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Carcinogenesis Oct 1997Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has...
Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.
Topics: Animals; Anticarcinogenic Agents; Endometrial Hyperplasia; Estrogen Antagonists; Fallopian Tubes; Female; Hyperplasia; Male; Mice; Polyps; Precancerous Conditions; Pregnancy; Prenatal Exposure Delayed Effects; Tamoxifen; Uterine Neoplasms; Uterus
PubMed: 9364013
DOI: 10.1093/carcin/18.10.2009 -
Indian Journal of Experimental Biology Jun 1997Relative progestational and antiprogestational profile of four contragestational agents, viz. RMI-12,936, RU-38,486, STS-557 and WIN-32,729, known to possess either or...
Relative progestational and antiprogestational profile of four contragestational agents, viz. RMI-12,936, RU-38,486, STS-557 and WIN-32,729, known to possess either or both the properties in other test systems, was determined in immature rats using deciduoma induction as marker. The deciduoma was produced by needle traumatization in one of the uterine horn, and the extent of stimulation was analysed, both macro and microscopically, against the control nontraumatized horn. The results indicated that the agents which demonstrated better potentiality(ies) as progestational and/or antiprogestational in this bioassay exhibit contraceptive efficacy at relatively lower doses as compared to those that showed mild to moderate potentiality.
Topics: Animals; Decidua; Female; Progestins; Rats; Rats, Sprague-Dawley; Uterus
PubMed: 9357161
DOI: No ID Found -
The Journal of Veterinary Medical... Mar 1997The effect of ovariectomy in the early first half of the diestrus was examined on the induction or maintenance of suture-induced canine deciduoma. Ovariectomy...
The effect of ovariectomy in the early first half of the diestrus was examined on the induction or maintenance of suture-induced canine deciduoma. Ovariectomy immediately, or some days, after the insertion of suture had no effect on the induction or maintenance of deciduoma. Even when ovariectomy was performed within 4 days before insertion, deciduoma could be induced in spite of there being no ovary. However, when ovariectomy was done 4 or more days before suture insertion, the rate of deciduoma was decreased or no deciduoma was induced. These results indicate that the influence of the ovary on the endometrium may persist for at least 4 days after ovariectomy. Ovariectomy after the suture insertion had few effects. It is suggested that canine uterine glands in the early first half of the diestrus maintain a certain degree of self-proliferative ability even after ovariectomy, and thus canine deciduoma is not as dependent on the ovary that of the rodentia.
Topics: Animals; Body Weight; Cell Division; Decidua; Diestrus; Dogs; Female; Laparotomy; Ovariectomy; Ovary; Suture Techniques; Uterus
PubMed: 9101486
DOI: 10.1292/jvms.59.227 -
The Journal of Veterinary Medical... Mar 1997Bitches were examined to see whether canine deciduoma could be induced at some reproductive stages with the different conditions of corpora lutea by inserting a silk...
Bitches were examined to see whether canine deciduoma could be induced at some reproductive stages with the different conditions of corpora lutea by inserting a silk suture into the uterine lumen. The bitches stimulated in the early and middle stages of diestrus or in unilateral pregnancy corresponding to these diestrous stages formed deciduoma at a high induction rate, however, no difference in the strength of decidual reaction between the pregnant and diestrous stages was recognized. On the other hand, no reaction could be seen in bitches in late diestrus, the late stage of unilateral pregnancy or the post partum repair phase in which stromal decidual cells similar to those of the rodentia can be seen. In already implanted uteri, however, no deciduoma was formed in the interplacental areas. Even though the corpora lutea were functional, new additional stimulations were not accepted at the interplacental area in which the uterine horn had already been influenced by fertilized ova. From these results, it was suggested that in the dog as well as the rodentia, the endometrium has to be under the influence of functional corpora lutea in order to form deciduoma.
Topics: Animals; Cell Division; Corpus Luteum; Decidua; Dogs; Estrus; Female; Ovary; Pregnancy; Reproduction; Uterus
PubMed: 9101477
DOI: 10.1292/jvms.59.185 -
Progesterone withdrawal and RU-486 treatment stimulate apoptosis in specific uterine decidual cells.Cell Death and Differentiation Jan 1997Progesterone secretion is required for the growth and differentiation of endometrial stromal cells to form decidual cells. For many cells where a growth factor supports...
Progesterone secretion is required for the growth and differentiation of endometrial stromal cells to form decidual cells. For many cells where a growth factor supports cell growth and proliferation, withdrawal of the growth factor initiates apoptosis. This study determined the time course and tissue location of apoptosis in deciduomal tissue after withdrawal of progesterone or injection of the antiprogestin, RU-486. Total DNA was isolated from decidual tissues at intervals after experimental treatments and separated electrophoretically. Internucleosomal DNA fragmentation characteristic of apoptosis was measured by quantitating levels of the 200 bp fragment. Apoptotic cells in tissue sections were detected by direct immunoperoxidase detection of digoxigenin-labeled DNA. Decidual apoptosis reached maximal levels at 12 h after withdrawal of progesterone or injection of RU-486. Increased concentrations of apoptotic cells were observed at the periphery of the growing deciduoma and in the antimesometrial deciduoma near the luminal epithelium after both treatments. These results suggest the withdrawal of progestin initiates apoptosis in cells at the early stages of decidualization.
PubMed: 16465213
DOI: 10.1038/sj.cdd.4400202 -
The Anatomical Record Jan 1997Permeability of thin-walled vessels of the endometrium could be a prerequisite for deciduoma formation. Exogenous gonadotropins alter endometrial morphology and inhibit...
BACKGROUND
Permeability of thin-walled vessels of the endometrium could be a prerequisite for deciduoma formation. Exogenous gonadotropins alter endometrial morphology and inhibit vascular permeability on the day of implantation. The aim of this study was to investigate the effect of exogenous gonadotropins on vascular permeability in the peri-implantation period and relate this to deciduoma formation.
METHODS
Female rats were hyperstimulated with follicle-stimulating hormone and human chorionic gonadotropin prior to mating. Control animals were not injected. Endometrial tissue was collected at 4.5, 5.5, and 6.5 days after mating. Tissue was processed for electron microscopy.
RESULTS
The presence of thin-walled fenestrated vessels and decidualised stromal cells were found in all control groups. With the exception of one fenestration, which occurred in a vessel from one hyperstimulated animal on 5.5 days of pregnancy, no fenestrations were found in the vessels of hyperstimulated animals. Decidualisation of stromal cells did not occur in these animals.
CONCLUSION
Hyperstimulation with exogenous gonadotropins inhibits vascular permeability and subsequent decidualisation. Implantation thus fails to occur.
Topics: Animals; Blood Vessels; Capillary Permeability; Decidua; Embryonic Development; Endometrium; Female; Follicle Stimulating Hormone; Male; Microscopy, Electron; Pregnancy; Rats; Rats, Sprague-Dawley
PubMed: 8986298
DOI: 10.1002/(SICI)1097-0185(199701)247:1<20::AID-AR3>3.0.CO;2-J -
Molecular Reproduction and Development Dec 1996Embryo implantation in the mouse is a highly orchestrated process, a key aspect of which is the invasion of trophoblast cells of the blastocyst into the maternal uterine...
Embryo implantation in the mouse is a highly orchestrated process, a key aspect of which is the invasion of trophoblast cells of the blastocyst into the maternal uterine endometrium. Invasion is facilitated via proteinases expressed by trophoblast cells and balanced by expression of inhibitors of proteinases in the maternal decidua. The predominant proteinase expressed by trophectodermal derivatives of the implanting mouse embryo is matrix metalloproteinase-9 (MMP-9; gelatinase B). Using in situ hybridization, transcripts for MMP-9 were detected in trophoblast cells of the embryo from the earliest stage of decidual formation (day 6.0) examined. MMP-9 transcripts were localized to trophoblast giant cells at the periphery of the embryo at the egg cylinder stage (day 7.0). By the neural-fold stage (day 8.5), expression was restricted to giant cells adjacent to the maternal side of the developing placenta, and by day 9.5 few MMP-9-positive cells remained. The major tissue inhibitor of metalloproteinases (TIMP) produced during this period was TIMP-3. Transcripts encoding TIMP-3 were detected from day 6.0-7.0 in the maternal decidua immediately adjacent to embryonic cells expressing MMP-9. The intensity of TIMP-3 expression in later-stage embryos declined in parallel with MMP-9 expression. Maternal TIMP-3 expression also occurred in the absence of embryonic MMP-9 expression in decidual reactions induced by parthenogenetic embryos (where MMP-9 positive cells were not detected) or in oil-induced deciduomas. These results support the hypothesis that MMP-9 is an important mediator of cellular invasiveness during embryo implantation, and that TIMP-3 serves as a regulator within the uterus to restrict invasion to the site of implantation.
Topics: Animals; Collagenases; Decidua; Embryo Transfer; Embryo, Mammalian; Female; Matrix Metalloproteinase 9; Metalloendopeptidases; Mice; Proteins; RNA, Messenger; Tissue Inhibitor of Metalloproteinase-3; Uterus
PubMed: 8956284
DOI: 10.1002/(SICI)1098-2795(199612)45:4<458::AID-MRD8>3.0.CO;2-Q -
Biology of Reproduction Sep 1996In the mouse, estrogen and progesterone are required to prime the uterus for decidual cell reaction (DCR) in response to an intraluminal stimulus and, once DCR is...
In the mouse, estrogen and progesterone are required to prime the uterus for decidual cell reaction (DCR) in response to an intraluminal stimulus and, once DCR is induced, progesterone is required to maintain DCR. However, some evidence indicates that certain nonprogestational steroid hormones may also be involved in regulating DCR. The present study determined whether androgen plays any role in DCR. Adult CD1 mice were ovariectomized and treated with a regimen of estradiol and progesterone to prime the uterus for DCR and to maintain DCR. Sesame oil was injected into the uterine lumen to induce DCR on Day 5 of the treatment. DCR was determined by deciduomal weight-the difference between the wet weights of oil-injected and noninjected uterine horns. Testosterone, given at 1 mg/day during Days 3-5, could not replace progesterone in priming the uterus for DCR. However, the same dose of testosterone given during Days 6-8 maintained DCR. Alkaline phosphatase activity, a bio-marker for DCR, was present in the deciduoma maintained by either progesterone or testosterone, although the distribution of this enzyme activity was more intense in the antimesometrial pole in progesterone-maintained deciduoma. A nonaromatizable androgen, 5 alpha-dihydrotestosterone (DHT), was also effective in maintaining DCR, and this action of DHT was blocked by an androgen receptor antagonist, hydroxyflutamide. The relative potency of DHT in maintaining DCR was similar to that of progesterone. However, the regression of the deciduoma appeared to be advanced in DHT-treated mice. Ovariectomy on Day 6 of pregnancy resulted in resorption of the conceptus and regression of the decidua within 48 h. Treatment with DHT at the time of ovariectomy could not prevent fetal resorption, but it delayed the regression of decidua, as indicated, in part, by the presence of granulated metrial gland cells. In summary, androgen cannot prime the uterus for DCR, but it can maintain DCR once it is induced. The physiological significance of this finding remains to be determined.
Topics: Alkaline Phosphatase; Androgen Antagonists; Androgens; Animals; Decidua; Female; Fetal Resorption; Mice; Mice, Inbred Strains; Ovariectomy; Pregnancy; Time Factors
PubMed: 8862767
DOI: 10.1095/biolreprod55.3.519 -
Biology of Reproduction Sep 1996Rat endometrial stromal cells undergoing decidualization in vitro secrete urokinase-type plasminogen activator (uPA), and this secretion is regulated by prostaglandin...
Rat endometrial stromal cells undergoing decidualization in vitro secrete urokinase-type plasminogen activator (uPA), and this secretion is regulated by prostaglandin E2. The present study was undertaken to determine whether uPA and plasminogen activator inhibitor-1 (PAI-1) mRNAs are expressed in vivo in the decidua of pregnant rats and in the deciduoma of "pseudopregnant" rats. Total RNA was prepared from nondecidualized and decidualized endometrial tissues at various stages of early pregnancy and examined by Northern blot analysis using specific cDNA probes for rat uPA and PAI-1. There was little uPA mRNA in the endometrium during the first 5 days of pregnancy (Day 1 = the presence of sperm in the vagina). A high level of uPA mRNA was detected on Day 7, and it declined thereafter. There was a gradual increase in PAI-1 mRNA in the decidua from Day 7 of pregnancy, reaching a peak level on Day 15 when the decidua was transformed into the maternal placenta. (RNA was not analyzed beyond Day 15 of pregnancy in this study.) In situ hybridization studies verified that uPA mRNA was present in the decidua adjacent to the implanting embryo on Day 7. Plasminogen activator inhibitor-1 mRNA was scattered in the decidualized endometrium, but greater amounts of PAI-1 mRNA were found in the fetal tissue on Day 10 of pregnancy. Northern blot analysis of RNA from the deciduoma produced in ovariectomized, steroid-treated rats by intrauterine injection of oil demonstrated a similar temporal pattern of expression of uPA mRNA; i.e., the level of uPA mRNA was highest on Day 7 and decreased thereafter. The level of PAI-1 mRNA in deciduoma was not detectable by Northern blot technique during the first 10 days of pseudopregnancy. These findings confirm that uPA mRNA is present in vivo in rat decidual cells, independent of the presence of a conceptus. By contrast, the level of PAI-1 mRNA in the uterus is probably influenced by the presence of the conceptus.
Topics: Animals; Blotting, Northern; DNA Probes; Decidua; Densitometry; Endometrium; Enzyme Precursors; Female; In Situ Hybridization; Metalloendopeptidases; Ovariectomy; Plasminogen Activator Inhibitor 1; Pregnancy; Pseudopregnancy; RNA, Messenger; Rats; Rats, Sprague-Dawley; Urokinase-Type Plasminogen Activator
PubMed: 8862764
DOI: 10.1095/biolreprod55.3.493 -
Endocrine Journal Aug 1996The role of mesencephalic raphe nuclei in the induction of pseudopregnancy was investigated in female rats. The dorsal or median raphe nucleus lesions (DRL or MRL,...
The role of mesencephalic raphe nuclei in the induction of pseudopregnancy was investigated in female rats. The dorsal or median raphe nucleus lesions (DRL or MRL, respectively) were made by means of a radiofrequency lesion generator. Two or 3 weeks after the operation, in order to induce pseudopregnancy, the vagina was stimulated electrically on the day of proestrus or 1 mg/kg b.w. reserpine was injected on the day of diestrus I. Traumatization by passing thread to one uterine horn was performed to induce deciduoma 5 days after vaginal stimulation or 3 days after reserpine injection. As the results, decidual response was seen in most control and sham females in both vaginal stimulation and reserpine-treated groups. In contrast, incidences of deciduoma in DRL females with vaginal stimulation or reserpine-injection were significantly lower than those in control and sham groups. In the MRL females with either vaginal stimulation or reserpine-treatment, incidences of deciduoma were comparable to those of the control and sham operated groups. These results suggest that the dorsal raphe nucleus plays an important role in pseudopregnancy-inducing mechanisms in female rats.
Topics: Animals; Decidua; Electric Stimulation; Female; Proestrus; Pseudopregnancy; Raphe Nuclei; Rats; Rats, Wistar; Reserpine; Vagina
PubMed: 8930524
DOI: 10.1507/endocrj.43.369