Prevention of neonatal estrogen imprinting by vitamin A as indicated by estrogen receptor expression in the mouse vagina

Abstract

Treatment of female mice with estrogen during the neonatal period induces estrogen-independent persistent proliferation and cornification of the vaginal epithelium when the animals become adults. However, the occurrence of such irreversible vaginal changes is blocked by concurrent retinol acetate (RA) treatment. This study aimed to determine the expression pattern of estrogen receptor (ER) α and β in the vaginas of ovariectomized 35-day-old mice treated neonatally with 17β-estradiol (E₂) and/or RA. The amounts of ERα and ERβ mRNA molecules in the vaginal RNA samples were determined by competitive reverse transcription/polymerase chain reaction. The levels of both mRNAs were lower in ovariectomized mice that had been treated neonatally with E₂ but not in those treated with E₂ plus RA. Neonatal E₂ treatment caused a decrease in the percentage of ERα-immunoreactive cells in the vaginal stroma during adulthood, and concurrent RA treatment inhibited the decrease. The amount of each ER mRNA was also measured in the vaginas of mature mice treated with E₂ and RA; no inhibitory activity of RA was seen in the mature mice. Our studies indicate that, in mouse vagina, the irreversible effects of neonatal imprinting by estrogen might be prevented by the simultaneous administration of vitamin A through the inhibition of a decrease of the number of ER-expressing cells.