title: The mechanism underlying dibutyl phthalate induced shortened anogenital distance and hypospadias in rats.
abstract: OBJECTIVE
  The purpose of this study was to investigate the mechanism of dibutyl phthalate (DBP) induced hypospadias and shortened anogenital distance (AGD).
  
  
  METHODS
  AGD, hypospadias, and cryptorchidism incidence was observed in male offspring of DBP treated pregnant Wistar rats. Testicular development and testosterone levels of normal and DBP-treated rat embryos were compared.
  
  
  RESULTS
  Male offspring of 300mg and 900mg DBP-treated pregnant Wistar rats exhibited shortened average AGD compared with the control group. A 22.7% hypospadias incidence was observed in the 300mg group, but no offspring with cryptorchidism were identified. In the 900mg group, hypospadias and cryptorchidism incidence reached 43.5% and 17.4%, respectively. Between E15.5 and E17.5, the 300mg group exhibited delayed testicular development and testosterone secretion. However, testicular development and testosterone secretion subsequently recovered. The 300mg treated and control groups had similar measures after E19.5. Contrastingly, testicular development and testosterone secretion were significantly diminished throughout development in the 900mg group. Exogenous testosterone partially counteracted DBP-induced changes in the reproductive organs of male offspring of DBP-treated rats.
  
  
  CONCLUSIONS
  High-dose DBP exposure may induce testicular dysgenesis in rat embryos. Additionally, low-dose DBP may delay testicular development and testosterone secretion during urethral development. This disruption may result in hypospadias.
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Xuyong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: fengjiexiong008@163.com.
authors.forename: Jiexiong
authors.initials: J
authors.lastname: Feng
mesh_terms: D001003:Anal Canal / Q000002:abnormalities; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003456:Cryptorchidism / Q000139:chemically induced* / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005832:Genital Diseases, Male / Q000139:chemically induced / Q000378:metabolism; D007021:Hypospadias / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010968:Plasticizers; D003993:Dibutyl Phthalate; D013739:Testosterone
keywords: Anogenital distance (AGD); Dibutyl phthalate (DBP); Hypospadias; Testicular development