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  1. Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment
    Tan YY, Wade JD, Tregear GW, Summers RJ
    Br J Pharmacol, 1999 May;127(1):91-8.
    PMID: 10369460
    The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [33P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. The binding kinetics of [33P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achieved equilibrium after 60 min incubation at room temperature (23+/-1 degrees C) and dissociated slowly. The association and dissociation rate constants were 4.31+/-0.34x10(8) M(-1) x min(-1) and 1.55+/-0.38x10(-3) min(-1) respectively. Thus, the kinetic dissociation constant was 3.46+/-0.59 pM. Binding was saturable to a single population of non-interacting sites throughout atria, in uterine myometrium and the 5th layer of cerebral cortex. The binding affinities (pK(D)) of [33P]-human gene 2 relaxin (B33) were 8.92+/-0.09 in atrial myocardium and 8.79+/-0.04 in cerebral cortex of male rats, and 8.79+/-0.10 in uterine myometrium. Receptor densities in the cerebral cortex and atria were higher than in uterine myometrium, indicating that relaxin also has important roles in non-reproductive tissues. In male rats, treatment with 17beta-oestradiol (20 microg in 0.1 ml sesame oil s.c., 18-24 h) significantly decreased the density of relaxin receptors in atria and cerebral cortex. Identical treatment in female rats had no significant effect in atria and cerebral cortex, but it significantly increased the density of relaxin receptors in uterine myometrium. Relaxin binding was competitively displaced by porcine and rat native relaxins. Porcine native relaxin binds to the relaxin receptor in male rat atria (8.90+/-0.02), and cerebral cortex (8.90+/-0.03) and uterine myometrium (8.89+/-0.03) with affinities not significantly different from human gene 2 (B33) relaxin. Nevertheless, rat relaxin binds to the receptors with affinities (8.35+/-0.09 in atria, 8.22+/-0.07 in cerebral cortex and 8.48+/-0.06 in uterine myometrium) significantly less than human gene 2 (B33) and porcine relaxins. Quantitative receptor autoradiography is the method of choice for measurement of affinities and densities of relaxin receptor in atria, uterine myometrium and cerebral cortex. High densities were found in all these tissues. 17beta-oestradiol treatment produced complex effects where it increased the densities of relaxin receptors in uterus but decreased those in atria and cerebral cortex of the male rats, and had no effect on the atria and cerebral cortex of the female rats.
    Matched MeSH terms: Uterus/metabolism*
  2. Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration
    Salleh MN, Ismail P, Abdullah AS, Taufiq-Yap YH, Carmichael P
    IUBMB Life, 2004 Jul;56(7):409-16.
    PMID: 15545218
    Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.
    Matched MeSH terms: Uterus/metabolism
  3. Diabetes alters the mRNA expression of insulin-like growth factors and their receptors in the mouse fallopian tube and uterus during the preimplantation stages
    Zakaria R, Rajikin MH, Yaacob NS, Nor NM
    Reprod Biol, 2007 Mar;7(1):41-53.
    PMID: 17435832
    The possible role of insulin-like growth factors (IGFs) and their receptors (IGFRs) in the pathogenesis of diabetic embryopathy was investigated. Sexually mature female ICR mice of 6-8 weeks old were made diabetic by a single intraperitoneal injection with 200 mg/kg streptozotocin ten days prior to mating. Fallopian tubes and uterine tissues were obtained from the superovulated diabetic and normal mice 48, 72 and 96 hours following human chorionic gonadotropin (hCG) injection. The mRNA expression of IGF-1 and IGF-2 as well as their receptors was determined in the tissues using Real-time Polymerase Chain Reaction (Real-time PCR). The mRNA expression of IGF-1 in the fallopian tube and uterus of the diabetic mice was significantly lower 72 and 96 hours after hCG treatment, respectively, as compared to the controls. The mRNA expression of IGF-1R at 96 hours post-hCG treatment was significantly higher in the fallopian tube and lower in the uterus of the diabetic mice as compared to the controls. The mRNA expression IGF-2 in the fallopian tube was significantly higher 48 and 96 hours after hCG treatment, but was lower in the uterus of diabetic mice 96 hours after hCG treatment as compared to controls. The mRNA expression of IGF-2R in the diabetic mice was significantly higher 48 and 96 hours (the fallopian tube) and 48 hours (uterus) after hCG treatments as compared to the controls. In conclusion, an alteration in mRNA expression of IGFs and their receptors in the diabetic mice as observed in this study could possibly result in diabetic embryopathy.
    Matched MeSH terms: Uterus/metabolism*
  4. Immunolocalization of insulin-like growth factors and their receptors in the diabetic mouse oviduct and uterine tissues during the preimplantation period
    Zakaria R, Rajikin MH, Yaacob NS, Nor NM
    Acta Histochem, 2009;111(1):52-60.
    PMID: 18676006 DOI: 10.1016/j.acthis.2008.04.002
    The aim of the present study was to analyze the immunolocalization of insulin-like growth factor (IGF)-1 and IGF-2 and their receptors in the oviduct and uterus of control and diabetic mice. Sexually mature female ICR mice aged 6-8 weeks were rendered diabetic by streptozotocin (200 mg/kg, administered intraperitoneally). Oviductal and uterine tissues were obtained from the superovulated control and diabetic mice at 48, 72 and 96 h post-human chorionic gonadotropin (hCG) treatment. Localization of IGF-1, IGF-2, IGF-1R and IGF-2R was determined by immunohistochemistry and a semi-quantitative scoring of immunolabelling was performed using a standardized 5-point system. The immunohistochemical scorings for both IGF-1 and IGF-1R were significantly decreased in the oviducts of diabetic mice at 96 h post-hCG treatment. The scores for IGF-2 were significantly increased in the oviducts of diabetic mice at 48 and 72 h post-hCG treatment, and for IGF-2R at 72 h post-hCG treatment. However, there was no significant difference in the scores of IGFs and their receptors in the uterus of control and diabetic mice. In conclusion, the oviductal immunolabelling for IGFs and their receptors was significantly altered by maternal diabetes, which may be of importance in the pathogenesis of preimplantation diabetic embryopathy.
    Matched MeSH terms: Uterus/metabolism*
  5. Fulltext Progesterone downregulates oestrogen-induced expression of CFTR and SLC26A6 proteins and mRNA in rats' uteri
    Gholami K, Muniandy S, Salleh N
    J Biomed Biotechnol, 2012;2012:596084.
    PMID: 23226939 DOI: 10.1155/2012/596084
    Under progesterone (P) dominance, fluid loss assists uterine closure which is associated with pH reduction. We hypothesize that P inhibits uterine fluid secretion and HCO3⁻ transport.
    Matched MeSH terms: Uterus/metabolism*
  6. Fulltext Estrogen receptor modulatory effects of germinated brown rice bioactives in the uterus of rats through the regulation of estrogen-induced genes
    Muhammad SI, Maznah I, Mahmud RB, Saeed MI, Imam MU, Ishaka A
    Drug Des Devel Ther, 2013;7:1409-20.
    PMID: 24324328 DOI: 10.2147/DDDT.S50861
    The expression of genes regulated by estrogen in the uterus was studied in ovariectomized (OVX) rats treated with germinated brown rice (GBR) bioactives, and compared to Remifemin or estrogen at different doses to identify the regulation of these genes in the uterus and their molecular mechanisms.
    Matched MeSH terms: Uterus/metabolism
  7. Fulltext In-vivo functional study on the involvement of CFTR, SLC26A6, NHE-1 and CA isoenzymes II and XII in uterine fluid pH, volume and electrolyte regulation in rats under different sex-steroid influence
    Gholami K, Muniandy S, Salleh N
    Int J Med Sci, 2013;10(9):1121-34.
    PMID: 23869188 DOI: 10.7150/ijms.5918
    Precise control of uterine fluid pH, volume and electrolytes is important for the reproductive processes. In this study, we examined the functional involvement of multiple proteins including Cystic Fibrosis Transmembrane Regulator (CFTR), Cl(-)/HCO3 (-) exchanger (SLC26A6), sodium-hydrogen exchanger-1 (NHE-1) and carbonic anhydrase (CA) in the regulation of these uterine fluid parameters.
    Matched MeSH terms: Uterus/metabolism*
  8. Fulltext Differential expression of Na+/H+-exchanger (NHE-1, 2, and 4) proteins and mRNA in rodent's uterus under sex steroid effect and at different phases of the oestrous cycle
    Gholami K, Muniandy S, Salleh N
    Biomed Res Int, 2013;2013:840121.
    PMID: 23509787 DOI: 10.1155/2013/840121
    Precise uterine fluid pH regulation may involve the Na(+)/H(+)-exchanger (NHE). We hypothesized that NHE isoforms are differentially expressed under different sex steroid treatment and at different oestrous cycle phases which may explain the uterine fluid pH changes observed under these conditions.
    Matched MeSH terms: Uterus/metabolism*
  9. 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
    Mohd Mokhtar H, Giribabu N, Kassim N, Muniandy S, Salleh N
    J Steroid Biochem Mol Biol, 2014 Oct;144 Pt B:361-72.
    PMID: 25125390 DOI: 10.1016/j.jsbmb.2014.08.007
    Estrogen is known to stimulate uterine fluid and Cl(-) secretion via CFTR. This study investigated testosterone effect on these changes in a rat model.
    Matched MeSH terms: Uterus/metabolism
  10. Quercetin induces morphological and proliferative changes of rat's uteri under estrogen and progesterone influences
    Shahzad H, Giribabu N, Muniandy S, Salleh N
    Int J Clin Exp Pathol, 2014;7(9):5484-94.
    PMID: 25337190
    This study investigated the effect of 10 or 100 mg/kg/day quercetin on the uterus of ovariectomized adult female rats receiving sex-steroid replacement regime mimicking changes in hormonal profiles during the reproductive cycle. Following seven days of treatment with estrogen and progesterone with or without quercetin, uteri were harvested for histological and proliferative cell nuclear antigen (PCNA) protein and mRNA expression and PCNA protein distribution analyses. Our findings indicated that co-administration of 10 mg/kg/day quercetin with estrogen and progesterone caused a significant decrease in the size of uterine lumen and epithelial heights with lower PCNA protein and mRNA expression as compared to estrogen plus progesterone-only treatment (P < 0.05). Concomitant treatment with estrogen and progesterone with 100 mg/kg/day quercetin resulted in a marked increase in the number of glands with increased PCNA protein and mRNA expression. Significantly higher PCNA distribution was observed in the stroma and glands as compared to estrogen plus progesterone-only treatment (P < 0.05). In conclusion, at 10 mg/kg/day, quercetin affects uterine morphology but not proliferation, however at 100 mg/kg/day, quercetin induced significant stromal and glandular proliferation which could predispose the uterus towards neoplastic development.
    Matched MeSH terms: Uterus/metabolism
  11. Fulltext Genistein induces increase in fluid pH, Na+ and HCO3(-) concentration, SLC26A6 and SLC4A4 (NBCe1)-B expression in the uteri of ovariectomized rats
    Chinigarzadeh A, Kasim NF, Muniandy S, Kassim NM, Salleh N
    Int J Mol Sci, 2014;15(1):958-76.
    PMID: 24434640 DOI: 10.3390/ijms15010958
    Genistein has been reported to stimulate luminal HCO3(-) secretion. We hypothesized that genistein mediates this effect via SLC26A6 and SLC4A4 (NBCe1) transporters. Our study aimed to: investigate changes in uterine fluid pH, Na+ and HCO3(-) concentration and expression of uterine SLC26A6 and NBCe1 under genistein effect. Ovariectomized adult female rats received 25, 50 and 100 mg/kg/day genistein for a week with and without ICI 182780. A day after the last injection, in vivo uterine perfusion was performed to collect uterine fluid for Na+, HCO3(-) and pH determination. The animals were then sacrificed and uteri were removed for mRNA and protein expression analyses. SLC26A6 and NBCe1-A and NBCe1-B distribution were visualized by immunohistochemistry (IHC). Genistein at 50 and 100 mg/kg/day stimulates uterine fluid pH, Na+ and HCO3(-) concentration increase. Genistein at 100 mg/kg/day up-regulates the expression of SLC26A6 and SLC4A4 mRNA, which were reduced following concomitant ICI 182780 administration. In parallel, SLC26A6 and NBCe1-B protein expression were also increased following high dose genistein treatment and were localized mainly at the apical membrane of the luminal epithelia. SLC26A6 and NBCe1-B up-regulation by genistein could be responsible for the observed increase in the uterine fluid pH, Na+ and HCO3(-) concentration under this condition.
    Matched MeSH terms: Uterus/metabolism*
  12. Enhanced expression of sodium hydrogen exchanger (NHE)-1, 2 and 4 in the uteri of rat model for post-menopause under phytoestrogen genistein influence
    Chinigarzadeh A, Muniandy S, Salleh N
    Environ Toxicol Pharmacol, 2015 Jul;40(1):39-48.
    PMID: 26068551 DOI: 10.1016/j.etap.2015.05.003
    Maintaining near normal uterine fluid pH is important for restoring uterine function after menopause. We hypothesized that genistein could restore uterine fluid pH via its effect on NHE expression. This study therefore investigated changes in uterine NHE-1, 2 and 4 expression under genistein influence. Ovariectomized female rats received genistein (25, 50 or 100mg/kg/day) for seven consecutive days. Uteri were harvested and NHE-1, 2 and 4 mRNA expression were analyzed by Real-time PCR while distribution of these transporters' protein was observed by immunohistochemistry. Expression of NHE-1, 2 and 4 mRNA increased with increasing doses of genistein which was antagonized by ICI 182780. Under genistein influence, NHE-1, 2 and 4 proteins were found to be distributed at apical membrane of endometrial luminal epithelia. Enhanced expression of NHE-1, 2 and 4 in ovariectomised rat uteri by genistein might help to restore pH of uterine fluid which could be useful for women after menopause.
    Matched MeSH terms: Uterus/metabolism
  13. Testosterone Induces Increase in Aquaporin (AQP)-1, 5, and 7 Expressions in the Uteri of Ovariectomized Rats
    Salleh N, Mokhtar HM, Kassim NM, Giribabu N
    J. Membr. Biol., 2015 Dec;248(6):1097-105.
    PMID: 26198330 DOI: 10.1007/s00232-015-9823-8
    Testosterone has been reported to cause a decrease in uterine fluid volume in which this could involve the aquaporins (AQPs). This study aimed to investigate effect of testosterone on uterine AQP-1, 5, and 7 expressions in order to explain the reported reduction in uterine fluid volume under testosterone influence. Ovariectomized adult female rats received peanut oil, testosterone (1 mg/kg/day), estrogen (0.2 µg/kg/day), or combined estrogen plus testosterone for three consecutive days. Other groups received 3 days estrogen followed by 2 days either peanut oil or testosterone with or without flutamide or finasteride. A day after last injection, uteri were harvested, and the levels of AQP-1, 5, and 7 messenger RNA (mRNA) in uterine tissue homogenates were analyzed by real-time PCR (qPCR). Distributions of AQP-1, 5, and 7 proteins in uterus were observed by immunofluorescence. Levels of AQP-1 mRNA were elevated in rats receiving either estrogen or testosterone-only treatment; however, levels of AQP-5 and 7 mRNAs were elevated in rats receiving testosterone-only treatment. In rats pre-treated with estrogen, testosterone treatment resulted in higher AQP-1, 5, and 7 mRNA levels compared to vehicle treatment. Testosterone effects were antagonized by flutamide but not finasteride. Immunofluorescence study showed that AQP-1 was highly distributed in uterine lumenal epithelium following estrogen or testosterone-only treatment. However, AQP-5 and 7 distributions were high in uterine lumenal epithelium following testosterone-only treatment. Testosterone-induced up-regulation of AQP-1, 5, and 7 expressions in uterus could explain the observed reduction in uterine fluid volume as reported under this condition.
    Matched MeSH terms: Uterus/metabolism*
  14. Fulltext Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein
    Ismail N, Giribabu N, Muniandy S, Salleh N
    Int J Med Sci, 2015;12(6):468-77.
    PMID: 26078707 DOI: 10.7150/ijms.11210
    Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause.
    Matched MeSH terms: Uterus/metabolism
  15. Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats
    Karim K, Giribabu N, Muniandy S, Salleh N
    J. Membr. Biol., 2016 04;249(1-2):65-76.
    PMID: 26403527 DOI: 10.1007/s00232-015-9848-z
    We hypothesized that progesterone-induced decrease in uterine fluid pH involves V-ATPase. In this study, expression and functional activity of V-ATPase in uterus were investigated under progesterone influence. Ovariectomized adult female rats received subcutaneous injection of estradiol-17β (1 µg/kg/day) or progesterone (20 mg/kg/day) for 3 days or 3 days estradiol-17β followed by 3 days vehicle, progesterone, or estradiol-17β plus progesterone. Mifepristone, a progesterone receptor blocker, was concomitantly given to the rats which received progesterone. A day after last injection, rate of uterine fluid secretion, its HCO3 (-) concentration, and pH were determined via in vivo uterine perfusion in rats under anesthesia. V-ATPase inhibitor, bafilomycin, was introduced into the perfusion buffer, and changes in these parameters were observed. Expression of V-ATPase A1 and B1/2 proteins and mRNAs in uterus were quantified by Western blotting and real-time PCR, respectively. Distribution of these proteins was observed by immunohistochemistry. Our findings showed that under progesterone influence, uterine fluid secretion rate, HCO3 (-) concentration, and pH were significantly reduced. Administration of bafilomycin did not cause significant changes in fluid secretion rate; however, HCO3 (-) concentration and pH were significantly elevated. In parallel with these changes, expression of V-ATPase A1 and B1/2 proteins and mRNAs were significantly increased with these proteins highly distributed in uterine luminal and glandular epithelia. In conclusion, increased expression and functional activity of V-ATPase were most likely responsible for the decreased in uterine fluid pH observed under progesterone influence.
    Matched MeSH terms: Uterus/metabolism*
  16. Estradiol, progesterone and genistein differentially regulate levels of aquaporin (AQP)-1, 2, 5 and 7 expression in the uteri of ovariectomized, sex-steroid deficient rats
    Chinigarzadeh A, Muniandy S, Salleh N
    Steroids, 2016 11;115:47-55.
    PMID: 27521800 DOI: 10.1016/j.steroids.2016.08.007
    In this study, effects of estradiol, progesterone and genistein on uterine aquaporin (AQP)-1, 2, 5 and 7 expression were investigated in sex-steroid deficient state which could help to elucidate the mechanisms underlying uterine fluid volume changes that were reported under these hormone and hormone-like compound influences.

    METHODS: Uteri from ovariectomized, female Sprague-Dawley rats receiving seven days estradiol, progesterone or genistein (25, 50 and 100mg/kg/day) were harvested and levels of AQP-1, 2, 5 and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR (qPCR) respectively. Distribution of these proteins in uterus was observed by immunohistochemistry.

    RESULTS: Genistein caused a dose-dependent increase in uterine AQP-1, 2, 5 and 7 protein and mRNA expression, however at the levels lower than following estradiol or progesterone stimulations. Effects of genistein were antagonized by estradiol receptor blocker, ICI 182780. Estradiol caused the highest AQP-2 protein and mRNA expression while progesterone caused the highest AQP-1, 5 and 7 protein and mRNA expression in uterus. AQP-1, 2, 5 and 7 protein were found to be distributed in the myometrium as well as in uterine luminal and glandular epithelia and endometrial blood vessels. In conclusion, the observed effects of estradiol, progesterone and genistein on uterine AQP-1, 2, 5 and 7 expression could help to explain the differences in the amount of fluid accumulated in the uterus under these different conditions.

    Matched MeSH terms: Uterus/metabolism*
  17. Combinatorial effect of genistein and female sex-steroids on uterine fluid volume and secretion rate and aquaporin (AQP)-1, 2, 5, and 7 expression in the uterus in rats
    Chinigarzadeh A, Muniandy S, Salleh N
    Environ Toxicol, 2017 Mar;32(3):832-844.
    PMID: 27235753 DOI: 10.1002/tox.22283
    We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secretion rate and expression of aquaporin in the uterus by female sex-steroids, i.e., estrogen and progesterone. Therefore, the aims of this study were to investigate changes in these parameters in the presence of genistein and female sex-steroids.

    METHODS: Female Sprague-Dawley rats were ovariectomized and received 3-days estradiol-17β benzoate (E2) plus genistein (25, 50, or 100 mg kg(-1)  day(-1) ) or 3-days E2 followed by 3-days E2 plus progesterone with genistein (25, 50, or 100 mg kg(-1)  day(-1) ). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP-1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP-1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR respectively.

    RESULTS: Combined treatment of E2 with high dose genistein (50 and 100 mg kg(-1)  day(-1) ) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP-1, 2, 5, and 7 proteins and mRNAs in uterus (p 

    Matched MeSH terms: Uterus/metabolism
  18. Quercetin exerts preventive, ameliorative and prophylactic effects on cadmium chloride - induced oxidative stress in the uterus and ovaries of female Wistar rats
    Nna VU, Usman UZ, Ofutet EO, Owu DU
    Food Chem Toxicol, 2017 Apr;102:143-155.
    PMID: 28229914 DOI: 10.1016/j.fct.2017.02.010
    This study examined the possible protective effect of quercetin(QE) on cadmium chloride (CdCl2) - induced reproductive toxicity in female rats. Cadmium (Cd) accumulated in the uterus and ovaries of rats, decreased antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and raised the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the uterus and ovaries of rats. Serum concentrations of estradiol, progesterone, follicle stimulating hormone and luteinizing hormone decreased significantly after CdCl2 administration. Caspase-3 activity significantly increased in the ovaries, with an increase in Bax and a decrease in Bcl-2 protein expressions after CdCl2 treatment. Histopathology of the ovaries revealed significant decrease in follicle number, while the uterus showed cyst-like endometrial glands. All three models of QE treatment [pre-treatment (QE + CdCl2), post-treatment (CdCl2+QE), simultaneous treatment (CdCl2/QE)] decreased Cd accumulation, MDA, H2O2, and increased SOD, CAT and GPx activities in the uterus and ovaries, decreased apoptosis of follicular cells, and increased serum reproductive hormones. However, the QE pre-treated model offered better protection against CdCl2 relative to the other two models. These results suggest that, QE exerts multi-mechanistic protective effects against cadmium toxicity attributable to its antioxidant and anti-apoptotic actions.
    Matched MeSH terms: Uterus/metabolism
  19. Quercetin alters uterine fluid volume and aquaporin (AQP) subunits (AQP-1, 2, 5 & 7) expression in the uterus in the presence of sex-steroids in rats
    Shahzad H, Giribabu N, Karim K, Muniandy S, Kassim NM, Salleh N
    Reprod Toxicol, 2017 04;69:276-285.
    PMID: 28341573 DOI: 10.1016/j.reprotox.2017.03.012
    Effects of quercetin on uterine fluid volume and aquaporin (AQP) expression in the uterus were investigated. Estradiol (E) or estradiol followed by progesterone (E+P) were given to ovariectomised rats with or without quercetin (10, 50 or 100mg/kg/day) treatment. Uteri were harvested and its inner/outer circumference ratio was determined. AQP-1, 2, 5 and 7 mRNA and protein levels in uterus were quantified by Real-time PCR and Western blotting respectively. Protein distribution was observed by immunohistochemistry. Administration of quercetin in E-treated rats decreased the uterine fluid volume and uterine AQP-2 expression. In E+P-treated rats, administration of 100mg/kg/day quercetin increased uterine fluid volume, AQP-1 and 2 expression but decreased AQP-7 expression in uterus. AQP-1 was distributed in stromal blood vessels while AQP-2, 5 and 7 were distributed in uterine epithelium.

    CONCLUSIONS: Quercetin-induced changes in uterine fluid volume and AQP subunits expression in uterus could affect the uterine reproductive functions under different sex-steroid influence.

    Matched MeSH terms: Uterus/metabolism
  20. Isoflavone genistein inhibits estrogen-induced chloride and bicarbonate secretory mechanisms in the uterus in rats
    Chinigarzadeh A, Karim K, Muniandy S, Salleh N
    J Biochem Mol Toxicol, 2017 Apr;31(4).
    PMID: 27891704 DOI: 10.1002/jbt.21878
    We hypothesized that genistein could affect the chloride (Cl(-) ) and bicarbonate (HCO3(-) ) secretory mechanisms in uterus. Ovariectomized female rats were given estradiol or estradiol plus progesterone with 25, 50, or 100 mg/kg/day genistein. Following completion of the treatment, uterine fluid Cl(-) and HCO3(-) concentrations were determined by in vivo uterine perfusion. Uteri were subjected for molecular biological analysis (Western blot, qPCR, and immunohistochemistry) to detect levels of expression of Cystic Fibrosis transmembrane regulator (CFTR), Cl(-) /HCO3(-) exchanger (SLC26a6), Na(+) /HCO3(-) cotransporter (SLC4a4), and estrogen receptor (ER)-α and β. Coadministration of genistein resulted in decrease in Cl(-) and HCO3(-) concentrations and expression of CFTR, SLC26a6, SLC4a4, and ER-α and ER-β in the uteri of estradiol-treated rats. In estradiol plus progesterone-treated rats, a significant increase in the above parameters were observed following high-dose genistein treatment except for the SLC24a4 level. In conclusion, genistein-induced changes in the uterus could affect the reproductive processes that might result in infertility.
    Matched MeSH terms: Uterus/metabolism
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