Role of the epithelial-stromal interaction during the development and expression of ovary-independent vaginal hyperplasia

The tissue interactions involved in the induction and perpetuation of ovary-independent vaginal hyperplasia were studied by growing recombinants prepared with vaginal epithelium and stroma from untreated and neonatally estrogenized mice. As expected, recombinants prepared with untreated tissues developed an atrophied epithelium, while those prepared with estrogenized epithelium and stroma exhibited epithelial hyperplasia in ovariectomized hosts. Recombinants prepared with estrogenized stroma and untreated epithelium and the reciprocal recombination of untreated stroma and estrogenized epithelium also exhibited ovary-independent hyperplasia in many cases. This suggests that the expression of ovary-independent hyperplasia is due to irreversible changes in vaginal epithelium and inductive activities in vaginal stroma. Development of ovary-independent hyperplasia in response to neonatal exposure to estradiol is facilitated when the epithelial-stromal association is maintained and is blocked if this association is disrupted. Finally, Takasugi's (1971, Proc. Japan Acad. 47, 193–198) hypothesis, that the age-dependent loss in sensitivity of the vagina to permanent, irreversible effects of estradiol at 5 days postpartum is due to maturational changes in the epithelium, was confirmed through analysis of the developmental response of heterochronal vaginal recombinants.