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The relationship between prenatal exposure to BP-3 and Hirschsprung's disease

Weiwei Huo1, Peng Cai2, Minjian Chen1

  • 1State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

Chemosphere
|October 11, 2015
PubMed

Insights

Maternal exposure to Benzophenone-3 (BP-3), a common UV filter, is linked to Hirschsprung

Area of Science:

  • Environmental Health
  • Developmental Biology
  • Toxicology

Background:

  • Hirschsprung's disease (HSCR) is a congenital intestinal disorder caused by failed neural crest cell migration.
  • Environmental factors contributing to HSCR are not well understood.
  • Benzophenone-3 (BP-3), a widely used UV filter, exhibits endocrine-disrupting properties.

Purpose of the Study:

  • To investigate the association between maternal BP-3 exposure and HSCR in offspring.
  • To explore the underlying molecular mechanisms of BP-3's effects on neural crest cell migration.

Main Methods:

  • Case-control study analyzing BP-3 concentrations in maternal urine using ultra-high performance liquid chromatography.
  • In vitro studies assessing cytotoxicity and effects on cell migration (293T and SH-SY5Y cells).
  • Investigation of gene and microRNA expression, focusing on the SLIT2/ROBO1-miR-218-RET/PLAG1 pathway.

Main Results:

  • Maternal BP-3 exposure was significantly associated with HSCR in offspring.
  • BP-3 exposure inhibited the migration of neural crest-derived cells in vitro.
  • A dose-dependent relationship was observed between BP-3 exposure and RET expression, implicating the SLIT2/ROBO1-miR-218-RET/PLAG1 pathway.

Conclusions:

  • Maternal exposure to the UV filter BP-3 is a potential environmental risk factor for Hirschsprung's disease.
  • BP-3 disrupts neural crest cell migration, likely through the SLIT2/ROBO1-miR-218-RET/PLAG1 signaling pathway.
  • This study provides novel insights into the environmental etiology of HSCR.

Keywords:
Benzophenone-3Hirschsprung's diseaseMigrationPathwayReceptor tyrosine kinasemiR-218

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