8-fold relative to the baseline) after 2 hours. In neoDES-mice, c-fos mRNA level reached a peak showing a 2.1-fold increase compared with its baseline value 1 hour after E2 injection. Immunohistochemistry and in situ hybridization revealed that c-fos protein (Fos) and mRNA are induced in the epithelium and vascular endothelium in both groups. Most uterine epithelia of neoDES-mice revealed low sensitivity to the c-fos expression after E2 administration compared with those of vehicle-treated controls, whereas few epithelia showed high c-fos mRNA expression even at baseline. The c-jun mRNA concentration in the neoDES-mice uteri at baseline was 70% of that in vehicle-treated controls. At 1 hour after E2 injection, c-jun mRNA levels increased 1.8-fold in controls and 1.3-fold in the neoDES-mice relative to each baseline value. There were no significant differences in the distribution pattern of cjun protein (Jun) and mRNA in the uteri of either groups; E2 stimulated c-jun mRNA expression in the stromal and myometrial cells but suppressed it in the epithelial cells, whereas intensity of c-jun immunostaining increased in the three cell types. The permanent changes in the expression of estrogen-regulated protooncogenes, c-fos and c-jun genes, by neonatal DES exposure may be responsible for the wide range of abnormalities in the genital tract of mature animals.
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    Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol
    (Murcia : F. Hernández, 2003) Yamashita, S.; Takayanagi, A.; Shimizu, N.
    We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17ß-estradiol (E2) stimulation in the uteri of immature 3-week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the ontogenic expression of these genes in the uteri of DES-mice using immunohistochemistry and in situ hybridization. A single E2 injection induced the transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle-treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2 injection and that of protein expression was 2 to 3 hours after the injection. The expression of c-fos mRNA and protein after E2 stimulation was lower in the DES-mice than in the control animals. There were no significant differences in the c-jun expression patterns in both experimental groups before and after the E2 injection. The E2 injection transiently down-regulated the c-jun expression in the epithelium and up-regulated it in the stroma and myometrium. The uterine epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and 10, compared with those of controls. Neonatal DES treatment reduced c-Jun immuoreactivity in the uterine epithelium on days 4 and 10, and increased the reaction in the stroma on day 4. These results suggested that the neonatal DES treatment induces permanent changes in the c-fos expression pattern independent of the postpuberal secretion of ovarian steroids. The changes in the expression of c-fos and c-jun protooncogenes, particularly during postnatal development, are likely to play important roles in the production of uterine abnormalities in the DES-mice.
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    The immune microenvironment of cancer of the uterine cervix
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Mastrogeorgiou, Michail; Chatzikalil, Elena; Theocharis, Stamatios; Papoudou-Bai, Alexandra; Péoc’h, Michel; Mobarki, Mousa; Karpathiou, Georgia
    While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival.
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    The role of TNFα/p53 pathway in endometrial cancer mouse model administered with apple seed extract
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Kim, Sang Hwan
    y. Recent studies regarding the ability to relieve and reconstitute the endometrium in the treatment of endometrial cancer are limited. In this study, to analyze endometrial cancer, early endometrial cancer was induced by injecting a colon cancer cell line into the lower abdominal cavity of mice. Subsequently, the apple seed extract was administered orally to determine if the extract could affect the endometrial cancer. Administration of apple seed extract to the endometrial cancer model confirmed that the apoptosis suppressing mechanism was downregulated concurrently with the reduced expression of NF-κB. In contrast, the TNFα/p53 pathway upregulated the apoptosis. A number of clinical inferences could be derived from the results of this study; moreover, the administration of apple seed extract in a cancer metastasis model has not been reported in earlier toxicity induction studies. The results of this study indicated that the apple seed extract partially enhances apoptosis and the immune function related factors in endometrial cells. By improving tissue remodeling, the extract may help to restore the endometrium.
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    Uterine Müllerian adenosarcoma with histiocytic (xanthomatous) mesenchymal component
    (Murcia : F. Hernández, 1991) Reymundo García, C.; Toro Rojas, M.; Morales Jiménez, G.; López Beltrán, A.; Nogales Ortíz, F.
    We present an endometrial Müllerian adenosarcoma in which the sarcomatous component showed prominent nests of foamy cells that accounted for 50% of the neoplastic mesenchyma. Such foamy cells showed occasional cytological atypias and immunohistochemical features of histiocytic (macrophagic differentiation in the absence of changes that could substantiate the presence of an inflammatory infiltration of foamy histiocytes. These facts suggest histiocytic differentiation from neoplastic mesenchymal cells. Such differentiation has been reported in association with malignant mixed mesodermal tumor, but not in Müllerian adenosarcoma

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