• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.105-113
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• 2006

Objective: To investigate the role of ERK and $PPAR{\gamma}$ on the $TGF-{\beta}1$ induced human endometrial stromal cell decidualization in vitro. Method: Endometrial stromal cells are cultured under the following condition: DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4). $TGF-{\beta}1$ (5 ng/ml), Rosiglitazone (50 nM), and PD98059 ($20{\mu}M$) were added according to experimental purposes. Trypan-Blue and hematocytometer were utilized to count cell number. Enzyme-linked immunosorbent assay (ELISA) and western blotting were utilized to detect proteins. Result: $TGF-{\beta}1$ inhibited proliferation of cultured human endometrial stromal cells and induced expression of PGE2 and prolactin. This effect was mediated by Smad and ERK activation. Administration of rosiglitazone, $PPAR{\gamma}$ agonist, prevented $TGF-{\beta}1$ effect on cell proliferation. Furthermore, Rosiglitazone inhibited $TGF-{\beta}1$ induced activation of ERK, consequently reduced PGE2 and prolactin production. Conclusion: $TGF-{\beta}1$ induced decidualization of endometrial stromal cell through Smad and ERK phosphorylation. $PPAR{\gamma}$ acts as a negative regulator of human ndometrial cell decidualization in vitro.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.30-45
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• 2021

Objectives: This study was performed to investigate the effects of pregnancy-related four herbal medicines (Samul-tang, Onkyung-tang, Chokyungjongok-tang and Moutan Radicis Cortex) on the endometrial and placental cells. Methods: In this study, we examined viability and decidualization of telomerase immortalized human endometrial stromal cell lines (T-HESCs) and viability and invasion ability of human first trimester trophoblast cell lines Sw.71 by four herbal medicines (Samul-tang, Onkyung-tang, Chokyungjongok-tang and Moutan Radicis Cortex) Results: In the study, we showed that Samul-tang, Onkyung-tang, Chokyungjongok-tang increased decidualization marker prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in T-HESCs. Moutan Radicis Cortex decreased the mRNA level of PRL and IGFBP1, and the protein level of PRL and IGFBP1 had no significant effect. Moreover, four herbal medicines reduced invasion ability of Sw.71 cells. Conclusions: These results suggest that Samul-tang, Onkyung-tang, and Chokyungjongok-tang have beneficial effects on successful embryo implantation and pregnancy maintenance by increasing decidualization markers such as PRL and IGFBP1. Moutan Radicis Cortex reduces the mRNA levels of PRL and IGFBP1, which may adversely affect pregnancy. Further investigations are needed to elucidate the significance of the decreased invasive ability of Sw.71 cells induced by four herbal medications.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.1
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• pp.65-75
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• 2003

Objectives: To investigate the role of TGF (Transforming growth factor-$\beta$) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. Design: In the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-$\beta$1 are added. Methods: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining are utilized to detect proteins in the tissue. Results: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-$\beta$1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-$\beta$1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4, 325 pg/ml in E2-dominant and 2, 000 pg/ml in P4-dominant condition compare to 150 pg/ml in no hormone. In separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-$\beta$ and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. Conclusion: It is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-$\beta$ and HGF are two possible paracrine mediators in the human endometrial decidualization.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.207-216
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• 2010

Objective: This study was performed to clarify the role of HomeoboxA (HOXA) and its related signaling molecules in the decidualization of primary cultured endometrial cells. Methods: Human endometrial tissues were obtained by curettage of hysterectomy specimens from patients with conditions other than endometrial diseases. Tissues were minced and digested with Trypsin-EDTA for 20 min, $37^{\circ}C$. Cells were cultured with DMEM/F12 medium in $37^{\circ}C$, 5% $CO_2$ incubator for 24 hrs. Cells were treated with HOXA10 siRNA and added transforming growth factor (TGF)-${\beta}1$ (10 ng/mL) for 48 hrs to induces decidualization in vitro. Reverse transcription polymerase chain reaction analysis was accomplished to observe the expression of HOXA10, prolactin, cyclooxygenase (COX)-2, peroxisome proliferatoractivated receptor (PPAR)-$\gamma$, and wingless-type MMTV integration site family (Wnt). Results: HOXA10 expression was increased (1.8 fold vs. non-treated control) in TGF-${\beta}1$ treated cells. Decidualization marker, prolactin, was significantly increased in TGF-${\beta}1$ treated cells compared with HOXA10 siRNA treated cells. Endometrial cell differentiation marker, COX-2 was down-regulated by HOXA10 siRNA even if cells were treated with TGF-${\beta}1$. Wnt4 was down-regulated by treated with HOXA10 siRNA, this expression patters was not changed by TGF-${\beta}1$. Expression of PPAR-$\gamma$ was down regulated by TGF-${\beta}1$ in regardless of HOXA10 siRNA treatment. Conclusion: TGF-${\beta}1$ which is induced by progesterone in endometrial epithelial cells may induces stromal cell decidualization via HOXA10 and Wnt signaling cascade.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.02a
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• pp.29-29
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• 2003

No Abstract, See Full Text

• Clinical and Experimental Reproductive Medicine
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• v.22 no.2
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• pp.155-161
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• 1995

The present investigation has been undertaken to elucidate the differentiation mechanism the uterus which is the environment of the embryo development, by demonstrating the role of ovarian steroids hormone in the decidualization of the pseudopregnant rat uterus. To determine the effect of ovarine steroids and artificial stimulation (trauma) on the differenciation of the uterine endometrium and decidualization for implantation, attempt was made to measure concentrations of serum estradiol($E_2$), progesterone($P_4$) and nuclear $P_4$ receptor in the traumatized and non-traumatized uterine tissue of the pseudopregnant rat. The results obtained are as followings : The concentration of serum $E_2$ on day 9(implantation stage) was similar in both of intact pseudopregnant rat(47.63pg/ml) and normal pregnant rat(40.71pg/ml). And among the treated groups, $E_2$ concentration was highest in the $E_2$ treated group in comparision with intact control group(relative value; 73.27%). The concentration of serum $P_4$ was also highest in the $P_4$ treated group(23.12pg/ml). Relative value of $P_4$ treated group in comparision with intact group(24.88pg/ml) was 92.93%. The nuclear $P_4$ receptor levels in the artificial traumatized groups were higher compared with the non-traumatized control groups. This study, therefore, clearly demonstrates that the methods for inducing pseudopregnant (vagina tapping;120/min) and inducing decidualization(oil injection; 0.1ml/uterine horn) appear to be effective, $P_4$ appears to be effective in the differenciation of the uterine endometrial tissue for the implantation process. Concentration of serum $P_4$ seems to be well correlated with the level of the nuclear $P_4$ receptor during the early embryo development. These results seem to be well correlated with ALPase activities in the normal and pseudopregnant rat uterus shown in the previous study.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.3
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• pp.1-14
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• 2021

Methods: We investigated the ability to induce decidualization of human endometrial stromal cells and invasive ability of human trophoblast cells by water extract of three types herbal medicines (Dangguijakyak-san, Siryung-tang, Antae-eum) and ethanol extract on Scutellariae Radix. Results: In the process of decidualization of endometrial stromal cells, three herbal medicines including Dangguijakyak-san, Siryung-tang, and Scutellariae Radix increased the production of decidual markers such as prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1). However, Antae-eum increased mRNA levels of PRL and IGFBP and secretion of IGFBP in decidual stromal cells, but not PRL. Four herbal medicines inhibited the invasion of trophoblast cells. Conclusions: Four herbal medicines may play a role in implantation in women with reproductive failures. However, further studies are warranted to elucidate whether these medications are helpful in the maintenance of pregnancy.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.4
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• pp.295-302
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• 2002

Uterine cells carry out proliferation and differentiation for preparation the embryonic implantation during pregnancy. Therefore regulation of the cell proliferation is an essential step for uterine preparation, but there is not much information about the proliferation related genes in pregnant uterus. To identify these implantation specific genes, a PCR-select cDNA subtraction method was employed and got a few genes. One of the identified genes is a novel gene encoding oral tumor suppressor doc-1. To detect the doc-1 expression on the pregnant uterus, dot blotting, RT-PCR, and in situ hybridization were employed. Dot blotting revealed that doc-1 mRNA expression increase after implantation. During normal pregnancy, doc-1 mRNA expression was detected as early as day 1 of pregnancy with RT-PCR. Its expression was increased about 15 times after embryonic implantation. doc-1 transcript was localized in luminal epithelial cells but it was very faint during preimplantation. After starting the implantation, it localized in the stromal cells; heightened expression of doc-1 correlates with intense stromal cell proliferation surrounding the implanting blastocyst on day 6 morning. However in the decidualized cells, the intensity of localized doc-1 mRNA was weak. From those results, it is revealed that doc-1 express at pregnant uterus of the mouse. In addition it is suggested that doc-1 is the gene regulating the proliferation of the luminal epithelial cells and stromal cells during early implantation and decidualization.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.119-125
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• 2011

Implantation of an embryo occurs during the mid-secretory phase of the menstrual cycle, known as the "implantation window." During this implantation period, there are significant morphologic and functional changes in the endometrium, which is followed by decidualization. Many immune cells, such as dendritic and natural killer (NK) cells, increase in number in this period and early pregnancy. Recent works have revealed that antigen-presenting cells (APCs) and NK cells are involved in vascular remodeling of spiral arteries in the decidua and lack of APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role in the induction of immune tolerance during pregnancy. A balance between effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment and maintenance of pregnancy. The highly complicated endocrine-immune network works in decidualization of the endometrium and at the fetomaternal interface. We will discuss the role of immune cells in the implantation period and during early pregnancy.

• 대한생식의학회:학술대회논문집
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• 2005.11a
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• pp.114-114
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• 2005