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Carcinogenesis Aug 1996Rats administered tamoxifen for 3 months and then returned to a basal diet developed an increase in uterine weight for up to 9 months after tamoxifen exposure....
Rats administered tamoxifen for 3 months and then returned to a basal diet developed an increase in uterine weight for up to 9 months after tamoxifen exposure. Stereological analysis of the tamoxifen exposed rat uteri showed that there was a significant increase in the amount of uterine myometrium, for a further 9 months, subsequent to the discontinuation of tamoxifen. A low incidence of myometrial proliferations (deciduomas) and uterine tumours was found at the conclusion of the study (20 months). In contrast, continuous administration of tamoxifen to mice for 24 months produced hyperplasia of the uterine endometrial epithelium and atrophy of the myometrium for the first 3 months, followed by atrophy of both the endometrium and myometrium for the remaining 21 months of the study. No uterine tumours were found in mice treated with tamoxifen for 2 years. The use of stereological analysis on interim sacrifice rodent uteri indicated that sustained uterine tissue compartment effects can occur, with either the continuous administration of tamoxifen, or after its discontinuation. Tamoxifen can have an agonist and antagonist like effect on oestrogen activity in different tissue compartments of the mouse uterus, over the same time period. The particular relevance of the finding of uterine proliferation and atrophy in the rodent studies with tamoxifen is discussed with regard to women taking this drug.
Topics: Animals; Antineoplastic Agents, Hormonal; Endometrium; Female; Humans; Hyperplasia; Mice; Organ Size; Rats; Rats, Wistar; Tamoxifen; Uterus
PubMed: 8761412
DOI: 10.1093/carcin/17.8.1577 -
Biology of Reproduction Jun 1996In previous studies, we found that the human estrogen-regulated heat shock protein (hsp) 27 (human homologue of rat hsp25) is modulated in the endometrium during the...
In previous studies, we found that the human estrogen-regulated heat shock protein (hsp) 27 (human homologue of rat hsp25) is modulated in the endometrium during the different phases of the menstrual cycle and that it is present in endometrial predecidual cells and in decidual cells attached to the placenta. In the present report, we describe the cell type-specific pattern of hsp25 expression in the rat uterus during the periimplantation period as well as during early and late decidualization and placentation. The hsp25 expression pattern was also analyzed in pseudopregnant rats with deciduomas. Immunocytochemistry was performed with an antibody generated against a chimeric hybrid protein containing the N-terminal of the murine hsp25 and the C-terminal of the human hsp27. During pregnancy at the time of implantation, hsp25 was expressed in the endothelial cells of the endometrial vessels and in the luminal epithelium of the antimesometrial region. As pregnancy advanced, hsp25 appeared in predecidual/decidual cells close to the implantation region and then expanded to the mesometrial region. This expression pattern was very similar during pseudopregnancy. Hsp25 was strongly expressed in trophoblastic giant cells beginning on Day 11 of gestation; less expression was noted in the junctional and labyrinth zones of the chorioallantoic placenta (in some cells lining the vascular spaces). In all the disparate cell types that expressed hsp25, the presence of the protein did not correlate with cell proliferation or with apoptosis but with the state of differentiation. Some placental PRL-family members with molecular weights similar to that of hsp25 are also present in antimesometrial decidua and in differentiated trophoblast giant cells; therefore, in this study we eliminated the possibility that our antibody was recognizing prolactin. We also determined that the hybrid hsp25/27 protein did not bind prolactin receptors, and noted that the hsp25 immunostaining pattern was not identical to that of decidual prolactin. In conclusion, the striking cell type-specific timing of hsp25 expression points to hsp25 as a molecule that is important during the implantation, decidualization, and placentation processes.
Topics: Animals; Cell Membrane; Epithelial Cells; Epithelium; Female; HSP27 Heat-Shock Proteins; Heat-Shock Proteins; Immunohistochemistry; Myometrium; Neoplasm Proteins; Placenta; Pregnancy; Pregnancy, Animal; Prolactin; Pseudopregnancy; Rats; Rats, Wistar; Receptors, Prolactin; Uterus
PubMed: 8724361
DOI: 10.1095/biolreprod54.6.1326 -
Development (Cambridge, England) Jun 1996Gelatinase B, a matrix metalloproteinase (MMP) of high specific activity, is highly expressed and activated by mouse blastocysts in culture, and inhibition of this...
Gelatinase B, a matrix metalloproteinase (MMP) of high specific activity, is highly expressed and activated by mouse blastocysts in culture, and inhibition of this enzyme activity inhibits lysis of extracellular matrix (Behrendtsen, O., Alexander, C. M. and Werb, Z. (1992) Development 114, 447-456). Because gelatinase B expression is linked to invasive potential, we studied the expression of gelatinase B mRNA and protein in vivo, in implanting trophoblast giant cells, and found that it was expressed and activated during colonization of the maternal decidua. mRNAs for several other MMPs (stromelysin-1, stromelysin-3 and gelatinase A) and MMP inhibitors (TIMP-1 and TIMP-2) were expressed in the undifferentiated stroma toward the outside of the decidua, and TIMP-3 mRNA was expressed in primary and some mature decidual cells during their differentiation. Both mRNA and TIMP-3 protein were present at high concentrations transiently, and declined from 6.5 days post coitum onward, as the cells underwent apoptosis during the main period of gelatinase B expression and ectoplacental growth and expansion. To assess the function of MMPs during implantation and decidual development, we either injected a peptide hydroxamate MMP inhibitor into normal mice or studied transgenic mice overexpressing TIMP-1. In both cases, decidual length and overall size were reduced, and the embryo was displaced mesometrially. Embryo orientation was less strictly regulated in inhibitor-treated deciduae than in control deciduae. Morphogenesis and development of oil-induced deciduomas were also slowed in the presence of the inhibitor. We conclude that administration of MMP inhibitors retards decidual remodeling and growth, and we suggest that the MMPs expressed in precursor stromal cells promote their differentiation and expansion.
Topics: Animals; Apoptosis; Blastocyst; Cell Differentiation; Collagenases; Decidua; Embryo Transfer; Embryo, Mammalian; Extracellular Matrix; Female; Gelatinases; Gene Expression; Glycoproteins; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Metalloendopeptidases; Mice; Mice, Transgenic; Proteins; Stromal Cells; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-3; Tissue Inhibitor of Metalloproteinases; Trophoblasts
PubMed: 8674412
DOI: 10.1242/dev.122.6.1723 -
The Anatomical Record Mar 1996A decidual cell reaction can be induced in rodent endometrium by an intrauterine injection of oil. The epithelial lining is thought to be instrumental to transduce...
BACKGROUND
A decidual cell reaction can be induced in rodent endometrium by an intrauterine injection of oil. The epithelial lining is thought to be instrumental to transduce intralumenal stimuli for decidualization. One of the consequences of oil injection is the death of uterine epithelial cells. No information is available on the effect that sustained contact with oil has on the epithelium.
METHODS
A decidual cell reaction was induced in 4-day pseudopregnant mice by injection of 30 microliters of arachis oil into the uterine lumen. Samples from the uteri were collected 24, 48, and 72 h after the injection and prepared for transmission electron microscopy.
RESULTS
Twenty-four hours after the oil injection, some of the initial modifications of epithelial cell surfaces were very similar to those induced by the contact with the blastocyst during normal pregnancy. Uterine epithelial cells internalized injected oil and many cells were seen in various stages of degeneration. At 48 h, many epithelial cells were detached from the basal lamina. At 72 h, the uterine lining was re-established by flattened cells.
CONCLUSIONS
The contact of oil with the uterine epithelium of pseudo pregnant mice induces epithelial cell death in the antimesometrial region of the uterine crypt. There is, however, replacement of epithelial lining by epithelial cells, which probably migrate from the mesometrial region of the crypt. The prolonged presence of oil within the uterine lumen seems to induce cycles of epithelial cell death and replacement.
Topics: Animals; Cell Death; Cell Division; Decidua; Endometrium; Female; Mice; Microscopy, Electron; Peanut Oil; Plant Oils; Pregnancy; Time Factors
PubMed: 8742697
DOI: 10.1002/(SICI)1097-0185(199603)244:3<316::AID-AR4>3.0.CO;2-W -
Journal of Reproduction and Fertility Mar 1996Biotinylated lectins from Sambucus nigra (SNA) and Maackia amurensis (MAA), which bind to alpha 2,6-linked and alpha 2,3-linked sialyl residues, respectively, were used...
Biotinylated lectins from Sambucus nigra (SNA) and Maackia amurensis (MAA), which bind to alpha 2,6-linked and alpha 2,3-linked sialyl residues, respectively, were used as probes to study glycan terminal modifications associated with decidualization in the uterine stroma of pregnant rats and mice. Binding of lectins from Erythrina cristagalli (ECA), Phaseolus vulgaris (leukoagglutinin, L-PHA), Triticum vulgaris (WGA) and Bandeiraea simplicifolia (BSA-1B4) was also examined. Tissues from rats between day 5 and day 8 of gestation and mice between day 5 and day 7 of gestation were fixed in Bouin's solution and embedded in wax prior to lectin histochemistry. On day 7 in rats and day 6 in mice, there was a marked reduction in the binding of SNA in the subluminal decidua surrounding the implantation site. In rats, MAA binding to enlarged decidual cells around the implantation chamber was increased markedly, but there was no change in mice. In both species there was de novo binding of ECA in the SNA-negative area, suggesting that the loss of alpha 2,6-linked sialyl residues unmasks terminal N-acetyl lactosamine. These findings are consistent with previous evidence of a close structural and functional similarity between the artificially induced deciduoma and true decidua of rats and show identical changes to the glycosylation patterns previously found in differentiating rat deciduoma. In both species, therefore, decidua exhibits regionally specific terminal glycosylation. However, the species-specific expression of alpha 2,3-linked sialyl residues suggests distinct patterns of steroidally modulated sialyl transferase expression.
Topics: Animals; Decidua; Erythrina; Female; Gestational Age; Glycosylation; Histocytochemistry; Lectins; Mice; Mice, Inbred Strains; Phytohemagglutinins; Plant Lectins; Plants, Medicinal; Pregnancy; Rats; Rats, Sprague-Dawley; Ribosome Inactivating Proteins; Sialyltransferases; Species Specificity; Time Factors
PubMed: 8699407
DOI: 10.1530/jrf.0.1060241 -
Journal of Reproductive Immunology Feb 1996Expression and regulation of interleukin-6 (IL-6) and IL-1 beta were examined in the mouse deciduum and in experimentally induced deciduoma from 6 to 8 days postcoitum...
Expression and regulation of interleukin-6 (IL-6) and IL-1 beta were examined in the mouse deciduum and in experimentally induced deciduoma from 6 to 8 days postcoitum (1 dpc = vaginal plug), as well as in cultured mouse decidual cell preparations. Levels of these mRNAs in the deciduum and deciduoma were below the limits of detection by Northern blotting. However, enzymatic dispersion and culture of decidual cells and/or exposure to bacterial endotoxin-lipopolysaccharide (LPS) induced these mRNAs. IL-6 levels that accumulated in the culture medium (3990 pg/3 x 10(6) cells/day) were about 90-times higher than those of IL-1 beta (45 pg/3 x 10(6) cells/day). Progesterone (10(-7) M) modestly (40%) reduced the levels of IL-6 mRNA and protein during culture, whereas LPS dramatically (8-fold) and rapidly induced IL-6 and IL-1 beta mRNAs and proteins. In vivo, few IL-1 beta immunopositive cells were localized by immunohistochemistry in the 8 dpc deciduum. In contrast, IL-6 mRNA was localized by in situ hybridization in dispersed clusters of a few cells in the mesometrial deciduum near the center of the implantation site. LPS rapidly induced interleukin mRNAs in the deciduum and deciduoma. After LPS injection, IL-1 beta immunopositive cells were dispersed in the myometrium and mesometrial deciduum. In contrast, after LPS injection (2 h), IL-6 mRNA was abundant in 'cords' of cells that traverse the mesometrial deciduum longitudinally, as well as in cells dispersed throughout the myometrium. Thus, the IL-1 beta and IL-6 genes are expressed and regulated in distinct subsets of cells in the decidual bed. The pattern of F4/80 immunostaining is consistent with macrophages as the major, if not only, source of decidual IL-1 beta. IL-6 is also expressed in these cells. However, IL-6 gene expression is regulated in a distinct subset of cells located in the mesometrial decidual bed of the mouse.
Topics: Animals; Cells, Cultured; Decidua; Female; Gene Expression Regulation; Interleukin-1; Interleukin-6; Lipopolysaccharides; Mice; Pregnancy; RNA, Messenger
PubMed: 8920166
DOI: 10.1016/0165-0378(95)00953-1 -
The Journal of Veterinary Medical... Feb 1996This report deals with evaluation of histological characteristics of the canine deciduoma induced by insertion of the uterine grafts as a biological stimulus. Autografts...
This report deals with evaluation of histological characteristics of the canine deciduoma induced by insertion of the uterine grafts as a biological stimulus. Autografts induced severe uterine cystic endometrial hyperplasia, and the grafts were organized by maternal endometrium. On the other hand, allografts induced more severe hyperplasia of the uterine endometrium with stronger inflammation than autografts. Almost all allografts became necrotic and lytic in the uterine lumen. These results suggest that uterine grafts could induce deciduoma and that the maternal endometrium, though under the functional corpora lutea, recognized the uterine grafts to be a stimulant and showed severe cystic endometrial hyperplasia.
Topics: Animals; Decidua; Dog Diseases; Dogs; Endometrial Hyperplasia; Female; Transplantation, Autologous; Transplantation, Homologous; Uterus
PubMed: 8672586
DOI: 10.1292/jvms.58.151 -
Molecular Reproduction and Development Jan 1996The mouse metallothionein (MT) gene family consists of four known members (MT-I through IV) clustered on chromosome 8. Studies reported herein examine the expression and...
The mouse metallothionein (MT) gene family consists of four known members (MT-I through IV) clustered on chromosome 8. Studies reported herein examine the expression and regulation of the MT-III and MT-IV genes in specific cell types in the maternal reproductive tract, developing embryo, and fetus known to express the MT-I and -II genes. MT-III and MT-IV mRNAs were absent from the visceral yolk sac, placenta, and fetal liver, tissues with high levels of MT-I and MT-II mRNAs. In contrast, MT-III and MT-IV mRNAs were both abundant in the maternal deciduum, and in experimentally induced deciduoma on 7 and 8 days postcoitum (1 dpc = vaginal plug), as are MT-I and -II mRNAs. The abundance of each of these MT mRNAs increased coordinately during development of the deciduum (6-8 dpc), and in situ hybridization localized MT-I, MT-III, and MT-IV mRNAs to the secondary decidual zone of the antimesometrial region on 8 dpc, where in some regions all of the cells were apparently positive. Thus, all of the known mouse MT genes are co-expressed in at least some of the cells in the secondary decidual zone. Electrophoretic analysis of decidual MT suggested that the MT-I, -II, and -III isoforms are abundant proteins in the secondary deciduum. Bacterial endotoxin-lipopolysaccharide (LPS) and Zn are powerful inducers of MT-I and MT-II gene expression in many adult organs, whereas these agents apparently have little effect on MT-III and MT-IV gene expression. Neither of these agents significantly effected levels of decidual MT-III or MT-IV mRNAs in vivo or in primary cultures of decidual cells in vitro, and only modest effects of Zn on MT-I mRNA levels were noted. During 2 days of in vitro culture, decidual cell MT-I and MT-III mRNA levels remained elevated while MT-IV mRNA levels decreased. Thus, expression of the mouse MT gene locus in the deciduum appears to be developmentally regulated, and in this tissue, the MT genes are refractory to induction by Zn or inflammation.
Topics: Animals; Base Sequence; Chlorides; Cloning, Molecular; DNA Primers; Decidua; Embryonic and Fetal Development; Female; Gene Expression Regulation; Gestational Age; Liver; Metallothionein; Mice; Mice, Inbred Strains; Molecular Sequence Data; Multigene Family; Placenta; Polymerase Chain Reaction; Pregnancy; Pseudopregnancy; RNA, Messenger; Uterus; Yolk Sac; Zinc Compounds
PubMed: 8720110
DOI: 10.1002/(SICI)1098-2795(199601)43:1<25::AID-MRD4>3.0.CO;2-W -
Brain Research Bulletin 1996The effect of serotonin synthesis inhibitor, p-chlorophenylalanine (PCPA), on induction and maintenance of pseudopregnancy as indicated by deciduoma formation was...
The effect of serotonin synthesis inhibitor, p-chlorophenylalanine (PCPA), on induction and maintenance of pseudopregnancy as indicated by deciduoma formation was examined in female rats. Animals were injected with 1 mg/kg b.wt. of reserpine on the day of metestrus, and silk thread was passed through and placed in the left uterine horn 3 days after reserpine to induce deciduoma. PCPA (100 mg/kg b.wt.) was injected daily for 4 days before or after reserpine in 15 and 13 rats, respectively. A single injection of PCPA was administered before reserpine in nine females. In another group of rats (N = 16), instead of PCPA, saline was injected four times before reserpine. Nineteen female rats were treated with reserpine only as a control group. Results showed 89% of the control and 81.3% of the saline-treated females had massive deciduoma in traumatized uterine horn. In contrast, only 33.3% or 46.2% females with daily treatments of PCPA for 4 days before or after reserpine showed positive decidual reaction. In addition, 88.9% of females with single injection of PCPA possessed uterine horns with deciduoma. These results suggest that 4 days of treatment with PCPA eliminate induction and/or maintenance of pseudopregnancy. Thus, some levels of serotonin are required to induce and maintain pseudopregnancy.
Topics: Animals; Decidua; Female; Fenclonine; Pseudopregnancy; Rats; Rats, Wistar; Reserpine; Serotonin; Serotonin Agents
PubMed: 8705320
DOI: 10.1016/0361-9230(95)02117-5 -
European Journal of Gynaecological... 1996
Topics: Colon; Decidua; Fallopian Tubes; Female; Humans; Middle Aged; Ovary; Parity; Pregnancy
PubMed: 8654471
DOI: No ID Found