HYPERTROPHY AND HYPERPLASIA IN THE MOUSE UTERUS AFTER OESTROGEN TREATMENT: AN AUTORADIOGRAPHIC STUDY

1973 ◽  
Vol 56 (1) ◽  
pp. 133-NP ◽  
Author(s):  
L. MARTIN ◽  
C. A. FINN ◽  
GAIL TRINDER
Keyword(s):  
Cell Death ◽  
Dna Synthesis ◽  
Proliferative Response ◽  
Autoradiographic Study ◽  
Luminal Epithelium ◽  
Uterine Tissue ◽  
Mouse Uterus ◽  
Oestrogen Treatment ◽  
Ovariectomized Mice

SUMMARY The uteri of untreated ovariectomized mice consisted almost entirely of myometrium and connective tissue stroma. After oestrogenic stimulation these tissues underwent marked hypertrophy, but showed little proliferation. The luminal epithelium underwent marked hyperplasia, with most cells dividing twice to quadruple cell numbers by 35–40 h, when they made up 10–12% of the uterine tissue volume and 20% of the total uterine cell population. The proliferative response was rapid, highly synchronized and short-lived. The number of cells incorporating [3H]thymidine first increased 8·5 h after oestradiol-17β and by 13–16 h 60–70% were engaged in DNA synthesis. Up to 21 h cell-death was minimal. From 21 h onwards the proliferation rate declined and the rate of cell death increased. A second injection of oestrogen prevented the rise in death rate and produced a second smaller burst of DNA synthesis. Cells in DNA synthesis or mitosis were insensitive to oestrogen. A smaller proliferative response occurred in the glands: only 25% of cells entered DNA synthesis after the first injection of oestradiol and none after the second. Gland cells appeared to die in situ and there was no evidence that they migrated into the luminal epithelium.

CELL DIVISION AND DNA SYNTHESIS IN THE MOUSE UTERUS DURING CONTINUOUS OESTROGEN TREATMENT

1972 ◽  
Vol 55 (3) ◽  
pp. 507-513 ◽  
Author(s):  
AUDREY E. LEE
Keyword(s):  
Drinking Water ◽  
Cell Division ◽  
Dna Synthesis ◽  
Thymidine Incorporation ◽  
Initial Increase ◽  
Luminal Epithelium ◽  
Third Wave ◽  
Mouse Uterus ◽  
Oestrogen Treatment ◽  
Second Wave

SUMMARY Continuous oestrogen stimulation produced an initial increase in mitosis and [3H]thymidine incorporation in the mouse uterine luminal epithelium on days 2 and 3 of treatment, but activity fell to the level of the untreated uterus on days 4 and 5. The implications of this control of cell division are discussed. A second wave of activity occurred about a week later, and in the longest experiment a third wave was seen on days 19 to 21. This pattern was similar to that seen in the glandular epithelium. There was little cell division in the stroma or myometrium. The rhythm was not due to diurnal variation. It was seen after treatment with oestrone and oestradiol, given either by injection or in the drinking water.

THE EFFECTS OF OESTROGEN ON THE CELL CYCLE IN EPITHELIAL AND CONNECTIVE TISSUES OF THE MOUSE UTERUS

1972 ◽  
Vol 55 (1) ◽  
pp. 21-30 ◽  
Author(s):  
R. M. DAS
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
S Phase ◽  
Luminal Epithelium ◽  
Connective Tissues ◽  
Mouse Uterus ◽  
Oestrogen Treatment ◽  
Ovariectomized Mice ◽  
Generation Times ◽  
The Mean

SUMMARY The duration of stages of the cell cycle in the uterine epithelial and stromal tissues of ovariectomized mice was estimated by the labelled mitosis method. In untreated animals the mean duration of the S phase (DNA synthesis) was 10·5 h in the glandular and luminal epithelium. Oestrogen treatment shortened it to 6 h in both tissues. In the endometrial stroma of progesterone-treated mice the duration of S was 8 h; when oestrogen was given it increased slightly. The generation times estimated under steady-state conditions were 270,156 and 383 h respectively in the lumen, glands and stroma of untreated mice. After oestrogen stimulation the responses became highly synchronized.

HORMONAL CONTROL OF CELL DEATH IN THE LUMINAL EPITHELIUM OF THE MOUSE UTERUS

1981 ◽  
Vol 91 (2) ◽  
pp. 335-340 ◽  
Author(s):  
C. A. FINN ◽  
MARY PUBLICOVER
Keyword(s):  
Cell Death ◽  
Insoluble Fraction ◽  
S Phase ◽  
Hormonal Control ◽  
Scintillation Counting ◽  
Mouse Uterus ◽  
Trichloracetic Acid ◽  
Oestrogen Treatment ◽  
Ovariectomized Mice ◽  
Luminal Epithelial Cells

An attempt has been made to assess quantitatively the extent of cell death in the uterine epithelium after oestrogen treatment. [3H]Thymidine was injected into ovariectomized mice at an interval after oestrogen treatment when many of the luminal epithelial cells were in the S phase of mitosis. Uptake of [3H]thymidine was confirmed by autoradiography of sections of uterus and scintillation counting of trichloracetic acid-insoluble fraction of whole uterine horns. Radioactivity declined after the cessation of oestrogen treatment but remained high if treatment was continued. The decline appears to be correlated with the cell death previously demonstrated in histological sections of uteri under similar conditions.

scholarly journals Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation

Reproduction ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 919-929 ◽  
Author(s):  
Frankie J White ◽  
Robert C Burghardt ◽  
Jianbo Hu ◽  
Margaret M Joyce ◽  
Thomas E Spencer ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Immune Cells ◽  
Luminal Epithelium ◽  
Apical Surface ◽  
Wild Type ◽  
Mouse Uterus ◽  
Ovariectomized Mice ◽  
Vaginal Plug ◽  
Secreted Phosphoprotein 1

Secreted phosphoprotein 1 (SPP1, osteopontin) is the most highly upregulated extracellular matrix/adhesion molecule/cytokine in the receptive phase human uterus, and Spp1 null mice manifest decreased pregnancy rates during mid-gestation as compared with wild-type counterparts. We hypothesize that Spp1 is required for proliferation, migration, survival, adhesion, and remodeling of cells at the conceptus–maternal interface. Our objective was to define the temporal/spatial distribution and steroid regulation of Spp1 in mouse uterus during estrous cycle and early gestation.In situhybridization localizedSpp1to luminal epithelium (LE) and immune cells. LE expression was prominent at proestrus, decreased by estrus, and was nearly undetectable at diestrus. During pregnancy,Spp1mRNA was not detected in LE until day 4.5 (day 1 = vaginal plug).Spp1-expressing immune cells were scattered within the endometrial stroma throughout the estrous cycle and early pregnancy. Immunoreactive Spp1 was prominent at the apical LE surface by day 4.5 of pregnancy and Spp1 protein was also co-localized with subsets of CD45-positive (leukocytes) and F4/80-positive (macrophages) cells. In ovariectomized mice, estrogen, but not progesterone, inducedSpp1mRNA, whereas estrogen plus progesterone did not induceSpp1in LE. These results establish that estrogen regulates Spp1 in mouse LE and are the first to identify macrophages that produce Spp1 within the peri-implantation endometrium of any species. We suggest that Spp1 at the apical surface of LE provides a mechanism to bridge conceptus to LE during implantation, and that Spp1-positive macrophages within the stroma may be involved in uterine remodeling for conceptus invasion.

Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids

1996 ◽  
Vol 16 (2) ◽  
pp. 107-122 ◽  
Author(s):  
I Chakraborty ◽  
S K Das ◽  
J Wang ◽  
S K Dey
Keyword(s):  
Vascular Permeability ◽  
Combined Treatment ◽  
Developmental Expression ◽  
Luminal Epithelium ◽  
Mouse Uterus ◽  
Ovarian Steroids ◽  
Ovariectomized Mice ◽  
Cox 2 ◽  
Rate Limiting ◽  
Cox 1

ABSTRACT Cyclo-oxygenase (COX) is a rate-limiting enzyme that converts arachidonic acid to prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In the rodent, increased uterine vascular permeability at sites of blastocyst apposition is one of the earliest prerequisite events in the implantation process. This event is preceded by generalized uterine edema and luminal closure, and coincides with the initial attachment reaction between the trophectoderm and luminal epithelium. Vasoactive PGs are implicated in these processes. Here we demonstrate that COX genes are differentially regulated in the peri-implantation mouse uterus. During the preimplantation period (days 1–4), the COX-1 gene was expressed in the uterine epithelium mainly on day 4 until the initiation of attachment reaction in the evening after which the expression was downregulated. This COX-1 expression coincides with the generalized uterine edema required for luminal closure. In contrast, the COX-2 gene was expressed in the luminal epithelium and subepithelial stromal cells at the anti-mesometrial pole exclusively surrounding the blastocyst at the time of attachment reaction on day 4 and persisted through the morning of day 5. This uterine gene was not expressed at the sites of blastocyst apposition during progesterone (P4) treated delayed implantation, but was readily induced in the uterus surrounding the activated blastocysts after termination of the delay by estradiol-17β (E2). The results suggest that PG synthesis catalyzed by COX-2 is important for localized increased uterine vascular permeability and attachment reaction. The COX-1 gene that was downregulated from the time of attachment reaction on day 4 was again expressed in the mesometrial and anti-mesometrial secondary decidual beds on days 7 and 8. These results suggest that PGs generated by COX-1 are involved in decidualization and/or continued localized endometrial vascular permeability observed during this period. In contrast, the COX-2 gene, expressed at the anti-mesometrial pole on days 4 and 5, switched its expression to the mesometrial pole from day 6 onward. These results suggest that PGs produced at this site by COX-2 are involved in angiogenesis for the establishment of placenta. In the ovariectomized mice, the COX-1 gene was induced in the epithelium by a combined treatment with P4 and E2. However, P4 and/or E2 treatments failed to influence the uterine COX-2 gene. Overall, the results suggest that the uterine COX-1 gene is influenced by ovarian steroids, while the COX-2 gene is regulated by the implanting blastocyst during early pregnancy.

CHANGES IN CELL PROLIFERATION RATE IN MOUSE UTERINE EPITHELIUM DURING CONTINUOUS OESTROGEN TREATMENT

1974 ◽  
Vol 61 (1) ◽  
pp. 117-121 ◽  
Author(s):  
AUDREY E. LEE ◽  
L. A. ROGERS ◽  
GAIL TRINDER
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Mitotic Index ◽  
Cycle Time ◽  
Luminal Epithelium ◽  
Cell Cycle Time ◽  
Oestrogen Treatment ◽  
Probability Of Transition ◽  
The Mean

SUMMARY Fraction of labelled mitoses (FLM) curves were constructed for mouse uterine luminal epithelium during oestradiol treatment; on day 2 when mitosis was high, and on days 4 and 9 when mitosis was low. No difference was found between the duration of DNA synthesis on these 3 days. The distance between the first and second peaks, usually taken as an estimate of the mean cell cycle time, did not change significantly between days 2 and 4, although the labelling index fell from 38 to 8%. The second peaks of the FLM curves became progressively lower on the three days examined, which was consistent with the interpretation that there was a reduction in the probability of transition of cells from G1 (the post-mitotic period) into the replicative phase of the cell cycle, resulting in the observed fall in mitotic index.

Influence of oestrogen and progesterone on macrophage distribution in the mouse uterus

1990 ◽  
Vol 126 (3) ◽  
pp. 417-NP ◽  
Author(s):  
M. De ◽  
G. W. Wood
Keyword(s):  
Immunohistochemical Analysis ◽  
Absolute Number ◽  
Oestrous Cycle ◽  
Distributional Pattern ◽  
Uterine Tissue ◽  
Mouse Uterus ◽  
Macrophage Population ◽  
Ovariectomized Mice ◽  
Hormone Administration ◽  
Blastocyst Implantation

ABSTRACT Macrophages are constituents of all normal connective tissue including the murine uterus. Macrophages have been identified previously in endometrium and myometrium of pregnant and non-pregnant murine uterus using antibodies against macrophages. In the current study immunohistochemical analysis of murine uterus demonstrated that there were not significant quantitative differences in uterine macrophages between the dioestrous, pro-oestrous and oestrous stages. However, distributional changes occurred during the oestrous cycle. Macrophages were evenly distributed throughout uterine tissue during dioestrus, while, during pro-oestrus and oestrus, their concentration was highest in the subepithelial stroma. Because the oestrous cycle is hormonally regulated, we asked whether or not oestrogen and/or progesterone might influence macrophage distribution. Ovariectomy, which eliminates cyclical production of oestrogen and progesterone, resulted in a significant decrease in both the relative and the absolute number of uterine macrophages within 6 days. Injections of progesterone or oestrogen to ovariectomized mice resulted in restoration of uterine macrophage numbers. Injection of oestrogen plus progesterone in a regimen known to prepare the uterus for receptivity for blastocyst implantation increased the number of macrophages to levels which were consistently higher than those seen during oestrus. Moreover, following hormone administration macrophages were more concentrated in the subepithelial stroma, a distributional pattern which was most evident following injection of both hormones. The results suggest that both oestrogen and progesterone promote quantitative and distributional changes in the uterine macrophage population. Journal of Endocrinology (1990) 126, 417–424

scholarly journals In situ imaging reveals disparity between prostaglandin localization and abundance of prostaglandin synthases

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Kyle D. Duncan ◽  
Xiaofei Sun ◽  
Erin S. Baker ◽  
Sudhansu K. Dey ◽  
Ingela Lanekoff
Keyword(s):  
Mass Spectrometry Imaging ◽  
Rna Localization ◽  
Imaging Method ◽  
Related Protein ◽  
Uterine Tissue ◽  
Tissue Localization ◽  
Physiological Processes ◽  
Conditional Deletion ◽  
Regional Abundance

AbstractProstaglandins are important lipids involved in mediating many physiological processes, such as allergic responses, inflammation, and pregnancy. However, technical limitations of in-situ prostaglandin detection in tissue have led researchers to infer prostaglandin tissue distributions from localization of regulatory synthases, such as COX1 and COX2. Herein, we apply a novel mass spectrometry imaging method for direct in situ tissue localization of prostaglandins, and combine it with techniques for protein expression and RNA localization. We report that prostaglandin D2, its precursors, and downstream synthases co-localize with the highest expression of COX1, and not COX2. Further, we study tissue with a conditional deletion of transformation-related protein 53 where pregnancy success is low and confirm that PG levels are altered, although localization is conserved. Our studies reveal that the abundance of COX and prostaglandin D2 synthases in cellular regions does not mirror the regional abundance of prostaglandins. Thus, we deduce that prostaglandins tissue localization and abundance may not be inferred by COX or prostaglandin synthases in uterine tissue, and must be resolved by an in situ prostaglandin imaging.

Tumor Microenvironment-Triggered In-Situ Cancer Vaccines with Dual Immunogenic Cell Death Inductions for Elevated Antitumor and Antimetastatic Therapy

Nanoscale ◽  
2021 ◽  
Author(s):  
Jun Lin ◽  
Binbin Ding ◽  
Pan Zheng ◽  
Dong Li ◽  
Meifang Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
High Specificity ◽  
The Body ◽  
Immunogenic Cell Death ◽  
Specific Antigens

Cancer vaccine is to make tumor-specific antigens into vaccines, which then are injected back into the body to activate immune responses for cancer immunotherapy. Despite the high specificity and therapeutic...

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