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

Chemosphere. 2016 Feb;144:1091-7. doi: 10.1016/j.chemosphere.2015.09.019. Epub 2015 Oct 23.


Hirschsprung's disease (HSCR) is neonatal intestinal abnormality which derived from the faliure of enteric neural crest cells migration to hindgut during embryogenesis from 5 to 12 weeks. Currenly, the knowledge of environmental factors contributing to HSCR is still scarce. Benzophenone-3 (BP-3) is one of the most widely used UV filters, and has weak estrogen and strong anti-androgenic effects. In order to examine the effect of maternal BP-3 exposure on development of offspring and explore the potential mechanism, we conducted case and control study and in vitro study. In this work, BP-3 concertrations in maternal urine was detected by ultra-high performance liquid chromatography. Besides, we investigated the cytotoxicity and receptor tyrosine kinase (RET) expression in cells exposed to BP-3. The results showed that maternal BP-3 exposure was associated with offspring's HSCR in the population as well as inhibited migration of 293T and SH-SY5Y cells. What's more, we discovered dose-response relationship between RET expression and BP-3 exposure dose, and miR-218 and some other genes involved in SLIT2/ROBO1-miR-218-RET/PLAG1 pathway were also related to BP-3 exposure. Therefore, we deduced that BP-3 influenced cell migration via SLIT2/ROBO1-miR-218-RET/PLAG1 pathway. Our study firstly revealed the relationship between maternal BP-3 exposure and HSCR as well as its potential mechanism.

Keywords: Benzophenone-3; Hirschsprung's disease; Migration; Pathway; Receptor tyrosine kinase; miR-218.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzophenones / toxicity*
  • Benzophenones / urine
  • Case-Control Studies
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Environmental Pollutants / toxicity*
  • Environmental Pollutants / urine
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • HEK293 Cells
  • Hirschsprung Disease / chemically induced*
  • Hirschsprung Disease / epidemiology
  • Hirschsprung Disease / genetics
  • Humans
  • Male
  • Maternal Exposure / adverse effects*
  • MicroRNAs / genetics
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / epidemiology
  • Prenatal Exposure Delayed Effects / genetics
  • Proto-Oncogene Proteins c-ret / genetics


  • Benzophenones
  • Environmental Pollutants
  • MIRN218 microRNA, human
  • MicroRNAs
  • oxybenzone
  • Proto-Oncogene Proteins c-ret