The function of granulosa cells is regulated by various hormones and growth factors. Our aim is to clarify the regulation of vascular endothelial growth factor (VEGF) production induced by heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) in a human granulosa cell line, KGN. KGN cells were cultured and incubated for 24 h with HB-EGF and AR. The levels of VEGF in the culture media were measured by an enzyme-linked immunosorbent assay. The activation of MAP kinase in KGN cells was detected by Western blot analysis. VEGF production was significantly increased by HB-EGF or AR alone in a dose-dependent manner, whereas it was decreased by AG1478 or U0126. The MAP kinase activity was increased by treatment with HB-EGF or AR. The results suggested that VEGF is induced by HB-EGF and AR through mechanisms involving MAP kinase. The increase in VEGF may contribute to neovascularization, which in turn would promote various ovulation phenomena as well as follicular growth.

Background: In order to investigate the roles of epidermal growth factor (EGF) and transforming growth factor (TGF)-α in ovulation, we studied the production of interleukin (IL)-8 and growth-regulated oncogene (GRO)-α in cultured human granulosa-lutein cells. Methods: Granulosa-lutein cells obtained from the follicular fluids of in vitro fertilization and embryo transfer patients were cultured and treated with EGF, TGF-α, tumor necrosis factor (TNF)-α or 12-O-tetradecanoylphorbol 13-acetate (TPA). An immortalized granulosa cell line (GC1a) was also cultured and treated with EGF, TGF-α or mitogen-activated protein kinase kinase inhibitor. The supernatants were collected, and IL-8 and GRO-α were measured by ELISA. Results: The levels of IL-8 and GRO-α were significantly increased after treatment with EGF, TGF-α, TNF-α and TPA by primary cultured granulosa-lutein cells. The levels of IL-8 and GRO-α were also significantly increased after treatment with EGF or TGF-α in a dose-dependent manner by GC1a. When GC1a was treated with EGF, TGF-α or U0126, the levels of IL-8 and GRO-α were significantly decreased. Conclusion: Our data indicate that the production of IL-8 and GRO-α is upregulated by EGF and TGF-α. It is suggested that EGF and TGF-α may play an important role in luteinization processes involving IL-8 and GRO-α production.

A 37-year-old primigravida at 35 weeks of gestation presented with known anterior wall dominant placenta previa totalis and suspected placenta accreta was successfully treated with transfundal uterine (transverse) incision performed with prophylactic common iliac artery balloon occlusion. This new surgical approach could be an alternative procedure for avoiding excessive blood loss during caesarean delivery.

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