The Postnatal Ontogeny of Rat Uterine Glands and Age-Related Effects of 17β-Estradiol

In the uterus of the newborn rat, only the luminal epithelium is differentiated. Differentiation of musculature and glandular epithelium occurs postnatally, the latter originating as invaginations of the luminal epithelium into the stroma. Using unambiguous criteria for quantification of uterine glands, we find that uterine glands first appear on postnatal day 9 after which the increase in the number of glands is rapid and synchronous, with approximately 4.4 glands per uterine section reached by day 15. Between days 15 and 35, the number of glands per uterine section varied in a cyclic manner with an amplitude of approximately one gland per uterine section and a period of 6-7 days. Although exogenous 17 beta-estradiol (E2) administered on postnatal days 1-5 induced slight premature gland genesis, the number of glands per uterine section was approximately 30% lower between days 15-26 compared to untreated animals. Administration of E2 during the period of normal gland genesis (days 10-14) induced a dose-related delay in the onset of appearance of glands. After this, gland genesis proceeded at a normal rate; however, the maximum levels reached were again generally below those observed in untreated controls. E2 administered after uterine glands were established (days 20-24) induced a small increase in gland number compared to controls. E2 also induced temporary hypertrophy, hyperplasia, and cellular degeneration in the luminal epithelium during each of the dosing periods without corresponding changes in the stroma or myometrium. These data demonstrate that uterine gland genesis occurs between postnatal days 9-15 and that exogenous estrogen can alter, in an age-specific manner, both uterine gland genesis and the number of glands per uterine section.