scholarly journals Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy

1999 ◽  
Vol 22 (1) ◽  
pp. 91-101 ◽  
Author(s):  
SK Das ◽  
H Lim ◽  
BC Paria ◽  
SK Dey

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.

1995 ◽  
Vol 43 (10) ◽  
pp. 1053-1060 ◽  
Author(s):  
C S Moorhead ◽  
M Lawhun ◽  
G L Nieder

Uteri from non-pregnant and pregnant (Days 1-10) mice were examined for the presence of NADPH diaphorase (NADPH-d) activity by histochemical techniques. Macrophages positive for NADPH-d were observed in all uterine sections but appeared to migrate out of the implantation site and cluster in the mesometrium and interimplantation zones beginning on Day 4. NADPH-d activity was seen in the luminal and glandular epithelium and in several isolated fibers coursing through the myometrium. Many branches of the uterine artery also expressed activity, with the most intense staining in the vessels of the mesometrium. However, the most remarkable staining began on Day 6 within the primary decidual zone. When the stromal cells underwent decidualization, they began to show NADPH-d activity, with the pattern of activity matching the expanding area of decidualization. By Day 9 most of the decidual cell reaction had occurred and the mesometrial decidual staining began to decrease. However, the blood vessels and the cells surrounding the developing blood spaces continued to express activity, and heavy staining was evident within the antimesometrial decidua. No NADPH-d activity was seen in any of the trophoblast cells at any time, or in embryonic tissue, except on Day 8. NADPH-d has been used to identify nitric oxide (NO) synthase. Therefore, it may represent an NO-mediated paracrine control over decidual blood flow, myometrial quiescence, or immune response during pregnancy.


2013 ◽  
Vol 220 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Dang-Dang Li ◽  
Ying-Jie Gao ◽  
Xue-Chao Tian ◽  
Zhan-Qing Yang ◽  
Hang Cao ◽  
...  

Tryptophan 2,3-dioxygenase (Tdo2) is a rate-limiting enzyme which directs the conversion of tryptophan to kynurenine. The aim of this study was to examine the expression and regulation of Tdo2 in mouse uterus during decidualization. Tdo2 mRNA was mainly expressed in the decidua on days 6–8 of pregnancy. By real-time PCR, a high level of Tdo2 expression was observed in the uteri from days 6 to 8 of pregnancy, although Tdo2 expression was observed on days 1–8. Simultaneously, Tdo2 mRNA was also detected under in vivo and in vitro artificial decidualization. Estrogen, progesterone, and 8-bromoadenosine-cAMP could induce the expression of Tdo2 in the ovariectomized mouse uterus and uterine stromal cells. Tdo2 could regulate cell proliferation and stimulate the expression of decidual marker Dtprp in the uterine stromal cells and decidual cells. Overexpression of Tdo2 could upregulate the expression of Ahr, Cox2, and Vegf genes in uterine stromal cells, while Tdo2 inhibitor 680C91 could downregulate the expression of Cox2 and Vegf genes in uterine decidual cells. These data indicate that Tdo2 may play an important role during mouse decidualization and be regulated by estrogen, progesterone, and cAMP.


1982 ◽  
Vol 155 (5) ◽  
pp. 1537-1554 ◽  
Author(s):  
M Kearns ◽  
P K Lala

Decidual cells are considered to be the endproduct of a hormonally induced transformation of endometrial stromal cells of the uterus. However, the source of these precursors remains unknown. This study of evaluated the possibility of their bone marrow origin by an examination of the H-2 phenotype of decidual cells in pseudopregnant bone marrow chimeras. These chimeras were produced by repopulating lethally irradiated CBA/J female (H-2k) mice with bone marrow from (CBA/J x C57BL/6J) F1 female (H-2kb) mice. Pseudopregnancy was produced with a hormonal regimen followed by an oil-induced decidual stimulus. Chimerism was evaluated radioautographically by an identification of the donor-specific Kb phenotype on cells with an immunolabeling technique with monospecific anti-H-2 serum followed by radioiodinated protein A. The extent of chimerism as indicated by the degree of Kb labeling on decidual cells as well as macrophages contained within the decidual nodules was quantitatively compared with that seen on splenic lymphocytes. Fair to good chimerism, as reflected by labeling for the donor-specific marker (Kb), was seen on splenic lymphocytes and macrophages within the decidual nodules in 6 out of 11 animals. A similar level of chimerism was detected on decidual cells in all but one of these six, in which case this was low. One animal showed low chimerism in the spleen but good chimerism on the decidual cells. The remaining four mice were nonchimeric for all three cell types. These results indicate that decidual cells and macrophages appearing within the decidual nodules of pseudopregnant mice are ultimate descendants of bone marrow cells.


1995 ◽  
Vol 14 (2) ◽  
pp. 255-261 ◽  
Author(s):  
W-X Wu ◽  
J Brooks ◽  
A F Glasier ◽  
A S McNeilly

ABSTRACT Within the human utero-placental unit only decidualized stromal cells express mRNA for prolactin. However, it is not clear if the level of prolactin production is related to the number of decidualized cells or the capacity of individual decidual cells to synthesize prolactin, either or both of which parameters may change during pregnancy. In the present study, prolactin production at different stages of human pregnancy was examined using quantitative in situ hybridization to assess decidual prolactin mRNA abundance, immunocytochemistry to examine the prolactin content inside decidual cells and RIA to measure decidual prolactin output into amniotic fluid. Throughout pregnancy the proportion of stromal cells showing positive immunostaining and mRNA for prolactin increased. There was a parallel increase in decidual cell size which was correlated with an increase in prolactin gene expression and intensity of immuno-staining for prolactin in individual decidual cells. These changes in decidual cells were consistent with the changes in the concentration of prolactin in amniotic fluid. These results suggest that there is a close link between the level of prolactin gene expression and production of prolactin by individual decidual cells, which in turn is directly related to the process of decidualization that continues throughout human pregnancy.


Reproduction ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 247-257
Author(s):  
Vishakha Mahajan ◽  
Diana Osavlyuk ◽  
Philip C Logan ◽  
Satya Amirapu ◽  
Anna P Ponnampalam

DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs) facilitate methylation and hydroxymethylation of DNA, respectively. DNMTs are widely studied with conflicting results on their regulation in the endometrium. While the role of TETs in the endometrium remains relatively unexplored. Deregulated expression of TETs and DNMTs are associated with endometrial pathologies. The aim of this study is to characterize the temporal TET expression in endometrium and to determine the hormonal regulation of TETs in comparison to DNMTs. mRNA expressions were quantified by real-time PCR in endometrial tissues from cycling women and localization was determined by immunohistochemistry. Hormonal regulation was investigated in endometrial epithelial and stromal cell lines following a 24 and 48 h treatment cycle. TET1 and 3 mRNA expressions were significantly upregulated in the mid-secretory phase. TET protein expression was ubiquitous in endometrial epithelium throughout the menstrual cycle except during the late-secretory phase, while stromal staining was scattered. TET1 mRNA was significantly upregulated in response to estrogen in stromal cells. Transcriptions of all three TETs were induced in response to progesterone treatment in epithelial cells. Only DNMT3b in epithelial cells and DNMT1 in stromal cells were significantly upregulated upon 24-h estrogen exposure following a significant decrease of DNMT1 when treated with 24 h of estrogen and progesterone. This study suggests that TETs are expressed in a cell-specific, dynamic manner in the endometrium and are responsive to steroid hormones. Investigating the role of TETs individually and with respect to DNMTs, will help to elucidate gene regulatory mechanisms in endometrial biology and pathologies.


1978 ◽  
Vol 18 (3) ◽  
pp. 506-509 ◽  
Author(s):  
Barry E. Ledford ◽  
Judith C. Rankin ◽  
Veronica L. Froble ◽  
Martin J. Serra ◽  
Roger R. Markwald ◽  
...  

2018 ◽  
Vol 48 (6) ◽  
pp. 2399-2408 ◽  
Author(s):  
Kai Wang ◽  
Zhan-Qing Yang ◽  
Hai-Fan Yu ◽  
Yu-Si Wang ◽  
Bin Guo ◽  
...  

Background/Aims: High mobility group box 1 (Hmgb1) is associated with a variety of physiological processes including embryonic development, cell proliferation and differentiation, but little information is available regarding its biological role in decidualization. Methods: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to analyze the spatiotemporal expression of Hmgb1 in mouse uterus during the pre-implantation period, and explore its function and regulatory mechanisms during uterine decidualization. Results: Hmgb1 mRNA was obviously observed in uterine epithelium on day 2 and 3 of pregnancy, but its expression was scarcely detected on day 4 of pregnancy. With the onset of embryo implantation, abundant Hmgb1 expression was noted in the subluminal stromal cells around the implanting blastocyst at implantation sites. Meanwhile, the accumulation of Hmgb1 mRNA was visualized in the decidual cells. Hmgb1 advanced the proliferation of uterine stromal cells and induced the expression of prolactin family 8, subfamily a, member 2 (Prl8a2), a reliable differentiation marker for decidualization. In uterine stromal cells, cAMP analogue 8-Br-cAMP up-regulated the expression of Hmgb1, but the up-regulation was abrogated by protein kinase A (PKA) inhibitor H89. Silencing of Hmgb1 by specific siRNA impeded the induction of 8-Br-cAMP on Prl8a2. Further analysis evidenced that Hmgb1 was a critical mediator of Kruppel-like factor 5 (Klf5) function in stromal differentiation. Knockdown of bone morphogenetic protein 2 (Bmp2) prevented the up-regulation of Prl8a2 elicited by Hmgb1 overexpression, whereas addition of exogenous recombinant Bmp2 protein (rBmp2) reversed the repression of Hmgb1 siRNA on Prl8a2 expression. Conclusion: Hmgb1 may play an important role during mouse uterine decidualization.


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