title: The relationship between prenatal exposure to BP-3 and Hirschsprung's disease.
abstract: 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.
authors.affiliation: State 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.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huo
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cai
authors.affiliation: State 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.
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
authors.forename: Weibing
authors.initials: W
authors.lastname: Tang
authors.affiliation: State 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. Electronic address: yankaixia@njmu.edu.cn.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000328:Adult; D001577:Benzophenones / Q000633:toxicity* / Q000652:urine; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity* / Q000652:urine; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D057809:HEK293 Cells; D006627:Hirschsprung Disease / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D035683:MicroRNAs / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics
chemical_list: D001577:Benzophenones; D004785:Environmental Pollutants; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; C005290:oxybenzone; D051096:Proto-Oncogene Proteins c-ret
keywords: Benzophenone-3; Hirschsprung's disease; Migration; Pathway; Receptor tyrosine kinase; miR-218