Ryoko Minekawa

Rapid changes of flow-mediated dilatation after surgical menopause

OBJECTIVES Estrogen acts directly on endothelial nitric oxide synthase through a non-genomic mechanism, resulting in rapid dilatation of blood vessels. In this study, we examined the change of endothelial function after surgical menopause. METHODS In 20 subjects who underwent gynecological operations (ovariectomy (OVX) 12, sham (SHAM) operation 8), postoperative changes of flow-mediated dilatation (FMD) of the brachial artery were examined using ultrasonography. Postoperative changes of the response to nitroglycerin (NTG) were also studied in these patients. RESULTS In the OVX group, significant decreases of FMD were observed 1 week after the operation, although no changes were observed in the response to NTG. In the SHAM group, no remarkable changes of FMD or the response to NTG were observed after the operation. CONCLUSIONS OVX influences endothelium-dependent vasodilatation within as little as 1 week. Therefore, it may be important to address the rapid changes of circulation after surgical menopause in order to prevent cardiovascular disease.

Metal Transcription Factor-1 Is Involved in Hypoxia-Dependent Regulation of Placenta Growth Factor in Trophoblast-Derived Cells

Placenta growth factor (PlGF) is a placental angiogenic factor. Metal-responsive transcription factor (MTF)-1 was reported to take part in the hypoxic induction of PlGF in RAS-transformed mouse fibroblasts. We contrarily showed that PlGF mRNA and protein levels decreased under hypoxia in a choriocarcinoma BeWo cell line derived from trophoblast. In this report, we examined whether hypoxia-dependent regulation of the PlGF gene in these cells also depends on MTF-1. We analyzed the effect of hypoxia on MTF-1 expression, and it was revealed to be decreased. Moreover, MTF-1 small interfering RNA treatment decreased PlGF mRNA level. To investigate the transcription of PlGF under hypoxia, we cloned promoter region of the human PlGF. Promoter deletion analysis suggested that triple repeats of metal-responsive element located between -511 and -468 bp in the promoter are important for the hypoxic regulation of PlGF. Treatment with MTF-1 small interfering RNA resulted in the significant decreased luciferase activity in PlGF reporter constructs. Chromatin immunoprecipitation showed the binding of the MTF-1 protein to the promoter region. We examined MTF-1 immunoreactivity in trophoblasts of term placental tissue from patients with normal pregnancies and preeclampsia, which represents a condition of placental hypoxia. Immunoreactivity of the MTF-1 protein was decreased in placentas from pregnant women with preeclampsia when compared with those from normal pregnant women. Taken together, these findings suggest that MTF-1 is involved in hypoxia-dependent regulation of PlGF in trophoblast-derived cells.

Hyperreactio luteinalis Associated with Severe Twin-to-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies, with high perinatal loss and significant morbidity. The etiology of this syndrome remains unclear. Hyperreactio luteinalis is a rare benign condition characterized by maternal ovarian enlargement due to theca lutein cysts. We present 4 cases of hyperreactio luteinalis associated with severe TTTS. We detected maternal ovarian enlargement by prenatal ultrasonography in 2 cases, at the cesarean section in 1 case, and postpartum in 1 case. Three cases showed hydrops fetalis and all cases showed congestive cardiac failure. Serial amnioreduction was performed in all cases, and regression of hydrops fetalis and maternal ovarian enlargement occurred in 1 case. These cases suggest that the pathophysiology of TTTS is closely related to the etiology of hyperreactio luteinalis.

Hypoxia Represses the Differentiation of Rcho-1 Rat Trophoblast Giant Cells

Background: A hypoxic environment is known to be essential for early placentation. A low oxygen tension induces hypoxia-inducible factor-1 (HIF-1α) which may play an important role as a transcription factor in maintaining the proliferative and undifferentiated phenotype in human trophoblasts. Methods: We analyzed the effect of a low oxygen tension on the rat trophoblast giant cell differentiation pathway using Rcho-1 cells which were derived from rat choriocarcinomas and consist of trophoblast stem cells. Results: We found that a low oxygen tension suppressed the morphological changes and steroidogenesis during differentiation. The anticipated downregulation of the Id-1 transcription factor, a negative regulator of trophoblast giant cell differentiation, was not observed in the hypoxic environment. On the other hand, deferoxamine, which mimics hypoxia and induces HIF-1α, caused downregulation of Id-1 transcription factor and trophoblast giant cell differentiation. Conclusion: These results indicate that hypoxia represses rat trophoblast giant cell differentiation via an HIF-1α-independent pathway.

Endoscopic third ventriculostomy during pregnancy

ology (CVUE), was observed. The frequency of maternal complications in scleroderma patients is not increased compared with healthy controls, except for renal crisis [1]. Prematurity and preterm births are amajor problem. In a recent study, pretermbirths occurred in 29% of scleroderma pregnancies [3]. Detailed descriptions of placental findings in scleroderma are limited and include chronic villitis associated with decidual vasculopathy, placental infarcts, abruption, as well as normal placentas [2]. In a recent study of 13 placentas from 8 women with scleroderma, decidual vasculopathy was observed in 5 placentas and was associated with poor perinatal outcome [4]. Decidual vasculopathy reflects pathological deviations from normal placentation, such as fibrinoid necrosis of vessel walls, with or without foamy macrophages (atherosis), vasculitis, and presence of small muscularized thick-walled blood vessels [5]. In the present case PMD, and not decidual vasculopathy, was the most prominent placental finding. PMD is associated with IUGR. The typical features of PMD, that were also observed in this case, are stem villi with excessive proliferation of mesenchymatous tissue, with foci of myxoid degeneration, and large stromalmacrophages and vessels with fibromuscular sclerosis and thrombosis [6]. In conclusion, PMD, decidual vasculopathy, and other placental lesions associated with compromised uteroplacental perfusion may appear in scleroderma and are correlated with poor perinatal outcome.

Impact of maternal methylenetetrahydrofolate reductase C677T polymorphism on intervillous and decidual pathology with pregnancy loss

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and intervillous and decidual pathology in patients with pregnancy loss was investigated.