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Methods and Findings in Experimental... Sep 2008Acanthus montanus T. Anderson (Acanthaceae) possesses several medicinal properties; it is used in Cameroon as a folk medicine to treat pain, inflammation and threatened...
Acanthus montanus T. Anderson (Acanthaceae) possesses several medicinal properties; it is used in Cameroon as a folk medicine to treat pain, inflammation and threatened abortion. The aim of this study was to determine the effect of A. montanus aqueous extract on the estrous cycle pre- and postimplantation in rats and its mechanism of action. The estrous cycles of Wistar rats were monitored before, during and after oral administration of distilled water (control) or aqueous extract (62.5, 125, 250, 500, 1000 mg/kg/day). Furthermore, pregnant rats received the above doses of aqueous extract on days 1-6 (preimplantation) or 6-15 (postimplantation) of gestation and were sacrificed on day 8 or 20 of pregnancy, respectively. Moreover, aqueous extract (500 and 1000 mg/kg/day) was given to ovariectomized rats in the presence or absence of exogenously administered estrogen and/or progesterone and uterine weight and deciduoma count were evaluated. The extract, irrespective of dose, reversibly prolonged the metestrous and occasionally the diestrous stages of the estrous cycle. The extract did not alter the uterine wet weight or deciduoma count, suggesting a lack of estrogenic and progestational effects. At 1000 mg/kg/day, the extract caused appreciable preimplantation losses of 36.8 +/- 6.5% (P < 0.05), while none of the doses caused postimplantation losses. The extract also caused delayed fetal growth.
Topics: Acanthaceae; Animals; Blastocyst; Cameroon; Contraceptive Agents; Deciduoma; Diestrus; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Embryo Implantation; Embryo Loss; Estradiol; Female; Medicine, African Traditional; Metestrus; Ovariectomy; Plant Extracts; Pregnancy; Rats; Rats, Wistar; Teratogens; Uterus; Water
PubMed: 18985180
DOI: 10.1358/mf.2008.30.7.1254614 -
Theriogenology Aug 2008Cystic lesions in the uteri of bitches and queens arise from the uterine serosa, myometrium, or endometrium and include: serosal inclusion cysts, adenomyosis,... (Review)
Review
Cystic lesions in the uteri of bitches and queens arise from the uterine serosa, myometrium, or endometrium and include: serosal inclusion cysts, adenomyosis, endometrial polyps, cystic remnants of mesonephric ducts, and cysts associated with endometrial hyperplasia (both cystic glands and "pseudo-placentational" hyperplasia). Of these, "cystic endometrial hyperplasia (CEH)" is the most common and is frequently associated with pyometra. A second form of endometrial hyperplasia occurs in the bitch; although it was first described over 100 y ago, it is not widely recognized by clinicians or diagnostic pathologists. In this form, the endometrium proliferates in a highly organized manner, remodeling the uterine lining to closely resemble the histology of the endometrium at placentation sites in normal pregnancy. Although this lesion is very different from CEH, it is quite easy to induce in dogs during the luteal phase of their cycles and has been perhaps inappropriately proposed as modeling CEH. This lesion has been referred variously as "deciduoma", endometrial hyperplasia in pseudocyesis, and "maternal placental-like endometrial hyperplasia". An alternative name is suggested that is descriptive and draws attention to the difference between this lesion and CEH; the term pseudo-placentational endometrial hyperplasia (PEH) is proposed. The histopathology and pathogenesis of CEH and PEH are discussed. The objectives of this paper are to review the pathophysiology of cystic lesions of canine uterus, to demonstrate these using subgross photomicrographs taken from natural cases, and to present key diagnostic features of each.
Topics: Aging; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Endometrial Hyperplasia; Female
PubMed: 18550158
DOI: 10.1016/j.theriogenology.2008.04.041 -
Reproduction (Cambridge, England) Jun 2007Within the mouse endometrium, secreted phosphoprotein 1 (SPP1) gene expression is mainly expressed in the luminal epithelium and some macrophages around the onset of... (Comparative Study)
Comparative Study
The conceptus increases secreted phosphoprotein 1 gene expression in the mouse uterus during the progression of decidualization mainly due to its effects on uterine natural killer cells.
Within the mouse endometrium, secreted phosphoprotein 1 (SPP1) gene expression is mainly expressed in the luminal epithelium and some macrophages around the onset of implantation. However, during the progression of decidualization, it is expressed mainly in the mesometrial decidua. To date, the precise cell types responsible for the expression in the mesometrial decidua has not been absolutely identified. The goal of the present study was to assess the expression of SPP1 in uteri of pregnant mice (decidua) during the progression of decidualization and compared it with those undergoing artificially induced decidualization (deciduoma). Significantly (P<0.05) greater steady-state levels of SPP1 mRNA were seen in the decidua when compared with deciduoma. Further, in the decidua, the majority of the SPP1 protein was localized within a subpopulation of granulated uterine natural killer (uNK) cells but not co-localized to their granules. However, in addition to being localized to uNK cells, SPP1 protein was also detected in another cell type(s) that were not epidermal growth factor-like containing mucin-like hormone receptor-like sequence 1 protein-positive immune cells that are known to be present in the uterus at this time. Finally, decidual SPP1 expression dramatically decreased in uteri of interleukin-15-deficient mice that lack uNK cells. In conclusion, SPP1 expression is greater in the mouse decidua when compared with the deciduoma after the onset of implantation during the progression of decidualization. Finally, uNK cells were found to be the major source of SPP1 in the pregnant uterus during decidualization. SPP1 might play a key role in uNK killer cell functions in the uterus during decidualization.
Topics: Animals; Decidua; Deciduoma; Female; Gene Expression; Gene Expression Regulation, Developmental; Interleukin-15; Killer Cells, Natural; Mice; Mice, Inbred Strains; Mice, Knockout; Osteopontin; RNA, Messenger; Uterus
PubMed: 17636175
DOI: 10.1530/REP-07-0085 -
Veterinary Pathology Jul 2007The ovaries and uterus were collected after ovariohysterectomy from a 16-month-old Labrador bitch in diestrus that never mated. Discrete swellings were found in the...
The ovaries and uterus were collected after ovariohysterectomy from a 16-month-old Labrador bitch in diestrus that never mated. Discrete swellings were found in the uterine horns, with the macroscopic appearance of normal early pregnancy. At histologic examination, the endometrium, devoid of any conceptus and chorion, showed a marked proliferation, on the basis of which a diagnosis of deciduoma was made. A remarkable population of stromal eosinophilic granular lymphocytes was present, especially in the axis of the endometrial folds. Periodic acid-Schiff and Dolichos biflorus-lectin histochemical reaction and a panel of 10 immunohistochemical markers were used to characterize eosinophilic granular cells. Our findings allowed us to compare these granular cells with the granulated decidual cells, whose presence was until now described only in primates, rodents, or a few other epitheliochorial species. On the basis of our results, the importance of eosinophilic granular cells in a decidualization process is hypothesized to occur also in the bitch.
Topics: Animals; Deciduoma; Dog Diseases; Dogs; Female; Immunohistochemistry; Lymphocytes
PubMed: 17606515
DOI: 10.1354/vp.44-4-521 -
Endocrinology Sep 2007Transcriptomal changes in the uterine endometrium induced in response to the implanting embryo remain largely unknown. In this study, using Affymetrix mRNA expression...
Transcriptomal changes in the uterine endometrium induced in response to the implanting embryo remain largely unknown. In this study, using Affymetrix mRNA expression microarray analysis, we identified genes differentially expressed in the murine endometrium in the presence or absence of the embryo. Compared with the pseudopregnant deciduoma induced by a mechanical stimulus in the absence of an embryo, approximately 1500 genes (753 up-regulated, 686 down-regulated; P < 0.05) were differentially expressed by at least 1.2-fold in the uterine decidua of pregnancy. Most of these genes fall into five major biological categories that include binding (45%), catalysis (24%), signal transduction (10%), transcriptional regulators (5%), and transporters (5%). This strong, embryo-induced transcriptomal impact represented approximately 10% of the total number of genes expressed in the decidualizing endometrium. Validation studies with mRNA and protein confirmed existence of the phylogenetically conserved, embryo-regulated genes involved in the following: 1) hemostasis and inflammation; 2) interferon signaling; 3) tissue growth and remodeling; and 4) natural killer cell function. Interestingly, whereas expression of many growth factors and their cognate receptors were not different between the decidual and deciduomal endometria, a number of proteases that degrade growth factors were selectively up-regulated in the decidual tissue. Increased expression of IGF and activin A neutralizing factors (i.e. HtrA1 and Fstl3) correlated with reduced stromal cell mitosis, tissue growth, and mitogenic signaling in the decidual endometrium. These results support the hypothesis that the implanting murine embryo takes a proactive role in modulating endometrial gene expression and development during early gestation.
Topics: Animals; DNA Primers; Decidua; Embryonic Development; Endometrium; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Mice; Mice, Inbred ICR; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Pregnancy
PubMed: 17510242
DOI: 10.1210/en.2007-0268 -
Biology of Reproduction Apr 2007Uterine natural killer (uNK) cells are the most abundant lymphocytes in the uterus during early pregnancy and play a role in spiral arteriole modifications. In the...
Uterine natural killer (uNK) cells are the most abundant lymphocytes in the uterus during early pregnancy and play a role in spiral arteriole modifications. In the present study, we investigated whether uNK cell populations differed between mouse decidua and deciduoma. Histochemical staining using the Dolichos biflorus agglutinin (DBA) lectin was used to identify uNK cells and classify their stages of maturation. We found differences in the pattern of localization and density of uNK cells between the decidua and deciduoma at Days 2-4 after the onset of decidualization. The cells were more distributed and the densities were significantly greater in the mesometrial region of the decidua than in the deciduoma. Using double-labeling for DBA lectin binding and bromodeoxyuridine incorporation, we found that the higher number of uNK cells in the decidua was not due to an increase in uNK cell proliferation. Western blot analyses revealed that the increase in uNK cell number was accompanied by significant increases in the levels of interferon gamma (IFNG) and prointerleukin 18 when a conceptus was present. Vascular morphometry revealed that modifications of the spiral arterioles occurred in the mesometrial decidua but not in the deciduoma, which could be attributed to the differences observed in uNK cell number and IFNG production. The present study demonstrates that differences exist in uNK cell populations between the decidua and deciduoma, providing evidence that the conceptus generates signals that regulate uNK cell number and function in the uterus during implantation.
Topics: Animals; Cell Count; Cell Differentiation; Cell Proliferation; Embryo Implantation; Embryo, Mammalian; Female; Interferon-gamma; Interleukin-15; Interleukin-18; Killer Cells, Natural; Mice; Mice, Inbred Strains; Models, Biological; Pregnancy; Pregnancy, Animal; Uterus
PubMed: 17151350
DOI: 10.1095/biolreprod.106.056630 -
The National Medical Journal of India 2006[corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the...
BACKGROUND
[corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus.
METHODS
Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity.
RESULTS
The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone.
CONCLUSION
The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.
Topics: Abortifacient Agents, Steroidal; Animals; Deciduoma; Estrogen Receptor Modulators; Estrogens; Female; Mifepristone; Ovariectomy; Progesterone; Rats; Receptors, Estrogen; Receptors, Progesterone; Uterus
PubMed: 16756191
DOI: No ID Found -
Veterinary Pathology May 2006Deciduosarcoma is a rare, hormonally dependent neoplasm with features of malignancy, previously reported only in rabbits enrolled in chronic toxicology studies involving...
Deciduosarcoma is a rare, hormonally dependent neoplasm with features of malignancy, previously reported only in rabbits enrolled in chronic toxicology studies involving estrogens with or without progestins. An exploratory laparotomy was performed on a 6-year-old pet Dutch dwarf rabbit following palpation of a 6-cm-diameter abdominal mass. Grossly, the mass was fleshy and nodular, adhered to but not appearing to originate from the small intestine, with a smaller mass of similar appearance involving the uterus, and an effaced mesenteric lymph node. Histologically, the mass was characterized by spindloid cells and large epithelioid cells with abundant pale eosinophilic vacuolated cytoplasm and an infiltrative pattern of growth. Giant cells with large, bizarre, hyperchromatic nuclei were common. Cells were positive by immunohistochemistry for vimentin and progesterone and estrogen receptors and negative for pancytokeratin (AE1/AE3), cytokeratin 18, desmin, alpha-smooth muscle actin (SMA), and CD10. Based on histologic and immunohistochemical findings, a diagnosis of deciduosarcoma was made.
Topics: Animal Diseases; Animals; Deciduoma; Female; Rabbits; Sarcoma; Uterine Neoplasms
PubMed: 16672589
DOI: 10.1354/vp.43-3-377 -
Developmental Biology Jun 2006The uterus undergoes a series of dramatic changes in response to an implanting conceptus that, in some mammalian species, includes differentiation of the endometrial...
The uterus undergoes a series of dramatic changes in response to an implanting conceptus that, in some mammalian species, includes differentiation of the endometrial stroma into decidual tissue. This process, called decidualization, can be induced artificially in rodents indicating that the conceptus may not be essential for a proper maternal response in early pregnancy. In order to test this hypothesis, we determined if and how the conceptus affects uterine gene expression. We identified 5 genes (Angpt1, Angpt2, Dtprp, G1p2 and Prlpa) whose steady-state levels in the uterus undergoing decidualization depends on the presence of a conceptus. In situ hybridization revealed region-specific effects which suggested that various components of the conceptus and more than one signal from the conceptus are likely responsible for altering decidual cell function. Using cell culture models we found that trophoblast giant cells secrete a type I interferon-like molecule which can induce G1p2 expression in endometrial stromal cells. Finally, decidual Prlpa expression was reduced in the uterus adjacent to Hand1- and Ets2-deficient embryos, suggesting that normal trophoblast giant cells in the placenta are required for the conceptus-dependent effects on Prlpa expression in the mesometrial decidua. Overall, these results provide support for the hypothesis that molecular signals from the mouse conceptus have local effects on uterine gene expression during decidualization.
Topics: Angiopoietin-Like Protein 2; Angiopoietin-like Proteins; Angiopoietins; Animals; Basic Helix-Loop-Helix Transcription Factors; Blood Proteins; Cells, Cultured; Cytokines; Decidua; Deciduoma; Embryo, Mammalian; Endometrium; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Interferons; Male; Mice; Oligonucleotide Array Sequence Analysis; Paracrine Communication; Pregnancy; Pregnancy Proteins; Prolactin; Proto-Oncogene Protein c-ets-2; Ubiquitins
PubMed: 16616120
DOI: 10.1016/j.ydbio.2006.03.006 -
Cell and Tissue Research Jul 2006Uterine receptivity is prerequisite for the attachment of the embryo to the uterine epithelium and involves a specialized polarity-dependent property of uterine... (Comparative Study)
Comparative Study
Uterine receptivity is prerequisite for the attachment of the embryo to the uterine epithelium and involves a specialized polarity-dependent property of uterine epithelial (UE) cells. These UE cells, when polarized in culture, behave like cells in utero by exhibiting apico-basal polarity. In order to develop an implantation model in vitro, UE cells were polarized on extracellular matrix (ECM), and polarity was validated by response to estradiol-17beta administered exogenously. UE cells of pregnant rats at day-3 and day-4 post-coitum (p.c.) and of non-pregnant rats were cultured on bare and extracellular-matrix-coated petri dishes until confluency. Hatched blastocysts were transferred to the cultures, and adhesion was monitored every 24 h. Although blastocysts attached to UE cells that were taken from non-pregnant rats and from rats of day-3 p.c. and cultured on bare plastic, they failed to attach to these cells polarized on ECM. However, blastocysts attached firmly to UE cells that had been taken from rats of day-4 p.c. and polarized on ECM. Receptivity of UE cells taken from non-pregnant and pregnant (day-4 p.c.) rats was quantitated by flow cytometric estimation of cellular levels of beta3 integrin. The expression of beta3 integrin in UE cells from rats of day-4 p.c. was highly significant (P<0.01) when compared with its expression in UE cells from non-pregnant rats. The expression of beta3 integrin in UE cells of day-4 p.c. confirmed the receptivity of these cells to blastocyst implantation. Uterine receptivity was also validated in vivo by inducing the decidual cell reaction in rats ovariectomized on day-3 and day-4 p.c. Whereas remarkable deciduoma was noticed in the animals of day-4 p.c., it was absent in the animals of day-3 p.c., thereby indicating that the uterus was receptive on day-4 p.c. only. Thus, blastocysts do not attach to polarized UE cells that have been obtained from a non-receptive uterus. Attachment will occur only if the cells are obtained from a receptive uterus. UE cell receptivity is therefore essential for mimicking the process of implantation in vitro.
Topics: Animals; Blastocyst; Cell Adhesion; Cell Polarity; Coculture Techniques; Epithelial Cells; Extracellular Matrix; Female; Integrin beta3; Pregnancy; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Time Factors; Uterus
PubMed: 16528553
DOI: 10.1007/s00441-005-0109-9