Sex-specific alterations of cerebral cortical cell size in rats exposed prenatally to dioxin

J Appl Toxicol. 2006 Jan-Feb;26(1):25-34. doi: 10.1002/jat.1101.


Sex-specific patterns of cerebral cortical lateralization have been documented consistently in both the human and animal brain. Male rats tend to exhibit pronounced right hemisphere dominance compared with females, while females typically exhibit more diffuse lateralization patterns and greater left hemisphere bias compared with males. Prenatal TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin) exposure produces demasculinization of male offspring sexual behavior, suggesting interference with sexual differentiation of the brain. In previous studies, a reversal of cortical thickness patterns in rats was shown after prenatal TCDD exposure on gestational day 8 (GD 8). The current study, based on the same brain sections, attempted to define changes in the number of cortical cells and cell size distributions in brains of offspring from TCDD-treated dams. Pregnant females were given a single oral dose of 0 or 180 ng kg(-1) TCDD on GD 8. Cell counts and sizes were determined in 3-month-old offspring. Areas 17 and 18a at bregma -3.8 were analysed using digitized, enhanced images of brain sections produced by a photomicroscope fitted with a high-resolution digital camera. Prenatal TCDD exposure altered the relative proportions of smaller and larger cell sizes in male, but not in female offspring. Both exposed males and females, however, exhibited a significant reversal of hemispheric dominance based on cell number. These findings demonstrate that prenatal exposure to TCDD alters the normal patterns of cortical cell asymmetry in a manner consistent with our previous data on thickness patterns.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Count
  • Cell Size / drug effects*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / pathology
  • Dominance, Cerebral / drug effects*
  • Endocrine Disruptors / toxicity
  • Female
  • Male
  • Polychlorinated Dibenzodioxins / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors
  • Teratogens / toxicity*


  • Endocrine Disruptors
  • Polychlorinated Dibenzodioxins
  • Teratogens