[Habitual abortion].
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Abortion, Habitual↗
Biomedical subjects
Hidetaka Okada
Publications and source records attributed to Hidetaka Okada.
Cigarette smoke extract enhances oxytocin-induced rhythmic contractions of rat and human preterm myometrium.
Although smoking during pregnancy is a major risk factor for preterm delivery, the underlying mechanism by which smoking stimulates uterine contractions is still poorly understood. In the present study, we tried to clarify the effects of smoking on myometrial contractility induced by oxytocin (OT) using cigarette smoke extract (CSE). Myometrial strips, which were taken from the rat on day 16 of pregnancy, and from human preterm and term delivery groups, were incubated overnight with several doses of CSE at 37 degrees C under non-hormonal conditions. The uterine contractile sensitivity and activity (force and frequency) upon exposure to OT were investigated. Furthermore, the expression levels of oxytocin receptor (OTR) mRNA in the myometrial strips were investigated by real-time PCR. Contractile sensitivity to OT in the rat CSE (10(-7) pieces/ml) group was found to be significantly higher than in the control group (P < 0.05). Contractile activity did not differ between the CSE and control groups. The expression levels of rat OTR mRNA in the CSE (10(-7) pieces/ml) group were significantly higher than in the control group (P < 0.01). Similarly, in preterm myometrial strips, the expression levels of human OTR mRNA in the CSE (10(-7) pieces/ml) group were significantly higher than in the control group (P < 0.05). These findings suggest that CSE directly increases the contractile sensitivity of preterm myometrium in response to OT by upregulating the expression of OTR mRNA and thereby increases the risk of preterm delivery in women, who smoke during pregnancy.
Analysis of Variance↗
Serine peptidase HTRA3 is closely associated with human placental development and is elevated in pregnancy serum.
HTRA3 is a newly identified serine peptidase of the mammalian HTRA (high-temperature requirement factor A) family, that is upregulated dramatically during mouse placental development. The current study determined whether HTRA3 was involved in human placentation. During the menstrual cycle, HTRA3 was expressed primarily in the endometrial glands, being significantly upregulated toward the mid- to late secretory phases; prominent expression in the stroma detected only in the decidual cells in the late secretory phase. Thus, overall endometrial HTRA3 expression was highest in the late secretory phase, when the endometrium is prepared for maternal-trophoblast interaction. During the first trimester of pregnancy, both glandular and decidual HTRA3 expression increased further with the decidual upregulation being highly significant. The strong link between HTRA3 expression and endometrial stromal cell decidualization was further established in an in vitro model using primary endometrial stromal cells. HTRA3 was also expressed by certain trophoblast subtypes in the first-trimester placenta: strongly in the villous syncytiotrophoblast, trophoblast shell, and endovascular trophoblast and weakly in the distal portion of the trophoblast cell columns but not in villous cytotrophoblast, the proximal region of the cell columns, or interstitial trophoblast. Upregulation of HTRA3 expression in association with placental development was revealed by a significant elevation of this protein in the maternal serum during the first trimester. We thus propose that HTRA3 is a previously unrecognized factor closely associated with and potentially important for human placentation. This study established crucial groundwork for future investigations toward establishing the physiological roles of HTRA3 in human placentation.
Antibody Specificity↗
Expression of the endothelial cell differentiation gene 7 (EDG-7), a lysophosphatidic acid receptor, in ovarian tumor.
AIM: Lysophosphatidic acid (LPA) has received attention as a mitogen because the physiologically active lipid stimulates ovarian cancer cell growth by interacting with specific receptors, the endothelial cell differentiation gene (EDG) family. In the present study, we have investigated the expression of EDG-7 mRNA, part of the EDG family, in both human ovarian cancers and established human ovarian cancer cell lines. METHODS: RNA was extracted from six ovarian cancer cell lines and multiple cancerous and normal ovarian tissues. The expression of EDG-7 mRNA was measured using reverse transcription-polymerase chain reaction and northern blotting, using reduced glyceraldehyde-phosphate dehydrogenase and S26 as internal controls. RESULTS: Of the cell lines tested, EDG-7 mRNA was expressed most intensely in CRL-11731 and CRL-1572 and at a lesser but still substantial level in CRL-11732. The expression of EDG-7 mRNA was limited in MCAS, CRL-11730 and TYKnu. In the ovarian cancer tissues, EDG-7 mRNA was expressed most highly in endometrioid adenocarcinoma and serous cystadenocarcinoma. The expression of EDG-7 mRNA was limited in clear cell adenocarcinoma and undetectable in mucinous cystadenocarcinoma. CONCLUSIONS: The intense EDG-7 expression in ovarian cancers suggests that the relation between LPA and EDG-7 (an LPA receptor) is involved in cancer cell growth and proliferation in some histologic subtypes of ovarian cancer.
Case-Control Studies↗
Requirement for proprotein convertase 5/6 during decidualization of human endometrial stromal cells in vitro.
Decidualization of endometrial stromal cells (ESCs) is critical for embryo implantation and maintenance of pregnancy. Proprotein convertase (PC) 5/6 is suggested to play an important role in the processes of stromal cell decidualization and embryo implantation in the mouse. PC5/6 is a member of the PC family responsible for processing precursor proteins to their active forms by selective proteolysis. In this study, we investigated the regulation of PC5/6 mRNA and protein expression in human ESCs during decidualization in vitro. Real-time PCR analyses revealed a significant increase in PC5/6 mRNA levels in ESCs treated with 17 beta-estradiol (E(2)) plus medroxy-progesterone acetate during decidualization. On the other hand, E(2) alone did not increase PC5/6 mRNA expression. Intense PC5/6 immunoreactivity was observed in the cytoplasm of E(2) plus medroxy-progesterone acetate-treated ESCs (decidualized ESCs) compared with E(2)-treated ESCs on d 12 of culture (nondecidualized ESCs). This PC5/6 immunoreactivity was abolished by cotreatment with ZK 98299, a progesterone receptor antagonist. Western blotting revealed PC5/6 as approximately 120-kDa bands (pro- and mature forms) and a 65-kDa band (C-terminally truncated form) in decidualized ESCs. Using an antisense morpholino approach, prolactin production, a typical marker for decidualization, was significantly attenuated in decidualized ESCs after treatment with PC5/6 morpholino antisense oligonucleotides in comparison with controls. These results suggest that PC5/6 plays a key role for decidualization in human endometrium.
Cells, Cultured↗
Interleukin-1 inhibits interleukin-15 production by progesterone during in vitro decidualization in human.
Interleukin (IL)-15 is a novel cytokine that plays important roles in uterine natural killer cell function and one of the candidate genes that is upregulated during the window of implantation for human endometrium. IL-15 expression and production by human endometrial stromal cells (ESCs) is elevated during in vitro decidualization by progesterone (P). In the present study, we evaluated the effects of IL-1beta, a proinflammatory cytokine, on IL-15 production in ESCs. By enzyme-linked immunosorbent assay (ELISA), IL-1beta had no effect on IL-15 production from ESCs in short-term culture (for 24 h), whereas IL-1beta stimulated production of IL-8. However, using ELISA and Northern blot analyses we found that IL-1beta significantly inhibited P-induced IL-15 production and mRNA expression in long-term culture (for 12 days) of ESCs in vitro (P<0.01). This inhibition was not due to IL-1beta-mediated cytotoxicity, as ESCs cultured in the presence of IL-1beta showed no evidence of significant change in their viability. These results suggest that ovarian steroid hormones and IL-1beta regulate IL-15 mRNA expression and protein production in long-term culture, and that IL-1beta plays a role as a negative regulator of IL-15 production during decidualization in human endometrium.
Adult↗
Smoking enhances oxytocin-induced rhythmic myometrial contraction.
Although smoking during pregnancy is one of the major risk factors of premature delivery, the underlying mechanism by which smoking causes premature delivery is unknown. In the present study, we examined the effects of smoking on uterine contractility induced by oxytocin and prostaglandin F(2alpha). Rats inhaled either cigarette smoke or room air from Day 14 to Day 16 of pregnancy through an inhalation apparatus for experimental animals (type "Hamburg II"). After the rats were killed on Day 17 of pregnancy, the uterine contractile sensitivity and activity on exposure to oxytocin or prostaglandin F2alpha were investigated. The expression levels of oxytocin-receptor mRNA and prostaglandin F(2alpha) receptor mRNA in the uterus were investigated by reverse transcription-polymerase chain reaction. The contractile activity was assessed as the contractile force and the frequency of rhythmic contractions of myometrial strips that were treated with oxytocin or prostaglandin F(2alpha). The contractile sensitivity to oxytocin was significantly higher in the smoking group than in the control group (P < 0.01). Although the contractile force of oxytocin-induced contractions did not differ between the smoking and control groups, the frequency of contractions was significantly higher in the smoking group than in the control group (P < 0.01). On the other hand, no significant differences were found in the contractile sensitivity and activity in response to prostaglandin F(2alpha) between the smoking and control groups. The expression of oxytocin-receptor mRNA in the myometrium was significantly increased in the smoking group compared with the control group (P < 0.01). However, no significant difference was found in the level of expression of prostaglandin F(2alpha)-receptor mRNA between the two groups. These results suggest that smoking during pregnancy increases the contractile sensitivity and activity of the myometrium in response to oxytocin by up-regulating the expression of oxytocin-receptor mRNA. The effects of smoking on the contractile sensitivity and activity of the myometrium in response to oxytocin may increase the risk of premature delivery in smokers.
Animals↗
Expression of 20alpha-hydroxysteroid dehydrogenase mRNA in human endometrium and decidua.
Progesterone secreted from ovarian corpus luteum plays pivotal roles in endometrial differentiation, and local progesterone metabolism to regulate its concentration in endometrial tissues is essential for the successful implantation and maintenance of pregnancy. In this study, we evaluated the expression of mRNA for 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), a key enzyme which converts progesterone to a biologically inactive metabolite, in human endometrial tissues and cultured endometrial stromal cells as well as decidua and chorionic tissues of early pregnancy. The level of 20alpha-HSD mRNA expression in secretory phase endometrium was significantly higher than that in proliferative phase endometrium and chorionic tissues. The expression level in decidual tissue was also significantly higher than that in chorionic tissue. In cultured endometrial stromal cells, 20alpha-HSD mRNA expression was slightly enhanced at a lower progesterone concentration of 0.01 micromol/l, and an increase in its expression was significantly suppressed at higher concentrations of 1 micromol/l or greater. No effect on the gene expression was seen in cultured endometrial stromal cells with various concentrations of 17beta-estradiol. These results suggest that progesterone itself contributes to the regulation of local progesterone concentration through 20alpha-HSD levels in endometrial stromal cells at peri-implantation periods.
20-alpha-Hydroxysteroid Dehydrogenase↗