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Rev Bras Ginecol Obstet. 2006;28(2):101-106
DOI 10.1590/S0100-72032006000200005
PURPOSE: to evaluate the effects of conjugated equine estrogens (CEE) and raloxifene (Ral), alone or combined, on the rat endometrium. METHODS: fifty-six adult rats were ovariectomized and randomly divided into seven groups: GCont (control); GCEE (CEE 50 µg/kg); GCEE/25 (CEE 25 µg/kg); GRal/0.75 (Ral 0.75 mg/kg); GRal/0.4 (Ral 0.4 mg/kg); GCEERal (50/0.75) - (CEE 50 µg/kg + Ral 0.75 mg/kg), and GCEE-Ral (25/0.4) - (CEE 25 µg/kg + Ral 0.4 mg/kg). The drugs were orally administered (gavage) for 21 consecutive days. At the end of the experiment, all animals were anesthetized and sacrificed. Fragments of uterus were removed, fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by HE and submitted to histomorphometric evaluation. The following parameters were analyzed: thickness of superficial epithelium and number of endometrial glands/mm² and of blood vessels/mm². The data were evaluated using ANOVA followed by the Turkey-Kramer test. RESULTS: in the GCont and only Ral treatment (GRal/0.75 and GRal/0.4) the endometrium showed signals of atrophy. In the groups treated with only CEE signs of endometrial proliferation were observed, mainly in group GCEE/50. Also, there was endometrial proliferation in the groups that received combined CEE and Ral (Ral GCEE (50/0.75) and GCEE-Ral (25/0.4)), but it was more intensive in the animals treated with isolated estrogen than in those that received combined estrogen and raloxifene. CONCLUSION: raloxifene may partially block the action of estrogen on the castrated adult rat endometrium.
Summary
Rev Bras Ginecol Obstet. 2006;28(2):101-106
DOI 10.1590/S0100-72032006000200005
PURPOSE: to evaluate the effects of conjugated equine estrogens (CEE) and raloxifene (Ral), alone or combined, on the rat endometrium. METHODS: fifty-six adult rats were ovariectomized and randomly divided into seven groups: GCont (control); GCEE (CEE 50 µg/kg); GCEE/25 (CEE 25 µg/kg); GRal/0.75 (Ral 0.75 mg/kg); GRal/0.4 (Ral 0.4 mg/kg); GCEERal (50/0.75) - (CEE 50 µg/kg + Ral 0.75 mg/kg), and GCEE-Ral (25/0.4) - (CEE 25 µg/kg + Ral 0.4 mg/kg). The drugs were orally administered (gavage) for 21 consecutive days. At the end of the experiment, all animals were anesthetized and sacrificed. Fragments of uterus were removed, fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by HE and submitted to histomorphometric evaluation. The following parameters were analyzed: thickness of superficial epithelium and number of endometrial glands/mm² and of blood vessels/mm². The data were evaluated using ANOVA followed by the Turkey-Kramer test. RESULTS: in the GCont and only Ral treatment (GRal/0.75 and GRal/0.4) the endometrium showed signals of atrophy. In the groups treated with only CEE signs of endometrial proliferation were observed, mainly in group GCEE/50. Also, there was endometrial proliferation in the groups that received combined CEE and Ral (Ral GCEE (50/0.75) and GCEE-Ral (25/0.4)), but it was more intensive in the animals treated with isolated estrogen than in those that received combined estrogen and raloxifene. CONCLUSION: raloxifene may partially block the action of estrogen on the castrated adult rat endometrium.
Summary
Rev Bras Ginecol Obstet. 2011;33(7):119-122
Summary
Rev Bras Ginecol Obstet. 2011;33(7):119-122
Summary
Rev Bras Ginecol Obstet. 2013;35(4):159-163
DOI 10.1590/S0100-72032013000400005
PURPOSE: To evaluate the effects of electrical stimulation (ES) of the pelvic floor on the urethra of female rats. METHODS: Forty adult rats were divided at random into four groups of ten animals each: Ctrl - without intervention; Sham - not submitted to ES, but with an electrode inserted into the vagina; Exp6 - submitted to six sessions of ES of the pelvic floor, and Exp12 - submitted to 12 sessions of ES of the pelvic floor. At the end of the experiment, all animals were anesthetized and the middle third of the urethra was removed, fixed in Bouin's fluid and processed for histomorphometric study. Sections were stained with hematoxylin and eosin for morphological and morphometric description, and others were stained with picrosirius red for the quantitation of total collagen. The thicknesses of the muscle layer and of the epithelium were determined, in 4 quadrants of the urethra, by performing 20 measurements per animal. The number of blood vessels present in the lamina propria was counted in the four quadrants over an area of 10³ µm² per quadrant and the images were obtained using the image analysis program AxioVision® REL 4.3 (Carl Zeiss). The collagen and muscle fiber ratios in the urethrae were calculated from two images per quadrant of every slice stained with picrosirius red, employing the Imagelab® Program. Data were subjected to analysis of variance (ANOVA) and the Tukey-Kramer multiple comparison test (p<0.05). RESULTS: The morphometry of the collagen, number of blood vessels and thickness of the epithelium showed no significant changes; however, the thickness of the periurethral muscle tissue increased significantly in Exp12 group, compared to the other groups (Exp12*>Exp6==Ctrl==Sham; *p<0.05). CONCLUSION: Prolonged functional electric stimulation of the pelvic floor induced an increase in periurethral muscle thickness in rats.
Summary
Rev Bras Ginecol Obstet. 2013;35(4):159-163
DOI 10.1590/S0100-72032013000400005
PURPOSE: To evaluate the effects of electrical stimulation (ES) of the pelvic floor on the urethra of female rats. METHODS: Forty adult rats were divided at random into four groups of ten animals each: Ctrl - without intervention; Sham - not submitted to ES, but with an electrode inserted into the vagina; Exp6 - submitted to six sessions of ES of the pelvic floor, and Exp12 - submitted to 12 sessions of ES of the pelvic floor. At the end of the experiment, all animals were anesthetized and the middle third of the urethra was removed, fixed in Bouin's fluid and processed for histomorphometric study. Sections were stained with hematoxylin and eosin for morphological and morphometric description, and others were stained with picrosirius red for the quantitation of total collagen. The thicknesses of the muscle layer and of the epithelium were determined, in 4 quadrants of the urethra, by performing 20 measurements per animal. The number of blood vessels present in the lamina propria was counted in the four quadrants over an area of 10³ µm² per quadrant and the images were obtained using the image analysis program AxioVision® REL 4.3 (Carl Zeiss). The collagen and muscle fiber ratios in the urethrae were calculated from two images per quadrant of every slice stained with picrosirius red, employing the Imagelab® Program. Data were subjected to analysis of variance (ANOVA) and the Tukey-Kramer multiple comparison test (p<0.05). RESULTS: The morphometry of the collagen, number of blood vessels and thickness of the epithelium showed no significant changes; however, the thickness of the periurethral muscle tissue increased significantly in Exp12 group, compared to the other groups (Exp12*>Exp6==Ctrl==Sham; *p<0.05). CONCLUSION: Prolonged functional electric stimulation of the pelvic floor induced an increase in periurethral muscle thickness in rats.
Summary
Rev Bras Ginecol Obstet. 2006;28(3):184-189
DOI 10.1590/S0100-72032006000300008
PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.
Summary
Rev Bras Ginecol Obstet. 2006;28(3):184-189
DOI 10.1590/S0100-72032006000300008
PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.
Summary
Rev Bras Ginecol Obstet. 2011;33(5):225-230
DOI 10.1590/S0100-72032011000500004
PURPOSE: to evaluate the effect of administration of a stavudine/nelfinavir combination on the rat pregnancy by assessing maternal and concepts weights, as well as the number of implantations, fetuses, placentas, resorptions and maternal and fetal mortality. METHODS: forty adult pregnant Wistar rats of the EPM-1 strain were randomly divided into four groups: control (GCtrl - drug vehicle control, n=10), and three experimental groups, which were treated with an oral solution of stavudine/nelfinavir (ExpI - 1/40 mg/kg b.w., n=10; ExpII - 3/120 mg/kg b.w., n=10; ExpIII - 9/360 mg/kg b.w., n=10) from day 0 to the 20th day of pregnancy. Maternal body weights were determined at the start of the experiment and on the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereomicroscope for possible external malformations. Statistical analysis was performed by analysis of variance (ANOVA) complemented by the Kruskal-Wallis test (p<0.05). RESULTS: there was a progressive and gradual increase in body weight during the course of pregnancy in all groups, which was more evident in the final period, but with no significant difference between groups. The mean number of fetuses, placentas, implantations, and fetal and placental weights showed no significant differences between groups. Also, no resorptions or external malformations were found in the experimental groups. However, between the 8th and 14th days of gestation, there was one case of maternal mortality in each experimental group. CONCLUSIONS: the administration of a stavudine/nelfinavir combination had no deleterious effects on the concepts.
Summary
Rev Bras Ginecol Obstet. 2011;33(5):225-230
DOI 10.1590/S0100-72032011000500004
PURPOSE: to evaluate the effect of administration of a stavudine/nelfinavir combination on the rat pregnancy by assessing maternal and concepts weights, as well as the number of implantations, fetuses, placentas, resorptions and maternal and fetal mortality. METHODS: forty adult pregnant Wistar rats of the EPM-1 strain were randomly divided into four groups: control (GCtrl - drug vehicle control, n=10), and three experimental groups, which were treated with an oral solution of stavudine/nelfinavir (ExpI - 1/40 mg/kg b.w., n=10; ExpII - 3/120 mg/kg b.w., n=10; ExpIII - 9/360 mg/kg b.w., n=10) from day 0 to the 20th day of pregnancy. Maternal body weights were determined at the start of the experiment and on the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereomicroscope for possible external malformations. Statistical analysis was performed by analysis of variance (ANOVA) complemented by the Kruskal-Wallis test (p<0.05). RESULTS: there was a progressive and gradual increase in body weight during the course of pregnancy in all groups, which was more evident in the final period, but with no significant difference between groups. The mean number of fetuses, placentas, implantations, and fetal and placental weights showed no significant differences between groups. Also, no resorptions or external malformations were found in the experimental groups. However, between the 8th and 14th days of gestation, there was one case of maternal mortality in each experimental group. CONCLUSIONS: the administration of a stavudine/nelfinavir combination had no deleterious effects on the concepts.
Summary
Rev Bras Ginecol Obstet. 2006;28(4):227-231
DOI 10.1590/S0100-72032006000400004
PURPOSE: to evaluate histomorphometric changes in the rat myometrium upon treatment with isoflavones, as compared with estrogens, using histological and morphometric techniques. METHODS: twenty-eight oophorectomized adult rats were randomly divided into four treatment groups: GPropi = propylene glycol (control); GExtr10 - 10 mg/kg soybean extract; GExtr300 - 300 mg/kg soy bean extract; GCee - 200 µg/kg conjugated equine estrogens (Cee). Drugs or drug vehicle were administered by gavage once a day for 21 days. Upon sacrifice, the uteri were removed and weighed. Fragments of uterine horns were collected and fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by hematoxylin and eosin and evaluated microscopically by means of an image analyzer to quantify the myometrial thickness and the number of blood vessels and eosinophils. The data were studied by analysis of variance (ANOVA) followed by the Tukey-Kramer multiple comparison test. RESULTS: isoflavones in the concentration of 300 mg/kg induced a significant increase in the myometrium thickness (GExtr300=25.6±5.0 mm) compared to control (GPropi=5.5±0.5 mm). The effect of this high dose is similar to the estrogen effect (GCee=27.5±7.9 mm). In low doses (10 mg/kg), the effect was similar to control. Isoflavones (GExtr300) induced also an increase in the number of blood vessels (GPropi=3.5±1.6; GExtr300=10.2±3.6 vessels/mm²) and of eosinophils (CPropi=0.15±0.01; GExtr300=4.3±0.9 eosinophils/mm²). These effects were comparable to those produced by Cee treatment in GCee (9.2±1.1 eosinophils/mm²). CONCLUSION: a high-dose treatment with isoflavones (300 mg/kg per day, 21 days) elicited an estrogen-like, highly significant proliferative action on the rat myometrium.
Summary
Rev Bras Ginecol Obstet. 2006;28(4):227-231
DOI 10.1590/S0100-72032006000400004
PURPOSE: to evaluate histomorphometric changes in the rat myometrium upon treatment with isoflavones, as compared with estrogens, using histological and morphometric techniques. METHODS: twenty-eight oophorectomized adult rats were randomly divided into four treatment groups: GPropi = propylene glycol (control); GExtr10 - 10 mg/kg soybean extract; GExtr300 - 300 mg/kg soy bean extract; GCee - 200 µg/kg conjugated equine estrogens (Cee). Drugs or drug vehicle were administered by gavage once a day for 21 days. Upon sacrifice, the uteri were removed and weighed. Fragments of uterine horns were collected and fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by hematoxylin and eosin and evaluated microscopically by means of an image analyzer to quantify the myometrial thickness and the number of blood vessels and eosinophils. The data were studied by analysis of variance (ANOVA) followed by the Tukey-Kramer multiple comparison test. RESULTS: isoflavones in the concentration of 300 mg/kg induced a significant increase in the myometrium thickness (GExtr300=25.6±5.0 mm) compared to control (GPropi=5.5±0.5 mm). The effect of this high dose is similar to the estrogen effect (GCee=27.5±7.9 mm). In low doses (10 mg/kg), the effect was similar to control. Isoflavones (GExtr300) induced also an increase in the number of blood vessels (GPropi=3.5±1.6; GExtr300=10.2±3.6 vessels/mm²) and of eosinophils (CPropi=0.15±0.01; GExtr300=4.3±0.9 eosinophils/mm²). These effects were comparable to those produced by Cee treatment in GCee (9.2±1.1 eosinophils/mm²). CONCLUSION: a high-dose treatment with isoflavones (300 mg/kg per day, 21 days) elicited an estrogen-like, highly significant proliferative action on the rat myometrium.
Summary
Rev Bras Ginecol Obstet. 2007;29(5):248-252
DOI 10.1590/S0100-72032007000500005
PURPOSE: to analyze the isoflavone and estrogen effects on the postmenopausal quality of life. METHODS: this is a randomized and double-blind study with 79 postmenopausal patients, 12 months of amenorrhea, 40 years old or more and body mass index (BMI) above 30 kg/m². The participants were randomly divided into two treatment groups: GECP received orally two capsules, every 12 hours, one contained 0.625 mg conjugated equine estrogen and another placebo (n=33); GECS received two capsules of 150 mg extract of soy, with 60 mg isoflavone (n=32). Both treatments were administered for six months. The Quality Menopause Specific Questionnaire of Life was applied before and after one, three and six months of treatment. The parameters of gynecological cancer risk were evaluated. ANOVA and the Tukey test were used for data analysis. RESULTS: there was a reduction in the values of the vasomotor parameters after six months of treatment, 1.6±0.8 and 2.4±1.6, compared to before therapy, 4.0±2.2 and 4.2±2.3 in GECP and GECS, respectively. The psychological aspects showed reduction in values after six months of therapy, 2.5±1.2 and 2.9±1.4, compared to before treatment, 3.6±1.6 and 4.1±1.9 in GECP and GECS, respectively. Similar results were obtained on the physical aspects and in the sexual symptoms. CONCLUSIONS: isoflavones may positively act on life quality of postmenopausal women. This effect was similar to conjugated equine estrogen.
Summary
Rev Bras Ginecol Obstet. 2007;29(5):248-252
DOI 10.1590/S0100-72032007000500005
PURPOSE: to analyze the isoflavone and estrogen effects on the postmenopausal quality of life. METHODS: this is a randomized and double-blind study with 79 postmenopausal patients, 12 months of amenorrhea, 40 years old or more and body mass index (BMI) above 30 kg/m². The participants were randomly divided into two treatment groups: GECP received orally two capsules, every 12 hours, one contained 0.625 mg conjugated equine estrogen and another placebo (n=33); GECS received two capsules of 150 mg extract of soy, with 60 mg isoflavone (n=32). Both treatments were administered for six months. The Quality Menopause Specific Questionnaire of Life was applied before and after one, three and six months of treatment. The parameters of gynecological cancer risk were evaluated. ANOVA and the Tukey test were used for data analysis. RESULTS: there was a reduction in the values of the vasomotor parameters after six months of treatment, 1.6±0.8 and 2.4±1.6, compared to before therapy, 4.0±2.2 and 4.2±2.3 in GECP and GECS, respectively. The psychological aspects showed reduction in values after six months of therapy, 2.5±1.2 and 2.9±1.4, compared to before treatment, 3.6±1.6 and 4.1±1.9 in GECP and GECS, respectively. Similar results were obtained on the physical aspects and in the sexual symptoms. CONCLUSIONS: isoflavones may positively act on life quality of postmenopausal women. This effect was similar to conjugated equine estrogen.
Summary
Rev Bras Ginecol Obstet. 2011;33(9):264-269
DOI 10.1590/S0100-72032011000900008
PURPOSE: to evaluate the effects of high doses of genistein on the mammary glands of adult female rats. METHODS: Twenty-eight days after oophorectomy, 50 adult female rats were divided into five groups, as follows: a control group (Ctrl), three rats that received genistein (GEN) at the doses of 46 mg/kg (GEN46;), 125 mg/kg (GEN125) and 250 mg/kg (GEN250); one group received conjugated equine estrogen at the dose of 50 µg/g (ECE50). The substances were administered daily for 30 consecutive days by gavage and in the last week of the period of treatment, colpocytological exams were carried out for seven consecutive days. After treatment, the animals were anesthetized, blood samples were collected for estradiol and progesterone determination and the first pair of inguinal mammary glands was removed and processed for histomorphometric analysis. Collected data were subjected to analysis of variance supplemented by the Tukey-Kramer test (p<0.05). RESULTS: the ctrl group and the ones treated with different doses of GEN showed atrophic mammary glands, whereas the glands were more developed in the ECE group, where numerous mammary ducts and alveoli were observed. Morphometry showed a larger area of mammary parenchyma in the ECE group (98.870.1±550.4 µm²* per mm²; p<0.05) compared with other groups (Ctrl=36.875.6±443.4; GEN46=37.001.7±557.4; GEN125=36.480.8±658.3 and GEN250=37.502.8±669.3). The same occurred in the number of alveoli in the ECE group (33.2±6.9* per mm²; p<0.05) compared to the other groups (Ctrl=10.4±2.1, GEN46=11.2±3.1; GEN125=11.6±2.1 and GEN250=12.3±2.3). The estradiol level was higher in the ECE group compared to the other groups (9.4±1.7 pg/mL; p<0.05), whereas serum levels of progesterone were similar in all groups. CONCLUSION: the administration of genistein at high doses had no trophic effect on the mammary glands of rats.
Summary
Rev Bras Ginecol Obstet. 2011;33(9):264-269
DOI 10.1590/S0100-72032011000900008
PURPOSE: to evaluate the effects of high doses of genistein on the mammary glands of adult female rats. METHODS: Twenty-eight days after oophorectomy, 50 adult female rats were divided into five groups, as follows: a control group (Ctrl), three rats that received genistein (GEN) at the doses of 46 mg/kg (GEN46;), 125 mg/kg (GEN125) and 250 mg/kg (GEN250); one group received conjugated equine estrogen at the dose of 50 µg/g (ECE50). The substances were administered daily for 30 consecutive days by gavage and in the last week of the period of treatment, colpocytological exams were carried out for seven consecutive days. After treatment, the animals were anesthetized, blood samples were collected for estradiol and progesterone determination and the first pair of inguinal mammary glands was removed and processed for histomorphometric analysis. Collected data were subjected to analysis of variance supplemented by the Tukey-Kramer test (p<0.05). RESULTS: the ctrl group and the ones treated with different doses of GEN showed atrophic mammary glands, whereas the glands were more developed in the ECE group, where numerous mammary ducts and alveoli were observed. Morphometry showed a larger area of mammary parenchyma in the ECE group (98.870.1±550.4 µm²* per mm²; p<0.05) compared with other groups (Ctrl=36.875.6±443.4; GEN46=37.001.7±557.4; GEN125=36.480.8±658.3 and GEN250=37.502.8±669.3). The same occurred in the number of alveoli in the ECE group (33.2±6.9* per mm²; p<0.05) compared to the other groups (Ctrl=10.4±2.1, GEN46=11.2±3.1; GEN125=11.6±2.1 and GEN250=12.3±2.3). The estradiol level was higher in the ECE group compared to the other groups (9.4±1.7 pg/mL; p<0.05), whereas serum levels of progesterone were similar in all groups. CONCLUSION: the administration of genistein at high doses had no trophic effect on the mammary glands of rats.
