Uterus Of Adult Rats Research Articles

Histomorphological study of the effect of mint on the uterus and ovary of adult Wistar rats

Mentha piperita is a medicinal plant used for treating human diseases for thousands of years. However, the traditional medicinal usage of herbs by humans is imperfect and unscientific by modern standards. It is the result of countless trial-and-error tests that people have conducted, and so traditional usage points the way to natural therapeutic usage. "Natural" does not necessarily mean "safe." This study aimed to evaluate the effects of ethanolic extract of Mentha piperita leaves on histo-morphological changes in the ovary and uterus of adult female Wistar rats. Hence this study was undertaken to evaluate its impact on the gonadal organ in female Wistar albino rats in 18 female albino rats of age 6-8 weeks which were divided into 3 groups. Group I was treated as control, Group II and III received orally 200mg/kg and 400mg/kg of ethanolic extract of Mentha piperita respectively for 60 days. Then the rats were sacrificed and the ovaries and uterus were processed for haematoxylin and eosin staining to study the effect on the estrous phase, ovulation, and implantation. The ovarian germinal epithelium was found to be flattened at places and disrupted. The stroma shows more fibrosis with severe degeneration. Granulosa cells are also disrupted. Follicles show features of degeneration. Degenerating oocytes are also seen in places. The endometrium lining epithelium is disrupted, vascularity was increased and the myometrium has become edematous. It is shown in previous studies that Mentha arvensis, Mentha spicate (spearmint), and Mentha piperita have got adverse effects on the reproductive system but in our study on female fertility, we found that Mentha piperita showed increased folliculogenesis and many degenerated follicles at different stages of development.

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) causes multigenerational adverse effects on the uterus of F1 and F2 offspring rats.

Phthalates are one of the ubiquitous chemicals found in day-to-day products like food packaging, children's toys, and other consumer commodities. There is rising concern that repeated exposure to phthalates during pregnancy and lactation could have long-term effects on maternal and fetal health. We hypothesize that exposure to DEHP during the developmental windows might affect the expression of molecules that regulate uterine function and that this effect would be passed on to further generations. Rat dams were treated with olive oil (vehicle) or DEHP (100 mg/kg b.wt./day) orally from gestational day 9 (GD 9) to the end of lactation (PND 21). F0 maternal DEHP exposure resulted in multigenerational (F1 and F2) reproductive toxicity, as evidenced by an extended estrous cycle, decreased mating, fertility, and fecundity indices. Serum progesterone and estradiol levels were decreased and their cognate receptors (PR and ERα) in the uterus were decreased in the DEHP-exposed offspring rats. Further analysis of the expression of estrogen and progesterone regulatory genes such as Hox a11, VEGF A, Ihh, LIFR, EP4, PTCH, NR2F2, BMP2, and Wnt4 were reduced in the uteri of adult F1 and F2 generation rats born from DEHP-exposed F0 dams. Decreased expression of these crucial proteins due to DEHP exposure may lead to defects in epithelial proliferation and secretion, uterine receptivity, and decidualization in the uteri of successive generations. This study showed that maternal DEHP exposure impairs the expression of molecules that regulate uterine function and this multigenerational effect is transmitted via maternal lineage.

Effect of monosodium glutamate on serum sex hormones and uterine histology in female rats along with its molecular docking and in-silico toxicity

Monosodium glutamate (MSG) is commonly used worldwide as a food flavour enhancer by the food industry. The current study investigated the in vivo toxic effects of MSG on the uterus in adult female Sprague Dawley rats and in vitro using MCF-7 and MDA-MB-231 cells, computational toxicity and molecular docking. The average levels of progesterone and oestrogen in the MSG-treated animals significantly altered. Besides, the average uterine lumen area (μm2) was smaller than the control group. MSG showed high-affinity binding to acetylcholine receptors and disrupted the normal nerve signal with a predicted LD50 of 4500 mg/kg. MSG also demonstrated good binding affinity to human oestrogen receptors beta and some other proteins that have an oxidative stress role in the female reproductive organs. Therefore, a precaution should be taken when utilising this compound, especially for females under the risk factor of hormonal abnormality.

Association of Intrauterine Microbes with Endometrial Factors in Intrauterine Adhesion Formation and after Medicine Treatment.

Intrauterine adhesions (IUAs) have caused serious harm to women’s reproductive health. Although emerging evidence has linked intrauterine microbiome to gynecological diseases, the association of intrauterine microbiome with IUA, remains unknown. We performed metagenome-wide association, metabolomics, and transcriptomics studies on IUA and non-IUA uteri of adult rats to identify IUA-associated microbial species, which affected uterine metabolites and endometrial transcriptions. A rat model was used with one side of the duplex uterus undergoing IUA and the other remaining as a non-IUA control. Both 16S rRNA sequencing and metagenome-wide association analysis revealed that instead of Mycoplasmopsis specie in genital tract, murine lung pathogen Mycoplasmopsis pulmonis markedly increased in IUA samples and displayed a distinct positive interaction with the host immune system. Moreover, most of the IUA-enriched 58 metabolites positively correlate with M. pulmonis, which inversely correlates with a mitotic progression inhibitor named 3-hydroxycapric acid. A comparison of metabolic profiles of intrauterine flushing fluids from human patients with IUA, endometritis, and fallopian tube obstruction suggested that rat IUA shared much similarity to human IUA. The endometrial gene Tenascin-N, which is responsible for extracellular matrix of wounds, was highly up-regulated, while the key genes encoding parvalbumin, trophectoderm Dkkl1 and telomerase involved in leydig cells, trophectoderm cells, activated T cells and monocytes were dramatically down-regulated in rat IUA endometria. Treatment for rat IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN) did not reduce the incidence of IUA, though inflammatory factor IL-6 was dramatically down-regulated (96–86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse with a highly up-regulated B cell receptor signaling pathway, which may be associated with the significantly increased proportions of Ulvibacter or Staphylococcus. Our results suggest an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA and the possibility to intervene in IUA formation by targeting the causal factors, microbial infection, and Tenascin-like proteins.

The fertility assessment of normal cyclic Wistar rats following the administration of methanolic extract of Portulaca oleracea: an experimental study

BackgroundPurslane is a widely distributed shrub used for the treatment of different ailments. The increasing reproductive complications associated with herbal treatments have led to the need to critically evaluate the safety and/or reproductive potentials of commonly used plant extracts. This study investigated the reproductive effect of methanolic extracts of Portulaca oleracea (MEPO) in adult female Wistar rats.ResultsGroup C showed a significant decrease both in relative ovarian weight (p = 0.000), and relative uterine weight (p = 0.037), when compared with the control. There were no significant (p ˃ 0.05) changes in the levels of follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. When compared to the control, groups B and C showed abnormal estrous cycle and cycle arrest especially at the metestrus phase with mild congestion of a few blood vessels in the ovary and uterus.ConclusionsMEPO may possess some anti-fertility effect, as it disrupts the estrous cycle of adult female Wistar rats; although it has no major effect on the reproductive hormones, uterus, and ovarian histology of adult female Wistar rats. However, high dose consumption should be taken with precaution.

Localization (and profiles) of tyrosinephosphorylated proteins in female reproductive organs of adult rats.

ObjectiveTyrosine phosphorylation is an essential process in many biological systems, including the male reproductive system. The presence of tyrosine-phosphorylated (TyrPho) proteins has been well documented in male reproductive organs, but research in fertile females is still limited.MethodsThe ovary, oviduct, and uterus of adult female Sprague-Dawley rats in the estrus phase were used to localize TyrPho proteins using an immunohistochemical technique. These proteins were separated and their expression patterns were examined by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and Western blot analysis, respectively.ResultsTyrPho proteins were localized in the cytoplasm of the oocyte except the antral fluid; in the granulosa cells, theca cells, and stromal cells of the ovary; at the apical surface of oviductal epithelial cells; and in the basal epithelium and submucosa of the uterine wall. Moreover, we found that 72-, 43-, and 28-kDa TyrPho proteins were localized in the ovary, while 170-, 55-, and 43-kDa proteins were localized in the oviduct. In the uterus, we detected four major bands, corresponding to 61-, 55-, 54-, and 43-kDa TyrPho proteins.ConclusionGiven that these TyrPho proteins were found in major reproductive organs in the estrus phase, these proteins may play important roles in female fertility.

The effect of calabash chalk on the uterus of adult female Wistar rats

The study investigated the effect of calabash chalk on the uterus of adult female Wistar rats. The 15 female adult Wistar rats were randomly divided into groups A, B and C. Group A served as the control while groups B and C served as experimental groups. Their body weights were measured on a weekly basis throughout the experimental period. In addition to feed and water given to all groups, group A received distilled water only for 21 days, group B 40 mg/kg per body weight of non-salted calabash chalk for 21 days and group C 40 mg/kg per body weight of salted calabash chalk for 21 days. On the 22nd day the animals were sacrificed and their uterus harvested for histological studies. Data was analysed using one-way ANOVA and SPSS version 2.0. The body weight of animals in group B was significantly reduced (P<0.05) when compared to control group. The histological findings of the uterus revealed endometrial hyperplasia and presence of inflammatory cells in the group treated with non-salted calabash chalk and epithelial metaplasia coupled with endometrial hyperplasia in the group treated with salted calabash chalk. These hyperplastic and metaplastic effect could be attributed to the presence of lead in calabash chalk. Calabash chalk could cause histological changes in the uterus. Thus, prolonged or regular consumption of calabash chalk should be discouraged as it has been shown to have negative effect.

The effect of calabash chalk on the uterus of adult female Wistar rats

The effect of calabash chalk on the uterus of adult female Wistar rats

Effect of imidacloprid on antioxidant status and histopathological changes in ovary and uterus of adult female wistar rats

Imidacloprid is a neonicotinoid insecticide and has been extensively used as a crop pest and in pet flea control programme. In the present study, the effects of imidacloprid on ovary and uteri tissue was analyzed in adult female Wistar rats at two dose levels (19 and 38 mg/kg/day) administered orally for 10, 20 and 30 days. Effects were compared with respective control animals administered daily with 2% gum acacia. Parameters undertaken were organ weight, levels of cytoplasmic and membrane proteins, oxidative stress parameters viz. activities of SOD, GPx and levels of GSH and MDA and histopathological changes. IMI (38 mg/kg, 30 days) reduced cytoplamic proteins in both ovaries and uteri whereas this dose reduced membrane protein in ovaries only. IMI (38 mg/kg, 20 and 30 days) decreased SOD enzyme in both ovaries and uteri and GSH-Px levels in ovaries only. The GSH-Px levels were also seen with decreased levels in uteri with IMI (38 mg/kg) for 30 days. IMI (38 mg/kg, 20 and 30 days) induces degenerative changes in ovaries of rats. Hence, it is concluded from the present studies that administration of higher doses (38 mg/kg/day) of IMI for 20 and 30 days generated oxidative stress in ovaries and uteri of female rats.

Dexamethasone as endocrine disruptor; type I and type II (anti) oestrogenic actions on the ovary and uterus of adult Wistar rats (Rattus Novergicus).

ObjectiveDexamethasone is a widely used glucocorticoid, which has been prescribed increasingly in recent years. The effects of Dexamethasone on the ovary and uterus was investigated in present study.MethodsTwenty (20) adult female Wistar rats, weighing 130-170 g were assigned to four (4) groups of five (5) animals each. The rats in the control group received saline, while the rats in the experimental group was subjected to oral treatment of dexamethasone of 12 mg/kg, 10 mg/kg, and 7 mg/kg doses daily for a period of 10 days, respectively. The rats were slaughtered after 24 hours of the last administration, and the uterus and ovaries were harvested following abdominal incision. Histological and biochemical investigations were carried out and the results were analyzed using ANOVA with the Graph-Pad prism software package 6.ResultsThere was a significant decrease in the activities of the carbohydrate metabolic enzymes of the uterus in the dexamethasone-treated groups compared to the control group (p<0.05). Vacuolation, atrophy, thick epithelium, enlarged cells, inactive interstitial glands and follicular cyst, characterized the histological observation in the dexamethasone-treated groups in a dose-dependent manner.ConclusionThis present study revealed that high-dose dexamethasone causes multiple changes in the histological features of the ovary and uterus, exerting type I and type II anti-oestrogenic effects on the female reproductive compartment.

Impact of di-(2-ethylhexyl) phthalate on the uterus of adult Wistar rats.

Di-(2-ethylhexyl) phthalate (DEHP) is the most common plasticizer used in polyvinyl chloride-based plastics. DEHP is not covalently bound to the plastics and is easily released to the environment, resulting in human exposure. In this study, the adult rats were exposed to DEHP and its effects on the uterus was evaluated. Healthy adult female rats were treated with DEHP orally (with dose level 0, 1, 10, and 100 mg/kg body weight/day) for 30 days. No significant changes in the body weight and wet uterine weight were observed. Ovarian hormones and their receptor levels in the uterus were increased. Histological studies exhibited the structural abnormalities such as decrease in diameter, thinning of the layers and disruption in the glandular epithelium.

Effects of a glyphosate-based herbicide on the uterus of adult ovariectomized rats.

Glyphosate is the active ingredient of several herbicide formulations. Different reports suggest that glyphosate-based herbicides (GBHs) may act as endocrine disruptors. We evaluated the potential estrogenic effects of a GBH formulation using the uterotrophic assay. Adult ovariectomized rats were sc injected for 3 consecutive days with: saline solution (vehicle control), 2.10-5 g E2 /kg/day (uterotrophic dose; UE2 ), 2.10-7 g E2 /kg/day (nonuterotrophic dose; NUE2 ), or 0.5, 5, or 50mg GBH/kg/day of the. Twenty-four hours after the last injection, the uterus was removed and weighed and processed for histopathology and mRNA extraction. Epithelial cell proliferation and height and expression of estrogen-responsive genes were evaluated (estrogen receptors, ERα and ERβ; progesterone receptor, PR; complement 3, C3). Uterine weight and epithelial proliferation were not affected by GBH. However, the luminal epithelial cell height increased at GBH0.5. ERα mRNA was downregulated by all GBH doses and E2 groups, whereas PR and C3 mRNA were diminished by GBH0.5. GBH5-, GBH50-, and UE2 -treated rats showed downregulated ERα protein expression in luminal epithelial cells, while the receptor was upregulated in the stroma. GBH upregulated ERβ (GBH0.5-50) and PR (GBH5) expressions in glandular epithelial cells, similar effect to that of NUE2 group. These results indicate that, although the uterine weight was not affected, GBH modulates the expression of estrogen-sensitive genes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1191-1201, 2017.

Adverse effects of monosodium glutamate on the reproductive organs of adult Female albino rats and the possible ameliorated role of carob (Ceratonia Siliqua).

Monosodium glutamate (MSG) is a sodium salt of glutamic acid that enhances the flavor of certain foods. It plays an important role in the pathogenesis of anovulatory infertility. This study was carried out to evaluate the histological, histochemical as well as immunohistochemical effects of MSG on the ovaries, uterus and vagina of adult female Wistar rats and the possible ameliorative role of carob (Ceratonia Siliqua). In the present work, twenty- four Wistar rats were divided into four groups (n=6): Control group received 0.5ml saline solution, carob-group, feeding on diet containing 5% carob powder, MSG- treated group received 400 mg/kg b.wt and ameliorative group received MSG 400mg/kg b.wt simultaneously with feeding on diet containing 5% carob powder. In MSG treated rats, the serum estrogen level was significantly decreased. The histopathological results showed ovarian atretic follicles, fragmented oocyte, vascular congestion, and vacuolated stroma. The uterus exhibited a comparative reduction in the endometrial thickness and loss of endometrial glands associated with cellular hyperplasia and reduced vacuolated cells. In MSG treated group, the vaginal epithelium appeared relatively thin, folded and hypertrophied with sign of cornification. Histochemically, a weak reaction for PAS stain was remarked in investigated sections of MSG- treated rats. On the other side, an intense positive reaction for silver stain was recorded in the ovarian stroma and peripheral layers of atretic follicles as well as spreading in endometrium of uterus and lumina sheath of vagina. Immunohistochemically, MSG-treated group exhibited intense positive reaction for CD31and CD68 and activated caspase3 compared to carob-ameliorated MSG and the control. The authors concluded that, feeding of MSG-treated group on diet containing 5% carob powder led to marked amelioration of histopathological lesions induced in ovaries, uterus and vagina by MSG attributed to the biological benefits of its phytochemical components.

Effect of Hydroalcoholic Extract of Kelussia odoratissima Mozaffarian on Uterus Contractions of Mature Rats

Aims: Kelussia odoratissima is a plant from Umbelliferae family that has nutritional and pharmacological properties. The antispasmodic effect of this plant has been mentioned in Iranian traditional medicine. The aim of study was to assess the effect of alcoholic extract of Kelussia odoratissima on uterus contractions of adult rats. Materials & Methods: In this experimental study, 16 adult female Wistar rats were studied and were randomly divided into two groups (each consisted of 8 rats); receiver of Tyrod solution (first group) and receiver of Dejalon solution (second group) groups. A 10-15mm sample of uterus smooth muscle were placed in an organ bath containing Tyrod or Dejalon solution (10ml), and contractions were recorded with Isometric method after inducing with KCl and Oxytocin. The 0.125, 0.25 and 0.5mg/ml final concentrations of the alcoholic extract of Kelussia odoratissima was added to the organ bath. Data were statistically analyzed by SPSS 17 software using repeated measures ANOVA. Findings: The alcoholic extract of Kelussia odoratissima significantly decreased the KCl-induced (p<0.001) and Oxytocin-induced (p<0.002) contractions in a concentration dependent manner. Conclusion: The alcoholic extract of Kelussia odoratissima inhibits the contractions of adult rat uterus in a concentration dependent manner.

Developmental exposure to bisphenol A alters the differentiation and functional response of the adult rat uterus to estrogen treatment

We assessed the long-term effect of perinatal exposure to bisphenol A (BPA) on the rat uterus and the uterine response to estrogen (E2) replacement therapy. BPA (0.5 or 50μg/kg/day) was administered in the drinking water from gestational day 9 until weaning. We studied the uterus of female offspring on postnatal day (PND) 90 and 360, and the uterine E2 response on PND460 (PND460-E2). On PND90, BPA-exposed rats showed altered glandular proliferation and α-actin expression. On PND360, BPA exposure increased the incidence of abnormalities in the luminal and glandular epithelium. On PND460-E2, the multiplicity of glands with squamous metaplasia increased in BPA50 while the incidence of glands with daughter glands increased in BPA0.5. The expression of steroid receptors, p63 and IGF-I was modified in BPA-exposed rats on PND460-E2. The long-lasting effects of perinatal exposure to BPA included induction of abnormalities in uterine tissue and altered response to E2 replacement therapy.

Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats.

Thyroid hormones and oxidative stress play significant roles in the normal functioning of the female reproductive system. Nitric oxide (NO), a free radical synthesized by nitric oxide synthases (NOS), participates in the regulation of thyroid function and is also a good biomarker for assessment of the oxidative stress status. Therefore, the purpose of this study was to investigate effects of thyroid hormones on uterine antioxidative status in young adult rats. Thirty immature female Sprague-Dawley rats were randomly divided into three groups: control, hypothyroid (hypo-T) and hyperthyroid (hyper-T). The results showed the body weights decreased significantly in both the hypo-T and hyper-T groups and that uterine weights were decreased significantly in the hypo-T group. The serum concentrations of total triiodothyronine (T3) and thyroxine (T4), as well as estradiol (E2), were significantly decreased in the hypo-T group, but increased in the hyper-T group. The progesterone (P4) concentrations in the hypo- and hyperthyroid rats markedly decreased. Immunohistochemistry results provided evidence that thyroid hormone nuclear receptor α/β (TRα/β) and three NOS isoforms were located in different cell types of rat uteri. The NO content and total NOS and inducible NOS (iNOS) activities were markedly diminished in the hypo-T group but increased in the hyper-T group. Moreover, the activities of both glutathione peroxidase (GSH-Px) and catalase (CAT) exhibited significant decreases and increases in the hypo-T and hyper-T groups, respectively. The malondialdehyde (MDA) contents in both the hypo-T and hyper-T groups showed a significant increase. Total superoxide dismutase (T-SOD) activity in the hypo- and hyper-T rats markedly decreased. In conclusion, these results indicated that thyroid hormones have an important influence on the modulation of uterine antioxidative status.

Testosterone decreases fluid and chloride secretions in the uterus of adult female rats via down-regulating cystic fibrosis transmembrane regulator (CFTR) expression and functional activity

ObjectivesEstrogen is known to stimulate uterine fluid and Cl− secretion via CFTR. This study investigated testosterone effect on these changes in a rat model. MethodsOvariectomized adult female rats received estrogen for five days or estrogen for three days followed by two days peanut oil or testosterone either alone or in the presence of flutamide or finasteride. At the end of treatment, uteri were perfused with perfusate containing CFTRinh-172. The rate of fluid and Cl− secretion were determined. Dose-dependent effect of testosterone and effect of forskolin on fluid secretion rate were measured. Animals were sacrificed and uteri were removed for CFTR protein and mRNA expression analyses, histology and cAMP measurement. Morphology of uterus, levels of expression of CFTR protein and mRNA and distribution of CFTR protein were observed. ResultsEstrogen causes increase while testosterone causes decrease in uterine fluid and Cl− secretions. The effects of estrogen but not testosterone were antagonized by CFTRinh-172. Luminal fluid volume and apical expression of CFTR in the luminal epithelia were highest under estrogen and lowest under testosterone influences. Similar changes were observed in CFTR protein and mRNA expressions. Uterine cAMP level was highest under estrogen and lowest under testosterone influence. Forskolin increases fluid secretion rate in estrogen but not in testosterone-treated animals. Testosterone effects were dose-dependent and were antagonized by flutamide however, not finasteride. ConclusionsTestosterone inhibition of estrogen-induced uterine fluid and Cl− secretion occurs via inhibition of CFTR expression and functional activities. These changes could explain the adverse effects of testosterone on fertility.

Melatonin and ethanol intake exert opposite effects on circulating estradiol and progesterone and differentially regulate sex steroid receptors in the ovaries, oviducts, and uteri of adult rats

Chronic ethanol intake is associated with sex hormone disturbances, and it is well known that melatonin plays a key role in regulating several reproductive processes. We report the effects of ethanol intake and melatonin treatment (at doses of 100μg/100gBW/day) on sex hormones and steroid receptors in the ovaries, oviducts and uteri of ethanol-preferring rats. After 150 days of treatment, animals were euthanized, and tissue samples were harvested to evaluate androgen, estrogen, progesterone and melatonin receptor subunits (AR, ER-α and ER-β, PRA, PRB and MT1R, respectively). Melatonin decreased estradiol (E2) and increased progesterone (P4) and 6-sulfatoxymelatonin (6-STM), while an ethanol–melatonin combination reduced both P4 and E2. Ovarian AR was not influenced by either treatment, and oviduct AR was reduced after ethanol–melatonin combination. Oviduct ER-α, ER-β and uterine ER-β were down-regulated by either ethanol or melatonin. Conversely, ovarian PRA and PRB were positively regulated by ethanol and ethanol–melatonin combination, whereas PRA was down-regulated in the uterus and oviduct after ethanol consumption. MT1R was increased in ovaries and uteri of melatonin-treated rats. Ethanol and melatonin exert opposite effects on E2 and P4, and they differentially regulate the expression of sex steroid receptors in female reproductive tissues.

Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus

The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol.

Glycosaminoglycan profiles in the uterus of adult ovariectomized rats treated with estrogen and progestagen

To evaluate the effects of conjugated equine estrogens (CE) alone or in combination with medroxyprogesterone acetate (MPA) on glycosaminoglycans (GAGs) in the cervix and horns of the rat uterus. Thirty days after ovariectomy, adult rats were randomly divided into four groups: GI, control (treated with drug vehicle); GII, CE (50 μg/kg per day); GIII, MPA (0.2mg/kg per day), and GIV, CE+MPA (doses as in GII and GIII). Drugs and vehicle were given by gavage during 28 days. Afterwards the animals were anesthetized, the cervix and uterine horns were dissected out and the middle portion fixed in 10% formaldehyde solution; other portions were fixed in acetone for histological examination and glycosaminoglycan quantification, respectively. Agarose gel electrophoresis was used for sulfated GAG analyses, and hyaluronic acid was assayed with an ELISA-like method. Statistical analysis was done by the Student's t test and the Tukey-Kramer test (P<0.05). The cervix and uterine horn structures presented signs of atrophy in the control group (GI). The other groups, mainly groups III and IV, had histological aspects of proliferation. In all groups the concentration of sulfated GAGs (especially dermatan sulfate) was higher than that of non-sulfated GAGs, both in cervix and in uterine horns. Estrogens increased sulfated GAG concentration at the cervix and the horn, whereas in uterine horns the amounts of sulfated GAGs were decreased after estrogens plus MPA treatment. The concentration of hyaluronic acid in uterine horns was higher than in cervices. The profiling and amounts of glycosaminoglycans in the two portions of the rat uterus are uneven. Dermatan sulfate occurs in higher concentrations in both cervix and uterine horns. Sulfated GAGs in rat cervix were increased by estrogens plus MPA, but were decreased by MPA alone in uterine horns.