Toshiki Matsuura

Anti-Macrophage Inhibitory Factor Antibody Inhibits PMSG-hCG-Induced Follicular Growth and Ovulation in Mice

AbstractPurpose: To investigate the effect of an anti-MIF antibody on PMSG-hCG-induced murine follicular growth and ovulation and to determine whether MIF plays an essential role in this process. Methods: Mice were primed with an intraperitoneal injection of pregnant mare serum gonadotropin (PMSG) and were treated with an anti-rat MIF antibody and human chorionic gonadotropin (hCG) to induce ovulation. After that, the ovulated ova were counted. The ovaries were studied using standard histological procedures. Results: Ovaries treated with the anti-MIF antibody showed reduced numbers of growing follicles surrounded by granulosa cells and theca cells with a little proliferation compared with the control. The average numbers of ova collected from mice treated with the anti-MIF antibody were reduced compared with those collected from control mice. Conclusions: Anti-MIF antibody inhibits the follicular growth and ovulation in mice, and MIF may play an important role in the inflammatory reactions during follicle growth and ovulation.

Increased expression of vascular endothelial growth factor in placentas of p57Kip2 null embryos

Placentas of mice lacking p57Kip2 expression have trophoblastic hyperplasia. To elucidate the mechanism underlying this phenomenon, we studied expression of two angiogenic factors, vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). Immunohistochemical analysis with anti‐VEGF antibodies indicated that VEGF expression was stronger and more clearly detectable in placentas of p57Kip2 null embryos compared to wild‐type placentas. PlGF showed no significant differences between placentas of p57Kip2 null and wild‐type embryos. In quantitative analysis, placentas of p57Kip2 null embryos showed higher VEGF messenger (m)RNA and protein levels than did wild‐type placentas. PlGF mRNA and protein levels were not significantly different. These findings suggest that VEGF is involved in the hyperplasia that occurs in placentas of p57Kip2 null embryos.

Recombinant adenovirus vector bearing antisense macrophage migration inhibitory factor cDNA prevents acute lipopolysaccharide-induced liver failure in mice.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in delayed hypersensitivity and cellular immunity. MIF also acts as a proinflammatory cytokine and counterregulates the anti-inflammatory effects of glucocorticoids. Exogenous gene transfer mediated by adenovirus is useful to study a particular molecular function as well as to develop gene therapy strategies. A recombinant adenovirus containing sense and antisense murine MIF (mMIF) cDNA inserts was constructed using a cosmid-terminal protein complex method. The sense mMIF adenovirus (AxCA-mMIFS) efficiently induced mMIF in COS-7 cells that endogenously lack mMIF in a dose-dependent manner. In contrast, the antisense mMIF adenovirus (AxCA-mMIFAS) inhibited the expression of mMIF in NIH3T3 cells in a dose-dependent manner. To assess the pathophysiologic role of MIF in acute liver failure, we induced acute onset of liver damage in mice (male Jcl:ICR) by a combined treatment of Bacille Calmette-Guerin (BCG) and lipopolysaccharide (LPS). mMIF level in the liver of mice infected with AxCA-mMIFAS showed a significant reduction in MIF production in response to BCG-LPS compared with mice treated without viral infection and with AxCA-mMIFS. In addition, the immunohistochemical staining demonstrated that F4/80 antigen on macrophage was enhanced in liver infected with AxCA-mMIFS but reduced in liver infected with AxCA-mMIFAS. The staining intensity is correlated with the mMIF antigen level in liver tissue. The survival rate of mice infected with AxCA-mMIFAS was significantly higher than that of mice treated with PBS and infected with AxCA-LacZ in BCG-LPS. These results suggest that inhibition of MIF production, using recombinant adenovirus bearing the antisense MIF gene, reduced the mortality rate in BCG-LPS–induced liver failure in mice. This finding might aid in the further development of gene therapy targeting MIF.

Alteration of Integrins under Hypoxic Stress in Early Placenta and Choriocarcinoma Cell Line BeWo

Invasion of the trophoblast into the decidua and the myometrium is very important for the establishment of a normal pregnancy. This invasion is regulated by the expression of integrins in the trophoblast. Recently, it has been shown that invasion of the trophoblast is impaired in preeclampsia. We report the effect of hypoxia on the expression of integrins and extracellular matrices at the mRNA level in early placenta and BeWo cells. Tissue RNA levels of fibronectin and integrin α5 were significantly higher in the hypoxic condition than under normoxic conditions. In contrast, tissue RNA levels of integrin α1 were significantly lower for the hypoxic condition than those under normoxic conditions. Alteration of the integrin components and increases in fibronectin expression were observed in early placenta and BeWo cells under hypoxic conditions. These results suggest that hypoxic stress regulates the synthesis of integrin and fibronectin mRNAs in early placenta.

Morphologic characteristics of the placental basal plate in in vitro fertilization pregnancies: a possible association with the amount of bleeding in delivery.

The aim of the present study was to investigate the relationship between assisted reproductive technology procedures, the morphology of the basal plate of placentas, and amount of bleeding in deliveries. Fifty-five whole placentas (fresh-embryo transfer in the in vitro fertilization cycle [n = 6], frozen-thawed embryo transfer in the natural cycle [n = 13] or in the hormonal cycle [n = 10], and age-matched spontaneously conceived pregnancies [n = 26]) were retrospectively enrolled and histologically analyzed. The whole placentas were stored in our pathological division among 512 singleton pregnancies with vaginal deliveries (34-41 weeks of gestation) at Hamamatsu University Hospital. The morphology of the placental basal plate was examined using Azan staining. A total of 20 digital images (each 0.53 mm(2)) of microscopic fields were analyzed per placenta to measure the mean values of the vertical maximum thickness of Rohr and Nitabuch fibrinoid layers and % loss of decidua. The thickness of Rohr fibrinoid layer and % loss of decidua were significantly higher in the frozen-thawed embryo transfer in the hormonal cycle group than in the frozen-thawed embryo transfer in the natural cycle and spontaneously conceived pregnancy groups (each P < .01). The z scores for both the thickness of Rohr fibrinoid layer and % loss of decidua positively correlated with those for the amount of bleeding in deliveries (P < .05 each). Assisted reproductive technology procedures changed the morphology of the placental basal plate, suggesting a possible association with an increase in the amount of bleeding in deliveries.

Rare form of extraovarian peritoneal serous papillary carcinoma with solitary tumor in the abdominal wall: a case report and literature review.

Cases of cancer presenting with microscopically confirmed metastatic malignancies for which no primary site can be detected are a challenge to stage clinically. Adenocarcinoma of unknown primary site is a subtype with high frequency that has no standard treatment and a poor prognosis. A 32‐year‐old female was found to have a tumor in the abdominal wall. Tumorectomy was conducted. A pathological examination indicated serous papillary adenocarcinoma, and peritoneal or ovarian cancer was suspected. Exploratory laparotomy and partial resection of the ovaries were carried out, but there were no malignant findings in the peritoneum, ovarian tissue or ascitic fluid. This is an extremely rare case of serous papillary adenocarcinoma with a cystic tumor that was categorized as extraovarian peritoneal serous papillary carcinoma (EPSPC) without other clinical findings.