IDENTIFICATION OF USEFUL BIOMARKERS FOR RISK ASSESSMENT OF FETAL EXPOSURE TO ENVIRONMENTAL POLLUTION

• Project/Area Number: 16591641
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: JUNTENDO UNIVERSITY (2005-2006); Chiba University (2004)
• Principal Investigator: OSADA Hisao Shizuoka Hospital, OB & GY, Assistant Professor, 医学部, 講師 (30233505)
• Co-Investigator(Kenkyū-buntansha): SAKAMOTO Rie Chiba University Hospital, OB & GY, Assistant, 医学部附属病院, 助手 (00375635) ; SEKI Katsuyoshi Chiba University, Reproductive Med, Professor, 医学部附属病院, 助教授 (90272319) ; SEKIYA Souei Chiba University, Reproductive Med, Professor, 医学部附属病院, 教授 (00092065) ; NOMURA Fumio Chiba University, Molecular Diagnosis, Professor, 医学部附属病院, 教授 (80164739) ; MORI Chisato Chiba University, Bioenvironmental Med, Professor, 医学部附属病院, 教授 (90174375)
• Project Period (FY): 2004 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: fetus / environmental pollution / risk assessment / biomaker / proteinchip / 2 dimensional electrophoresis / umbilical cord blood / PCB (polychlorinated biphenyl) / 臍帯

Research Abstract

In this study, we tried to identify useful biomarkers for risk assessment of fetal exposure to PCB (polychlorinated biphenyl). The subjects were 52 women with singleton fetus, who followed normal pregnancy course and gave informed consent. PCB concentration levels in cord blood of their normal neonates were measured by high resolution gas chromatography-high resolution mass spectrometry. The highest 5 cases and lowest 5 cases in PCB levels were defined as the high and low concentration groups, respectively. The protein levels in cord blood samples of these 10 cases were measured and an agarose 2-dimensional difference gel electrophoresis (agarose 2D-DIGE) composed of molecular weight and isoelectric point was performed. The spots on the gel protein-stained, which had significant differences in signal levels between the high and low concentration groups, were collected. They were digested with trypsin in the gel and containing proteins were identified by ion-trapped type LC-MS/MS system. PCB concentrations (ng/g-wet) were distributed from 16 to 390. There were 5 spots having significantly higher staining signal levels in the high concentration group (MW: 60 KD, 40 KD, 40 KD, 35 KD, 35 KD). On the contrary, one spot had significantly higher staining signal levels in the low concentration group (01: 35 KD). There were a-fetoprotein, fibrinogen β-chain, and apolipoprotein E among the candidate proteins chosen by LC-MS/MS. β2-microglobulin, fibrinogen a-chain, and fibrinogen y-chain were chosen as the candidate proteins in the second protein analysis. In conclusion, the combination of agarose 2D-DIGE and LC-MS/MS clarified that there were multiple kinds of proteins associated with fetal exposure to PCB in cord blood and partially identified their compositions. Future studies will investigate whether above candidate proteins are useful biomarkers by prospectively analyzing association between protein levels in maternal serum and chemical levels in cord blood.

Research Products

• [Journal Article] Necessity to measure PCBs and organochlorine pesticide concentrations in human umbilical cords for fetal exposure assessment. (2005)
  • Author(s): Fukata, H., Omori, M., Osada, H., Todaka, E., Mori, C.
  • Journal Title: Environ. Health Perspect. 113 Pages: 297-303
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Fetal exposure to phytoestrogens - the difference of phytoestrogen status in mother and fetus. (2005)
  • Author(s): Todaka, E., Sakurai, K., Fukata, H., Miyagawa, H., Uzuki, M., Omori, M., Osada, H., Ikezuki, Y., Tsutsumi, O., Iguchi, T., Mori C.
  • Journal Title: Environ. Res. 99 Pages: 195-203
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Necessity to measure PCBs and organochlorine pesticide concentrations in human umbilical cords for fetal exposure assessment. (2005)
  • Author(s): Fukata, H., Omori, M., Osada, H., Todaka, E., Mori, C.
  • Journal Title: Environ.Health Perspect. 113 Pages: 297-303
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fetal exposure to phytoestrogens-the difference of phytoestrogen status in mother and fetus. (2005)
  • Author(s): Todaka, E., Sakurai, K., Fukata, H., Miyagawa, H., Uzuki, M., Omori, M., Osada, H., Ikezuki, Y., Tsutsumi, 0., Iguchi, T., Mori C.
  • Journal Title: Environ.Res. 99 Pages: 195-203
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The contamination levels of 3 organochlorines and the pattern of gene expressions in human umbilical cords from intra-pairs of twins at delivery.
  • Author(s): Omori-Inoue, M., Fukata, H., Komiyama, M., Todaka, E., Aburatani, H., Osada, H., Mori, C.
  • Journal Title: Reprod. Toxicol. (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The contamination levels of 3 organochlorines and the pattern of gene expressions in human umbilical cords from intra-pairs of twins at delivery.
  • Author(s): Omori-Inoue, M., Fukata, H., Komiyama, M., Todaka, E., Aburatani, H., Osada, H., Mori, C.
  • Journal Title: Reprod.Toxicol. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The contamination levels of 3 organochlorines and the pattern of gene expressions in human umbilical cords from intra-pairs of twins at delivery.
  • Author(s): Omori-Inoue, M., Fukata, H., Komiyama, M., Todaka, E., Aburatani, H., Osada, H., Mori, C.
  • Journal Title: Reprod. Toxicol. (in press)