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Human Reproduction (Oxford, England) Apr 1999With a view to elucidating the hormonal control of decidualization in rhesus monkey, we studied the effects of CDRI-85/287, a potent anti-oestrogen, on endometrial...
With a view to elucidating the hormonal control of decidualization in rhesus monkey, we studied the effects of CDRI-85/287, a potent anti-oestrogen, on endometrial steroid receptors in vivo and in vitro. Compound 85/287 was administered (i.m.) on days 8, 9 and 10 of steroid treatment cycle at a dose of 15 mg/monkey. Deciduoma was induced on day 16. Histological examination of endometrial tissue on days 24 and 30 of the cycle showed an apparent inhibition in uterine epithelial and subepithelial decidual cell plaque formation and a decrease in leukocytic infiltration into the stroma in anti-oestrogen-treated animals. As observed on day 24, a significant decrease in progesterone receptors (PR) (nuclear + cytosolic) was observed in the 85/287-treated group, whereas oestrogen receptor (ER) content remained unaltered. On day 30 total ER as well as total PR content was markedly reduced in treated animals. In-vitro results clearly demonstrated a competitive antagonism of 85/287 at the ER level only. The results are discussed in relation to the histological changes and modulation of steroid receptors, thereby suggesting the decidualization inhibitory activity of anti-oestrogen molecule 85/287 in primate species.
Topics: Animals; Benzopyrans; Contraceptives, Oral, Synthetic; Decidua; Endometrium; Estrogen Antagonists; Female; Macaca mulatta; Ovariectomy; Piperidines; Pregnancy; Receptors, Steroid
PubMed: 10221246
DOI: 10.1093/humrep/14.4.1090 -
Advances in Experimental Medicine and... 1998The antimitotic action of the systemic benzimidazole carbamate compound, benomyl, the basis for its fungitoxicity, was assessed in a mammalian system by selected...
The antimitotic action of the systemic benzimidazole carbamate compound, benomyl, the basis for its fungitoxicity, was assessed in a mammalian system by selected biochemical endpoints of endometrial proliferation during decidualization in rats. The deciduoma, artificially induced on Day 4 of pseudopregnancy (PG), represents the maternal portion of the placenta that attains maximal growth between Days 9-11 PG. Deciduoma induction by surgical uterine trauma normally prolongs PG into the decidualization process. Measured endometrial parameters were the wet weight, protein for hypertrophy, DNA indicative of hyperplasia; enzymatic biomarkers- isocitrate dehydrogenase (ICDH) and the matrix metalloproteinases (MMPs); and serum progesterone which hormonally maintains decidual growth. Benomyl was administered by oral gavage in daily doses (500 mg/kg/rat in corn oil for 5 days, PG Days 5-9) and animals were sacrificed on PG Day 10. Benomyl caused significant reduction (P < 0.001) in endometrial wet weight, protein and DNA concentrations. ICDH activity was also significantly reduced (P < 0.01) following benomyl treatment. Of the two MMP species (72 and 92 kDa), whereas the 72 kDa was only slightly affected, the 92 kDa MMP was suppressed 2-3 fold by benomyl. Benomyl was without effect on the progesterone concentration. The findings suggest that during decidualization in rats, the anti-deciduogenic, antimitotic action of post-traumal benomyl treatment which occurred via the biochemical molecules (protein, DNA, ICDH and the MMPs) apparently was not mediated by progesterone.
Topics: Animals; Benomyl; Cell Division; DNA; Decidua; Endometrium; Female; Fungicides, Industrial; Isocitrate Dehydrogenase; Progesterone; Proteins; Pseudopregnancy; Rats; Rats, Sprague-Dawley
PubMed: 10026946
DOI: 10.1007/978-1-4899-0089-0_19 -
The Anatomical Record Feb 1999Deciduoma induced by mechanical stimulation in pseudopregnant mice is similar to the decidua in normal pregnancy and it undergoes regression after a certain period.... (Comparative Study)
Comparative Study
Deciduoma induced by mechanical stimulation in pseudopregnant mice is similar to the decidua in normal pregnancy and it undergoes regression after a certain period. Therefore, we examined cell death in deciduomas which were induced by artificial stimulation. To analyze the regression mechanism of artificially induced deciduoma, DNA fragmentation, in situ 3'-DNA nick end labeling, and RT-PCR were performed on day 6 to 14 of pseudopregnancy. DNA fragmentation appeared on day 8 and it increased to day 10 of pseudopregnancy in the traumatized uterine horn. A large number of apoptotic cells were found on day 10 in the periphery of deciduoma at the antimesometrial side. Deciduoma underwent degeneration on day 11 of pseudopregnancy. Expression of tumor necrosis factor-alpha (TNF-alpha) mRNA was high on days 8 and 10, then decreased, whereas the expression increased again on day 14. TNF-alpha protein was expressed from day 8 to day 12, showing a peak expression on day 10 when deciduoma reached maximum weight. Serum progesterone level was high in the traumatized pseudopregnant mice on day 6, then it gradually decreased. Life span of deciduoma was prolonged 4 days more by daily injection of progesterone. A reduction in serum progesterone coincides with TNF-alpha increase, resulting in an increase of apoptotic deciduomal cells at the regression period, and that the life span of deciduoma is prolonged by additive supply of progesterone.
Topics: Animals; Apoptosis; DNA Fragmentation; Decidua; Electrophoresis, Agar Gel; Female; Immunoblotting; In Situ Hybridization; Mice; Mice, Inbred ICR; Progesterone; Pseudopregnancy; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Tumor Necrosis Factor-alpha; Uterus
PubMed: 9972805
DOI: 10.1002/(SICI)1097-0185(19990201)254:2<205::AID-AR6>3.0.CO;2-K -
Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy.Journal of Molecular Endocrinology Feb 1999In the mouse, the attachment reaction between the blastocyst trophectoderm and the receptive uterine luminal epithelium occurs at 2200-2300 h on day 4 of pregnancy and...
In the mouse, the attachment reaction between the blastocyst trophectoderm and the receptive uterine luminal epithelium occurs at 2200-2300 h on day 4 of pregnancy and is rapidly followed by transformation of stromal cells into decidual cells (decidual cell reaction). This process can also be induced experimentally (deciduoma) by intraluminal oil infusion in the uterus on day 4 of pseudopregnancy. The decidual cell reaction is associated with up- and down-regulation of many genes in a cell-specific manner. Using mRNA differential display, we identified cyclin D3 as one of the genes that is upregulated in the uterus at the sites of blastocyst apposition during the attachment reaction. The levels of expression were low in the morning of days 1-4 as determined by Northern hybridization. In situ hybridization analysis showed that on days 1 and 2, signals were primarily localized in uterine epithelial cells, while signals were detected in both the stromal and epithelial cells on days 3 and 4. In contrast, with the initiation and progression of decidualization on days 5, 6 and 7, the levels of cyclin D3 mRNA were remarkably upregulated in stromal cells both at the mesometrial and the antimesometrial poles. However, on day 8, signals were primarily localized in stromal cells at the mesometrial decidual bed. Implanting blastocysts on these days also expressed cyclin D3 mRNA. In the progesterone-treated delayed implanting mice, the uterine levels of cyclin D3 mRNA were modest at the sites of blastocyst apposition, but were upregulated with the onset of implantation by estradiol-17beta. However, the decidual expression of cyclin D3 mRNA was not dependent on the presence of blastocysts, since increased expression also occurred in experimentally induced deciduoma in the absence of blastocysts. The importance of cyclin D3 in decidualization was further examined in Hoxa-10-deficient mice which show defective decidualization. The expression of cyclin D3 mRNA in Hoxa-10(-/-) uteri on day 5 was severely compromised after application of a deciduogenic stimulus on day 4 of pseudopregnancy. Collectively, the results suggest that cyclin D3 could be important for the process of decidualization.
Topics: Animals; Blastocyst; Cyclin D3; Cyclins; DNA, Complementary; DNA-Binding Proteins; Decidua; Embryo Implantation; Epithelial Cells; Female; Homeobox A10 Proteins; Homeodomain Proteins; In Situ Hybridization; Mice; Mice, Knockout; Molecular Probe Techniques; Polymerase Chain Reaction; Pregnancy; Pregnancy, Animal; Pseudopregnancy; RNA, Messenger; Sesame Oil; Stromal Cells; Subtraction Technique; Uterus
PubMed: 9924184
DOI: 10.1677/jme.0.0220091 -
Developmental Genetics 1998Adhesive mechanisms are considered to be of crucial importance for blastocyst adherence to the uterine wall, as well as for the interactions between embryonal and...
Adhesive mechanisms are considered to be of crucial importance for blastocyst adherence to the uterine wall, as well as for the interactions between embryonal and decidual tissues during hemochorial placenta formation. Epithelial V-like Antigen (Eva) is a novel homophilic adhesion molecule of the immunoglobulin superfamily, which during mouse embryonic development is expressed by various differentiating epithelia. In the present paper we describe Eva expression during mouse trophoblast invasion and placental morphogenesis, analysing day 5.5 to 18.5 postcoitum (p.c.) placentas and deciduomas by in situ hybridization. Eva transcripts were detected in spongiotrophoblast cells from 7.5 to 18.5 days p.c. Expression was uniform at early stages, but after day 11.5, p.c. became limited to the invasive subpopulation of spongiotrophoblasts (known as glycogen cells). Trophoblast giant cells did not express Eva in any of the stages analysed. Besides trophoblasts, also early postimplantation decidua was positive for Eva transcripts. In decidual tissue, Eva expression was present at day 5.5 p.c., peaked at day 7.5 p.c., and declined on successive days. The expression pattern of Eva transcripts suggests that during mouse placenta formation, its protein product may play a role in the processes of trophoblast invasion, decidual response, and trophoblast-decidual interaction.
Topics: Animals; Cell Adhesion Molecules; Embryonic and Fetal Development; Female; Gene Expression Regulation, Developmental; In Situ Hybridization; Mice; Morphogenesis; Placenta; Pregnancy
PubMed: 9883583
DOI: 10.1002/(SICI)1520-6408(1998)23:4<317::AID-DVG6>3.0.CO;2-O -
Comparative Biochemistry and... Aug 1998The purpose of this study was to investigate time-related interactions between the estrogen receptors, mediators of steroidal regulation of uterine growth, and an...
The purpose of this study was to investigate time-related interactions between the estrogen receptors, mediators of steroidal regulation of uterine growth, and an extracellular regulatory enzyme, the matrix metalloproteinases (MMPs) engaged in connective tissue degradation and remodeling that are fundamental to implantation and placentation. Pseudopregnant rats, in which the decidual response, the basis for decidualization, was surgically induced on day 4 of pseudopregnancy (PG), were sacrificed on PG days 3, 6, 9, and 15 for retrieval of uterine tissues for assays: the radioligand binding assay for the estrogen receptors and substrate zymography for the MMPs. Following increases on PG day 3, there were time-dependent decreases in the cytosolic low and high capacity estrogen receptors during deciduoma development (PG days 6-9) and regression (PG day 15) in both the endometrium and myometrium. Moreover, whereas the low capacity estrogen receptor levels were only slightly decreased (PG days 6-15), the high capacity receptors were reduced on day 6 (P < 0.001) and were completely diminished during PG days 9 and 15. In contrast, the MMPs (92 and 72 kDa) activities were increased from PG days 6-15 (P < 0.05) over the pre-decidual induction values on PG day 3 in both uterine compartments. The results suggest that deciduoma induction can modulate the concentration of cytosolic estrogen receptor subtypes and MMP activities in rats. The inverse time-dependent interrelationship between these cellular and extracellular components during deciduoma development and regression imply that the remodeling role of the MMPs may be enhanced by the reduced cytosolic estrogen receptor/estrogen action.
Topics: Animals; Endometrium; Female; Image Processing, Computer-Assisted; Metalloendopeptidases; Molecular Weight; Myometrium; Pseudopregnancy; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Uterus
PubMed: 9827042
DOI: 10.1016/s0742-8413(98)10006-3 -
The Journal of Veterinary Medical... May 1998Histological variations of canine deciduoma which was induced in the non pregnant horn at several stages of unilateral pregnancy were examined. In the first half of the...
Histological variations of canine deciduoma which was induced in the non pregnant horn at several stages of unilateral pregnancy were examined. In the first half of the unilateral pregnancy, deciduoma was characterized by the cystic glandular hyperplasia corresponding to each of the stages in normal early placentation. In the second half, deciduoma could not be induced and few histological reactions were recognized. The endometrium looked normal for late diestrus with no growth of the uterine glands. These differences might reflect the latent strength of the uterine glands to proliferate and dilate in the stimulated periods.
Topics: Animals; Cell Division; Decidua; Diestrus; Dogs; Endometrium; Female; Gestational Age; Hyperplasia; Hysterectomy; Placenta; Pregnancy; Pregnancy, Animal; Time Factors
PubMed: 9637298
DOI: 10.1292/jvms.60.623 -
Clinical and Experimental Pharmacology... 19981. The present study investigated the time-dependent inhibitory responses of endometrial growth and inducible nitric oxide synthase (iNOS) to dexamethasone during...
1. The present study investigated the time-dependent inhibitory responses of endometrial growth and inducible nitric oxide synthase (iNOS) to dexamethasone during deciduoma development that was surgically induced on day 4 of pseudopregnancy (PG). 2. Groups of rats (n = 6) were subcutaneously injected with dexamethasone (1.5 mg/rat per day) for 3 days (PG days 1-3, 4-6, 7-9, 10-12 and 12-15). Rats in each group were killed on the last injection day. 3. Dexamethasone produced comparable temporal inhibitory changes in endometrial growth (wet weight, protein and DNA concentrations; P<0.0001) and in iNOS activity (130 kDa protein band), which peaked after PG days 4-6 and 7-9 pretreatments. 4. Endometrial matrix metalloproteinases (72 and 92 kDa) activity profiles displayed maximal reductions (36 and 53%, respectively) following PG days 4-6 pretreatment. Serum progesterone levels were equally (P<0.0001) but asynchronously inhibited by dexamethasone on PG days 9 and 12. 5. Dexamethasone inhibition of endometrial growth and in situ iNOS was most pronounced during decidual development (PG days 4-9). Minor reductions in these endometrial parameters occurred before deciduoma induction (PG days 1-3) and during deciduoma regression (PG days 10-15). 6. These results indicate that, in the endometrium, the iNOS/endogenous nitric oxide system may be linked to the biochemical and metabolic mechanisms responsible for the developmental responsiveness of the deciduoma to dexamethasone exposure. These time-dependent changes in endometrial growth and iNOS apparently were not mediated by progesterone.
Topics: Animals; Anti-Inflammatory Agents; Collagenases; Decidua; Dexamethasone; Drug Administration Schedule; Endometrium; Enzyme Induction; Female; Gelatinases; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Metalloendopeptidases; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley
PubMed: 9590576
DOI: 10.1111/j.1440-1681.1998.t01-14-.x -
Journal of Reproduction and Fertility Jan 1998Parathyroid hormone-related protein (PTHrP) was detected at 32.8 +/- 3.9 pmol 1-1 in uterine luminal fluid from immature rats treated with oestradiol. As mRNA encoding...
Parathyroid hormone-related protein (PTHrP) was detected at 32.8 +/- 3.9 pmol 1-1 in uterine luminal fluid from immature rats treated with oestradiol. As mRNA encoding PTHrP has previously been localized to implantation sites in pregnant rats, the role of luminal PTHrP during pregnancy was explored. Infusion of a parathyroid hormone (PTH)/PTHrP receptor antagonist, [Asn10,Leu11]PTHrP(7-34) amide, into the uterine lumen during pregnancy in rats resulted in excessive decidualization. This effect was also observed after intrauterine infusion of a monoclonal antibody raised against PTHrP. The effect of infusion of PTH/PTHrP receptor antagonist was dependent upon successful implantation, was dose-dependent and confined to the treated horn. A decrease in the number of apoptotic decidual cells in antagonist-infused uterine horns compared with vehicle or non-infused horns was detected immunohistochemically at day 13 of pregnancy, and this decrease is likely to contribute to the 'over-decidualization' observed. In pseudopregnant rats, infusion of PTH/PTHrP receptor antagonist into the uterine lumen resulted in an increase in uterine wet weight of the infused horn compared with the non-infused horn, indicating a direct effect on deciduoma formation. Thus, activation of the PTH/PTHrP receptor by locally produced PTHrP appears to be crucial for normal decidualization during pregnancy in rats.
Topics: Animals; Apoptosis; Decidua; Female; Hormone Antagonists; Immunohistochemistry; Organ Size; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Parathyroid Hormone; Uterus
PubMed: 9538330
DOI: 10.1530/jrf.0.1120059 -
Journal of Reproduction and Fertility Jan 1998The interaction between parathyroid hormone-related protein (PTHrP) and the parathyroid hormone (PTH)/PTHrP receptor is thought to play a role in the growth and...
Expression of parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor in the rat uterus during early pregnancy and following artificial deciduoma induction.
The interaction between parathyroid hormone-related protein (PTHrP) and the parathyroid hormone (PTH)/PTHrP receptor is thought to play a role in the growth and differentiation of various tissues throughout fetal development in the rodent. The aim of the present study was to define the patterns of expression of PTHrP and of the PTH/PTHrP receptor in the rat uterus during the early stages of normal pregnancy, and following artificial induction of a decidual reaction. Using hybridization histochemistry, we have shown that the receptor gene is switched on early in pregnancy (by 1.5 days post coitum) in the endometrial stromal cells that surround the lumen. These cells include the anti-mesometrial subepithelial stromal cells that are destined to become decidualized. This pattern continues until 5.0 days post coitum, when PTHrP is switched on in antimesometrial luminal epithelial cells that line the implantation chamber. Stromal cells underlying the implantation chamber then downregulate transcription of the receptor gene, and within 12 h differentiate into decidual cells. A similar pattern was seen in uteri in which a decidual reaction had been induced artificially. Therefore, it may be postulated that in early pregnancy the endometrial stroma initiates transcription of the gene for the PTH/PTHrP receptor and is thus 'primed' for the PTHrP signal from the luminal epithelial cells. Some time after receiving the signal, the endometrial stromal cells downregulate the receptor gene, and this appears to be a trigger for the terminal differentiation of the stromal cells into decidual cells. These results suggest that PTHrP, acting through the PTH/PTHrP receptor, plays a role in the initiation of a decidual reaction during early pregnancy by regulating the differentiation of endometrial stromal cells into decidual cells.
Topics: Animals; Cell Differentiation; Decidua; Estrus; Female; Gene Expression; In Situ Hybridization; Parathyroid Hormone-Related Protein; Pregnancy; Pregnancy, Animal; Proteins; Rats; Rats, Sprague-Dawley; Receptor, Parathyroid Hormone, Type 1; Receptors, Parathyroid Hormone; Uterus
PubMed: 9538324
DOI: 10.1530/jrf.0.1120001