Revista Brasileira de Ginecologia e Obstetrícia (Aug 2009)
Efeitos da hiperprolactinemia sobre o útero de camundongos no proestro Hyperprolactinemia effects on the female mice uterus during proestrous
Abstract
OBJETIVO: avaliar o efeito da hiperprolactinemia induzida pela metoclopramida sobre o endométrio e miométrio de camundongos fêmeas na fase de proestro. MÉTODOS: 24 camundongos fêmeas foram divididas aleatoriamente em dois grupos: GCtr/controle e GExp/tratadas com metoclopramida (6,7 µg/g por dia). Após 50 dias, os animais foram sacrificados na fase de proestro, e o sangue foi coletado para determinação dos níveis de estradiol, progesterona e prolactina. Os cornos uterinos foram removidos e fixados em formol a 10%; foram, então, processados para inclusão em parafina. Cortes de 4 µm foram corados pela hematoxilina-eosina (H/E). Na análise morfológica, foi utilizado microscópio de luz, da marca Carl Zeiss, com objetivas variando de 4 a 400 X, para caracterização de cada corte histológico. Na análise morfométrica, foi avaliada a espessura do epitélio superficial, da lâmina própria e do miométrio, com auxílio de um analisador de imagem (AxionVision, Carl Zeiss) acoplado ao microscópio de luz (Carl Zeiss). A análise estatística foi realizada pela ANOVA seguida pelo teste Wilcoxon. O valor de p foi considerado significante quando PURPOSE: to evaluate the effect of hyperprolactinemia induced by metoclopramide on the endometrium and myometrium of female mice in the proestrus phase. METHODS: 24 female mice were randomly divided in two groups: CtrG/control and ExpG/treated with metoclopramide (6.7 mg/g daily). After 50 days, the animals were sacrificed in the proestrus phase, and the blood was collected to determine the levels of estradiol, progesterone and prolactin. The uterine horns were removed, fixed in 10% formaldehyde and processed before being included in paraffin. Slices of 4 µm were stained by hematoxylin and eosin (H/E). In the morphological analysis, a Carl Zeiss light microscope, with objectives varying from 4 to 400 X was used for each histological slice characterization. In the morphometrical analysis, the superficial epithelium, the lamina propria and the myometrium thickness were evaluated, with the help of an image analyzer (AxionVision - Carl Zeiss) attached to the light microscope (Carl Zeiss). The statistical analysis was done by ANOVA, followed by the Wilcoxon test. P-value was considered as significant, when <0.05. RESULTS: our findings have shown an increase in the seric levels of prolactin (295.6±38.0 ng/mL) and significant decrease in the progesterone levels (11.3±0.9 ng/mL) in the ExpG, as compared to the CtrG (45.5±5.2 ng/mL and 18.2±1.6 ng/mL, respectively; p<0.001). Concerning the seric level of estradiol, significant differences between the groups were not obtained (ExpG=119.1±12.3 pg/mL and CtrG=122.7±8.4 pg/mL; p=0.418). The morphological study has shown that the uterus from the ExpG presented the endometrium with more developed superficial epithelium and lamina propria, as compared to the CtrG, the same happening with the myometrium. The thickness morphometrical values of the luminal epithelium (8.0±1.1 µm) and endometrium (116.2±21.1x10² µm) from the CtrG were lower than the ones from the ExpG (10.2±0.8 µm and 163.2±23.3x10² µm, respectively) with p<0.05. Nevertheless, data obtained in the myometrium have not shown significant differences between the groups (CtrG=152.2±25.2x10² µm and ExpG=140.8±18.0x10² µm). CONCLUSIONS: data have shown that hyperprolactinemia induced by metoclopramide determines endometrial proliferation and interferes with the ovarian function, mainly in the progesterone production.
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