The orl rat with inherited cryptorchidism has increased susceptibility to the testicular effects of in utero dibutyl phthalate exposure

Toxicol Sci. 2008 Oct;105(2):360-7. doi: 10.1093/toxsci/kfn140. Epub 2008 Jul 10.


Phenotype results from interactions between genetics and environment, but for most environmental chemical exposures, such interactions are theoretical. The phenotypic response of the testis to in utero dibutyl phthalate (DBP) exposure was compared between two strains of Long-Evans (LE) rats, the orl substrain with inherited cryptorchidism and an outbred (wt) strain. orl and wt LE rats were exposed daily between gestational day (GD) 12 and GD21 to DBP dose levels ranging from 50 to 200 mg/kg by oral gavage and sensitive phthalate testicular end points examined at either GD19, GD21, or postnatal day (PND) 21. At 50 mg/kg DBP, GD19 expression of Cyp17a1, Insl3, and Scarb1 was significantly reduced in orl but not wt testis. At GD21, statistically significant differential strain effects (orl more sensitive than wt) were observed for testicular expression of Scarb1 at 50 and 200 mg/kg DBP and Star at 200 mg/kg DBP. Similarly, DBP exposure disproportionately increased GD21 seminiferous cord diameters and numbers of multinucleated germ cells in the orl strain. At PND21, body weight-corrected testis weights were lowered significantly by DBP exposure at all dose levels in the orl strain but not in wt rats. While the frequency of undescended testes after 200 mg/kg DBP exposure in the orl strain appeared increased, these data were not statistically significant. These results demonstrated enhanced sensitivity of the orl rat to phthalate exposure as compared to its parent strain, a potentially important model of the effects of gene-environment interaction on development of male reproductive malformations.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Cryptorchidism / embryology*
  • Cryptorchidism / enzymology
  • Cryptorchidism / genetics
  • Cryptorchidism / pathology
  • Dibutyl Phthalate / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Gestational Age
  • Insulin / metabolism
  • Male
  • Organ Size
  • Phenotype
  • Phosphoproteins / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Proteins / metabolism
  • Rats
  • Rats, Long-Evans
  • Scavenger Receptors, Class B / metabolism
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Testis / drug effects*
  • Testis / embryology
  • Testis / enzymology
  • Testis / pathology


  • Insulin
  • Leydig insulin-like protein
  • Phosphoproteins
  • Proteins
  • Scarb1 protein, rat
  • Scavenger Receptors, Class B
  • steroidogenic acute regulatory protein
  • Dibutyl Phthalate
  • Steroid 17-alpha-Hydroxylase