Effects of high-dose isoflavones on rat uterus.
OBJECTIVE
To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats.


METHODS
Adult, ovariectomized virgin rats (n = 40) were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl) or different doses of genistein: 42 (group GES42), 125 (GES125), or 250 (GES250) µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10% formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number of eosinophils in the lamina propria were analyzed. ANOVA and the Tukey-Kramer test were used for statistical analyses.


RESULTS
Uterine weight, endometrial glandular area, and number of glands and eosinophils were all higher in GES250 > G125 than in the other groups (GES250 > GES125 > GES42 = GCtrl; p < 0.05). Morphological data showed signs of endometrial proliferation upon treatment with genistein, especially in animals in GES125 and GES250 compared to other groups. In all animals in GES250, signs of uterine squamous metaplasia were observed.


CONCLUSIONS
A short treatment period with high daily doses of isoflavones can promote endometrial squamous metaplasia in ovariectomized rats.
Departamento de Morfologia e Genética, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil. adricarbonellfisio@hotmail.com
Adriana Aparecida Ferraz
AA
Carbonel
Ricardo Santos
RS
Simões
Regiane Helena Barros Rabelo
RH
Santos
Maria Cândida Pinheiro
MC
Baracat
Manuel de Jesus
Mde J
Simões
Edmund Chada
EC
Baracat
José Maria
JM
Soares Júnior
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000097:blood*; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology; D007529:Isoflavones / Q000008:administration & dosage* / Q000494:pharmacology; D010052:Ovariectomy; D011374:Progesterone / Q000097:blood*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D007529:Isoflavones; D011374:Progesterone; D004958:Estradiol; C004742:daidzein; C086566:glycitein; D019833:Genistein