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Peroral Estradiol Is Sufficient to Induce Carcinogen-Induced Mammary Tumorigenesis in Ovariectomized Rats without Progesterone

Fig 4

Treatment with E leads to increased uterine metaplasia in treated animals.

Cross sections of uteri were stained with hematoxylin and eosin. A toxicological pathologist staged and graded the slides from 0–3 for each category leading to scores of stage + grade, specifically focusing on the uterine lumen (arrows) and not on dilated ducts (arrow heads). Images are representative of 0+0 (relatively normal), 1+1, 2+2, and 3+3 respectively. The larger images were taken at 20X magnification and the inset at 4X magnification. Scores were derived by adding stage and grade to get a final score of 0–6. P4 only and OVX animals were not included in analysis as all uteri were atrophied and not metaplastic. Uterine scores are expressed as mean ± SEM; n = 8; p < 0.05, Kruskal-Wallis test with Dunn’s Multiple Comparison’s posttest; different letters denote significant difference.

Fig 4

doi: https://doi.org/10.1371/journal.pone.0162662.g004