SUMMARY INTRODUCTION Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. OBJECTIVES To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17β-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.
Objective: To evaluate the histomorphometric and immunohistochemical changes in interstitial cells and ovarian follicles of rats treated with metformin during and after induction of permanent estrus. Methods: Thirty-two adult-female rats with regular estrous cycle were equally divided into four groups: 1) GCtrl - at estrous phase. 2) GPCOS - at permanent-estrous phase. 3) GMet1 - rats and daily treated with metformin (12.5 mg/Kg) during 60 consecutive days, as preventive form and 4) GMet2 - PCOS rats, which remained exposed to 60 days of continuous illumination and treated with metformin. After that, the animals were euthanized, and the ovaries were removed and processed for paraffin embedding. Sections were stained with H.E. for histomorphometry or subjected to immunohistochemistry for Ki-67 and cleaved caspase-3 (Casp-3) detections. Results: The GPCOS showed lack of corpus luteum and several ovarian cysts, as well as interstitial-like cells. The presence of corpus luteum and a significant increase in primary and antral follicles were observed in Mel-treated groups, which also showed a decrease in the number of ovarian cysts and in the area occupied by interstitial-like cells. The presence of corpus luteum along with an increase in the number of primary follicles in the Met2 group were noticed (p<0,01). A significant reduction in number of cysts and in the area occupied by interstitial cells, as well as a decrease in nuclear volume of interstitial cells, were noticed in the Met-treated groups, mainly in the Met2 group. The percentage of cell proliferation was significantly higher in granulosa cells of the Met-treated groups than PCOS group, mainly in the GMet2 (p<0,01), which was similar to the GCtrl group. On the other hand, the percentage of apoptosis (cleaved-caspase-3- positive cells) was significantly higher in the granulosa cells of GPCOS and Met-treated groups than the GCtrl group, but without significant difference, which showed weak cleaved caspase-3 immunoreactivity in those cells. Conclusion: The ovaries of rats treated with metformin showed a decrease in nuclear volume and in the area occupied by interstitial cells, presence of corpus luteum, in addition to a decrease in the number of cysts.
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