Biomedical subjects

Mikio Momoeda

Publications and source records attributed to Mikio Momoeda.

12 recordsLinked to original sources

PubMed2004

Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia.

Sufficient cytotrophoblast (CT) invasion into the uterine wall and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of vascular endothelial growth factor (VEGF) family molecules is confirmed in placental cells including CTs, but it is not elucidated how the VEGF system in CTs is controlled by oxygen tension and how it is involved in the development of placental circulation. To address this, we explored the effect of oxygen tension on the expression of VEGF, placenta growth factor (PlGF), and their antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1) using ELISA and real-time PCR in a primary CT cell culture. For comparison, the same was conducted in parallel using other cells comprising placenta, such as human umbilical vein endothelial cells (HUVECs) and villous fibroblasts (VFs). Reduced oxygen resulted in a pronounced increase in sFlt-1 mRNA amount and sFlt-1 release into the culture media in CTs, whereas this was not the case with HUVECs and VFs. Free (not bound to sFlt-1) VEGF was not detected in CT culture media regardless of oxygen concentration, even though VEGF expression was stimulated by reduced oxygen in CTs, which was similar to the stimulation in HUVECs and VFs. Free PlGF was also diminished in CT culture media by reduced oxygen. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced oxygen, which could consequently antagonize angiogenic activity of VEGF and PlGF. The presented findings might provide a framework with which to understand the mechanism of uterine vascular remodeling and its perturbations as exemplified in preeclampsia.

Cell Line, Tumor↗

PubMed2004

Concentration of osteoprotegerin (OPG) in peritoneal fluid is increased in women with endometriosis.

BACKGROUND: Failure of apoptosis of refluxed endometrial cells within the peritoneal cavity is a possible etiologic factor for development of endometriosis. Osteoprotegerin (OPG) is a survival factor that exerts its effect by binding to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), thus preventing TRAIL from binding to the apoptosis receptors DR4 and DR5. In the present study, we addressed the possibility that the TRAIL/OPG system is involved in the pathogenesis of endometriosis. METHODS: Concentrations of OPG and TRAIL in the peritoneal fluid (PF) of women with or without endometriosis were measured using specific enzyme-linked immunoabsorbent assay. The expression of DR4 and DR5 in the endometriotic tissue was examined by reverse transcription-polymerase chain reaction. RESULTS: OPG concentrations in PF of women with endometriosis were significantly higher than those of women without endometriosis (P=0.006). With respect to the stages of the disease, the concentrations of OPG in women with stage III/IV endometriosis were significantly higher than in those without endometriosis and those with stage I/II endometriosis. On the other hand, the ratios of TRAIL/OPG concentrations were significantly lower in stage III/IV endometriosis compared to those in non-endometriosis and stage I/II endometriosis. DR5 mRNA expression was clearly detected in all the endometriotic tissues studied. CONCLUSIONS: These findings suggest that the TRAIL/OPG system is involved in the pathophysiology of endometriosis, possibly affecting the apoptosis of endometriotic cells.

Adult↗

PubMed2004

Differences in serum bisphenol a concentrations in premenopausal normal women and women with endometrial hyperplasia.

Exposure to endocrine disrupting chemicals (EDCs) has been raised in relation to its potential for adverse health outcomes. Bisphenol A (BPA) is an estrogenic EDC widely found in plastic products. We determined BPA concentrations in premenopausal women by an enzyme-linked immunosorbent assay and evaluated possible linkage between its contamination levels and endometrial hyperplasia, an estrogen-related disorder of the uterus. It has been implied that higher levels of BPA, which binds to estrogen receptor and plays estrogenic roles may, enhance endometrial hyperplasia. Serum BPA was detectable in all subjects and its concentrations in healthy controls with normal endometrium were 2.5 +/- 1.5 ng/ml (mean +/- SD). BPA levels in patients with simple endometrial hyperplasia with benign nature were 2.9 +/- 2.0 ng/ml and were not significantly different from the controls. Unexpectedly, BPA levels in patients with complex endometrial hyperplasia with malignant potential were 1.4 +/- 0.4 ng/ml and significantly lower compared to both control and simple endometrial hyperplasia groups. In addition, we measured the serum BPA levels in postmenopausal endometrial cancer patient (1.4 +/- 0.5 ng/ml), which were also significantly lower than control and simple endometrial hyperplasia groups. These findings suggest the presence of associations between BPA exposure and complex endometrial hyperplasia and endometrial cancer. The mode of action of BPA may be more complex than expected and the contradictory results may serve as a clue to addressing the mechanisms of linkage between occurrence of estrogen-dependent diseases and endocrine disruption.

Benzhydryl Compounds↗

PubMed2003

Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells.

BACKGROUND: To achieve human embryonic stem (ES) cell-based transplantation therapies, allogeneic transplantation models of nonhuman primates would be useful. We have prepared cynomolgus ES cells genetically marked with the green fluorescent protein (GFP). The cells were transplanted into the allogeneic fetus, taking advantage of the fact that the fetus is so immunologically immature as not to induce immune responses to transplanted cells and that fetal tissue compartments are rapidly expanding and thus providing space for the engraftment. METHODS: Cynomolgus ES cells were genetically modified to express the GFP gene using a simian immunodeficiency viral vector or electroporation. These cells were transplanted in utero with ultrasound guidance into the cynomolgus fetus in the abdominal cavity (n=2) or liver (n=2) at the end of the first trimester. Three fetuses were delivered 1 month after transplantation, and the other, 3 months after transplantation. Fetal tissues were examined for transplanted cell progeny by quantitative polymerase chain reaction and in situ polymerase chain reaction of the GFP sequence. RESULTS: A fluorescent tumor, obviously derived from transplanted ES cells, was found in the thoracic cavity at 3 months after transplantation in one fetus. However, transplanted cell progeny were also detected (approximately 1%) without teratomas in multiple fetal tissues. The cells were solitary and indistinguishable from surrounding host cells. CONCLUSIONS: Transplanted cynomolgus ES cells can be engrafted in allogeneic fetuses. The cells will, however, form a tumor if they "leak" into an improper space such as the thoracic cavity.

Animals↗

PubMed2003

Concentrations of interferon-gamma-induced protein-10 (IP-10), an antiangiogenic substance, are decreased in peritoneal fluid of women with advanced endometriosis.

PROBLEM: To assess whether interferon-gamma-induced protein-10 (IP-10), a chemokine that has antiangiogenic activities, may be involved in the pathogenesis of endometriosis. METHOD OF STUDY: A total of 120 patients undergoing laparoscopy for pain and/or infertility were recruited, and peritoneal fluid (PF) and bone marrow derived cells in PF were collected. Concentrations of IP-10 in PF were measured with a specific enzyme-linked immunosorbent assay. Expression of IP-10 and IP-10 receptor, CXCR3, in bone marrow derived cells in PF, peritoneum and endometriotic cells was analyzed by reverse transcription-polymerase chain reaction. RESULTS: All of the PF samples examined contained detectable concentrations of IP-10. In women with advanced stages of endometriosis, IP-10 concentrations in PF were significantly lower than those of women in early stages (P = 0.02). The IP-10 concentrations in women with advanced endometriosis also appeared to be lower than those without endometriosis although the difference was statistically marginal (P = 0.06). The expression of both IP-10 and CXCR3 was clearly detected in the bone marrow derived cells in PF, peritoneum and endometriotic stromal cells. CONCLUSIONS: Decreased concentrations of IP-10 in PF from women with advanced stages of endometriosis may imply that the peritoneal environment of these women is permissive to the development of the disease by enhancing angiogenesis and/or modulating inflammatory/immunological responses.

Adult↗

PubMed2003

Upregulation of interleukin-8 by hypoxia in human ovaries.

PROBLEM: To evaluate the effect of hypoxia on interleukin (IL)-8 expression in human ovarian follicles. METHOD OF STUDY: Follicular fluid (FF) from each follicle was separately collected from women undergoing in vitro fertilization and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL-1alpha/beta, IL-8, and tumor necrosis factor (TNF)-alpha in FF were measured. Isolated granulosa-lutein cells (GLC) from obtained FF were cultured under normoxic or hypoxic conditions, and concentrations of IL-8 in culture media were measured. RESULTS: Simple regression analysis demonstrated a significant negative correlation between the concentrations of IL-8 and oxygen in FF (r = 0.50, P < 0.0001). However, none of the concentrations of progesterone, estradiol, IL-1beta, and TNF-alpha in FF showed a significant correlation with IL-8 concentrations. Hypoxia stimulated the secretion of IL-8 by cultured GLC over twofolds compared with a normoxic control (P < 0.05). CONCLUSIONS: These findings suggest that IL-8, like other angiogenic factors, is upregulated under hypoxic condition, which argues that hypoxia in the ovarian follicles comes into play in ovarian functions by inducing a range of proangiogenic and chemoattractive substances.

Adult↗

PubMed2003

Characteristic images of deeply infiltrating rectosigmoid endometriosis on transvaginal and transrectal ultrasonography.

BACKGROUND: To evaluate the usefulness of transvaginal and transrectal ultrasonography for diagnosis and management of deeply infiltrating rectosigmoid endometriosis. METHODS: A series of six patients (aged 32-39 years) with rectosigmoid endometriosis underwent transvaginal and transrectal ultrasonography. In three patients undergoing surgical resection of the intestine, the ultrasonographic findings were compared with macroscopic and microscopic findings. In one patient, sequential observations of the lesion using ultrasonography were conducted before and after medical treatment and following childbirth. RESULTS: In all cases, the lesion was detected as a hypoechoic irregular-shaped area surrounded by a hyperechoic rim located posterior to the uterus, with size ranging from 18 x 17 to 29 x 28 mm in diameter. The comparison of the ultrasonographical findings with histology revealed that the hypoechoic irregular-shaped area corresponded to a layer of hypertrophic muscularis propria of the lesion, while the hyperechoic rim represented the layer including the mucosa, submucosa and serosa. In one patient, the lesion decreased in size and lost its central hypoechoic area after childbirth in association with pain relief. CONCLUSIONS: Transvaginal and transrectal ultrasonography provides characteristic appearances for rectosigmoid endometriosis that correlate well with its histological findings. The procedures would be useful in the management of rectosigmoid endometriosis.

Adult↗

PubMed2002

Soluble FLT-1 expression suppresses carcinomatous ascites in nude mice bearing ovarian cancer.

Vascular endothelial growth factor (VEGF), a bifunctional protein enhancing vascular permeability and stimulating endothelial growth, is thought to be responsible for fluid accumulation and angiogenesis in ascites tumors. To investigate the effects of stable expression of the soluble form of Flt-1 VEGF receptor (sFlt-1), a known endogenous inhibitor of VEGF, on the malignant ascites tumors, we cotransduced RMG-1 human ovarian cancer cells with adeno-associated virus vectors carrying the sFlt-1 cDNA and Neo gene or Neo gene alone and isolated both the sFlt-1-expressing clone and the Neo-expressing clone. In vitro growth characteristics were essentially the same. As expected, conditioned medium collected from the sFlt-1-expressing cells significantly inhibited the human umbilical vein endothelial cell proliferation in the presence of recombinant VEGF. Expression of sFlt-1 significantly suppressed RMG-1 cell-induced angiogenesis in vivo in the mouse dorsal air sac assay model. We then inoculated sFlt-1- or Neo alone-expressing cells i.p. into female BALB/c nude mice. The average volume of ascites fluid, number of leaked RBCs, and number of cancer cells were significantly lower in mice injected with sFlt-1-expressing cells than in the controls. Survival time was significantly prolonged in mice injected with sFlt-1-expressing cells. These results suggest that inhibition of VEGF activity by sFlt-1 expression may provide a means to control carcinomatous ascites and angiogenesis of malignant ascites tumors.

Animals↗

PubMed2002

Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-midluteal estradiol levels in IVF cycles.

PURPOSE: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. METHODS: The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (< 100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. RESULTS: Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100-500 pg/mL) and high (> 500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). CONCLUSIONS: hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.

Adult↗

PubMed2002

Role of laparoscopy in the treatment of endometriosis-associated infertility.

Endometriosis is assumed to be one of the causative factors of infertility, although the mechanism remains to be elucidated. Mechanical factors distorting the pelvic anatomy and/or changes in the biochemical and cellular environment in the peritoneal cavity are possible contributing factors impairing fertility. Laparoscopy is a widely used diagnostic and therapeutic means of treating endometriosis-associated infertility. However, pregnancy outcome after laparoscopy varies depending on preexisting tubal adhesions and endometriosis. Without tubal adhesions, the pregnancy rate is essentially the same irrespective of the presence or stages of endoemetriosis. Minimal/mild endometriosis benefited the most from laparoscopic manipulation when tubal adhesions were present. On the other hand, IVF-ET outcome of patients who previously underwent laparoscopy was not influenced by preexisiting tubal adhesions and endometriosis.

Adult↗

PubMed2002

Is endometriosis really associated with pain?

To address the contrasting findings regarding how pain is related to endometriosis, the relationship between pain and stage of endometriosis was dissected differently by the chief complaint to eliminate selection biases. A total of 1,092 women with endometriosis were classified into two groups depending on their chief complaint, i.e., infertility (infertility group; n = 476) or pain (pain group; n = 616). The correlations between disease stage and various types of pain were analyzed differently in each group. The frequencies of chronic pelvic pain and dyspareunia increased with disease stage either in the infertility group, in the pain group or in the aggregate. On the other hand, no significant relation between the severity of dysmenorrhea and disease stage was observed in the aggregate. Interestingly, a parallel increase in the severity of dysmenorrhea with disease stage was observed in the infertility group, but not in the pain group. In view of selection biases involved in analyzing endometriosis associated with pain, these results could be seen to support the contention that chronic pelvic pain, dyspareunia and dysmenorrhea are in fact related to the extent of endometriosis.

Adolescent↗

PubMed2002

The activity of bisphenol A depends on both the estrogen receptor subtype and the cell type.

Bisphenol A (BPA), a monomer of plastic used in consumer products, is abundant in the environment and enters the body by ingestion or adsorption. In order to characterize the estrogenic effect of BPA, we performed luciferase assay on three independent cell lines derived from different tissues transfected with either human ERalpha cDNA or ERbeta cDNA. The estrogenic activities of BPA were detectable in all cell lines via both ERalpha and ERbeta. In 293T cells and Hec-1 cells, the estrogenic activities were significantly decreased when cells expressing ERalpha were incubated with 10(-6) M BPA in the presence of 10(-8) M 17beta-estradiol (E2) while the activities via ERbeta were essentially unchanged in the same conditions. Interestingly, no reduction of estrogenic activity was detected in HOS-TE85 cells via either ERalpha or ERbeta. Our results indicate that BPA only acts as an agonist of estrogen via ERbeta whereas it has dual actions as an agonist and antagonist in some types of cells via ERalpha. Thus, the activity of BPA may depend on the ER subtype and the tissue involved.

Benzhydryl Compounds↗