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Endocrinology Jul 2003An 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,...
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.
Topics: Animals; Cytokines; Decidua; Embryo Implantation; Female; Gene Expression; In Situ Hybridization; Male; Mice; Mice, Inbred ICR; Pregnancy; Pseudopregnancy; RNA, Messenger; Ubiquitins; Up-Regulation; Uterus
PubMed: 12810567
DOI: 10.1210/en.2002-0031 -
Indian Journal of Physiology and... Jan 2003An understanding of the cellular and molecular basis of blastocyst implantation in the human remains as yet a black box, however, a few experimental models using human... (Review)
Review
An understanding of the cellular and molecular basis of blastocyst implantation in the human remains as yet a black box, however, a few experimental models using human and non-human primate species have addressed this issue. This review attempts to highlight, based on experimental evidence, the paradigm shifts in our understanding of the endocrine basis of embryo implantation, and the nature of dialogue between a growing, viable conceptus and maternal endometrial cells in the establishment of 'receptivity' for blastocyst implantation. It is being proposed that an existing inflammation paradigm of blastocyst implantation could be tested using an experimental model to compare tissue behaviour of conceptus associated endometrial cells with that occurring after induction of deciduoma in hormone-primed uterus. We anticipate that an in vitro model of blastocyst implantation using the experimental models of homotypic and heterotypic cultures of uterine epithelial and stromal fibroblast cells expressing structural and functional phenotypic responses as observed in situ may provide us with necessary clues about the temporal and spatial nature of cellular and molecular functions involving various endocrine and paracrine factors at implantation.
Topics: Animals; Blastocyst; Embryo Implantation; Embryo, Mammalian; Endometrium; Female; Humans; Models, Biological
PubMed: 12708120
DOI: No ID Found -
Indian Journal of Experimental Biology Aug 2002Enzymes adenosine deaminase (ADA) and 5-nucleotidase (5-'NT) are known to play active role in tissue/cell proliferation and differentiation. To validate this the two... (Comparative Study)
Comparative Study
Enzymes adenosine deaminase (ADA) and 5-nucleotidase (5-'NT) are known to play active role in tissue/cell proliferation and differentiation. To validate this the two enzymes were studied in artificially induced deciduoma of rat and hamster. The deciduoma was induced by traumatizing one of the uterine horns of progesterone primed animals. Non traumatized horn served as control. The animals were later maintained on progesterone, given alone (Gr.I) or conjointly with estrogen (Gr.II). The weight of each uterine horn was recorded to determine the formation of deciduoma. There was no marked difference between the weights of traumatized and control horn on day 2 post-traumatization (PT), but a progressive rise was noticed after this day in both species. The ADA activity however differed, day and species wise. While in the rats of Gr.I it was low in the traumatized horn on all the days, in the hamsters it was remarkably high from day 2 to 6 PT. In the rats of Gr.II also the activity though was low in the traumatized horn, but on day 2 and 4 only; on day 6 and 7 PT it increased markedly. In hamster, on the contrary, again the enzyme activity was remarkably high on all the three days. The 5'-NT activity, however, did not show any marked difference between the two horns under Gr.I and II in both species. It was rather high in the control horn of each group. The results suggest: (I) the progesterone alone though produces a significant rise in the uterine weight of traumatized horn in both species, the ADA activity increases only in hamster, (2) under the conjoint treatment also the enzyme activity remains high in hamster; and (3) the activity of enzyme 5'-NT does not alter during the deciduoma formation in both the species.
Topics: 5'-Nucleotidase; Adenosine Deaminase; Animals; Cricetinae; Deciduoma; Estrogen Antagonists; Estrogens; Female; Mesocricetus; Organ Size; Ovariectomy; Progesterone; Rats; Rats, Sprague-Dawley; Uterus
PubMed: 12597017
DOI: No ID Found -
Ultrastructural Pathology 2002Deciduoid mesothelioma was first described in young females and in the peritoneum, which led to the suggestion that deciduoid mesothelioma was a distinct subtype with... (Review)
Review
Deciduoid mesothelioma was first described in young females and in the peritoneum, which led to the suggestion that deciduoid mesothelioma was a distinct subtype with specific clinical and pathologic features. Later reports, however, have shown that this type of mesothelioma may also occur in elderly people and in the pleura. Cases reported in the literature so far are limited, and the disease is not well defined. The authors report the histologic, immunohistochemical, ultrastructural, and clinical findings of 5 cases of deciduoid mesothelioma, and review the literature reports. The results demonstrate that the presence of numerous cytoplasmic intermediate filaments, either dispersed or bundled, appear to be the likely ultrastructural basis for the deciduoid histologic appearance. Twenty-one cases of deciduoid mesothelioma were identified in the literature. Analyses of these 21 cases and the authors' 5 cases showed an age range of 13-78 years (median 53 years) and a slight female predominance (female to male ratio of 1.4:1). Fourteen of 26 cases (54%) occurred in the peritoneum. Seven of 20 patients (35%) had a documented history of asbestos exposure. Fifteen of 20 patients died, with a mean survival time of 7.33 months (range 1-21 months). Five of 20 patients were alive at a follow-up time of 8 months to 5 years. These findings suggest that the so-called deciduoid mesothelioma has some clinical and pathologic features that are dissimilar to mesothelioma in general. Whether it truly represents a pathogenetically distinct variant or merely an expansion of the morphologic spectrum awaits further studies.
Topics: Abdominal Neoplasms; Aged; Deciduoma; Female; Follow-Up Studies; Humans; Immunohistochemistry; Male; Mesothelioma; Middle Aged; Pleural Neoplasms
PubMed: 12537760
DOI: 10.1080/0913120290104647 -
Biology of Reproduction Oct 2002Ovarian hormonal signaling is essential for proper functioning of the uterus in the establishment of pregnancy. Previous studies have demonstrated that decidualization,...
Ovarian hormonal signaling is essential for proper functioning of the uterus in the establishment of pregnancy. Previous studies have demonstrated that decidualization, a stromal transformation that occurs in response to embryo implantation, can be elicited in the uterus of estrogen receptor alpha knockout (alphaERKO) mice in the absence of the estrogen dependence normally seen in wild-type (WT) mice for this response. While the alphaERKO stromal compartment demonstrated the necessary decidual response, embryo implantation is a process initiated in the epithelial layer, a uterine component that lacks estrogen responsiveness in the alphaERKO. To determine if the alphaERKO uterus would be competent for implantation, donor embryos were transferred into the uterine lumen of WT and alphaERKO females that had been ovariectomized and treated with exogenous estradiol and progesterone to mimic early pregnancy. No implantation occurred in the alphaERKO, while implantation sites containing live embryos were seen in similarly treated WT uteri, indicating that functional estrogen receptor alpha (ERalpha) is required for implantation. Previous observations of estrogen-independent decidualization in the alphaERKO prompted investigation of the mechanism leading to estrogen independence of this process. The disruption of progesterone receptor (PR), Hoxa10, Cox2, or LIF in transgenic mice results in the loss of decidualization response. Therefore, the expression of these genes was studied in WT and alphaERKO uteri by comparing expression following vehicle, progesterone alone (P), or estradiol priming followed by progesterone with nidatory estradiol (E+Pe) and by comparing expression following the above hormonal manipulations in addition to luminal infusion of oil used previously as decidualization-initiating stimulus. The whole-uterus level of PR and Hoxa10 mRNAs did not vary; however, the PR protein was induced in the stroma 24 h after oil infusion. Interestingly, in the WT, this induction was most apparent in samples receiving E+Pe, while in the alphaERKO samples, the induction occurred independent of any hormone priming. Cox2 protein and mRNA increased in both WT and alphaERKO samples 2 h after oil infusion in all three of the treatment groups. In the WT samples, Cox2 levels remained elevated 24 h after oil infusion only in the E+Pe treatment group; however, the elevated Cox2 was seen in samples taken 24 h after oil infusion in all three alphaERKO treatment groups. The alphaERKO uterine tissue appeared to sustain more extensive damage when examined 24 h after oil infusion. Severe trauma, such as crushing of the uterine tissue, has previously been shown to remove the requirement for nidatory estradiol for deciduomas to develop, indicating that the greater susceptibility of alphaERKO uterine tissue to damage from intraluminal oil infusion is contributing to decidualization in the absence of ERalpha. Leukemia inhibitory factor (LIF) mRNA was also induced following estradiol treatment in the WT, but also following oil infusion in WT samples that were not treated with estradiol. In contrast, estradiol does not induce LIF mRNA in the alphaERKO, but oil infusion leads to a robust increase in LIF in all alphaERKO sample groups. LIF binds and activates its membrane receptor, which initiates responses including the phosphorylation and nuclear translocation of Stat3 transcription factor. Thus, Stat3 phosphorylation was studied in WT and alphaERKO samples and found to be induced following oil infusion in all samples. Together, these and previous observations illustrate that estrogen is essential for epithelial proliferation and embryo implantation and that estrogen is dispensable for stromal decidualization in the alphaERKO, as the essential genes and signals required for the response are still induced.
Topics: Animals; Cyclooxygenase 2; DNA-Binding Proteins; Decidua; Embryo Implantation; Embryo Transfer; Estradiol; Estrogen Receptor alpha; Estrogens; Female; Gene Expression; Growth Inhibitors; Homeobox A10 Proteins; Homeodomain Proteins; Immunohistochemistry; Interleukin-6; Isoenzymes; Leukemia Inhibitory Factor; Lymphokines; Mice; Mice, Knockout; Phosphorylation; Pregnancy; Progesterone; Prostaglandin-Endoperoxide Synthases; Receptors, Estrogen; Receptors, Progesterone; STAT3 Transcription Factor; Sesame Oil; Signal Transduction; Trans-Activators; Uterus
PubMed: 12297545
DOI: 10.1095/biolreprod67.4.1268 -
American Journal of Reproductive... Apr 2002To study effects of interleukin-11 (IL-11) on blastocyst development and decidualization.
PROBLEM
To study effects of interleukin-11 (IL-11) on blastocyst development and decidualization.
METHOD OF STUDY
Rats, injected with buffer (C) or IL-11 [1 mg/kg/day = high dose (HD), 60 microg/kg/week = low dose (LD)-1, 30 microg/kg twice a week = low dose (LD)-2] were made pregnant or pseudopregnant to obtain blastocysts or deciduomata.
RESULTS
As compared with C, more LD-2 blastocysts hatched in culture, while hatching and attachment of HD blastocysts was decreased. Blastocysts from untreated rats in IL-11 supplemented medium (4 ng/mL) demonstrated increased hatching and attachment. The weight of the decidualized uterus in HD and LD-2 pseudopregnant rats was reduced as compared with C and LD- 1. On deciduomata sections from IL-11 treated rats, the area inside the uterine muscle layer was reduced, and mitotic over pycnotic indices were increased in the anti-mesometrial area and decreased in the mesometrial area.
CONCLUSIONS
Low doses of IL-11 improve hatching and attachment of blastocysts, but both high and low doses impair decidualization.
Topics: Animals; Blastocyst; Decidua; Deciduoma; Desmin; Embryo Implantation; Female; Interleukin-11; Mitosis; Pregnancy; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar
PubMed: 12069390
DOI: 10.1034/j.1600-0897.2002.01070.x -
International Journal of Hygiene and... Feb 2002The results of the study demonstrate that the weak estrogenic action of bisphenol A (a daily subcutaneous dose of 200 mg/kg on 4 consecutive days, administered before or...
The results of the study demonstrate that the weak estrogenic action of bisphenol A (a daily subcutaneous dose of 200 mg/kg on 4 consecutive days, administered before or after decidual induction that occurs on day 4 of pseudopregnancy) on deciduoma growth in pseudopregnant Sprague-Dawley rats, was functionally associated with the hormonal status of the uterus. Whereas bisphenol A displayed uterotrophic action during the pre-decidual, estrogen related period, it inhibited decidual growth and progesterone secretion during the post-decidual, progesterone-dominated period. The estrogenic action of bisphenol A on uterine decidual growth was not correlated with the reduced levels of estrogen receptor binding sites and mRNA expression, nor the unchanged serum estradiol concentrations. BPA action appeared to be antagonized by progesterone.
Topics: Animals; Benzhydryl Compounds; Decidua; Estrogens, Non-Steroidal; Female; Phenols; Pseudopregnancy; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Uterus
PubMed: 11885360
DOI: 10.1078/1438-4639-00115 -
Reproductive Toxicology (Elmsford, N.Y.) 2001Butadiene diepoxide (BDE), a reactive metabolite of 1,3-butadiene that is an important industrial chemical used in synthetic rubber production causes a dose-dependent...
Butadiene diepoxide (BDE), a reactive metabolite of 1,3-butadiene that is an important industrial chemical used in synthetic rubber production causes a dose-dependent inhibition of deciduoma development in pseudopregnant Sprague-Dawley rats. This study used 4 daily i.p. BDE doses of 0.20, 0.25, 0.30, 0.35, or 0.40 to characterize mechanisms that may be responsible for the antideciduoma effect. Pseudopregnant rats were treated either before (pseudopregnancy [PPG] days 1-4) or after (PPG days 5-9) deciduoma induction by endometrial trauma with a blunt needle. Animals were killed on PPG day 9 and evaluated for serum progesterone and endometrial protein and DNA. RT-PCR was used to measure message for estrogen receptor (ER) alpha and pituitary adenylate cyclase-activating polypeptide (PACAP). Substrate zymography and Western blotting were used respectively to measure matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase. The antideciduoma effects of BDE were associated with decreases in endometrial weight, protein, and DNA, with decreases in serum progesterone, and with decreases in PACAP message and MMP-9. A reduction in NOS was identified at the highest dose of BDE. Message for estrogen receptor (ER) alpha was not affected at any dose. We conclude that the reduction in decidual proliferation was direct and appeared to be associated with either 1) a decrease in the effectiveness of the deciduogenic stimulation and/or a weakened endometrial sensitivity to the stimulus; or 2) an effect on deciduoma development. Molecular mechanisms that apparently contributed to BDE inhibition of decidual metabolism included the synthesis of protein and DNA involved in decidual growth, the synthesis and activation of a matrix metalloproteinase for degradation of the extracellular matrix that is essential for tissue remodeling during deciduoma development, and the nitric oxide/nitric oxide synthase and pituitary adenylate cyclase-activating peptide systems that are involved in promoting vasodilation and increased vascular permeability to enhance the availability of substrates for maximal deciduoma growth. The ovotoxicity of BDE, which has previously been established, may indirectly affect decidual proliferation by reducing progesterone, the preeminent endocrine regulator of deciduoma development. The findings also suggest that BDE may possess no estrogenic action since it was associated with endometrial weight loss and unaltered levels of the estrogen receptor alpha mRNA expression.
Topics: Animals; Butadienes; Cell Division; DNA; DNA Primers; Decidua; Dose-Response Relationship, Drug; Estrogen Receptor alpha; Female; Injections, Intraperitoneal; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Neuropeptides; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Organ Size; Pituitary Adenylate Cyclase-Activating Polypeptide; Pregnancy; Progesterone; Proteins; Pseudopregnancy; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 11390169
DOI: 10.1016/s0890-6238(01)00121-6 -
Comparative Biochemistry and... May 2001Pituitary adenylate cyclase-activating peptide (PACAP), a novel compound with vasoactive intestinal polypeptide-like activity, was recently shown to be localized in the... (Comparative Study)
Comparative Study
Temporal relationships among uterine pituitary adenylate cyclase-activating polypeptide, decidual prolactin-related protein and progesterone receptor mRNAs expressions during decidualization and gestation in rats.
Pituitary adenylate cyclase-activating peptide (PACAP), a novel compound with vasoactive intestinal polypeptide-like activity, was recently shown to be localized in the neuronal endings of the human uterus. The purpose of the present study was to assess the functional presence of PACAP mRNA in the decidual endometrium and its relationship to the expression levels of decidual prolactin-related protein (dPRP) and the progesterone receptor mRNAs during decidualization and pregnancy in Sprague-Dawley rats. PACAP was constitutively and temporally expressed in the decidual endometrium and gravid uterus. The time-dependent correlated expression levels of PACAP, dPRP and the progesterone receptor were induced by the neurogenic reproductive signals, i.e. the vagino-cervical/deciduogenic stimuli of decidualization and by the normal equivalent stimuli of mating/blastocyst implantation of gestation. Correlation among the mRNA expression levels of PACAP, dPRP and the progesterone receptor and the coordinated inhibitory actions of the anti-progesterone (RU-486) suggest that there is also correlated time-dependent steroid regulation of the mRNA levels of PACAP, dPRP and the progesterone receptor in the decidual and pregnant uteri. One possible functional meaning for the time-related localization of endometrial/uterine PACAP could be to facilitate endometrial blood flow and increase the availability of metabolic substrates to the developing deciduoma or embryo. The study demonstrates the potential importance of PACAP expression in the regulation of the maternal feto-placental component and suggests a prominent reproductive role for the neuropeptide in mammalian pregnancy.
Topics: Animals; DNA Primers; Decidua; Endometrium; Female; Glycoproteins; Hormone Antagonists; Male; Mifepristone; Neurotransmitter Agents; Pregnancy; Pregnancy Proteins; Pregnancy-Associated alpha 2-Macroglobulins; Prolactin; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptors, Progesterone; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Uterus
PubMed: 11369298
DOI: 10.1016/s1532-0456(01)00177-6 -
Cells, Tissues, Organs 2001Decidual cells are endometrial fibroblasts that redifferentiate during pregnancy in several species of mammals. In this work, we describe a subpopulation of resident...
Decidual cells are endometrial fibroblasts that redifferentiate during pregnancy in several species of mammals. In this work, we describe a subpopulation of resident decidual cells in the mouse endometrium that are joined by intercellular junctions and have cytoplasmic granules. Decidualization was induced in pseudopregnant mice on the 4th day of pseudopregnancy by injection of 30 microl of arachis oil into the uterine lumen. The uteri were collected on day 8 of pseudopregnancy (at 4 p.m., 8 p.m. and 11 p.m.) and on day 9 (at 8 a.m.). The tissues were fixed for light and electron microscopy. During day 8 of pseudopregnancy, granulated cells were present at the antimesometrial pole of the endometrium; they were concentrated at the periphery of the antimesometrial decidua and disappeared on day 9 of pseudopregnancy. The cytoplasm of the granulated decidual cells had acidophilic granules that stained also with periodic acid-Schiff (PAS). These granules stained with anti-rat prolactin antibody in both light and electron microscope immunocytochemical preparations. Vacuoles of various sizes were always present in the granulated cells. A PAS-positive and prolactin-stained material was often deposited at the periphery of the vacuoles. Our results indicate that the granulated decidual cells are the source of decidual prolactin which accumulates in cytoplasmic granules. These granulated cells therefore form a transient gland in the mouse antimesometrial endometrium (granulated decidual gland).
Topics: Animals; Cytoplasmic Granules; Decidua; Female; Immunohistochemistry; Mice; Microscopy, Electron; Pregnancy; Prolactin
PubMed: 11275692
DOI: 10.1159/000047842