Effects of tamoxifen administration in rat vaginas: an ultrastructural and light microscopy study

Background: Tamoxifen (TAM) inhibits the initiation of carcinogen induced rat mammary tumours and is administrered for extended periods after the initiation of carcinogenesis. It is also a widely used treatment for breast and gynaecological cancer.

Objective: In this study, we aimed to investigate tamoxifen (TAM) administration on vagen development in rats.

Material & methods: Twenty sexually mature and pregnant Wistar albino rats were chosen as the animal model. They were divided into two groups. Group I: Control group, Group II: Tamoxifen applied (between gestational day 16 and 21 days); 100 microg tamoxifen citrate (TAM) in 0.05 ml saline subcutaneously per day/animal. After birth, all female rats were sacrificed on the 60th day and were taken vaginal tissue. Transmission electron microscopy and light microscopy have been used to study changes to the vaginal epithelium.

Results: A statistically significant reduction of birth body weight was noted in the experimental group of rats when compared to the control group (P < 0.05). We saw increase in the thickness of the epithelium layer and irregularity and disappearance of microscopic papilla, cytoplasmic vacuolation in cells of the surface layer, thin and irregular basal membrane, lateral junction of cells were destroyed in the TAM treated groups. In conclusion, neonatal tamoxifen administration affects vagina epithelium and lead to decreasing birth body weight and vaginal adenosis.

Tamoxifen; Vagina; Ultrastructural changes; Rat; Adenosis-like lesion

[1] Furr B. J. A., Jordon V. C.: "The pharmacology and clinical uses of tamoxifen". Pharmacol. T her., 1984, 25,127.

[2] Pasqualini J. R., Giarnbiagi N., Sumida C., Nuguyen B. L., Gelly C., Maryrand C., Lecerf F.: "Biological responses of tamoxifen in the fetal and newborn vagina and uterus of guinea-pig and in the R-27 mammary cancer cell line". J. Steroid Biochem., 1986, 24, 99.

[3] Pasqualini J. R., Nguyen B. L., Sumida C., Giarnbiagi N., Mayrand C.: "Tamoxifen and progesterone effects in target tissues during the perinatal period". J. Steroid Biochem., 1986, 25 (5b), 853.

[4] Cunha G. R., Taguchi D., Narnikawa, R.: "Teratogenic effect of clomiphene, tarnoxifen, and diethylstilbestrol on the developing human female genital tract". Hum. Pathol., 1987, 18, 1132.

[5] Jordon V.C.: "Biochemical pharmacology of antiestrogen action". Pharmac. Rev., 1984, 36, 245.

[6] Gottardis M. M., Jordon V. C.: "Biological basis of tarnoxifen as a chemopreventative agent". Cancer Detection and Prevention, 1993, 17(1).

[7] Saunders R. D., Trapp R. B.: "Basic and Clinical Bio statistics", 2nd ed., Appleton& Lange (ed.) Prentice-Hall, Norwalk, CT. 1994, 140.

[8] Tuffery, A. A.: "Laboratory Animals: An Introduction for New Experimenters". Great Britain, 1987, 88.

[9] Nguyen B. L., Grambiagi N.: "Estrogen and progesterona receptors in the fetal and newborn vagina of guinea pig: biological, morphological and ultrastructural responses to tamoxifen and estradiol". Endocrinology, 1986, 119, 978.

[10] Carthew P.,E dwards R. E.,N olan B. M.,M artin E. A.,H eydon R T., White I. N., Tucker M. J.: "Tamoxifen induces endometrial and vaginal cancer in rats in absence of endometrial hyperplasia". Carcinogenesis, 2000, 21 (4), 793.

[11] Taguchi O., Nizhizuka Y.: "Reproductive tract abnormalities in female mice treted neonatally with tamoxifen". Am. J. Gynecol., 1985, 151 (5), 675.

[12] Mc Guire W. L.: "Abnormal reproductive development in rats after neonatally administered antiestrogen (tamoxifen)". Biol. Reprod., 1979, 21, 1087.

[13] Iguchi T., Hirokawa M., Takasugi N.: "Occurrence of genital tracct abnormalities and bladder hernia in female mice exposed neonatally to tamoxifen". Toxicology, 1986, 42, 1.

[14] Yoshida M., Kudoh K., Katsuda S., Takahashi M., Ando J., Maekawa A.: "Inhibition effects of uterine endometrial carcinogenesis in Donryu rats by tamoxifen". Cancer Lett., 1998, 11, 134(1), 43.

[15] Matsuda A., Higuchi K., Karasawa M., Yoneyama S., Deguchi J., Miyamoto M.: "Fourteen-day oral combination dose toxicity study of CGS 16949 A (aromatase inhibitor) with 5-fluorouracil or tamoxifen in rats". J. Toxicol. Sci., 1997, 22 (1), 1.