Masahiro Mitsunari

Role of Cytokines in Progression of Endometriosis

Peritoneal fluid in women with endometriosis contains an increased number of activated macrophages that secrete a variety of cytokines, including interleukin (IL)-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor-α (TNF-α). Cytokines may be involved in the control of implantation and the growth of endometrial cells outside the uterus. In addition, several cytokines have been implicated in or directly associated with angiogenic activity in endometriosis. There could be a relationship between the levels of cytokines in the peritoneal fluid of patients with endometriosis and the status of the lesions in such patients. Peritoneal endometriosis can be classified as having red, black, or white lesions. Red lesions are known to be an active form of early endometriosis, because vascularization and mitotic activity are shown to be most prominent in these lesions. We found that the peritoneal fluid levels of TNF-α and IL-8 were significantly higher in patients with endometriosis, and correlated with the size and number of active lesions. In addition, TNF-α and IL-8 stimulated the growth of ectopic endometrial stromal cells. These cytokines with angiogenic activity may therefore have significant roles in the pathogenesis of endometriosis.

Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients with ovarian endometriomas

OBJECTIVE To determine whether serum interleukin (IL)-6 can be measured in patients with ovarian endometriomas and whether these measurements are useful in managing this disease. DESIGN A controlled clinical study and an in vitro study. SETTING Department of Obstetrics and Gynecology, Tottori University, Japan.Twenty-two patients with ovarian endometriomas. INTERVENTION(S) Laparoscopic cystectomy for ovarian endometriomas was performed. Gonadotropin-releasing hormone (GnRH) agonist was administered for 3 months in nine patients before laparoscopic surgery. Endometriotic stromal cells obtained from patients with endometriomas with or without GnRH agonist treatment were cultured. MAIN OUTCOME MEASURES(S) IL-6 concentrations in serum or supernatant of the cell culture were measured using ELISA. RESULTS The serum concentration of IL-6 in patients with endometriomas was higher at the time of diagnosis than in those without endometriomas. Laparoscopic surgery significantly reduced serum levels of IL-6. Serum IL-6 concentrations also decreased after treatment with GnRH agonist. IL-6 production was attenuated in the endometriotic stromal cells obtained from patients with GnRH agonist treatment compared with patients without such treatment. CONCLUSION(S) GnRH agonist treatment may decrease IL-6 production in endometriotic cells. Measurement of serum IL-6 concentrations may be of value in managing patients with endometriomas.

Cervical Ureaplasma urealyticum colonization might be associated with increased incidence of preterm delivery in pregnant women without prophlogistic microorganisms on routine examination.

Aim: We examined whether the detection of Ureaplasma urealyticum DNA in the cervix is associated with preterm labor and delivery.

Interleukin-1beta-induced expression of IL-6 and production of human chorionic gonadotropin in human trophoblast cells via nuclear factor-kappaB activation.

Problem:  The cytokine, interleukin‐6 (IL‐6), stimulates the production of human chorionic gonadotropine (hCG) in chorionic cells. The purpose of this study was to examine the role of nuclear factor‐κB (NF‐κB) during the induction of IL‐6 by IL‐1β in human trophoblast cells.

Coculture with a human granulosa cell line enhanced the development of murine preimplantation embryos via SCF/c-kit system.

AbstractPurpose: To evaluate the effect on the coculture of murine embryos with a human ovarian granulosa tumor derived cell line (KGN cells). Methods: We observed microscopically the growth of murine preimplantation embryos in the coculture system with KGN cells or in the presence with exogenous stem cell factor (SCF). The reverse transcriptase–polymerase chain reaction (RT-PCR) method was used to analyze the gene expression of SCF in KGN cells cocultured with murine embryos. Results: The coculture system with KGN cells significantly increased the rate of embryo development to late blastocyst and to hatching stage. We also found that coculture with murine embryos enhanced the gene expression of SCF in KGN cells. Adding human recombinant SCF to the medium significantly enhanced embryo development to late blastocyst and hatching stage. Conclusions: KGN cells may facilitate preimplantion embryo development through SCF/c-kit paracrine system.

Autocrine Effects of Transforming Growth Factor-α on the Development of Preimplantation Mouse Embryos

Purpose:We wished to explore the role of transforming growth factor (TGF)-α in mouse embryonic development.Methods:We examined the gene expression of TGF-α and epidermal growth factor receptor (EGFR) in mouse blastocysts by the reverse transcription–polymerase chain reaction and evaluated the effects of TGF-α on the development of preimplantation mouse embryos using TGF-α antisense oligodeoxynucleotide. Mouse teratocarcinoma F9 cells were also a subject of this study.Results:Gene transcripts of TGF-α and EGFR were present in both blastocysts and F9 cells. TGF-α significantly stimulated the rate of blastocoel expansion in early-cavitating blastocysts and the proliferation of F9 cells. Northern blot analysis showed that TGF-α gene expression in F9 cells was markedly suppressed in the presence of TGF-α antisense oligodeoxynucleotide. TGF-α antisense oligonucleotide significantly reduced the rate of blastocoel expansion and the growth of F9 cells. The inhibitory effects of TGF-α antisense oligonucleotide on blastocysts and F9 cells were reversed by the addition of TGF-α.Conclusions:The present observations suggest that TGF-α acts as an autocrine factor in the development of preimplantation mouse embryos.