Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts

H. Konishi, Mikiya Nakatsuka, C. Chekir, S. Noguchi, Yasuhiko Kamada, A. Sasaki, Y. Hiramatsu

Research output: Contribution to journalArticle

39 Citations (Scopus)

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-1β, 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-1β 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-1β 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-κB 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.

Original languageEnglish
Pages (from-to)2156-2162
Number of pages7
JournalHuman Reproduction
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2004

Fingerprint

Macrophage Inflammatory Proteins
Advanced Glycosylation End Products
Trophoblasts
First Pregnancy Trimester
Chemokines
Apoptosis
Chorionic Gonadotropin
Nitric Oxide Synthase
Bisbenzimidazole
Chorionic Villi
Placentation
Serine Proteinase Inhibitors
In Situ Nick-End Labeling
Smoke
Autoimmune Diseases
Culture Media
Transcription Factors
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

Keywords

  • Advanced glycation end product
  • Apoptosis
  • Chemokines
  • Protease inhibitor
  • Trophoblasts

ASJC Scopus subject areas

  • Physiology
  • Developmental Biology
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts. / Konishi, H.; Nakatsuka, Mikiya; Chekir, C.; Noguchi, S.; Kamada, Yasuhiko; Sasaki, A.; Hiramatsu, Y.

In: Human Reproduction, Vol. 19, No. 9, 09.2004, p. 2156-2162.

Research output: Contribution to journalArticle

Konishi, H. ; Nakatsuka, Mikiya ; Chekir, C. ; Noguchi, S. ; Kamada, Yasuhiko ; Sasaki, A. ; Hiramatsu, Y. / Advanced glycation end products induce secretion of chemokines and apoptosis in human first trimester trophoblasts. In: Human Reproduction. 2004 ; Vol. 19, No. 9. pp. 2156-2162.
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