Selective effects of perinatal estrogen on proliferation and new neurons in hippocampus and piriform cortex of rats at weaning.

BACKGROUND

A recent report links heightened prenatal amniotic estrogen levels to an increased risk of autism spectrum disorder (ASD). In this study, we examined the developmental effects of perinatal estrogen treatment on stem cell activity in weaned rats.

METHODS

Sprague-Dawley rats received ethinyl estradiol (EE2, 10 µg/kg/day) or vehicle orally from gestational day 6 until parturition. Offspring were then treated with the same daily dose from postnatal days (PNDs) 1-21. The effects of perinatal estrogen treatment on stem cell activities in the subgranular zone (SGZ) of the hippocampus and the piriform cortex were evaluated in male and female rat pups.

RESULTS

EE treatment increased the total Ki67-immunoreactive (Ki67-ir) cell counts in the SGZ of males and females (p < 0.05). However, no treatment or sex differences were detectable in the density of the doublecortin (DCX)-immunoreactive (DCX-ir) deposits in the hippocampus. In the piriform cortex, no treatment or sex differences were detected in Ki67-ir cell counts. However, the EE treatment significantly reduced the DCX-ir cell count in male, but not female rats (male EE group = 292 ± 22/mm, male vehicle group = 402 ± 19/mm, female EE group = 342 ± 15/mm, female vehicle group = 331 ± 9/mm).

CONCLUSIONS

Perinatal estrogen treatment increased hippocampal Ki67-ir cell counts in both sexes and selectively reduced DCX-ir cell counts in the piriform cortex of males. These data suggest that exposure to abnormally high levels of estrogens early in life may have an impact on neural cell development. Alterations in development so early in life may have long-term cognitive impact.