Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts
Authors: Konishi, H.; Nakatsuka, M.; Chekir, C.; Noguchi, S.; Kamada, Y.; Sasaki, A.; Hiramatsu, Y.
Source: Human Reproduction, Volume 19, Number 9, September 2004 , pp. 2156-2162(7)
Publisher: Oxford University Press
Abstract:BACKGROUND: We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or that smoke, on human trophoblasts. METHODS: First trimester human chorionic villi of 6–10 week gestation were obtained. Expression and localization of the receptor for AGEs (RAGE) was examined by western blotting and immunohistochemistry. Macrophage inflammatory protein (MIP)-1α and MIP-1, regulated upon activation, normal T-cell expressed and secreted (RANTES), and human chorionic gonadotropin (hCG) in culture medium were measured by ELISA. Trophoblastic apoptosis was evaluated by the Hoechst 33258 staining and the in situ nick end labeling technique. RESULTS: RAGE was localized in trophoblasts. AGEs significantly stimulated secretion of both MIP-1α and MIP-1 from trophoblasts in a time- and dose-dependent manner. AGEs significantly induced apoptosis and reduced secretion of hCG. Increased secretions of MIP-1α and MIP-1 by AGEs were significantly suppressed by inhibitors of nitric oxide synthase (NOS) or nafamostat mesilate, a synthetic serine protease inhibitor and a suppressor of transcription factor, NF-B activation. These agents also suppressed the effects of AGEs on hCG secretion and trophoblastic apoptosis. CONCLUSIONS: These AGE-mediated changes in trophoblasts may lead to impairment of implantation and placentation. NOS inhibitors or nafamostat mesilate may modify these effects.
Document Type: Research Article
Affiliations: To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Okayama University Medical School, 2-5-1 Shikata, Okayama City, Okayama, 700-8558 Japan.ext. 7320);, Tel: 086 223 7151 (, Fax: 086 225 9570, Email: email@example.com
Publication date: September 2004
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.