Manipulation of pre and postnatal androgen environments and anogenital distance in rats

Toxicology. 2016 Aug 10:368-369:152-161. doi: 10.1016/j.tox.2016.08.021. Epub 2016 Sep 14.

Abstract

We examined the anogenital distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13-20 with vehicle, flutamide (20mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750mg/kg/day), or testosterone (1.0mg/kg/day). After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days 23-53. In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats. Postnatal flutamide, DEHP, and testosterone induced slight but significant reductions in male AGD. Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero, although it can also be slightly responsive to changes in the androgen environment following pubertal exposure.

Keywords: Androgens; Anogenital Distance; Anogenital distance (AGD); Anti-androgens; DEHP; Endocrine Disruptors; Flutamide; Rats; Testosterone.

MeSH terms

  • Androgen Antagonists / toxicity*
  • Androgens / physiology*
  • Animals
  • Diethylhexyl Phthalate / toxicity
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Flutamide / toxicity
  • Male
  • Organ Size / drug effects
  • Penis / abnormalities*
  • Penis / drug effects
  • Pregnancy
  • Pregnancy Outcome
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Spermatids / drug effects
  • Spermatids / metabolism
  • Testis / abnormalities*
  • Testis / drug effects
  • Testosterone / biosynthesis

Substances

  • Androgen Antagonists
  • Androgens
  • Testosterone
  • Flutamide
  • Diethylhexyl Phthalate