title: In utero exposure of high-dose di- n-butyl phthalate resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal male rat offspring.
abstract: OBJECTIVE
  To investigate the effects of in utero exposure to high-dose di- n-butyl phthalate (DBP) on testicular cell apoptosis in late embryonic and pubertal male rat offspring.
  
  
  METHODS
  Twenty pregnant Sprague-Dawley (SD) rats were divided into two groups. During gestation day (GD) 12 to GD 19, control group was given 1 ml day-1of olive oil and experimental group was given DBP 500 mg kg-1day-1by gavage. On GD 19.5 and postnatal day (PND) 45, the testes were removed. Morphological analysis of the testes was observed by transmission electron microscopy and hematoxylin and eosin (H&E) staining. Testicular cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of Bcl-2, Bax, and p53 was presented by immunohistochemistry (IHC) and western blot. Data of the two groups was compared using independent samples t-test and Mann-Whitney test by SPSS 20.0.
  
  
  RESULTS
  H&E staining showed that spermatogenetic cells were significantly decreased in DBP exposed pubertal rat testis. The apoptosis index of testes in DBP-treated group was significantly lower on GD 19.5 but higher on PND 45 than that of the controls ( p < 0.01). IHC and western blot revealed significantly increased expression of Bcl-2 in GD 19.5 rat testis and Bax and p53 in PND 45 rat testis after DBP exposure, compared with the control ( p < 0.05).
  
  
  CONCLUSIONS
  In utero exposure of high-dose DBP resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal rat offspring. The overexpression of Bcl-2, Bax, and p53 might be related to the occurrence of abnormal apoptosis and finally produce male infertility.
authors.affiliation: 1 Department of Urology, BenQ Medical Center, Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: 1 Department of Urology, BenQ Medical Center, Nanjing Medical University, Nanjing, China.
authors.forename: K
authors.initials: K
authors.lastname: Liao
authors.affiliation: 1 Department of Urology, BenQ Medical Center, Nanjing Medical University, Nanjing, China.
authors.forename: H-F
authors.initials: HF
authors.lastname: Wu
authors.affiliation: 2 School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: H-C
authors.initials: HC
authors.lastname: Lu
authors.affiliation: 2 School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: 2 School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: 3 Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003456:Cryptorchidism / Q000139:chemically induced; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D012734:Disorders of Sex Development / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects; D005260:Female; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000166:cytology*
chemical_list: D003993:Dibutyl Phthalate
keywords: Testicular dysgenesis; apoptosis; di-n-butyl phthalate; rat