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Ovariectomized Mice (ovariectomized + mouse)
Selected AbstractsDouble Oestrogen Receptor , and , Knockout Mice Reveal Differences in Neural Oestrogen-Mediated Progestin Receptor Induction and Female Sexual BehaviourJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2003A. E. Kudwa Abstract To test the hypothesis that oestrogen receptor , (ER,) and ER, act together to mediate the actions of oestrogen in the ventromedial hypothalamus (VMH), we used mice with single or double knockout mutations of the ER, and ER, genes. Ovariectomized mice were implanted with 17,-oestradiol and killed 5 days later. Oestradiol treatment promoted progestin receptor (PR)-immunoreactivity (-ir) in the VMH of all genotypes, but was maximal in brains of wild-type and ER,KO females. Analysis of specific VMH subregions revealed that PR-ir induction was limited to the caudal VMH in ER,KO and ER,,KO mice. In the rostral VMH, oestradiol only induced PR-ir in wild-type and ER,KO mice, and the number of PR-ir neurones in this region was greater in ER,KO than wild-type females. Next, we tested the ability of a dopamine agonist and progesterone to facilitate sexual behaviour in females lacking functional ER,, ER,, or both receptors. Ovariectomized mice were implanted with oestradiol, and tested for sexual behaviour three times after administration of the dopamine agonist, apomorphine, followed by two tests concurrent with progesterone treatment and a final test with just apomorphine treatment. ER,KO and ER,,KO females failed to display lordosis under any testing conditions, while ER,KO females exhibited lordosis behaviour equal to that of wild-type females. Our data show that a subpopulation of PR-ir neurones is induced by oestradiol in the caudal VMH of female mice lacking both ER, and ER, genes. We hypothesize that this action of oestradiol is either mediated by a novel ER or by the mutant portion of the AF2 subregion of the ER, gene present in ER,KO brain. However, despite the presence of PR in VMH, females lacking a functional ER, gene do not display sexual behaviour, via either ligand-dependent or -independent activation. [source] Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Niina M. Saarinen Abstract In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial. In postmenopausal mammary cancer xenograft model, flaxseed (FS), a rich source of plant lignans, reduced breast cancer growth, while soy protein (SP), a rich source of isoflavones, enhanced it. The intake of phytoestrogens is increasing particularly among postmenopausal women, emphasizing the importance of elucidating their interactive effects on breast cancer. Our study determined the effect of FS and SP diets, alone and in combination, on the established human breast cancer MCF-7 tumor growth in ovariectomized athymic nude mice. Tumor bearing mice were divided into 4 groups and fed for 25 weeks either the basal diet (BD), or BD supplemented with 10% FS, 20% SP or 10% FS and 20% SP. After estrogen deprivation, FS regressed the tumor size similar to that of control. SP initially regressed the tumors but starting at week 13, the tumors regressed significantly less than in control and 43% of the tumors were regrowing until the end of the experiment and were significantly larger in size than in control. The combination of SP with FS reduced the tumor growth similar to that of control, as suggested also by the reduced tumor cell proliferation index. In conclusion, dietary FS did not stimulate the growth of estrogen responsive MCF-7 cancers in ovariectomized mice, while long-term consumption of SP did. Furthermore, FS reduced the tumor growth stimulating effect of SP to the same level as control, suggesting tumor growth attenuating effect of FS. © 2006 Wiley-Liss, Inc. [source] Only Male Mice Show Sensitization of Handling-Induced Convulsions Across Repeated Ethanol Withdrawal CyclesALCOHOLISM, Issue 3 2007L.M. Veatch Background: Alcohol abuse, especially when experienced in multiple cycles of chronic abuse and withdrawal, leads to a sensitization of central nervous system hyperexcitability that may culminate in overt expression of seizures. In spite of the growing prevalence of alcohol abuse and dependence in females shown in recent epidemiologic studies, evidence of sexual dimorphism in the expression of alcohol withdrawal-induced seizures and the development of seizure sensitization following multiple cycles of ethanol (EtOH) exposure and withdrawal has not been examined in either animal models or in clinical reports. Methods: Subjects in these experiments were male and female C3H/Hecr mice. The female mice were intact or ovariectomized, with ovariectomized mice receiving 17- , -estradiol or placebo pellets. All mice were exposed to 4 cycles of exposure to 16-hour EtOH vapor, separated by 8-hour withdrawal periods. During each 8-hour withdrawal, hourly assessment of seizure propensity was assessed as handling-induced convulsions. Additional assessments were taken up to 72 hours after the final EtOH withdrawal cycle. Results: Male and female mice showed similar seizure propensity during an initial withdrawal from chronic EtOH. Across subsequent withdrawal cycles, however, male mice exhibited a robust increase in seizure severity beginning with the third withdrawal cycle. In marked contrast, female mice failed to demonstrate sensitization of seizure severity. The lack of seizure sensitization following up to 4 cycles of alcohol exposure and withdrawal could not be explained by hormonal status (presence or absence of estrogen) or by sex differences in blood alcohol levels. Conclusions: Male and female mice exposed to the same number of cycles of EtOH withdrawal demonstrate differences in expression of seizures. Males show the typical sensitization of seizures, or kindling response, which has been reported clinically as well as in animal models, but females do not. The reason for the lack of seizure sensitization in female mice remains to be elucidated, but may be related to sex differences in alcohol effects on excitatory/inhibitory neurotransmission, rather than to hormonal or blood alcohol level differences. [source] Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterusMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2009Mahinč Ivanga Abstract In rodents, the uterus of a mature female undergoes changes during the uterine cycle, under the control of steroid hormones. 5,-Dihydrotestosterone (DHT) is recognized to play an important role in the regulation of androgen action in normal endometrium. Using microarray technology, a screening analysis of genes responding to DHT in the uterus of ovariectomized mice, has allowed us to highlight multiple genes of the ATM/Gadd45g pathway that are modulated following exposure to DHT. Two phases of regulation were identified. In the early phase, the expression of genes involved in the G2/M arrest is rapidly increased, followed by the repression of genes of the G1/S checkpoint, and by the induction of transcriptional regulators. Later, i.e. from 12 to 24 hr, genes involved in G2/M transition, cytoarchitectural and lipid-related genes are stimulated by DHT while immunity-related genes appear to be differentially regulated by the hormone. These results show that a physiological dose of DHT induces the transcription of genes promoting the cell cycle progression in mice. Profile determination of temporal uterine gene expression at the transcriptional level enables us to suggest that the DHT modulation of genes involved in ATM/Gadd45g signaling in an ATM- or p53-independent manner, could play an important role in the cyclical changes of uterine cells in the mouse uterus. Mol. Reprod. Dev. 76: 278,288, 2009. © 2008 Wiley-Liss, Inc. [source] Differential expression and activation of Stat3 during mouse embryo implantation and decidualizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2004Chun-Bo Teng Abstract Signal transducer and activator of transcription (STATs) can be activated by many cytokines and growth factors. Stat3, a member of STAT family, is essential for embryonic development. Stat3 is specifically activated during mouse embryo implantation. This study was to investigate the expression, activation, and regulation of Stat3 in mouse uterus during early pregnancy, pseudopregnancy, delayed implantation, artificial decidualization, and hormonal treatments using in situ hybridization and immunohistochemistry. There was a strong level of Stat3 phosphorylation in the luminal epithelium only at the midnight of day 4 pregnancy, which coincides with attachment reaction between the blastocyst and luminal epithelium. However, there was no detectable Stat3 phosphorylation at the corresponding period during pseudopregnancy. On day 5 of pregnancy, Stat3 phosphorylation was strongly observed in the luminal epithelium and the stroma surrounding the implanting blastocyst at implantation sites, but not at the inter-implantation sites. Stat3 phosphorylation was also not detected on day 5 of pseudopregnancy. Stat3 phosphorylation was at a high level in the decidual cells on days 6,8 of pregnancy. Under artificial decidualization, Stat3 was also phosphorylated in the decidual cells. In the ovariectomized mice, there was no Stat3 expression and activation in the uterus. Progesterone had no obvious effects. However, Stat3 mRNA expression and phosphorylation were significantly stimulated by estrogen treatment. Our data suggest that Stat3 phosphorylation may be important for mouse embryo implantation and decidualization, and may also be regulated by maternal estrogen. Mol. Reprod. Dev. 69: 1,10, 2004. © Wiley-Liss, Inc. [source] Peroxisome proliferator-activated receptor delta expression and regulation in mouse uterus during embryo implantation and decidualizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2003Nai-Zheng Ding Abstract The aim of this study was to examine the expression and regulation of peroxisome proliferator-activated receptor (PPAR) PPAR, gene in mouse uterus during early pregnancy by in situ hybridization and immunohistochemistry. PPAR, expression under pseudopregnancy, delayed implantation, hormonal treatment, and artificial decidualization was also investigated. There was a very low level of PPAR, expression on days 1,4 of pregnancy. On day 5 when embryo implanted, PPAR, expression was exclusively observed in the subluminal stroma surrounding the implanting blastocyst. No corresponding signals were seen in the uterus on day 5 of pregnancy. There was no detectable PPAR, signal under delayed implantation. Once delayed implantation was terminated by estrogen treatment and embryo implanted, a strong level of PPAR, expression was induced in the subluminal stroma surrounding the implanting blastocyst. Estrogen treatment induced a moderate level of PPAR, expression in the glandular epithelium, while progesterone treatment had no effects in the ovariectomized mice. A strong level of PPAR, expression was seen in the decidua on days 6,8 of pregnancy. PPAR, expression was also induced under artificial decidualization. These data suggest that PPAR, expression at implantation sites require the presence of an active blastocyst and may play an essential role for blastocyst implantation. Mol. Reprod. Dev. 66: 218,224, 2003. © 2003 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Effects of Cyclic Versus Sustained Estrogen Administration on Peripheral Immune Functions in Ovariectomized MiceAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Jing Li Citation Li J, McMurray RW. Effects of cyclic versus sustained estrogen administration on peripheral immune functions in ovariectomized mice. Am J Reprod Immunol 2010; 63: 274,281 Problem, Estrogens have multiple influences on immune functions. We aimed to compare the effects of cyclic versus sustained estrogen treatments under the same accumulated dose on peripheral immune functions in ovariectomized mice. Method of study, Ovariectomized adult Balb/c mice were treated with estradiol (E2) by s.c. injection once every 4 days (total 44.8 ,g) or by pellet implantation (total 44.2 ,g). After 6 weeks of treatment, all animals were immunized with DNP-KLH. Peripheral immune functions were assessed 10 days later. Results, Both cyclic and sustained E2 treatments significantly reduced the percentage of splenic B220+sIgM+ cells, enhanced IFN-, production and suppressed IL-6 secretion from Con A-stimulated splenocytes, and increased serum anti-DNP antibody levels. No differences were found in the above responses or in uterine weight gain between the two regimens of E2 administration. Conclusion, There are no differential effects on peripheral immune functions between cyclic and sustained estrogen administration under the same total dose. [source] Effects of female steroid hormones on A-type K+ currents in murine colonTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006Elizabeth A. H. Beckett Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause. [source] Preventive Effects of Isoflavones, Genistein and Daidzein, on Estradiol-17,-related Endometrial Carcinogenesis in MiceCANCER SCIENCE, Issue 7 2001Zenglin Lian The effects of isoflavones (genistein and daidzein) on endometrial carcinogenesis in mice were investigated in two experiments. In the short-term experiment (2 weeks), single subcutaneous (s.c.) administration of genistein [1 mg/30 g body weight (b.w.)] significantly decreased the levels of estradiol-l7, (E2) (5 ppm in diet)-induced expression of c-jun, interleukin-l, (IL-l,) and tumor necrosis factor-a (TNF-a) mRNAs in the uteri of ovariectomized mice (P<0.005, P<0.05 and P<0.01, respectively). Daidzein significantly inhibited E2-induced expression of c-fos and IL-l, (P<0.01, P<0.01 respectively). In the long-term experiment (30 weeks), 140 female ICR mice were given N-methyl-N-nitrosourea-containing solution (1 mg/100 g b.w.) and normal saline (as controls) into their left and right uterine corpora, respectively. They were divided into six groups; group 1 was given E2 (in diet) alone. Group 2 was given E2 and genistein (1 mg/30 g b.w., s.c., every four weeks). Group 3 was exposed to E2 and daidzein (1 mg/30 g b.w., s.c., every four weeks). Groups 4 and 5 respectively received genistein and daidzein, and were kept on the basal diet. Group 6 was kept on the basal diet and served as a control. At the termination of the experiment, incidences of endometrial adenocarcinoma and atypical endometrial hyperplasia of the group given E2 and genistein or daidzein were significantly lower than of the group with E2 alone (P<0.01 and P<0.05, respectively). It is suggested that both genistein and daidzein have an inhibitory effect on estrogen-related endometrial carcinogenesis in mice, possibly by suppressing expression of estrogen-induced estrogen-related genes c-fos and c-jun, and internal cytokines IL-l, and TNF-, through a cytokine and estrogen receptor-mediated pathway. [source] | |||||||||||||