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Sample records for pregnant female rats

  1. Vitamin A supplementation to pregnant and breastfeeding female rats induces oxidative stress in the neonatal lung.

    PubMed

    Pasquali, Matheus Augusto de Bittencourt; Schnorr, Carlos Eduardo; Feistauer, Lucas Brambilla Hilbig; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2010-11-01

    Vitamin A is an essential micronutrient that regulates many biological processes through modulation of retinoic acid receptor-responsive genes. Vitamin A acts as a systemic antioxidant, participating in the modulation of diverse redox mechanisms involved in physiological and pathological processes. Different studies, however, observed that vitamin A and other retinoids may induce pro-oxidant/deleterious actions under certain conditions, leading to impairment of brain and lung function. Here, we studied the effect of vitamin A treatment at oral doses of 100 IU/kg, 200 IU/kg, and 300 IU/kg to female rats (Rattus norvegicus) during pregnancy and lactation on oxidative parameters of lungs from the offspring vitamin A supplementation induced increases in lipoperoxidation, protein carbonyl, activities of the antioxidant enzymes superoxide dismutase and catalase (200 IU/kg, and 300 IU/kg), and decreased sulphydryl protein (500 IU/kg) content in the neonatal lung. PMID:20679000

  2. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS

    PubMed Central

    LOTH, Eduardo Alexandre; CECATTO, Vanessa; BIAZIM, Samia Khalil; FERREIRA, José Henrique Fermino; DANIELLI, Caroline; GENSKE, Rodrigo Daniel; GANDRA, Rinaldo Ferreira; de FRANCO, Marcello Fabiano

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring.

  3. Similar profile of urinary and faecal metabolites of 14C-carmoisine in male and pregnant female rats after oral administration.

    PubMed

    Tragni, E; Flaminio, L M; Galli, C L; Marinovich, M

    1985-10-01

    Pregnant rats received 14C-Carmoisine (200 mg kg-1; 25 microCi) by gavage on days 16-19 of gestation. The animals were killed and maternal tissues, amniotic fluid, placentae, foetal membranes and foetuses were analyzed for radioactivity. No evidence for the transplacental transfer of 14C-Carmoisine or its metabolites was obtained. Male rats were given a single oral administration of 14C-Carmoisine (200 mg kg-1; 25 microCi) and killed at different times after dosing. In both male and female animals, more than 90% of the radioactivity was excreted in faeces and urine within 64 h, and the results suggested that there was no significant absorption of the azodye and no preferential concentration of the red food colour or its metabolites in any particular tissue. Analyses by HPLC, combined with a radioactivity monitor (RAM), of urine and faeces of such animals show that five radioactive peaks were present in the radiochromatogram in addition to unmodified Carmoisine. The mean peak shows the retention time and the u.v. spectrum of authentic naphthionic acid. The results demonstrate that the pregnancy does not affect the kinetic and the metabolic profile of a single oral administration of the azodye Carmoisine given at different days of gestation. PMID:4056304

  4. Energy balance of pregnant diabetic rats.

    PubMed

    Yamada, Ruth; Griggio, Mauro A; Luz, Jacqueline

    2002-05-01

    Pregnancy and diabetes lead to metabolic alterations in the energy balance that may not be completely independent. The objective of the present study was to look at the alterations induced by type 1 diabetes mellitus on the energy balance of pregnant rats and the offspring. Diabetes was induced by streptozotocin injection 15 d before the starting of pregnancy. The rats had their energy balance variables followed for 21 d. Protein, fat and energy content of dams was determined from samples of the carcasses. Pregnancy led to increased energy intake, energy gain and energy expenditure as well as higher gross food efficiency than non-pregnant counterparts. Diabetes increased metabolizable energy intake but not the energy gain of the animals: they had very high energy expenditure, so that diabetes blocked the improvement in gross food efficiency shown during pregnancy. Offspring from diabetic dams were born with lower body weight. Pregnant animals did not present the usual energy storage as seen by lower energy gain of diabetic dams as well as by the lower fat content in the carcasses of pregnant diabetic rats. It is concluded that diabetes impairs the energy variables usually enhanced by pregnancy alone. PMID:12010589

  5. Effects of exposure to microwaves on cellular immunity and placental steroids in pregnant rats.

    PubMed Central

    Nakamura, H; Seto, T; Nagase, H; Yoshida, M; Dan, S; Ogino, K

    1997-01-01

    OBJECTIVES: Microwaves produce various detrimental changes based on actions of heat or non-specific stress, although the effects of microwaves on pregnant organisms has not been uniform. This study was designed to clarify the effect of exposure to microwaves during pregnancy on endocrine and immune functions. METHODS: Natural killer cell activity and natural killer cell subsets in the spleen were measured, as well as some endocrine indicators in blood--corticosterone and adrenocorticotrophic hormone (ACTH) as indices of the hypothalamic-pituitary-adrenal axis--beta-endorphin, oestradiol, and progesterone in six female virgin rats and six pregnant rats (nine to 11 days gestation) exposed to microwaves at 10 mW/cm2 incident power density at 2450 MHz for 90 minutes. The same measurements were performed in control rats (six virgin and six pregnant rats). RESULTS: Skin temperature in virgin and pregnant rats increased immediately after exposure to microwaves. Although splenic activity of natural killer cells and any of the subset populations identified by the monoclonal antibodies CD16 and CD57 did not differ in virgin rats with or without exposure to microwaves, pregnant rats exposed to microwaves showed a significant reduction of splenic activity of natural killer cells and CD16+CD57-. Although corticosterone and ACTH increased, and oestradiol decreased in exposed virgin and pregnant rats, microwaves produced significant increases in beta-endorphin and progesterone only in pregnant rats. CONCLUSIONS: Microwaves at the power of 10 mW/cm2 produced activation of the hypothalamic-pituitary-adrenal axis and increased oestradiol in both virgin and pregnant rats, suggesting that microwaves greatly stress pregnant organisms. These findings in pregnant rats suggest that--with exposure to microwaves--pregnancy induces immunosuppression, which could result in successful maintainance of pregnancy. This enhancement of adaptability to heat stress with pregnancy may be mediated by activation of placental progesterone and placental or pituitary beta-endorphin. PMID:9423582

  6. The effects of female sexual hormones on the expression and function of ?1A- and ?1D-adrenoceptor subtypes in the late-pregnant rat myometrium.

    PubMed

    Bta, Judit; Hajagos-Tth, Judit; Ducza, Eszter; Samavati, Reza; Borsodi, Anna; Benyhe, Sndor; Gspr, Rbert

    2015-12-15

    The aim of the study was to investigate the roles of ?1-adrenoceptor subtypes in the last-day pregnant rat uterus in vitro by the administration of subtype-specific antagonists (the ?1A-adrenoceptor antagonist WB 4101 and the ?1D-adrenoceptor antagonist BMY 7378) after 17?-estradiol or progesterone pretreatment. In isolated organ bath studies, contractions were elicited with (-)-noradrenaline (10(-8)-10(-5)M) in the presence of propranolol (10(-5)M) and yohimbine (10(-6)M) in order to avoid ?-, and ?2-adrenergic action. The myometrial expressions of the ?1-adrenoceptor subtypes were determined by means of the real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting techniques. The activated G protein levels were investigated through radiolabelled GTP binding assays. Both 17?-estradiol and progesterone pretreatment changed the myometrial contracting effect of (-)-noradrenaline. In the presence of WB 4101, progesterone pretreatment decreased the (-)-noradrenaline-induced myometrial contraction. In the presence of BMY 7378, both the 17?-estradiol and the progesterone pretreatment reduced the effect of (-)-noradrenaline. The mRNA and protein expressions of the ?1A-adrenoceptors were decreased after 17?-estradiol pretreatment. (-)-Noradrenaline increased the [(35)S]GTP?S binding of the ?1-adrenoceptors, which was most markedly elevated by progesterone. Pertussis toxin inhibited the [(35)S]GTP?S binding-stimulating effect of (-)-noradrenaline, indicating the role of Gi proteins in the signal mechanisms. 17?-estradiol pretreatment blocks the expression of the ?1A-adrenoceptors, whereas it does not influence the expression of the ?1D-adrenoceptors. Progesterone pretreatment does not have any effect on the myometrial mRNA and protein expressions of the ?1-adrenoceptors, but it alters the G protein coupling of these receptors, promoting a Gi-dependent pathway. PMID:26593425

  7. Effects of stress early in gestation on hippocampal neurogenesis and glucocorticoid receptor density in pregnant rats.

    PubMed

    Pawluski, J L; Csszr, E; Savage, E; Martinez-Claros, M; Steinbusch, H W M; van den Hove, D

    2015-04-01

    Pregnancy is a time of marked neural, physiological and behavioral plasticity in the female and is often a time when women are more vulnerable to stress and stress-related diseases, such as depression and anxiety. Unfortunately the impact of stress during gestation on neurobiological processes of the mother has yet to be fully determined, particularly with regard to changes in the hippocampus; a brain area that plays an important role in stress-related diseases. The present study aimed to determine how stress early in pregnancy may affect hippocampal plasticity in the pregnant female and whether these effects differ from those in virgin females. For this purpose, adult age-matched pregnant and virgin female Sprague-Dawley rats were divided into two conditions: (1) Control and (2) Stress. Females in the stress condition were restrained during days 5-11 of gestation and at matched time-points in virgin females. All pregnant females received an injection of bromodeoxyuridine (BrdU) on day 1 of gestation and were sacrificed 21 days later. The same procedure was carried out at matched time points in virgin females. Results show that for number of Ki67-immunoreactive (ir) cells and doublecortin (DCX)-ir cells, there were significant interactions between reproductive state (pregnant/virgin) and stress exposure (p=.05, p=.04, respectively) with control virgin and stressed pregnant females having more Ki67-ir cells than control pregnant females and more DCX-ir cells than stressed virgin females. Results also show that pregnant females had significantly greater glucocorticoid receptor (GR) density in the CA1, CA3 and granule cell layer compared to virgin females. In addition, there was a main effect of stress on GR density in the CA3 region, with stressed females having significantly lower GR density compared to control females (p=.01). This work adds to our understanding of how stress and reproductive state affect plasticity in the female hippocampus. PMID:25655215

  8. Tenofovir rescue therapy in pregnant females with chronic hepatitis B

    PubMed Central

    Hu, Yu-Hong; Liu, Min; Yi, Wei; Cao, Yan-Jun; Cai, Hao-Dong

    2015-01-01

    AIM: To evaluate the safety and efficacy of tenofovir monotherapy in pregnant females resistant to lamivudine or telbivudine. The effect of tenofovir on the fetus was also assessed. METHODS: The clinical data of 17 females were reviewed in this study. Adverse events and pregnancy outcomes from January 1, 2011 to June 30, 2013 were evaluated in the Department of Gynecology and Obstetrics of Beijing Ditan Hospital, Capital Medical University, Beijing, China. These pregnant females developed lamivudine (LAM)- or telbivudine (LdT)-resistant chronic hepatitis B and received tenofovir (TDF) therapy (300 mg/d), and its curative effect, maternal and perinatal adverse events, fetal growth and development, and neonatal prognosis were evaluated. RESULTS: The median hepatitis B virus (HBV) DNA level in the pregnant females with LAM or LdT resistance was 5.9 (range, 4.2-7.2) log10 copies/mL before the initiation of TDF. Ten of these females had abnormal alanine aminotransferase (ALT) levels. The patients were treated with TDF for a median of 24 wk (range, 12-40 wk). Fourteen females (82.4%) had an HBV DNA level of < 500 copies/mL at the time of delivery. This decrease was statistically significant (P < 0.0001). Serum ALT levels were normalized in all subjects with an elevated serum ALT level at baseline (P = 0.0003). There were no significant changes in serum creatinine and phosphorus levels during TDF treatment. In addition, no adverse events related to TDF treatment were observed. Seventeen females delivered 17 live infants, and all infants had good Apgar scores. The mean birth weight was 3226.5 ± 331.7 g, and the mean length at birth was 50.4 ± 1.1 cm. The growth and development of the infants was normal at birth, and no infants had birth defects related to TDF treatment. Eleven infants completed HBV vaccination and had no evidence of vertical transmission. CONCLUSION: The use of TDF in pregnant females with chronic HBV and LAM or LdT resistance was safe and effective. PMID:25741161

  9. Luteal activity of pregnant rats with hypo-and hyperthyroidism

    PubMed Central

    2014-01-01

    Background Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are also a cause of miscarriage and stillbirth. Because of that, we evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats. Methods Seventy-two adult female rats were equally distributed into three groups: hypothyroid, hyperthyroid and control. Hypo- and hyperthyroidism were induced by the daily administration of propylthiouracil and L-thyroxine, respectively. The administration began five days before becoming pregnant and the animals were sacrificed at days 10, 14, and 19 of gestation. We performed an immunohistochemical analysis to evaluate the expression of CDC-47, VEGF, Flk-1 (VEGF receptor) and COX-2. Apoptosis was evaluated by the TUNEL assay. We assessed the gene expression of VEGF, Flk-1, caspase 3, COX-2 and PGF2? receptor using real time RT-PCR. The data were analyzed by SNK test. Results Hypothyroidism reduced COX-2 expression on day 10 and 19 (P?pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period. PMID:25298361

  10. Rat lung phospholipid fatty acid composition in prepregnant, pregnant, and lactating rats: relationship to ozone-induced pulmonary toxicity.

    PubMed

    Gunnison, A F; Finkelstein, I

    1997-01-01

    Our laboratory has demonstrated recently that pulmonary inflammation induced by acute ozone exposure is much more severe in late stage pregnant and lactating rats than in postlactating rats or age-matched virgin females. It is currently widely believed that such pulmonary damage results, at least in part, from the reaction of ozone at sites of unsaturation in phospholipid fatty acid (PLFA) molecules located in the epithelial fluid layer lining the lung surfaces and/or the plasma membranes of epithelial cells underlying this fluid layer. The objective of this study was to compare the PLFA composition of lung tissue and surfactant from ozone-sensitive late stage pregnant and lactating rats with comparable tissue from relatively ozone-insensitive age-matched prepregnant (virgin female) rats to explore the possibility that changes in lung PLFA composition during pregnancy and/or lactation contribute to the enhanced sensitivity of these physiologic states to ozone. In addition, the correlation of changes in plasma PLFA composition with those in lung was investigated. There were minor differences in the composition of lung tissue and surfactant PLFAs between prepregnant rats and pregnant rats at day 17 of gestation and only slightly greater differences between prepregnant and lactating rats. Changes from the prepregnant state in the PLFA composition of lung tissue, but not surfactant, correlated with changes in the plasma only in lactating rats and not in pregnant rats. Overall, the double bond index of PLFAs in surfactant and lung tissue was decreased in pregnant and lactating rats compared with prepregnant rats. Thus, the increased sensitivity of pregnant and lactating rats to ozone-induced lung injury cannot be attributed to an increased availability of unsaturated fatty acids. In addition, the arachidonic acid composition of phospholipids did not appear to explain differences between prepregnant rats and pregnant or lactating rats in their inflammatory response to ozone. In conclusion, there is no evidence that the relatively minor changes in lung tissue PLFA composition which occur during pregnancy and lactation predispose rats in these physiologic states to ozone-induced pulmonary toxicity. PMID:9042669

  11. Megaloblastic hematopoiesis in a 20 year old pregnant female

    PubMed Central

    Trivette, Evan T.; Hoedebecke, Kyle; Berry-Cabán, Cristóbal S.; Jacobs, Brandy R.

    2013-01-01

    Summary Background: Nitrous oxide can cause disordered blood cell proliferation and lead to pancytopenia and altered immune function. Case Report: A young pregnant female patient presented after binge nitrous oxide abuse with altered mental status and abnormal vital signs. From her initial assessment she was noted to have pancytopenia and was found to have megaloblastic, hyper-cellular changes in a subsequent bone marrow biopsy. This presentation was determined to be secondary to toxic effects after heavy use of nitrous oxide. Conclusions: Nitrous oxide exposure, including use as an inhalant, over 12 hours can lead to bone marrow abnormalities such as megaloblastic hematopoiesis. PMID:23569553

  12. Curt Richter and the female rat.

    PubMed

    Geary, Nori

    2007-09-01

    Richter fully appreciated the fundamental biological importance of sex differences, in particular the challenges of female reproductive function to the two classes of behavior that most engaged him, endogenous rhythms and "self-regulatory" behaviors. Indeed, his contributions in these areas justify honoring him as one of the founders of behavioral neuroendocrinology. During the 1920s Richter, together with Wang, Kinder and other students, performed elegant phenomenological and mechanistic studies of sex differences in rats' spontaneous locomotor activity, nest building, and food intake. All of these behaviors display rhythms entrained to the ovarian cycle in female rats, and Richter's analyses of them formed the bases of many current areas of behavioral neuroscience. Slightly later, Richter made fundamentally important discoveries related to nutrient self-selection in pregnant and lactating rats, including changes in micronutrient and macronutrient selection. These data played a major role in the development of his concept of behavioral regulation of homeostasis. Unfortunately, some of these discoveries are rarely recalled. This is both historically regrettable and potentially an impediment to contemporary research progress. PMID:17544544

  13. THE EFFECT OF IMIDAN ADMINISTERED TO PREGNANT RATS

    EPA Science Inventory

    The purpose of this study was to evaluate the teratogenic potential of Imidan in Wistar rats. Accordingly, groups of pregnant Wistar rats received Imidan by either a single or multiple dose protocol and their fetuses were examined for gross, soft tissue, and skeletal defects. In ...

  14. Perinatal androgenic exposure and reproductive health effects female rat offspring.

    PubMed

    Guerra, Marina T; Silva, Raquel F; Luchiari, Heloise R; Sanabria, Marciana; Kempinas, Wilma De Grava

    2014-01-01

    Environmental contaminants known as endocrine-disrupting chemicals (EDC) have been associated with adverse effects on reproductive processes. These chemicals may mimic or antagonize endogenous hormones, disrupting reproductive functions. Although preliminary studies focused on environmental estrogens, the presence of compounds with androgenic activity has also been described. This study examines exposure of female pregnant and lactating rats to low doses of androgens and assesses potential effects on female offspring. Pregnant Wistar rats were exposed to testosterone propionate (TP) at doses of 0.05, 0.1, or 0.2 mg/kg or corn oil (vehicle), subcutaneously, to determine influence on reproductive health of female offspring. There were two exposure groups: (1) rats treated from gestational day (GD) 12 until GD 20; and (2) animals treated from GD 12 until the end of lactation. Perinatal exposure to TP produced increased anogenital distance after birth and diminished height of uterine glandular epithelium at puberty in animals exposed to 0.2 mg/kg. However, these alterations were not sufficient to impair sexual differentiation and normal physiology of the female rat reproductive tract. PMID:24617542

  15. GESTATIONAL EXPOSURE TO NONYLPHENOL CAUSES PRECOCIOUS MAMMARY GLAND DEVELOPMENT IN FEMALE RAT OFFSPRING

    EPA Science Inventory

    This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on ge...

  16. The effects of stress on plasma ACTH and corticosterone in young and aging pregnant rats and their fetuses

    SciTech Connect

    Erisman, S. ); Carnes, M. Univ. of Wisconsin, Madison ); Takahashi, L.K.; Lent, S.J. )

    1990-01-01

    Compared to younger rats, old rats exhibit prolonged elevations of plasma ACTH and corticosterone (CORT) in response to stress. In addition, CORT crosses the placenta. To investigate whether fetuses of older rats may be exposed to higher concentrations of CORT during development than fetuses of young rats, we compared the effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in young and aging pregnant rats and their 19-day-old fetuses. The plasma of the mothers and fetuses was assayed for ACTH and CORT by radioimmunoassay. Both young and aging pregnant rats showed a significant increase in plasma ACTH and CORT immediately after exposure to stress. However, aging rats had more prolonged elevation of ACTH and CORT than young rats. This suggests that, like old male rats, aging pregnant rats have an alteration in feedback inhibition of the HPA axis. Prolonged elevation of CORT was also seen in fetuses of aging mothers. These results have important implications concerning the effects of stress during pregnancy at different maternal ages, and for the potential deleterious consequences of prolonged prenatal elevation in stress hormones on the offspring of aging females.

  17. Mercury 203 distribution in pregnant and nonpregnant rats following systemic infusions with thiol-containing amino acids

    SciTech Connect

    Aschner, M.; Clarkson, T.W.

    1987-12-01

    Near-term pregnant (gestational day 17) and nonpregnant Long-Evans female rats were continuously infused into the external jugular vein with 0.1 mmole/hour L-cysteine, 0.1 mmole/hour L-leucine, or saline. At 24, 48, and 72 hours, 50 mumole/hour (/sup 203/Hg)-MeHgCl was administered over 1 hour. Total /sup 203/Hg body burden, brain, kidney, liver, and blood /sup 203/Hg concentrations were determined at 96 hours by gamma scintillation spectrometry. Despite significantly greater /sup 203/Hg whole body retention in the pregnant animals /sup 203/Hg concentrations in blood, brain, kidney, and liver were higher in nonpregnant rats. In addition, brain /sup 203/Hg concentrations in both pregnant and virgin rats were significantly higher in L-cysteine-treated rats compared with controls. These results suggest that the fetus may act as a sink for MeHg, thus decreasing /sup 203/Hg concentrations in maternal blood, brain, kidney, and liver. Furthermore, the data indicate that brain uptake of methylmercury in both pregnant and nonpregnant rats is enhanced by chronic L-cysteine infusion, lending support to the hypothesis that methylmercury in the rat may be translocated across the blood-brain barrier by the neutral amino acid carrier transport system.

  18. PVP formulated Fullerene (C60) increases Rho-kinase dependent Vascular Tissue Contractility in Pregnant Sprague Dawley Rats

    PubMed Central

    Vidanapathirana, Achini K.; Thompson, Leslie C.; Mann, Erin. E.; Odom, Jillian T.; Holland, Nathan A.; Sumner, Susan J.; Han, Li; Lewin, Anita H.; Fennell, Timothy R.; Brown, Jared M.; Wingard, Christopher J.

    2014-01-01

    Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that, polyvinylpyrorrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and non-pregnant female Sprague Dawley rats. Vascular responses were assessed using wire myography 24 hours post-exposure. Increased stress generation was observed in uterine artery, thoracic aorta and umbilical vein. Rho-Rho-kinase mediated force maintenance was increased in arterial segments from C60/PVP exposed pregnant rats when compared to PVP exposed rats. Our findings suggest that intravenous exposure to C60/PVP during pregnancy increases vascular tissue contractility of the uterine artery through elements of Rho-Rho-kinase signaling during late stages of pregnancy. PMID:25088243

  19. PVP formulated fullerene (C60) increases Rho-kinase dependent vascular tissue contractility in pregnant Sprague Dawley rats.

    PubMed

    Vidanapathirana, Achini K; Thompson, Leslie C; Mann, Erin E; Odom, Jillian T; Holland, Nathan A; Sumner, Susan J; Han, Li; Lewin, Anita H; Fennell, Timothy R; Brown, Jared M; Wingard, Christopher J

    2014-11-01

    Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that polyvinylpyrrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and non-pregnant female Sprague Dawley rats. Vascular responses were assessed using wire myography 24h post-exposure. Increased stress generation was observed in uterine artery, thoracic aorta and umbilical vein. Rho-Rho-kinase mediated force maintenance was increased in arterial segments from C60/PVP exposed pregnant rats when compared to PVP exposed rats. Our findings suggest that intravenous exposure to C60/PVP during pregnancy increases vascular tissue contractility of the uterine artery through elements of Rho-Rho-kinase signaling during late stages of pregnancy. PMID:25088243

  20. Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats.

    PubMed

    Bandele, O J; Stine, C B; Ferguson, M; Black, T; Olejnik, N; Keltner, Z; Evans, E R; Crosby, T C; Reimschuessel, R; Sprando, R L

    2014-12-01

    Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000?mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity. PMID:25455896

  1. ATRAZINE DISPOSITION IN PREGNANT AND LACTATING LONG-EVANS RATS

    EPA Science Inventory

    Atrazine (ATR) is a widely used herbicide shown to delay early mammary development in female offspring of gestationally exposed rats. The effects of ATR can be induced by in utero exposure and/or suckling from a dam exposed during late pregnancy, but ATR is reported to have a hal...

  2. A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency

    EPA Science Inventory

    A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...

  3. Plasma amino acid concentrations in pregnant rats and in 21-day foetuses.

    PubMed Central

    Palou, A; Arola, L; Alemany, M

    1977-01-01

    Plasma amino acid concentrations were determined in virgin female rats, in pregnant rats (12 and 21 days after impregnation) and in 21-day foetuses. The total amino acid concentration in plasma decreases significantly with pregnancy, being lower at 12 than at 21 days. Alanine, glutamine+glutamate and other 'gluconeogenic' amino acids decrease dramatically by mid-term, but regain their original concentrations at the end of the pregnancy. With most other amino acids, mainly the essential ones, the trend is towards lower concentrations which are maintained throughout pregnancy. These data agree with known nitrogen-conservation schemes in pregnancy and with the important demands on amino acids provoked by foetal growth. In the 21-day foetuses, concentrations of individual amino acids are considerably higher than in their mothers, with high plasma foetal/maternal concentration ratios, especially for lysine, phenylalanine and hydroxy-proline, suggesting active protein biosynthesis and turnover. All other amino acids also have high concentration ratios, presumably owing to their requirement by the foetuses for growth. Alanine, glutamine+glutamate, asparagine+aspartate, glycine, serine and threonine form a lower proportion of the total amino acids in foetuses than in the virgin controls or pregnant rats, probably owing to their role primarily in energy metabolism in the adults. The results indicate that at this phase of foetal growth, the placental amino acid uptake is considerable and seems to be higher than immediately before birth. PMID:901417

  4. Polyaromatic compounds alter placental protein synthesis in pregnant rats

    SciTech Connect

    Shiverick, K.T.; Ogilvie, S.; Medrano, T. )

    1991-03-15

    The administration of the polyaromatic compounds {beta}-naphthoflavone ({beta}NF) and 3-methylcholanthrene (3MC) to pregnant rats during mid-gestation has been shown to produce marked feto-placental growth retardation. This study examined secretory protein synthesis in placental tissue from rats following administration of {beta}NF on gestation days (gd) 11-14 or 3MC on gd 12-14. Explants of placental basal zone tissue were cultured for 24 hours in serum-free medium in the presence of ({sup 3}H)leucine. Secreted proteins were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis followed by either fluorography or immunostaining. Total incorporation of ({sup 3}H)leucine into secreted proteins was not altered in BZ explants from {beta}NF or 3MC-treated animals. However a selective decrease was observed in ({sup 3}H)leucine incorporation into a major complex of proteins with apparent molecular weight of 25-30,000 and isoelectric point between 5.3 to 5.7. This group of proteins has been further identified as being related to rat pituitary growth hormone (GH) using N-terminal amino acid microsequencing of individual spots from 2-D SDS-PA gels. This is the first report that synthesis of GH-related proteins by rat placenta is decreased following {beta}NF and 3MC administration, a change which may underlie the feto-placental growth retardation associated with these polyaromatic compounds.

  5. Placentophagia in Weanling Female Laboratory Rats

    PubMed Central

    Harding, Kaitlyn M.; Lonstein, Joseph S.

    2014-01-01

    Placentophagia is common in parturient mammals and offers physiological and behavioral advantages for mothers. In natural environments, weanlings are often present during the birth of younger siblings, but it is unknown if weanling rats are placentophagic or prefer placenta over other substances. To examine this, primiparous rats were remated during the postpartum estrus and weanling females remained in the nest during their mothers next parturition. Continuous observation revealed that 58% of weanlings were placentophagic. To determine if this placentophagia occurs away from parturient mothers, weanling females still living in their natal nest were offered placenta, liver, or cake frosting in a novel chamber. They ingested more placenta and liver than frosting. Thus, many weanling female laboratory rats are placentophagic during birth of younger siblings but do not selectively prefer placenta when tested outside their natal nest. Consequences of placentophagia by weanlings are unknown, but it may promote their alloparenting or postpartum mothering. PMID:24604548

  6. Hypergravity induced prolactin surge in female rats

    NASA Technical Reports Server (NTRS)

    Megory, E.; Oyama, J.

    1985-01-01

    Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study it is found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats of HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

  7. Fear of becoming pregnant among female healthcare students in Spain

    PubMed Central

    Navarro-Cremades, Felipe; Arroyo-Sebastián, María del Ángel; Gómez-Pérez, Luis; Sepehri, Armina; Martínez-Pérez, Salvador; Marhuenda-Amorós, Dolores; Rizo-Baeza, María Mercedes; Gil-Guillén, Vicente Francisco

    2015-01-01

    The inconsistent use of hormonal contraceptive methods can result, during the first year of use, in one in twelve women still having an undesired pregnancy. This may lead to women experiencing fear of becoming pregnant (FBP). We have only found one study examining the proportion of FBP among women who used hormonal contraceptives. To gather further scientific evidence we undertook an observational, cross-sectional study involving 472 women at a Spanish university in 2005–2009. The inclusion criteria were having had vaginal intercourse with a man in the previous three months and usual use for contraception of a male condom or hormonal contraceptives, or no method of contraception. The outcome was FBP. The secondary variables were contraceptive method used (oral contraceptives; condom; none), desire to increase the frequency of sexual relations, frequency of sexual intercourse with the partner, the sexual partner not always able to ejaculate, desire to increase the partner’s time before orgasm, age and being in a stable relationship. A multivariate logistic regression model was used to determine the associated factors. Of the 472 women, 171 experienced FBP (36.2%). Factors significantly associated (p < 0.05) with this FBP were method of contraception (condom and none), desire to increase the partner’s ability to delay orgasm and higher frequency of sexual intercourse with the partner. There was a high proportion of FBP, depending on the use of efficient contraceptive methods. A possible solution to this problem may reside in educational programmes. Qualitative studies would be useful to design these programmes. PMID:26336643

  8. Fear of becoming pregnant among female healthcare students in Spain.

    PubMed

    Navarro-Cremades, Felipe; Palazn-Bru, Antonio; Arroyo-Sebastin, Mara Del ngel; Gmez-Prez, Luis; Sepehri, Armina; Martnez-Prez, Salvador; Marhuenda-Amors, Dolores; Rizo-Baeza, Mara Mercedes; Gil-Guilln, Vicente Francisco

    2015-01-01

    The inconsistent use of hormonal contraceptive methods can result, during the first year of use, in one in twelve women still having an undesired pregnancy. This may lead to women experiencing fear of becoming pregnant (FBP). We have only found one study examining the proportion of FBP among women who used hormonal contraceptives. To gather further scientific evidence we undertook an observational, cross-sectional study involving 472 women at a Spanish university in 2005-2009. The inclusion criteria were having had vaginal intercourse with a man in the previous three months and usual use for contraception of a male condom or hormonal contraceptives, or no method of contraception. The outcome was FBP. The secondary variables were contraceptive method used (oral contraceptives; condom; none), desire to increase the frequency of sexual relations, frequency of sexual intercourse with the partner, the sexual partner not always able to ejaculate, desire to increase the partner's time before orgasm, age and being in a stable relationship. A multivariate logistic regression model was used to determine the associated factors. Of the 472 women, 171 experienced FBP (36.2%). Factors significantly associated (p < 0.05) with this FBP were method of contraception (condom and none), desire to increase the partner's ability to delay orgasm and higher frequency of sexual intercourse with the partner. There was a high proportion of FBP, depending on the use of efficient contraceptive methods. A possible solution to this problem may reside in educational programmes. Qualitative studies would be useful to design these programmes. PMID:26336643

  9. The accumulation and histological effects of organometallic fungicides propineb and maneb in the livers of pregnant rats and their offspring.

    PubMed

    Deveci, E; Guven, K; Bashan, M; Onen, A; de Pomerai, D

    1999-05-01

    Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb (Zn-containing dithiocarbamate) and 250 ppm maneb (Mn-containing dithiocarbamate), from the 6th day of gestation up to birth. We found that the body weights of both newborn litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the livers of fungicide-treated pregnant females and the offspring showed a variety of histopathological effects. Moreover, the analysis of Zn and Mn concentrations in the livers of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the liver were higher than those of controls. Similarly, the hepatic metal concentrations were significantly increased in the litters, indicating the transplacental passage of the organometallic fungicides. PMID:10349609

  10. Why does a high-fat diet induce preeclampsia-like symptoms in pregnant rats

    PubMed Central

    Ge, Jing; Wang, Jun; Xue, Dan; Zhu, Zhengsheng; Chen, Zhenyu; Li, Xiaoqiu; Su, Dongfeng; Du, Juan

    2013-01-01

    Changes in neurotransmitter levels in the brain play an important role in epilepsy-like attacks after pregnancy-induced preeclampsia-eclampsia. Metabotropic glutamate receptor 1 participates in the onset of lipid metabolism disorder-induced preeclampsia. Pregnant rats were fed with a high-fat diet for 20 days. Thus, these pregnant rats experienced preeclampsia-like syndromes such as tension and proteinuria. Simultaneously, metabotropic glutamate receptor 1 mRNA and protein expressions were upregulated in the rat hippocampus. These findings indicate that increased sion of metabotropic glutamate receptor 1 promotes the occurrence of high-fat diet-induced preeclampsia in pregnant rats. PMID:25206496

  11. The effects of spaceflight on mammary metabolism in pregnant rats

    NASA Technical Reports Server (NTRS)

    Plaut, K.; Maple, R.; Vyas, C.; Munaim, S.; Darling, A.; Casey, T.; Alberts, J. R.

    1999-01-01

    The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P < 0.05), and incorporation into fatty acids increased 300% (P < 0.005) compared to controls. It is unclear whether the enhanced glucose use is due to spaceflight or a response to landing. Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of beta-casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.

  12. Histomorphometric changes of small intestine in pregnant rat

    PubMed Central

    Sabet Sarvestani, Fatemeh; Rahmanifar, Farhad; Tamadon, Amin

    2015-01-01

    Food intake of rats increases during pregnancy. This requires changes in the structure of the small intestine to absorb additional food. The aim of the present study was to investigate the morphological changes in the layers of small intestine in rats during pregnancy. Duodenum, jejunum and ileum of 18 pregnant Sprague-Dawley rats (day 7, 14 and 21 of pregnancy) were collected. Villous height and width and thickness of lamina propria, tunica muscularis entirely and separately (circular and longitudinal layers) were measured on transverse sections. During pregnancy increasing villi length and muscular layer thickness was observed in duodenum. Furthermore, along with the progress of gestation greatest histomorphometric change in small intestine was observed in the jejunum. The reduction in the ileum histomorphologic indices was observed during pregnancy. In conclusion, increase in histomorphologic indices of duodenum and jejunum supplies more capacity of duodenum to digest food intake during pregnancy and decrease in these indices in ileum controls the absorption of excess produced amino acids and glucose by hyperphagia. PMID:25992254

  13. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences.

    PubMed

    Dean, Afshan; van den Driesche, Sander; Wang, Yili; McKinnell, Chris; Macpherson, Sheila; Eddie, Sharon L; Kinnell, Hazel; Hurtado-Gonzalez, Pablo; Chambers, Tom J; Stevenson, Kerrie; Wolfinger, Elke; Hrabalkova, Lenka; Calarrao, Ana; Bayne, Rosey Al; Hagen, Casper P; Mitchell, Rod T; Anderson, Richard A; Sharpe, Richard M

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters. PMID:26813099

  14. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    PubMed Central

    Dean, Afshan; van den Driesche, Sander; Wang, Yili; McKinnell, Chris; Macpherson, Sheila; Eddie, Sharon L.; Kinnell, Hazel; Hurtado-Gonzalez, Pablo; Chambers, Tom J.; Stevenson, Kerrie; Wolfinger, Elke; Hrabalkova, Lenka; Calarrao, Ana; Bayne, Rosey AL; Hagen, Casper P.; Mitchell, Rod T.; Anderson, Richard A.; Sharpe, Richard M.

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters. PMID:26813099

  15. Susceptibility of fetal, virgin, pregnant and lactating rats for the induction of mammary tumors by gamma rays

    SciTech Connect

    Inano, Hiroshi; Suzuki, Heiko; Onoda, Makoto; Yamanouchi, Hiroshi

    1996-06-01

    Pregnant Wistar-MS rats received a whole-body irradiation of 0-2.6 Gy {gamma} rays at day 20 of pregnancy. The mother rats were implanted with a diethylstilbestrol (DES) pellet 30 days after weaning, and the female pups delivered by the irradiated mother were treated with DES after maturation. Lactating rats were irradiated with {gamma} rays 21 days after parturition and then treated with DES. Virgin rats 70 days of age were also irradiated and then administered DES. The rats which received intrauterine irradiation did not develop mammary tumors in the mother rats and lactating rats increased in a dose-dependent manner with increasing doses of {gamma} rays up to 2.1 Gy. With 0.1-1 Gy, the incidence of adenocarcinoma in the mother rats was significantly lower than that observed in the lactating rats. However, the incidence in the mother rats irradiated with 1.0-1.5 Gy was significantly higher than that of virgin rats treated with the corresponding {gamma}-ray doses. These findings suggest that the susceptibility of the mammary glands to radiation depends upon the differentiation at the time of exposure. 22 refs., 4 figs., 2 tabs.

  16. Cadmium toxicity in the thyroid gland of pregnant rats

    SciTech Connect

    Yoshizuka, M.; Mori, N.; Hamasaki, K.; Tanaka, I.; Yokoyama, M.; Hara, K.; Doi, Y.; Umezu, Y.; Araki, H.; Sakamoto, Y. )

    1991-08-01

    The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X-ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones.

  17. Pregnant rats treated with a high-fat/prooxidant Western diet with ANG II and TNF-? are resistant to elevations in blood pressure and renal oxidative stress.

    PubMed

    Cunningham, Mark W; West, Crystal A; Wen, Xuerong; Deng, Aihua; Baylis, Chris

    2015-06-01

    Oxidative stress and inflammation are risk factors for hypertension in pregnancy. Here, we examined the 24-h mean arterial pressure (MAP) via telemetry and the nitric oxide (NO) and redox systems in the kidney cortex, medulla, and aorta of virgin and pregnant rats treated with a high-fat/prooxidant Western diet (HFD), ANG II, and TNF-?. Female Sprague-Dawley rats were given a normal diet (ND) or a HFD for 8 wk before mating. Day 6 of pregnancy and age-matched virgins were implanted with minipumps infusing saline or ANG II (150 ngkg(-1)min(-1)) + TNF-? (75 ng/day) for 14 days. Groups consisted of Virgin + ND + Saline (V+ND) (n = 7), Virgin + HFD +ANG II and TNF-? (V+HFD) (n = 7), Pregnant + ND + Saline (P+ND) (n = 6), and Pregnant + HFD + ANG II and TNF-? (P+HFD) (n = 8). After day 6 of minipump implantation, V+HFD rats displayed an increase in MAP on days 7, 8, and 10-15 vs. V+ND rats. P+HFD rats, after day 6 of minipump implantation, showed an increase in MAP only on day 7 vs. P+ND rats. P+HFD rats had a normal fall in 24-h MAP, hematocrit, plasma protein concentration, and osmolality at late pregnancy. No change in kidney cortex, medulla, or aortic oxidative stress in P+HFD rats. P+HFD rats displayed a decrease in nNOS? abundance, but no change in kidney cortex NOx content vs. P+ND rats. Pregnant rats subjected to a chronic HFD and prooxidant and proinflammatory insults have a blunted increase in 24-h MAP and renal oxidative stress. Our data suggest renal NO bioavailability is not altered in pregnant rats treated with a HFD, ANG II, and TNF-?. PMID:25810384

  18. Histopathological changes in pregnant rat's liver following repeated halothane exposure.

    PubMed

    Atallah, M M; el-Serafy, A K; Abd el-Hady, S L; Mowafy, T K

    1985-10-01

    Adult white rats were divided into 3 groups; 6 rats each, (two males and four females). Group I was exposed to 1.5% halothane for 20 minutes every other day for 6 exposures. The rats were mated and exposed another 10 exposures. Group II was given 0.1% phenobarbitone in milk one week before, and during the period of exposure to halothane which was similar to the first group. Group III was kept as a control. At the suspected date of delivery, the rats were sacrificed, and specimens were taken from the liver for hematoxylin and eosin stain, PAS reaction and Sudan black stain. Repeated exposure to halothane did not affect the pregnancy rate, but it resulted in hepatic focal and centrilobular necrosis with glycogen poverty and moderate lipid content. The portal spaces showed thick connective tissue and lymphocytic infiltration. Phenobarbitone reduced the pregnancy rate and resulted in 16.5% fetal mortality with more hepatic necrosis and increase in glycogen and lipid content. PMID:4079832

  19. Goal setting and control orientation of pregnant / parenting female adolescents in the GRADS program.

    PubMed

    White, S D; Cummings, M N

    1995-03-01

    The Graduation, Reality, and Dual-role Skills (GRADS) home economics program helps at-risk pregnant/parenting teens graduate from high school, set life goals, and feel empowered. It was initiated in Ohio in 1980 and started in New Mexico in 1989. The authors investigated whether female GRADS students differed from nonpregnant/nonparenting female teens in terms of the types of goals they perceive to be most important, the tendency to set goals, and control orientation. Comparisons were made between 37 female GRADS students in the program for one year or more, 46 female GRADS students new to the program, and 68 nonpregnant/nonparenting female students from an English class. The data were collected during Fall 1992 from eight sites in New Mexico. Analysis of the data found the existence of significant differences regarding participants' most important goals, but no significant differences in goal orientation or locus of control among the three groups. GRADS students were highly concerned about interpersonal relationships, while the nonpregnant/nonparenting students were highly interested in personal concerns. Pregnant and/or parenting teens were more like their nonpregnant/nonparenting peers than different, with the differences in goals seeming to reflect different priorities. PMID:12290149

  20. Testosterone and muscle hypertrophy in female rats

    NASA Technical Reports Server (NTRS)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  1. Elevated Testosterone Reduces Uterine Blood Flow, Spiral Artery Elongation, and Placental Oxygenation in Pregnant Rats.

    PubMed

    Gopalakrishnan, Kathirvel; Mishra, Jay S; Chinnathambi, Vijayakumar; Vincent, Kathleen L; Patrikeev, Igor; Motamedi, Massoud; Saade, George R; Hankins, Gary D; Sathishkumar, Kunju

    2016-03-01

    Elevated maternal testosterone levels are shown to cause fetal growth restriction, eventually culminating in sex-specific adult-onset hypertension that is more pronounced in males than in females. In this study, we tested whether uteroplacental and fetoplacental disturbances underlie fetal growth restriction and if these changes vary in male and female placentas. Pregnant Sprague-Dawley rats were injected with vehicle (n=16) or testosterone propionate (0.5 mg/kg per day from gestation day 15-19; n=16). On gestation day 20, we quantified uterine artery blood flow using microultrasound, visualized placental arterial network using x-ray microcomputed tomography, determined fetoplacental hypoxia using pimonidazole and hypoxia-inducible factor-1?, and used Affymetrix array to determine changes in placental expression of genes involved in vascular development. Plasma testosterone levels increased 2-fold in testosterone-injected rats. Placental and fetal weights were lower in rats with elevated testosterone. Uterine artery blood flow was lower, and resistance index was higher in the testosterone group. Radial and spiral artery diameter and length, the number of fetoplacental arterial branches, and umbilical artery diameter were reduced in the testosterone group. In addition, markers of hypoxia in the placentas and fetuses were elevated in the testosterone group. The magnitude of changes in placental vasculature and hypoxia was greater in males than in females and was associated with sex-specific alteration of unique sets of genes involved in angiogenesis and blood vessel morphogenesis. The results demonstrate that elevated testosterone during gestation induces a decrease in uterine arterial blood flow and fetal sex-related uteroplacental vascular changes, which may set the stage for subsequent sex differences in adult-onset diseases. PMID:26781277

  2. Effect of Acipimox on Plasma Lipids and Glucose/Insulin in Pregnant Rats

    PubMed Central

    Snchez-Vera, I.; Viana, M.; Herrera, E.; Indart, A.

    2002-01-01

    To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (IV) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance. PMID:12546276

  3. Changing patterns of daily rhythmicity across reproductive states in diurnal female Nile grass rats (Arvicanthis niloticus)

    PubMed Central

    Schradera, Jessica A.; Walaszczykb, Erin J.; Smalea, Laura

    2009-01-01

    SCHRADER, J.A., E. J. WALASZCZYK, AND L. SMALE. Changing patterns of daily rhythmicity across reproductive states in diurnal female Nile grass rats (Arvicanthis niloticus). PHYSIOL BEHAV XX(X) XXX-XXX, XXXX. -- A suite of changes in circadian rhythms have been described in nocturnal rodents as females go through pregnancy and lactation, but there is no information on such patterns in diurnal species. As the challenges faced by these two groups of animals are somewhat different, we characterized changes in activity and core body temperature (Tb) in female diurnal Nile grass rats (Arvicanthis niloticus) as they went through a series of reproductive states: virgin, pregnant, pregnant and lactating, lactating only, and post-weaning. The phase of neither rhythm varied, but the amplitude did. Females increased their overall levels of daily activity from early to late pregnancy, regardless of whether they were also lactating. The pattern of activity was less rhythmic during early than mid-lactation, in both non-pregnant and pregnant females, as a consequence of a decrease in daytime relative to nighttime activity. The Tb rhythm amplitude dropped from mid-pregnancy through mid-lactation, and there were rises in Tb troughs during the mid-light and mid-dark phases of the day, though pregnancy and lactation affected Tb at these times in somewhat different ways. This study demonstrates that rhythms in diurnal grass rats change during pregnancy and lactation in different ways than those of nocturnal species that have been studied to date and that the effects of pregnancy and lactation are not additive in any simple way. PMID:19744504

  4. The UF Family of hybrid phantoms of the pregnant female for computational radiation dosimetry

    NASA Astrophysics Data System (ADS)

    Maynard, Matthew R.; Long, Nelia S.; Moawad, Nash S.; Shifrin, Roger Y.; Geyer, Amy M.; Fong, Grant; Bolch, Wesley E.

    2014-08-01

    Efforts to assess in utero radiation doses and related quantities to the developing fetus should account for the presence of the surrounding maternal tissues. Maternal tissues can provide varying levels of protection to the fetus by shielding externally-emitted radiation or, alternatively, can become sources of internally-emitted radiation following the biokinetic uptake of medically-administered radiopharmaceuticals or radionuclides located in the surrounding environment—as in the case of the European Union’s SOLO project (Epidemiological Studies of Exposed Southern Urals Populations). The University of Florida had previously addressed limitations in available computational phantom representation of the developing fetus by constructing a series of hybrid computational fetal phantoms at eight different ages and three weight percentiles. Using CT image sets of pregnant patients contoured using 3D-DOCTORTM, the eight 50th percentile fetal phantoms from that study were systematically combined in RhinocerosTM with the UF adult non-pregnant female to yield a series of reference pregnant female phantoms at fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. Deformable, non-uniform rational B-spline surfaces were utilized to alter contoured maternal anatomy in order to (1) accurately position and orient each fetus and surrounding maternal tissues and (2) match target masses of maternal soft tissue organs to reference data reported in the literature.

  5. Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant and non-pregnant female rabbits after single high dose inhalation exposure.

    PubMed

    Schmidt, Tobias; Bertermann, Rdiger; Rusch, George M; Hoffman, Gary M; Dekant, Wolfgang

    2012-08-15

    2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnant women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1h. For metabolite identification by (19)F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 22.35 ?mol) and pregnant female (50.47 19.72 ?mol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 38.87 ?mol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. PMID:22664346

  6. Effect of thienorphine on the isolated uterine strips from pregnant rats.

    PubMed

    Zhou, Peilan; Yan, Lingdi; Yong, Zheng; Yu, Gang; Dong, Huajin; Yan, Hui; Su, Ruibin; Gong, Zehui

    2013-03-01

    Opioid dependence is a serious worldwide health problem. Buprenorphine was used as an alternative to methadone for the treatment of opioid dependence, especially for pregnant women. Thienorphine was a partial opioid agonist with long-lasting antinociceptive effect and high oral bioavailability compared with its analogue buprenorphine. Till now, there was still no research about the effect of thienorphine on the isolated uterine muscles. This study examined the effects of thienorphine on the isolated rat oestrus and pregnant uterine strips. Area under the curve (AUC), amplitude and frequency were studied. Thienorphine induced a concentration-dependent decrease in the frequency and amplitude of the contraction on the isolated oestrus and pregnant uterine strips. Thienorphine exhibited less inhibition on the contractile amplitude of the isolated uterine strips from pregnant rats with the IC50 of 54.11 ± 7.41 μΜ, compared with buprenorphine (IC50, 19.42 ± 2.34 μΜ). In addition, thienorphine also exhibited less inhibition on the contractile frequency of the isolated uterine strips from pregnant rats, with the IC50 of 70.68 ± 12.44 μΜ, compared with buprenorphine (IC50, 19.20 ± 3.87 μΜ). On the isolated uterine muscle from pregnant rats, the AUC was decreased by thienorphine but was less potent than buprenorphine, the IC50 was 37.31 ± 7.43 μΜ for thienorphine and 13.52 ± 2.03 μΜ for buprenorphine. Thienorphine exhibited longer duration on the isolated rat pregnant uterine strips than buprenorphine. Thienorphine has less influence and longer duration on the isolated rat uterine muscles during pregnancy, which may be a new useful candidate for the opioid dependent pregnant women. PMID:23416213

  7. Euglycemic Hyperinsulinemia Increases Blood Pressure in Pregnant Rats Independent of Placental Antiangiogenic and Inflammatory Factors

    PubMed Central

    2013-01-01

    BACKGROUND Although pregnancies associated with hyperinsulinemia and altered placental angiogenic and inflammatory factors are at increased risk for developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental factors and blood pressure regulation during pregnancy are unclear. We hypothesized that chronic hyperinsulinemia results in increased placental soluble fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor ? (TNF- ?) levels and hypertension in pregnant rats. METHODS On gestational day (GD) 14, Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin. Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of 1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and heart rate (HR) were assessed in conscious rats by indwelling carotid catheters, followed by collections of blood, placentas, and fetuses. In addition to pl acental sFlt-1 and TNF-? levels, circulating insulin, glucose, leptin, cholesterol, triglyceride, and free fatty acid concentrations were measured. RESULTS MAP was higher in pregnant + insulin vs. normal pregnant rats; however, HR was similar between groups. Although litter size and placental weight were comparable, fetuses from pregnant + insulin rats were heavier. Importantly, circulating insulin concentration was elevated in the pregnant + insulin group, with no change in glucose level. Moreover, circulating leptin, cholesterol, triglyceride, and free fatty acid concentrations were increased in the pregnant + insulin group. There were no differences in placental sFlt-1 and TNF-? concentrations between groups. CONCLUSIONS In summary, sustained euglycemic hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise blood pressure in pregnancy independent of recognized placental factors associated with preeclampsia. PMID:23955606

  8. Distribution and biomarker of carbon-14 labeled fullerene C60 ([(14) C(U)]C60 ) in pregnant and lactating rats and their offspring after maternal intravenous exposure.

    PubMed

    Snyder, Rodney W; Fennell, Timothy R; Wingard, Christopher J; Mortensen, Ninell P; Holland, Nathan A; Shannahan, Jonathan H; Pathmasiri, Wimal; Lewin, Anita H; Sumner, Susan C J

    2015-12-01

    A comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon-14 labeled C60 ([(14) C(U)]C60 ). Rats were administered [(14) C(U)]C60 (~0.2?mg [(14) C(U)]C60 kg(-1) body weight) or 5% polyvinylpyrrolidone (PVP)-saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24?h or 8?days), GD15 (terminated after 24?h or 4?days), or GD18 (terminated after 24?h). Lactating rats were injected on postnatal day 8 and terminated after 24?h, 3 or 11?days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11?days after [(14) C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [(14) C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [(14) C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl-tRNA biosynthesis. This study demonstrated that [(14) C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. PMID:26081520

  9. Effect of protein quality on weight and composition of the carcass in pregnant and non pregnant rats.

    PubMed

    Verdú, M C; López Frias, M; Mataix, F J; Campos, M S

    1988-01-01

    The effect of diets with different protein qualities on net weight and on the composition of the carcass (the animal being skinned and gutted) were studied in pregnant and non-pregnant rats of the Wistar breed. The animals were fed with diets containing the following protein sources: casein + 5% DL-methionine, beans and a mix of beans and wheat, all with a protein level of 14%. Percentage weight gains in the carcass were in all cases greater in non-gestating animals than in gestating animals. The water content of the body was similar in all the groups tested. The quality of protein did not affect nitrogen content; however, a smaller proportion of nitrogen was observed in gestating animals than in non-gestating animals. With respect to fat content of the carcass, a greater quantity of fat was observed in the bodies of gestating rats than in non-gestating rats, which was only significant in the case of the bean-wheat mix diet. Within each group of gestating and non-gestating rats, there was a greater quantity of fat in those animals fed with casein. PMID:3393210

  10. Disposition of inorganic mercury in pregnant rats and their offspring.

    PubMed

    Oliveira, Cláudia S; Joshee, Lucy; Zalups, Rudolfs K; Pereira, Maria E; Bridges, Christy C

    2015-09-01

    Environmental toxicants such as methylmercury have been shown to negatively impact fetal health. Despite the prevalence of inorganic mercury (Hg(2+)) in the environment and the ability of methylmercury to biotransform into Hg(2+), little is known about the ability of Hg(2+) to cross the placenta into fetal tissues. Therefore, it is important to understand the handing and disposition of Hg(2+) in the reproductive system. The purpose of the current study was to assess the disposition and transport of Hg(2+) in placental and fetal tissues, and to test the hypothesis that acute renal injury in dams can alter the accumulation of Hg(2+) in fetal tissues. Pregnant Wistar rats were injected intravenously with 0.5 or 2.5 μmol kg(-1) HgCl2 for 6 or 48 h and the disposition of Hg(2+) was measured. Accumulation of Hg(2+) in the placenta was rapid and dose-dependent. Very little Hg(2+) was eliminated during the initial 48 h after exposure. When dams were exposed to the low dose of HgCl2, fetal accumulation of Hg(2+) increased between 6h and 48 h, while at the higher dose, accumulation was similar at each time point. Within fetal organs, the greatest concentration of Hg(2+) (nmol/g) was localized in the kidneys, followed by the liver and brain. A dose-dependent increase in the accumulation of Hg(2+) in fetal organs was observed, suggesting that continued maternal exposure may lead to increased fetal exposure. Taken together, these data indicate that Hg(2+) is capable of crossing the placenta and gaining access to fetal organs in a dose-dependent manner. PMID:26196528

  11. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    PubMed Central

    Ventrucci, Gislaine; de Mello, Maria Alice Roston; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones. PMID:11955290

  12. Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant and non-pregnant female rabbits after single high dose inhalation exposure

    SciTech Connect

    Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.; Hoffman, Gary M.; Dekant, Wolfgang

    2012-08-15

    2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnant women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1 h. For metabolite identification by {sup 19}F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 μmol) and pregnant female (50.47 ± 19.72 μmol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 μmol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. -- Highlights: ► No lethality and clinical signs were observed. ► No differences in metabolic pattern between pregnant and non-pregnant rabbits. ► Rapid and similar metabolite excretion in all groups. ► Very low amount of biotransformation in all groups (< 0.1%).

  13. Blood concentrations of gonadotrophins, prolactin and gonadal steroids in males and in non-pregnant and pregnant female African elephants (Loxodonta africana).

    PubMed

    McNeilly, A S; Martin, R D; Hodges, J K; Smuts, G L

    1983-01-01

    No seasonal variation in any of the hormones measured was apparent in males or females. Testosterone levels in males increased around puberty (10-11 years) and remained significantly higher in adult than prepubertal males. This was not accompanied by any significant change in levels of LH, FSH or prolactin. In non-pregnant females there was no apparent difference in levels of LH, FSH or prolactin with age. There was a significant increase in progesterone around puberty (12 years) but there was considerable overlap in values between prepubertal and adult females. During pregnancy, progesterone levels were significantly higher than in non-pregnant females with maximum levels occurring at mid-pregnancy (9-12 months). However, there was considerable overlap in values between non-pregnancy and pregnancy. Concentrations of LH and FSH decreased significantly during mid-pregnancy while prolactin levels increased dramatically during pregnancy; after 7 months of gestation until term levels were always at least 8 ng/ml greater than in any non-pregnant female. It is suggested that this consistent increase in plasma/serum levels of prolactin can be used to diagnose pregnancy in the elephant. PMID:6401810

  14. Aggressive hemangioma of the spine in a pregnant female: a case report and literature review.

    PubMed

    Demirkale, İsmail; De Iure, Federico; Terzi, Silvia; Gasbarrini, Alessandro

    2016-04-01

    Type and timing of treatment for symptomatic hemangiomas in pregnant females are challenging due to fetus survival and conflicts in neurological recovery. In this article, we report a 40-year-old female patient at pregnancy week 23 with a complicated hemangioma at T1 level. Physical examination revealed an incomplete spastic paraplegia. Patient did not accept any surgery due to child's death risk. Patient was started corticoid treatment and no more weight bearing was allowed. At the 28th week of pregnancy, the patient underwent cesarean section immediately followed by selective arterial embolization, decompression, fixation, and radiotherapy. At two-year follow-up, the patient was pain free, without any signs of local recurrence and with complete neurological recovery. A multidisciplinary approach is mandatory to save the life of the fetus without damaging the spinal cord functions of the mother. PMID:26874635

  15. Phasic Oscillations of Extracellular Potassium (Ko) in Pregnant Rat Myometrium

    PubMed Central

    Young, Roger C.; Goloman, Gabriela

    2013-01-01

    K-sensitive microelectrodes were used to measure K+ within the extracellular space (Ko) of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used. Double-barreled electrodes allowed monitoring of electrical activity 15 microns from the site of Ko measurement. From double-barreled electrode experiments, the bioelectrical burst started first, and then Ko began to rise 0.6 0.1 seconds later. This delay indicates that K+ leaves the cells in response to local electrical activity rather than vice versa. Four control experiments were performed to assess the influence of electrical artifacts caused by tissue motion on Ko values. When observed, artifacts were negative and transient, and hence would result in an underestimation of Ko rises. Artifacts were minimized when tissue motion was minimized by fixing the tissue at both ends. At 37C, 7 single barreled experiments and 45 contractions were analyzed. Resting Ko was within 1 mM of bath K+ (5 mM) at the beginning and end of the experiments. Ko rose during the contraction, fell after the completion of the contraction, and normalized before the next contraction began. Peak Ko values observed during force production were 18.8 5.9 mM, a value high enough to modulate tissue-level electrical activity. Ko required 15.7 2.8 seconds to normalize halfway (t50). Six experiments expressing 38 contractions were performed at 24C. The contraction period was longer at 24C. Values for peak Ko (26.2 9.9 mM) and t50 (29.816.2 sec) were both larger than at 37C (p<0.0003 for both). The direct relationships between peak Ko, t50 and the contraction period, suggest elevations in Ko may modulate contraction frequency. The myometrial interstitial space appears to be functionally important, and Ko metabolism may participate in cell-cell interactions. PMID:23724127

  16. Loss of Anticontractile Effect of Perivascular Adipose Tissue on Pregnant Rats: A Potential Role of Tumor Necrosis Factor-?.

    PubMed

    Al-Jarallah, Aishah; Oriowo, Mabayoje A

    2016-02-01

    The present investigation examined the effect of pregnancy on the anticontractile effect of perivascular adipose tissue (PVAT) on the rat. Ring segments of the aorta, with and without PVAT, were set up in organ baths for isometric tension recording. In both groups, concentration-response curves to 5-hydroxytryptamine (5-HT) were displaced to the right with a reduction of the maximum response in aorta segments with PVAT. The anticontractile effect of PVAT was attenuated on segments from pregnant rats. 4-Aminopyridine (4-AP), an inhibitor of voltage-gated potassium (Kv) channels, enhanced 5-HT-induced contractions of aorta segments from pregnant and nonpregnant rats only when PVAT was attached. There was no difference in the effect of 4-aminopyridine on 5-HT-induced contractions of aorta segments with PVAT from pregnant and nonpregnant rats. There was also no significant difference in the expression of Kv7.4 channels in aorta segments (with PVAT) between pregnant and nonpregnant rats. Tumor necrosis factor-? (TNF-?) was detected in PVAT from pregnant and nonpregnant rats. The level of TNF-? was significantly greater in PVAT from pregnant rats. Treatment of pregnant rats with pentoxyphyline significantly reduced the level of TNF-? in the PVAT and restored the anticontractile effect of PVAT on aorta segments from pregnant rats. Finally, TNF-? (10 ng/mL) potentiated 5-HT-induced contractions of PVAT-containing pregnant rat aorta. These results would suggest that the loss of anticontractile effect of PVAT in pregnant rat aorta could be due to enhanced production of TNF-? in the PVAT in these rats. PMID:26848638

  17. Effects of age and pregnancy on cytochrome P450 induction by octamethyltetracyclosiloxane in female Sprague-Dawley rats.

    PubMed

    Falany, Charles N; Li, Ge

    2005-01-01

    Dimethylcyclosiloxanes (DMCS) are components of silicone gel containing implants and are known inducers of human drug metabolizing enzymes. The effects of the major DMCS, octamethyltetracyclosiloxane (D4) on cytochrome P450 (CYP) induction were examined in young adult, mature, and pregnant female Sprague-Dawley rats. Also, the ability of D4 administered to pregnant dams to affect CYP expression in fetal liver was examined. Female young, mature, and pregnant Sprague-Dawley rats were administered 0, 5, 20, and 100 mg/kg D4 daily by gavage for 8 days. Liver microsomal CYP (CYP2B, CYP3A, CYP1A) concentrations were evaluated by Western blots using specific antisera, and CYP activities were assayed using CYP selective assays. D4 treatment resulted in a significant induction of CYP2B and CYP3A isoforms. CYP induction was dose and age dependent. A comparison of the inducibility of CYP3A protein by D4 in rats from different age groups showed that the degree of increase was the highest in the pregnant rats at doses of 20 mg/kg D4 or higher. The mature rats had a lesser degree of responsiveness than did the young rats at the dose of 100 mg/ kg D4. Significant increases in CYP2B immunoreactive protein concentrations were observed in young and mature rats given D4 at doses >5 mg/kg and in pregnant rats at doses >20 mg/kg. Maximal CYP2B induction detected with blotting was more than 90-fold in mature rats; however, no significant changes were detected in CYP1A expression. There was a 20% increase of liver to body weight ratio in the mature rats treated with 100 mg/kg D4. D4 has different inductive properties in female rats of different ages and reproductive status. Also, D4 administered to the pregnant dam is capable of inducing CYP expression in fetal liver as well as decreasing fetal body weight. PMID:15849718

  18. Green Tea Extract Increases mRNA Expression of Enzymes Which Influence Epigenetic Marks in Newborn Female Offspring from Undernourished Pregnant Mother

    PubMed Central

    Sun, Yongkun; Mukai, Yuuka; Tanaka, Masato; Saito, Takeshi; Sato, Shin; Kurasaki, Masaaki

    2013-01-01

    Biochemical and toxicological properties of catechin remain unclear, e.g.; how catechin affects female offspring from undernourished pregnant dams. Here, to elucidate effects of low prenatal protein on female offspring health status, changes of enzymes which modify epigenetic marks related with metabolism in kidneys from newborns were investigated after continuously administering catechin extracted from green tea to lactating maternal rats after pregnant undernourishment. We found that green tea extract intake during lactation up-regulated the activation of AMP-activated protein kinase in young female offspring from protein-restricted dams and modulated the AMP-activated protein kinase pathway in the kidney. This pathway was indicated to be stimulated by SIRT1 gene expression. The feeding of green tea extract to protein-restricted dams during lactation is likely to up-regulate AMP-activated protein kinase activation and may partly lead to alterations of the AMP-activated protein kinase pathway in female offspring kidneys. In addition, energy metabolism in fetal and offspring period with green tea extract administration might be related to enzymes which modify epigenetic marks such as DNA methyltransferase 1 and 3a. PMID:24009774

  19. Green tea extract increases mRNA expression of enzymes which influence epigenetic marks in newborn female offspring from undernourished pregnant mother.

    PubMed

    Sun, Yongkun; Mukai, Yuuka; Tanaka, Masato; Saito, Takeshi; Sato, Shin; Kurasaki, Masaaki

    2013-01-01

    Biochemical and toxicological properties of catechin remain unclear, e.g.; how catechin affects female offspring from undernourished pregnant dams. Here, to elucidate effects of low prenatal protein on female offspring health status, changes of enzymes which modify epigenetic marks related with metabolism in kidneys from newborns were investigated after continuously administering catechin extracted from green tea to lactating maternal rats after pregnant undernourishment. We found that green tea extract intake during lactation up-regulated the activation of AMP-activated protein kinase in young female offspring from protein-restricted dams and modulated the AMP-activated protein kinase pathway in the kidney. This pathway was indicated to be stimulated by SIRT1 gene expression. The feeding of green tea extract to protein-restricted dams during lactation is likely to up-regulate AMP-activated protein kinase activation and may partly lead to alterations of the AMP-activated protein kinase pathway in female offspring kidneys. In addition, energy metabolism in fetal and offspring period with green tea extract administration might be related to enzymes which modify epigenetic marks such as DNA methyltransferase 1 and 3a. PMID:24009774

  20. ALTERED ZN STATUS BY A-HEDERIN IN THE PREGNANT RAT AND ITS RELATIONSHIP TO ADVERSE DEVELOPMENTAL OUTCOME

    EPA Science Inventory

    The hypothesis that hepatic metallothionein (MT) induction in the pregnant animal results in a Zn deficiency in the embryo was tested by treating pregnant rats with a-hederin, reported to induce MT in rat liver. orphological development was assessed in term fetuses. ingle dose of...

  1. Effects of low doses of alcohol on delta-9-tetrahydrocannabinol's effects in pregnant rats

    SciTech Connect

    Abel, E.L.; Subramanian, M.G. )

    1990-01-01

    Pregnant rats were intubated with 50 mg/kg of delta-9-tetrahydrocannabinol (THC) or with THC plus alcohol to determine if a low dose of alcohol would significantly increase blood levels of THC. On the basis of this study, a second study was conducted in which pregnant rats were intubated with THC plus alcohol from gestation day six to parturition. THC reduced birth weights but did not significantly affect litter size or passive avoidance learning. Alcohol did not have a significant effect on offspring birth weight nor did it interact with THC to affect offspring.

  2. Cadmium toxicity to the cornea of pregnant rats: Electron microscopy and x-ray microanalysis

    SciTech Connect

    Yoshizuka, M.; McCarthy, K.J.; Kaye, G.I.; Fujimoto, S. )

    1990-05-01

    Cadmium toxicity to the cornea of pregnant rats was studied using the electron microscope and x-ray microanalyzer. In in-vivo experiments, severe corneal edema occurred in pregnant dams that received intraperitoneal injections of cadmium sulphate for 4 days during gestation, but not in nonpregnant rats. Prominent swelling of mitochondria and the occurrence of intra- and intercellular vacuoles in the corneal endothelium were observed only in pregnant dams. In in-vitro experiments, electron-dense deposits consisting of cadmium-oxine complexes were preferentially found in swollen mitochondria of the endothelial cells. Cadmium peaks were obtained from these deposits with x-ray microanalysis. These data suggest that the corneal edema observed after administration of cadmium may imply the disturbance of pump function and barrier function of the corneal endothelium due to the primary toxic effects of this metal on mitochondria.

  3. DEVELOPMENTAL EFFECTS OF TRICHLOROACETONITRILE ADMINISTERED IN CORN OIL TO PREGNANT LONG-EVANS RATS

    EPA Science Inventory

    Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced ...

  4. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT

    EPA Science Inventory

    EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT.

    S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive T...

  5. FAILURE OF PHENOBARBITAL TO INDUCE RAT HEPATIC MICROSOMAL UDP-GLUCURONYLTRANSFERASE TOWARD PHENOLPHTHALEIN

    EPA Science Inventory

    Phenobarbital pretreatment was found not to induce Triton X-100 activated hepatic microsomal neonatal UDP-glucuronyltransferase activity towards phenolphthalein in male, female and pregnant female rats.

  6. Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat.

    PubMed

    Beausjour, Annie; Houde, Vronique; Bibeau, Karine; Gaudet, Rbecca; St-Louis, Jean; Brochu, Michle

    2007-10-01

    Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na(+)-K(+)-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-alpha)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na(+)-K(+)-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF(2alpha), and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension. PMID:17652367

  7. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

    PubMed Central

    Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

  8. Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring.

    PubMed

    El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H

    2010-01-01

    Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in fibrinoid necrosis. Oral supplementation with Allium sativum (100 mg/ kg) ameliorated these effects in myocardium muscle of mothers and offspring; however the dorsal aorta of mothers showed partial amelioration. Hypercholesterolemic mothers exhibited marked alterations in serum TCL, TG, LDL and CK activity. Supplementation with Allium sativum ameliorated the drastic biochemical alterations. Concerning pregnancy, hypercholesterolemia increased the incidence of abortion and abnormalities of the newborn including decreased body weight, reduced ossification of axial (mandible) and appendicular bones. All these effects were markedly ameliorated by supplementation with Allium sativum. The author finally concluded that hypercholesterolemia exhibits pathological alterations of myocardiai muscles reducing its optimal capacity for pumping blood to different body organs along with atherosclerosis of dorsal aorta which intern affect the progress of gestation and development of both morphological and skeletal abnormalities. Allium sativum-supplementation leads to amelioration of both mother and their offspring investigated parameters as a result of its antioxidant activity. PMID:20607041

  9. Reproductive development and function of female rats exposed to di-eta-butyl-phthalate (DBP) in utero and during lactation.

    PubMed

    Guerra, Marina T; Scarano, Wellerson R; de Toledo, Fabola C; Franci, Janete A A; Kempinas, Wilma De G

    2010-01-01

    Phthalates are environmental contaminants used in the production of plastics, cosmetics and medical devices. Studies on the effects of phthalates on female reproductive health are particularly sparse and mostly restricted to high-dose exposure in rats. In the present study, pregnant rats were treated with 100mg/kg-d of di-eta-butyl-phthalate (DBP) or only the vehicle (control group), from GD 12 to GD 20 for evaluation of reproductive outcomes and fetal gonads analysis (F0), and from GD 12 to PND 21 to evaluate reproductive development and function on F1 female offspring. Results showed that all parameters were comparable between groups, although there was a significant increase in the fetal weight after DBP exposure. However, the body weight at birth was normal. Based on these data we can conclude that, in these experimental conditions, DBP did not disturb the reproductive development or function of female rats. PMID:19850123

  10. Reproductive senescence, fertility and reproductive tumour profile in ageing female Han Wistar rats.

    PubMed

    Mitchard, Terri L; Klein, Stephanie

    2016-01-01

    A study using vehicle administration in 104 female rats investigated reproductive aging in Han Wistar rats as a useful tool to interprete carcinogenicity studies where hormonal patterns are perturbated. From 16 weeks of age oestrous cycles were monitored every 6 weeks to investigate reproductive ageing. A subset of 20 females was used to assess fertility at 21 months of age. The animals were necropsied after 106-107 weeks on study and female reproductive organs, mammary glands and pituitary glands were examined for hyperplasias and/or tumours. The majority of rats had regular oestrous cycles up to 6 months of age. After this age, there was a rapid decline in the number of rats with regular oestrous cycles and an increase in irregular cycles and cycles in persistent di-oestrus with an occasional pro-oestrus. By the end of the study, the majority of animals were acyclic and the few remaining cyclic animals had irregular cycles. In the fertility assessment, 19/20 animals mated but only four animals became pregnant. These pregnant animals had normal numbers of corpora lutea of pregnancy but had high pre-implantation losses and could not sustain a viable pregnancy. 65 animals (62.5%) showed adenomas and/or pituitary hyperplasia in the pituitary gland at necropsy. The pituitary tumours were likely to be prolactin secreting that give rise to pseudopregnancy and mammary tumours, demonstrated by the fact that 43/65 (66%) of the affected animals had histopathological signs of these conditions. Multiple corpora lutea were found in 61% of all animals at time of termination. Only one uterine tumour was seen in this study probably due to lack of persistent oestrus seen in these animals. PMID:26655996

  11. Mammary gland proliferation in female rats: effects of the estrous cycle, pseudo-pregnancy and age.

    PubMed

    Hvid, Henning; Thorup, Inger; Sjgren, Ingrid; Oleksiewicz, Martin B; Jensen, Henrik E

    2012-05-01

    Assessment of mammary gland proliferation in rats is an important endpoint in preclinical safety studies of pharmaceutical compounds. However, existing data on mammary gland proliferation in rats during the estrous cycle is conflicting, and it is unknown whether mammary gland proliferation differs between young and mature female virgin rats. Additionally, it is unclear which of the commonly applied markers of proliferating cells that is optimal for assessment of rat mammary gland proliferation. In this study the caudal thoracic, the abdominal and the cranial inguinal (i.e., the 3rd the 4th and the 5th) mammary gland were collected from 29 young and 26 mature non-treated, virgin female Sprague Dawley rats. Estrous cycle stage was determined from repeated vaginal smears and histological examination of the reproductive organs. Proliferation of mammary epithelium was assessed by immunohistochemistry using three markers: PCNA, Ki67, and BrdU. Proliferation of the mammary epithelium occurred mainly in the terminal end buds in the young animals. Epithelial proliferation was significantly increased during metestrus compared to the other phases. Mammary gland proliferation in pseudo-pregnant females was increased compared to proestrus, estrus and diestrus, but not metestrus. Except during estrus no difference in mammary gland proliferation was observed between young and mature female rats, and no significant differences was observed between different mammary glands. The percentages of PCNA-, Ki67- and BrdU-positive epithelial cells were significantly correlated. In conclusion, the variation in normal proliferation between estrous cycle stages and animals with an irregular estrous cycle should be considered in toxico-pathological studies of mammary gland proliferation. PMID:20951558

  12. RADAR Reference Adult, Pediatric, and Pregnant Female Phantom Series for Internal and External Dosimetry

    PubMed Central

    Stabin, Michael G.; Xu, X. George; Emmons, Mary A.; Segars, W. Paul; Shi, Chengyu; Fernald, Michael J.

    2015-01-01

    A new generation of reference computational phantoms, based on image-based models tied to the reference masses defined by the International Commission on Radiological Protection (ICRP) for dose calculations, is presented. Methods Anatomic models based on nonuniform rational b-spline modeling techniques were used to define reference male and female adults, 15-y-olds, 10-y-olds, 5-y-olds, 1-y-olds, newborns, and pregnant women at 3 stages of gestation, using the defined reference organ masses in ICRP publication 89. Absorbed fractions and specific absorbed fractions for internal emitters were derived using standard Monte Carlo radiation transport simulation codes. Results Differences were notable between many pairs of organs in specific absorbed fractions because of the improved realism of the models, with adjacent organs usually closer and sometimes touching. Final estimates of absorbed dose for radiopharmaceuticals, for example, were only slightly different overall, as many of the differences were small and most pronounced at low radiation energies. Some new important organs were defined (salivary glands, prostate, eyes, and esophagus), and the identity of a few gastrointestinal tract organs changed. Conclusion A new generation of reference models for standardized internal and external dose calculations has been defined. The models will be implemented in standardized software for internal dose calculations and be used to produce new standardized dose estimates for radiopharmaceuticals and other applications. PMID:22967805

  13. Infective endocarditis due to Bacillus cereus in a pregnant female: A case report and literature review

    PubMed Central

    Shah, Mahek; Patnaik, Soumya; Wongrakpanich, Supakanya; Alhamshari, Yaser; Alnabelsi, Talal

    2015-01-01

    Incidence of infective endocarditis during pregnancy is around 0.006% with high maternal and fetal mortality. Bacillus cereus is an extremely rare cause for endocarditis in intravenous drug abusers (IVDA) or those with valvular disease or devices such as pacemakers. We report a case of B. cereus endocarditis, which, to the best of our knowledge, has never been reported in pregnancy. A 30-year-old, 25-week pregnant female presented with right shoulder pain, swelling and erythema on the lateral aspect of deltoid muscle from large abscess over her deltoid muscle. She was found to have a vegetation on the native tricuspid valve. Cultures from abscess fluid and blood cultures grew B. cereus, she was appropriately treated with antimicrobials and had favorable outcomes. There are <20 cases of B. cereus endocarditis reported but none during pregnancy. When cultures grow unusual organisms the case must be thoroughly investigated. This case illustrates a rare situation (endocarditis in pregnancy) with an unusual outcome (B. cereus) on an uncommon valve (tricuspid valve). PMID:26793477

  14. The interaction between prenatal stress and neonatal handling on nociceptive response latencies in male and female rats.

    PubMed

    Smythe, J W; McCormick, C M; Rochford, J; Meaney, M J

    1994-05-01

    Neonatal handling produces physiological and behavioral changes that persist into adulthood. These effects are opposite to those resulting from prenatal stress (PS). We examined the interaction between PS and handling on nociception in adult male and female rats. Randomly selected pregnant rats were subjected to restraint stress on days 13-17 of gestation for 25 min each day, or left undisturbed. At birth, selected stressed/nonstressed litters were assigned to be handled. handling consisted of 15 min of separation from the dam, once per day, from postnatal days 1-14. At 4 months of age, rats were placed on a 50 degrees C hot plate, and their latencies to paw lick were recorded. Prenatal stress and handling interacted to affect latencies in male rats. Handled (H)/PS rats had significantly lower paw lick latencies than nonhandled (NH)/PS rats (p < 0.05). However, handling had no effect on the male offspring of control dams. Handling elevated paw lick latencies in the female offspring of control dams, an effect that was most pronounced in diestrous vs. estrous rats. The NH/PS rats showed significantly elevated latencies compared to NH/NS rats (p < 0.05). These results suggest that handling effects on nociception are most apparent in rats subjected to PS; in males at least, these effects would otherwise not be present. PMID:8022921

  15. The location of pacemakers in the uteri of pregnant guinea pigs and rats.

    PubMed

    Lammers, Wim J E P; Stephen, Betty; Al-Sultan, Mahmood Ahmed; Subramanya, Sandeep B; Blanks, Andrew M

    2015-12-01

    The pregnant uterus is a smooth muscle organ whose pattern of contraction is dictated by the propagation of electrical impulses. Such electrical activity may originate from one or more pacemakers, but the location of these sites has not yet been determined. To detect the location of the pacemaker in the gravid uterus, two approaches were used: 1) determine the site from where the contraction started using isolated uteri from the pregnant guinea pig, and videotape their contractions; and 2) record, in isolated uteri from pregnant term rats, with 240 extracellular electrodes simultaneously, and determine where the electrical bursts started. In both the contractile and electrophysiological experiments, there was not a single, specific pacemaker area. However, most contractions (guinea pig 87%) and bursts (rat 76%) started close to the mesometrial border (mean 2.7 4.0 mm SD in guinea pigs and 1.3 1.4 mm in rats). In addition, in the rat, most sites of initiations were located closer to the ovarial end of the horn (mean distance from the ovarial end 6.0 6.2 mm SD), whereas such an orientation was not seen in the guinea pig. In both guinea pig and rat uteri at term, there is not one specific pacemaker area. Rather, contractile and electrical activity may arise from any site, with the majority starting close to the mesometrial border. Furthermore, in the rat, most activities started at the ovarial end of the horn. This may suggest a slightly different pattern of contraction in both species. PMID:26377559

  16. Adaptive plasticity of vaginal innervation in term pregnant rats.

    PubMed

    Liao, Zhaohui; Smith, Peter G

    2011-12-01

    Changes in reproductive status place varied functional demands on the vagina. These include receptivity to male intromission and sperm transport in estrus, barrier functions during early pregnancy, and providing a conduit for fetal passage at parturition. Peripheral innervation regulates vaginal function, which in turn may be influenced by circulating reproductive hormones. We assessed vaginal innervation in diestrus and estrus (before and after the estrous cycle surge in estrogen), and in the early (low estrogen) and late (high estrogen) stages in pregnancy. In vaginal sections from cycling rats, axons immunoreactive for the pan-neuronal marker protein gene product 9.5 (PGP 9.5) showed a small reduction at estrus relative to diestrus, but this difference did not persist after correcting for changes in target size. No changes were detected in axons immunoreactive for tyrosine hydroxylase (sympathetic), vesicular acetylcholine transporter (parasympathetic), or calcitonin gene-related peptide and transient receptor potential vanilloid type 1 (TRPV-1; sensory nociceptors). In rats at 10 days of pregnancy, innervation was similar to that observed in cycling rats. However, at 21 days of pregnancy, axons immunoreactive for PGP 9.5 and each of the subpopulation-selective markers were significantly reduced both when expressed as percentage of sectional area or after correcting for changes in target size. Because peripheral nerves regulate vaginal smooth muscle tone, blood flow, and pain sensitivity, reductions in innervation may represent important adaptive mechanisms facilitating parturition. PMID:21666101

  17. Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

    PubMed Central

    Kanca, Halit; Yar, Atiye Seda; Helvacioğlu, Fatma; Menevşe, Sevda; Çalgüner, Engin; Erdoğan, Deniz

    2014-01-01

    In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term. PMID:24136214

  18. SAF values for internal photon emitters calculated for the RPI-P pregnant-female models using Monte Carlo methods

    SciTech Connect

    Shi, C. Y.; Xu, X. George; Stabin, Michael G.

    2008-07-15

    Estimates of radiation absorbed doses from radionuclides internally deposited in a pregnant woman and her fetus are very important due to elevated fetal radiosensitivity. This paper reports a set of specific absorbed fractions (SAFs) for use with the dosimetry schema developed by the Society of Nuclear Medicine's Medical Internal Radiation Dose (MIRD) Committee. The calculations were based on three newly constructed pregnant female anatomic models, called RPI-P3, RPI-P6, and RPI-P9, that represent adult females at 3-, 6-, and 9-month gestational periods, respectively. Advanced Boundary REPresentation (BREP) surface-geometry modeling methods were used to create anatomically realistic geometries and organ volumes that were carefully adjusted to agree with the latest ICRP reference values. A Monte Carlo user code, EGS4-VLSI, was used to simulate internal photon emitters ranging from 10 keV to 4 MeV. SAF values were calculated and compared with previous data derived from stylized models of simplified geometries and with a model of a 7.5-month pregnant female developed previously from partial-body CT images. The results show considerable differences between these models for low energy photons, but generally good agreement at higher energies. These differences are caused mainly by different organ shapes and positions. Other factors, such as the organ mass, the source-to-target-organ centroid distance, and the Monte Carlo code used in each study, played lesser roles in the observed differences in these. Since the SAF values reported in this study are based on models that are anatomically more realistic than previous models, these data are recommended for future applications as standard reference values in internal dosimetry involving pregnant females.

  19. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    Del Cerro, M C R; Ortega, E; Gmez, F; Segovia, S; Prez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. PMID:26163152

  20. Possible mechanism for accelerated atherogenesis in male versus female rats

    SciTech Connect

    Staprans, I.; Felts, J.M.

    1989-03-01

    Dietary fat and cholesterol enter the circulation as chylomicrons. They are removed from the circulation by attachment to lipoprotein lipase located on the endothelial surfaces. As the result of lipoprotein lipase action, chylomicrons are partially hydrolyzed and then reenter the circulation as remnants, which are rapidly cleared by the liver. We investigated the fate of /sup 3/H-retinol- and /sup 14/C-cholesterol-labeled chylomicrons injected into male and female rats. The disappearance curves of chylomicrons from the circulation were not significantly different in males and females, which suggests that translocation from plasma to endothelium is similar for both sexes. However, in male rats, the dwell time of chylomicrons on the endothelium was significantly prolonged. At 10 and 20 minutes after chylomicron injection, more label was found in the livers of female than male rats. The opposite was true for hearts. Male hearts contained significantly more endothelium-bound chylomicrons when compared with female hearts. This increase in dwell time may allow greater cholesterol deposition in the endothelium of male rats. The more rapid processing of chylomicrons was associated with a 300% greater postheparin lipoprotein lipase in female rats, which suggests a greater enzyme density at chylomicron attachment points on endothelium.

  1. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    PubMed

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus. PMID:26483343

  2. Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.

    PubMed

    Zhang, Qianqian; Ye, Xiangfeng; Wang, Lingzhi; Peng, Bangjie; Zhang, Yingxue; Bao, Jie; Li, Wanfang; Wei, Jinfeng; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2016-02-01

    The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage. PMID:26619782

  3. Enhanced endothelin receptor type B-mediated vasodilation and underlying [Ca2+]i in mesenteric microvessels of pregnant rats

    PubMed Central

    Mazzuca, Marc Q; Dang, Yiping; Khalil, Raouf A

    2013-01-01

    Background and Purpose Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ETAR), but could activate ETBR in the endothelium and release vasodilator substances. However, the roles of ETBR in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear. Experimental Approach Pressurized mesenteric microvessels from pregnant and virgin Sprague–Dawley rats were loaded with fura-2/AM for simultaneous measurement of diameter and [Ca2+]i. Key Results High KCl (51 mM) and phenylephrine (PHE) caused increases in vasoconstriction and [Ca2+]i that were similar in pregnant and virgin rats. ET-1 caused vasoconstriction that was less in pregnant than virgin rats, with small increases in [Ca2+]i. Pretreatment with the ETBR antagonist BQ-788 caused greater enhancement of ET-1-induced vasoconstriction in pregnant rats. ACh caused endothelium-dependent relaxation and decreased [Ca2+]i, and was more potent in pregnant than in virgin rats. ET-1 + ETAR antagonist BQ-123, and the ETBR agonists sarafotoxin 6c (S6c) and IRL-1620 caused greater vasodilation in pregnant than in virgin rats with no changes in [Ca2+]i, suggesting up-regulated ETBR-mediated relaxation pathways. ACh-, S6c- and IRL-1620-induced relaxation was reduced by the NO synthase inhibitor Nω-nitro-l-arginine methyl ester, and abolished by tetraethylammonium or endothelium removal. Western blots revealed greater amount of ETBR in intact microvessels of pregnant than virgin rats, but reduced levels in endothelium-denuded microvessels, supporting a role of endothelial ETBR. Conclusions and Implications The enhanced ETBR-mediated microvascular relaxation may contribute to the decreased vasoconstriction and vascular resistance during pregnancy. PMID:23646960

  4. A case of semi-combusted pregnant female in the Phoenician-Punic necropolis of Monte Sirai (Carbonia, Sardinia, Italy).

    PubMed

    Piga, G; Guirguis, M; Thompson, T J U; Isidro, A; Enzo, S; Malgosa, A

    2016-02-01

    We present a case of a pregnant woman with the fetus skeletal remains in situ, belonging to the Phoenician-Punic necropolis of Monte Sirai (Sardinia, Italy). The burial dates back to the late 6th to early 5th century BCE. Of the unborn fetal cases documented in the literature this is amongst the oldest four and it represents the first documented case of a pregnant woman in the Phoenician and Punic necropolis literature. A physico-chemical investigation of bones combining X-ray diffraction and Fourier transform-infrared spectroscopy suggests that the female skeleton and fetus were subjected to an incomplete heat treatment according to a funerary practice, perhaps limited to the period of early 5th century BCE, that appears to be peculiar to this site. PMID:26421607

  5. Role of the availability of substrates on hepatic and renal gluconeogenesis in the fasted late pregnant rat

    SciTech Connect

    Zorzano, A.; Lasuncion, M.A.; Herrera, E.

    1986-04-01

    Studies were conducted to examine the role of gluconeogenetic substrate availability on glucose production in the fasted late pregnant rat. Virgin and 21-day pregnant rats were studied after 24 hours' food deprivation. Pregnant animals showed decreased circulating glucose and gluconeogenic amino acid and increased plasma glycerol concentration. Glucose formation was studied in vivo two, five, and ten minutes after the intravenous administration of two concentrations of /sup 14/C-alanine, /sup 14/C-pyruvate, or /sup 14/C-glycerol. Concentrations of 0.2 mmols of /sup 14/C-glycerol or /sup 14/C-pyruvate, but not of /sup 14/C-alanine, enhanced /sup 14/C-glucose production in pregnant rats, whereas 1 mmol of any of the three /sup 14/C-substrates always enhanced /sup 14/C-glucose production in these rats. Both 1 mmol/L and 5 mmol/L /sup 14/C-alanine increased /sup 14/C-glucose formation in 90-minute-incubated liver slices of fasted pregnant rats, in spite of decreased cytosolic activity of alanine aminotransferase. The three substrates enhanced in vitro renal gluconeogenesis in pregnant rats. Under all experimental conditions studied, labeled glycerol was converted more efficiently into glucose than equivalent amounts of any other substrate used, and this difference was greater in pregnant, than in virgin animals. Results indicate that, in spite of enhanced gluconeogenetic activity, maternal glucose production in the fasted state at late gestation is limited by the deficiency of certain substrates, such as amino acids. It is proposed that glycerol derived from enhanced maternal adipose tissue lipolysis constitutes a preferential gluconeogenetic substrate in comparison with others, such as alanine, that are more efficiently transferred through the placenta to the fetus.

  6. Toxicological effects of cypermethrin on female albino rats.

    PubMed

    Sangha, G K; Kaur, Kamalpreet; Khera, K S; Singh, Balwinder

    2011-01-01

    A study was undertaken to evaluate the effects of cypermethrin on reproduction of female albino rats. The experimental rats were fed cypermethrin at 50 mg/kg b. wt. continuously for a period of 2 and 4 weeks. Feed and water intake was also noted daily for control, vehicle treated and cypermethrin-treated rats. It was observed that there was no effect on feed and water intake in treated rats as compared to the control group. Chronic exposure to cypermethrin for 4 weeks resulted in loose fecal pellets and hyperirritability in the treated rats. Treatment related mortality also occurred at the 4(th) wk of treatment. Significant changes in body weight and various organ weights due to cypermethrin were observed along with disruption of estrous cycle in rats. The body weight gain in treated rats was lower at both 2 and 4 weeks as compared to the control rats. The weight of liver and spleen decreased, while that of kidneys increased as compared to the control rats. Thyroid and adrenal showed increase in weight at both 2 and 4 weeks of treatments. PMID:21430912

  7. Seizures and reproductive function: insights from female rats with epilepsy

    PubMed Central

    Scharfman, Helen E.; Kim, Michelle; Hintz, Tana M.; MacLusky, Neil J.

    2009-01-01

    OBJECTIVE Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome (PCOS), but it has been difficult to dissociate the effects of epilepsy per se from the role of antiepileptic drugs (AEDs). To distinguish the effects of chronic seizures from AEDs, we used the laboratory rat, where an epileptic condition can be induced without concomitant AED treatment. METHODS Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus (SE), which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed epileptic. Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop SE. Ovarian cyclicity and weight gain were evaluated for 2-3 months. Serum hormone levels were assayed from trunk blood, collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if SE did not occur. Ovarian cysts and weight gain were significantly greater in epileptic rats than controls, whether rats maintained cyclicity or not. Serum testosterone was elevated in epileptic rats, but estradiol, progesterone and prolactin were not. INTERPRETATIONS The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels. Although caution is required when comparing female rats to women, the data suggest that epilepsy per se may be sufficient to induce abnormalities in the control of the ovary. PMID:19107990

  8. Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention.

    PubMed

    West, Crystal A; McDonough, Alicia A; Masilamani, Shyama M E; Verlander, Jill W; Baylis, Chris

    2015-07-01

    Pregnancy is characterized by plasma volume expansion due to Na(+) retention, driven by aldosterone. The aldosterone-responsive epithelial Na(+) channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na(+)-Cl(-) cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na(+) channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K(+) intake or other undefined mechanisms. PMID:25925254

  9. Tumorigenic effects of dichloroacetic acid in female F344 rats

    EPA Science Inventory

    Introduction: Dichloroacetic acid (DCA) is a halogenated organic acid produced during oxidant disinfection of drinking water. Prior studies indicate that DCA may increase liver tumors in mice. Here we evaluated the hepatic tumorigenicity of DCA in female rats when given alone ...

  10. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    ERIC Educational Resources Information Center

    Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.

    2008-01-01

    Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or…

  11. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    ERIC Educational Resources Information Center

    Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.

    2008-01-01

    Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or

  12. POSSIBLE ANTIESTROGENIC ACTIVITY OF LINDANE IN FEMALE RATS (JOURNAL VERSION)

    EPA Science Inventory

    During chronic treatment of weanling female rats with daily injections (0.069 mmol/kg of gamma-hexachlorocyclohexane (lindane, gamma-HCH), the treatment induced a significant 20% increase in body weight after 110 days. Further investigation with 0, 5, 10, 20 and 40 mg/kg lindane ...

  13. Placental transfer and tissue localization of [14C]carmoisine in the pregnant rat.

    PubMed

    Galli, C L; Marinovich, M; Costa, L G; Giavini, E

    1982-02-01

    Pregnant Sprague-Dawley rats received [14C]Carmoisine (200 mg/kg; 25 microCi) by gavage, on days 16-19 of gestation. Animals were killed on day 19 of gestation, 2, 16, 64 h after dosing and blood, maternal tissues, amniotic fluids, placentae, fetal membranes and fetuses were analyzed for radioactivity. No evidence for the transplacental transfer of [14C]Carmoisine or its metabolites was obtained. More than 90% of the radioactivity was excreted in feces and urine within 64 h. PMID:7080094

  14. To Madagascar and back: long-distance, return migration across open ocean by a pregnant female bull shark Carcharhinus leucas.

    PubMed

    Lea, J S E; Humphries, N E; Clarke, C R; Sims, D W

    2015-12-01

    A large, pregnant, female bull shark Carcharhinus leucas was tracked migrating from Seychelles across open ocean to south-east Madagascar, c. 2000 km away, and back again. In Madagascar, the shark spent a prolonged period shallower than 5 m, consistent with entering estuarine habitat to pup, and upon return to Seychelles the shark was slender and no longer gravid. This represents an unprecedented return migration across the open ocean for a C. leucas and highlights the need for international collaboration to manage the regional C. leucas population sustainably. PMID:26511427

  15. Aspects of the Development of Housing for the Spaceflight of Pregnant and Lactating Rats with Neonates

    NASA Technical Reports Server (NTRS)

    Hinds, William E.; Mayer, David J.; Evans, Juli; Spratt, Shahn; Lane, Philip K.; Rodriguez, Shari L.; Navidi, Meena; Armstrong, Rachel; Lemos, Bonnie; Dalton, Bonnie P. (Technical Monitor)

    1996-01-01

    Recent and upcoming spaceflights are investigating the effect of weightlessness on developing neural and organ systems. Pregnant rats and dams with neonates have to be accommodated in cages that support the special requirements of these animals. Extensive ground testing of cage concepts, the effect of launch and landing stresses on the maintenance of pregnancy and maternal behavior at different neonatal ages, and techniques for monitoring adaptability to change are discussed. A spaceflight opportunity for the NlH.R3 payload of rat families at three different postnatal ages demonstrated that the survival of very young animals was not good but that older newborns could be returned to Earth in reasonably good health. The development of cages for the Research Animal Holding Facility (RAHF) to support the flight of neonates on Neurolab was continued and incorporated modifications that were demonstrated by the NIH.R3 flight. Other modifications to the RAHF are discussed. Data from biocompatibility and experiment verification testing are presented.

  16. 3. Impact of altered gravity on CNS development and behavior in male and female rats

    NASA Astrophysics Data System (ADS)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be surmised that males and females may respond differently to the microgravity encountered in space. Supported by NIEHS grant ES11946-01 awarded to E. S-S.

  17. "Some guys have all the luck": mate preference influences paced-mating behavior in female rats.

    PubMed

    Lovell, Jennifer L; Diehl, Abby; Joyce, Elizabeth; Cohn, Jenifer; Lopez, Jose; Guarraci, Fay A

    2007-03-16

    In the present study, mating behavior was observed in female rats that were given the opportunity to mate with two males simultaneously. Three groups of females were tested: 1) sexually nave, naturally cycling rats in proestrous; 2) sexually nave, hormone-primed, ovariectomized (OVX) rats; and 3) hormone-primed, OVX rats tested 1 week after sexual receptivity testing. One male rat was determined to be the preferred male for each female, if she spent more time with him during a mating test. Independent of sexual experience, female rats were less likely to leave their preferred male than their non-preferred male following intromissions. However, when they left their preferred male, they returned to him faster than to their non-preferred male. This effect of preference was slightly more robust in the OVX rats. When female rats from Group 2 were tested with the same pair of males for 3 additional tests, each female's preference for a particular male was stable. That is, a female rat preferred the same male in approximately 3 out of the 4 tests, which is more likely than would be expected by chance. In a final experiment, pairs of male rats were tested with different females once weekly to determine if different females would prefer particular males consistently. Although no male rat was preferred by all females, females consistently preferred the same male from each pair during approximately 70% of the tests. In conclusion, female mate preference may have adaptive significance for the reproductive success of rats. PMID:17178134

  18. A Method for Recording Urethral Pressure Profiles in Female Rats

    PubMed Central

    Xu, Shengfei; Li, Xiaohui; Xu, Lei; Chen, Biao; Tan, Huibing; Du, Guanghui

    2015-01-01

    Aims Urethral pressure profile (UPP) and leak-point pressure (LPP) measurements as well as external urethral sphincter (EUS) electromyography (EMG) and videourodynamic analyses are the primary methods for evaluating urethral function in humans. However, UPP recording in female rats, a widely used animal model, is challenging due to their small body sizes. This study reports a novel method for recording UPP in female rats. Materials and Methods Seventeen anesthetized female rats were studied. LPP data for 14 rats were included. The other 3 rats were excluded because of death or abnormal urogenital organs. UPP curves were recorded using a modified water-perfusion catheter system, with the lateral hole facing the 3-, 6-, 9-, and 12-oclock positions in a randomized sequence. LPP, functional urethral length (FUL) and maximum urethral closure pressure (MUCP) were analyzed. Results The mean LPP was 64.39 20.29 cm H2O. The mean FUL and MUCP values at the 3-, 6-, 9-, and 12-oclock positions were 12.90 1.20, 16.70 1.95, 13.90 2.42, and 11.60 0.97 mm, respectively, and 38.70 11.85, 33.90 11.82, 37.40 11.95, and 71.90 23.01 cm H2O, respectively. The FUL at the 6-oclock position and MUCP at the 12-oclock position were significantly greater than those at the other 3 positions. The FUL and MUCP of repeated UPP recordings were not significantly different than those of the first recordings. Conclusions UPP recording using a modified method based on a water-perfusion catheter system is feasible and replicable in female rats. It produces UPP curves that sensitively and appreciably reflect detailed pressure changes at different points within the urethra and thus provides opportunity to evaluate urethral structures, especially the urethral sphincter, in detail. These results may enhance the utility of female rat models in research of urinary sphincter mechanisms. PMID:26502072

  19. Reproductive toxicity associated with acrylamide treatment in male and female rats

    SciTech Connect

    Zenick, H.; Hope, E.; Smith, M.K.

    1986-01-01

    The present study was designed to evaluate the influence of acrylamide (ACR) on male and female reproductive function. Male rats received ACR in drinking water (50, 100, or 200 ppm) for up to 10 wk. Copulatory behavior, semen, and (for controls and 100 ppm only) fertility and fetal outcomes were evaluated. Females received ACR (25, 50, 100 ppm) for 2 wk prior to initiation of breeding and then throughout gestation and lactation. Hindlimb splaying was apparent in the 200-ppm males by wk 4; less severe splaying appeared in the 100-ppm group at wk 8. Disruptions in copulatory behavior preceded the appearance of this ataxia. These disruptions in mating performance interfered with ejaculatory processes and subsequent transport of sperm, since semen was found in the uterus of only 1 of the 15 females mated with the 100-ppm males at wk 9. Moreover, only 33% of the females mated with the 100-ppm males were pregnant. Postimplantation loss was also significantly increased in this group. Hindlimb splaying appeared in the females receiving 100 ppm ACR during wk 1-2 of pregnancy. Body weight and fluid intake were also depressed. Dams in the 50-ppm group showed depression in these parameters during the last 2 wk of lactation. ACR did not significantly affect mating performance of the females, pregnancy rates, litter size, or survival. However, ACR did significantly depress pup body weight at birth (100-ppm group) and weight gain during lactation through postweaning, d 42 (50- and 100-ppm groups). Vaginal patency was delayed in the 100-ppm group only.

  20. Prevention of female reproductive system cancer among rural and urban Polish pregnant women.

    PubMed

    Bojar, Iwona; Bili?ski, Przemys?aw; Boyle, Peter; Zato?ski, Witold; Marcinkowski, Jerzy T; Wojty?a, Andrzej

    2011-06-01

    Based on data obtained from the system MoZMaD - PL (Polish Mother and Child Health Monitoring System; an equivalent of the American system PRAMS (Pregnancy Risk Assessment Monitoring System). In the developed countries prevention programmes proved to be efficient in reducing morbidity and mortality due to breast and cervical cancer. In Poland, these diseases still constitute a very big problem, despite relatively easy and early diagnostics of pathological conditions preceding their development. The objective of the study was analysis of the usage of prophylactic examinations and the assessment of knowledge concerning risk factors of the development of reproductive cancers among pregnant women from rural and urban environments in Poland. The study was based on questionnaire forms within the Pregnancy Risk Assessment Monitoring System (MoZMaD - PL) implemented in Poland. The precise date of the study for the whole of Poland is announced annually by the Chief Sanitary Inspector. The questionnaire forms were correctly completed in 2010 by 2,877 women. The replies to the questions were introduced by surveyors into the MoZMaD - PL system central database managed by the Institute of Agricultural Medicine in Lublin. The results obtained were subjected to statistical analysis. The studies of pregnant women in Poland showed that the situation with respect to the performance of prevention examinations for cervical cancer was significantly worse among rural than urban women. Pregnant women from both rural and urban areas very rarely had breast USG performed. Awareness concerning cervical cancer risk factors was lower among rural than urban women. Also, knowledge concerning the examinations which should be performed for the prevention of breast cancer was poorer among rural, compared to urban women. The recognition of the attitudes of women at reproductive age towards prevention examinations is necessary in order to effectively plan health education and social health promotion campaigns aimed at limiting morbidity and mortality due to cancerous diseases. PMID:21736284

  1. Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Wade, C. E.

    2003-01-01

    Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

  2. Impact of chronic stressors on the anxiety profile of pregnant rats.

    PubMed

    de Brito Guzzo, Soliani Flaviane Cristina; Rafael, Cabbia; Matheus Fitipaldi, Batistela; Amarylis Garcia, Almeida; Vincius Dias, Kmpel; Luiz, Yamauchi Junior; Fernando, Frei; Telma Gonalves Carneiro Spera de, Andrade

    2015-04-01

    The manifestation of anxiety during pregnancy can be caused by multiple factors and may have emotional and physical consequences for both the mother and the fetus. The prevalence of gestational anxiety has grown in recent years, making the development of studies for its comprehension essential. Thus, the aim of this investigation was to evaluate the effects of predictable and unpredictable chronic stressors on the anxiety profile of rats in three distinct stages of pregnancy (1st, 2nd and 3rd weeks). Wistar dams were divided into three groups: control, social separation and unpredictable chronic stress. Behavioral assessments were conducted in the Elevated Plus-Maze at the end of the 1st, 2nd and 3rd weeks of gestation. The results showed that there was increased anxiety in the proximity of parturition in control dams. Chronic stressors differentially affected the behavior of pregnant rats according to the gestational period where they were applied: social separation decreased anxiety at the end of the 3rd week, while unpredictable chronic stress caused increased anxiety, especially at the end of the 2nd gestational week. These results show that there is a critical time during pregnancy for the onset of anxiety in control rats, depending on the gestational stage. The exposure to different types of chronic stressors may result in distinct behaviors related to this disorder. PMID:25665962

  3. Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.

    PubMed

    Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M

    2012-10-01

    The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal. PMID:24159687

  4. Congenital hydrocephalus following X-irradiation of pregnant rats on an early gestational day

    SciTech Connect

    Takeuchi, I.K.; Takeuchi, Y.K.

    1986-03-01

    When pregnant rats were X-irradiated at a dose of 100 R on gestational day 9.5, a considerable number of postnatally-viable hydrocephalic offspring resulted, all of which were accompanied with bilateral micro- or anophthalmia. Histological studies revealed that the cerebral aqueduct of the congenital hydrocephalic brain was severely stenosed, and the subcommissural organ was reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. From embryological studies, it was considered that the maldevelopment of the subcommissural organ in the X-irradiated fetus might cause a reduction in the amount of its secretions which function as a cushion preventing complete closure of the cerebral aqueduct during fetal life, resulting in stenosis of the cerebral aqueduct.

  5. Decreased duration of pentobarbital-induced narcosis in immature and adult female rats prenatally exposed to cimetidine

    SciTech Connect

    Donnelly, D.A.; Iba, M.M.

    1986-03-01

    The effect of prenatal cimetidine exposure (PreCM) on the duration of pentobarbital-induced narcosis (DPN) was assessed in immature (14- and 28-day old) and adult (50-60-day old) male and female rats. PreCM exposure was accomplished by treating mothers with cimetidine (CM) (20 mg/kg, ip) daily for the last two days of gestation and then (0.01% in drinking water) throughout lactation. Pregnant mothers of untreated offspring (Con) received saline. PreCM decreased DPN to 505 +/- 33 min (from 611 +/- 23 min in Con) and 393 +/- 190 min (from 686 +/- 44 min in Con) in 14-day old male and female rats, respectively. Similarly, PreCM decreased DPN to 88 +/- 15 min (from 134 +/- 3 min in Con) and 102 +/- 19 min (from 171 +/- 44 min in Con) in 28-day old male and female rats, respectively. At 21 days, PreCM did not alter DPN in either sex. At 50-60 days, however, it decreased DPN to 144 +/- 41 min (from 238 +/- 7 min in Con) in females but had no effect in males; PreCM also increased the plasma clearance of administered /sup 14/C-pentobarbital more in females than in males. The effects of PreCM, particularly the long-term effects, were most prominent in female rats and were the opposite of those of postnatal treatment with CM. The results together with those of studies with hepatic microsomes suggest that PreCM may have resulted in the induction of hepatic drug-metabolizing enzymes during the perinatal period.

  6. Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Bhat, G. K.; Yang, H.; Sridaran, R.

    2001-01-01

    The purpose of this study was to assess whether simulated conditions of microgravity induce changes in the production of progesterone by luteal cells of the pregnant rat ovary using an in vitro model system. The microgravity environment was simulated using either a high aspect ratio vessel (HARV) bioreactor with free fall or a clinostat without free fall of cells. A mixed population of luteal cells isolated from the corpora lutea of day 8 pregnant rats was attached to cytodex microcarrier beads (cytodex 3). These anchorage dependent cells were placed in equal numbers in the HARV or a spinner flask control vessel in culture conditions. It was found that HARV significantly reduced the daily production of progesterone from day 1 through day 8 compared to controls. Scanning electron microscopy showed that cells attached to the microcarrier beads throughout the duration of the experiment in both types of culture vessels. Cells cultured in chamber slide flasks and placed in a clinostat yielded similar results when compared to those in the HARV. Also, when they were stained by Oil Red-O for lipid droplets, the clinostat flasks showed a larger number of stained cells compared to control flasks at 48 h. Further, the relative amount of Oil Red-O staining per milligram of protein was found to be higher in the clinostat than in the control cells at 48 h. It is speculated that the increase in the level of lipid content in cells subjected to simulated conditions of microgravity may be due to a disruption in cholesterol transport and/or lesions in the steroidogenic pathway leading to a fall in the synthesis of progesterone. Additionally, the fall in progesterone in simulated conditions of microgravity could be due to apoptosis of luteal cells.

  7. Quantitation of protein phosphorylation in pregnant rat uteri using stable isotope dimethyl labeling coupled with IMAC.

    PubMed

    Huang, Sheng-Yu; Tsai, Mei-Ling; Wu, Chin-Jen; Hsu, Jue-Liang; Ho, Shih-Hsin; Chen, Shu-Hui

    2006-03-01

    Quantitative analysis of protein phosphorylation provides important insights into molecular signaling mechanisms and a better understanding of many cellular processes. In this study, we coupled stable isotope dimethyl labeling with immobilized metal affinity chromatography (IMAC) enrichment to quantify protein phosphorylation at MS-determined phosphorylation sites. The proposed method was first characterized using alpha- and beta-casein as two model phosphoproteins, and further applied to the analysis of pregnant rat uteri with and without treatment with 8-bromo-cGMP. Dimethyl labeling has several significant advantages: global, fast (within 5 min) and complete (near 100%). Our results indicate that the labeling has no adverse effect on the IMAC enrichment for tryptic peptides having single and multiple phosphorylation sites. Moreover, the enhanced a1 signal and the complete reaction by dimethyl labeling provide unequivocal identification of both the N-terminal amino acid and the number of the labeling site. Using these two criteria in data validation, which is particularly important for identifying phosphoproteins, we found that the confidence in interpreting dimethyl-labeled peptides had greatly increased. In the analysis of late gestation rat uteri, the abundance ratio between treated and un-treated phosphopeptide signals ranged from 0.51 to 1.69 with an average of around 1.01 +/- 0.25. The obtained ratio of the phosphorylation levels at Ser 15 of HSP27 was further confirmed by the consistent results obtained from Western blot analyses. Based on the analysis of the results, it is interesting to note that the activated cGMP dependent protein kinase G (PKG) seems to affect the phosphorylation of proteins associated with the inhibition of cell migration and proliferation, redistribution of actin-associated proteins, and the increase of protein synthesis in late-gestation uteri. These observations provide important evidence suggesting that activated PKG may play a critical role in the shift of pregnant uteri from proliferative to hypertrophic states. PMID:16470654

  8. Female-specific hypertension loci on rat chromosome 13

    PubMed Central

    Hoffman, Matthew J.; Flister, Michael J.; Nunez, Lizbeth; Xiao, Bing; Greene, Andrew S.; Jacob, Howard J.; Moreno, Carol

    2013-01-01

    A 3.7 Mb region of rat chromosome 13 (45.249.0 Mb) affects blood pressure (BP) in females only, indicating the presence of gender-specific BP loci in close proximity to the Renin locus. In the present study, we used a series of Dahl salt-sensitive/Mcwi (SS)-13 Brown Norway (BN) congenic rat strains to further resolve BP loci within this region. We identified 3 BP loci affecting female rats only, of which the 2 smaller loci (line9BP3 and line9BP4) were functionally characterized by sequence and expression analysis. Compared with SS, the presence of a 591 Kb region of BN chromosome 13 (line9BP3) significantly lowered BP by 21 mmHg on an 8% NaCl diet (1537 vs 1745 mmHg, P<0.001). Unexpectedly, the addition of 23 Kb of BN chromosome 13 (line9BP4) completely erased the female-specific BP protection on 8% NaCl diet, suggesting that BN hypertensive allele(s) reside in this region. The congenic interval of the protective line 9F strain contains 3 genes (Optc, Prelp, and Fmod) and the hypertensive line 9E contains 1 additional gene (Btg2). Sequence analysis of the 2 BP loci revealed a total of 282 intergenic variants, with no coding variants. Analysis of gene expression by RT-qPCR revealed strain- and gender-specific differences in Prelp, Fmod, and Btg2 expression, implicating these as novel candidate genes for female-specific hypertension. PMID:23817491

  9. Maternal taurine supplementation in the late pregnant rat stimulates postnatal growth and induces obesity and insulin resistance in adult offspring

    PubMed Central

    Hultman, Karin; Alexanderson, Camilla; Mannerås, Louise; Sandberg, Mats; Holmäng, Agneta; Jansson, Thomas

    2007-01-01

    An adequate supply of taurine during fetal life is important for normal beta-cell development and insulin action. An altered availability of taurine may programme glucose metabolism in utero and result in type 2 diabetes in adult age. We examined whether maternal taurine supplementation in late pregnant rats affects postnatal growth, adult body composition, insulin sensitivity and endogenous insulin secretion in intrauterine growth restricted (IUGR) and normal offspring. Uterine artery ligation or sham operations were performed on gestational day (GD) 19. Taurine supplementation was given to half of the dams from GD 18 until term, resulting in four groups of offspring: sham (n = 22), sham/taurine (n = 22), IUGR (n = 22) and IUGR/taurine (n = 24). The offspring were studied at 12 weeks of age. In offspring with normal birth weight, fetal taurine supplementation markedly stimulated postnatal growth. In sham/taurine females, fat depots, plasma free fatty acid and leptin concentrations were increased, and insulin sensitivity was reduced. Insulin sensitivity was unaltered in IUGR and IUGR/taurine offspring. However, whereas IUGR offspring showed little catch-up growth, 50% of IUGR/taurine animals displayed complete catch-up at 12 weeks of age, and these animals had increased fat depots and reduced insulin sensitivity. In conclusion, taurine supplementation in late gestation resulted in accelerated postnatal growth, which was associated with adult obesity and insulin resistance in both IUGR and normal offspring. This effect was particularly evident in females. These data suggest that fetal taurine availability is an important determinant for postnatal growth, insulin sensitivity and fat accumulation. PMID:17204495

  10. Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression.

    PubMed

    Gilbert, Jeffrey S; Gilbert, Sara A B; Arany, Marietta; Granger, Joey P

    2009-02-01

    Recent clinical studies indicate that an excess of angiostatic factors, such as soluble endoglin (sEng), is related to the occurrence of preeclampsia. Although recent clinical studies report that sEng is increased in preeclamptic women, the mechanisms underlying its overexpression remain unclear. Evidence suggests that hypoxia and induction of heme oxygenase-1 have opposing effects on sEng expression, the former stimulatory and the latter inhibitory. Hence, we hypothesized that placental ischemia because of reduced uterine perfusion pressure (RUPP) in the pregnant rat would increase sEng expression and decrease heme oxygenase-1. Mean arterial pressure was obtained via arterial catheter, and serum and placental proteins were measured by Western blot. Mean arterial pressure was increased (132+/-3 mm Hg versus 102+/-2 mm Hg; P<0.001), and fetal (2.35+/-0.05 g versus 1.76+/-0.08 g; P<0.001) and placental weight were decreased (0.47+/-0.04 g versus 0.58+/-0.03 g; P<0.01) in the RUPP compared with normal pregnant controls. Serum sEng (0.10+/-0.02 arbitrary pixel units [apu] versus 0.05+/-0.01 apu; P<0.05) and placental endoglin (4.7+/-2.3 apu versus 1.45+/-0.42 apu; P<0.05) were increased along with placental hypoxia inducible factor-1 alpha (1.42+/-0.25 apu versus 0.68+/-0.09 apu; P<0.05) expression in the RUPP versus the normal pregnant dams. Placental HO-1 (1.4+/-0.3 apu versus 2.5+/-0.1 apu; P<0.05) expression decreased in the RUPP compared with normal pregnant dams. The present findings support our hypothesis that placental ischemia because of RUPP increases the expression of sEng and shifts the balance of angiogenic factors in the maternal circulation toward an angiostatic state. The present study provides further evidence that placental ischemia is a strong in vivo stimulus of angiostatic factors during pregnancy. PMID:19075097

  11. Experimental analysis of the relationship between simulated low-velocity rear-end collisions and fetal outcomes of pregnant rats.

    PubMed

    Hitosugi, Masahito; Motozawa, Yasuki; Kawato, Hitoshi; Nagai, Toshiaki; Tokudome, Shogo

    2009-07-01

    Our study aimed to define the risk for a human fetus of rear-end vehicle collisions. We therefore performed drop tests using pregnant SLC Wistar rats. Pressure applied to the rat uterus and rectum at various stages of acceleration was measured. After being dropped, rats were observed throughout pregnancy. At birth, the numbers, weight and the occurrence of physical anomalies among pups were followed-up for 28 days. Uterine pressure increased exponentially from 2.1 +/- 0.3 kPa at 19-fold gravity (G) to 13.9 +/- 0.8 kPa at 92-fold G. These values are much lower than the mechanical failure level of human fetal membrane tissue or of those at risk of adverse fetal outcomes. Neither the average number of offspring per pregnant rat nor the average body weight of newborn pups differed significantly between control pregnant rats and those which had been exposed to acceleration of 46-fold or 92-fold G. Other variables such as maternal mental distress, motion effects of amniotic fluid or seatbelt-induced uterine injuries might contribute to fetal loss. PMID:19787994

  12. Effects of d- and l-limonene on the pregnant rat myometrium in vitro

    PubMed Central

    Hajagos-Tóth, Judit; Hódi, Ágnes; Seres, Adrienn B.; Gáspár, Róbert

    2015-01-01

    Aim To study the effects of d- and l-limonene on pregnant rat myometrial contractility in vitro, and investigate how these effects are modified by other agents. D- and l-limonene (10−13-10−8 M) caused myometrial contraction in a dose-dependent manner. Methods Contractions of uterine rings from 22-day-pregnant rats were measured in an organ bath in the presence of d- or l-limonene (10−13-10−8 M) and nifedipine (10−8 M), tetraethyl-ammonium (10−3 M), theophylline (10−5 M), or paxilline (10−5 M). Uterine cyclic adenosine monophosphate (cAMP) level was detected by enzyme immunoassay. Oxidative damage was induced by methylglyoxal (3 × 10−2 M) and the alteration was measured via noradrenaline (1 × 10−9 to 3 × 10−5 M) -induced contractions. Results Pre-treatment with nifedipine (10−8 M), tetraethylammonium (10−3 M), and theophylline (10−5 M) attenuated the contracting effect of d- and l-limonene, while in the presence of paxilline (10−5 M) d- and l-limonene were ineffective. The two enantiomers decreased the myometrial cAMP level, but after paxilline pretreatment the cAMP level was not altered compared with the control value. Additionally, l-limonene (10−6 M) diminished consequences of oxidative damage caused by methylglyoxal (3 × 10−2 M) on contractility, whereas d-limonene was ineffective. Conclusion Our findings suggest that l-limonene has an antioxidant effect and that both d-and l-limonene cause myometrial contraction through activation of the A2A receptor and opening of the voltage-gated Ca2+ channel. It is possible that limonene-containing products increase the pregnant uterus contractility and their use should be avoided during pregnancy. PMID:26526880

  13. Effects of Perinatal Polychlorinated Biphenyls on Adult Female Rat Reproduction: Development, Reproductive Physiology, and Second Generational Effects

    PubMed Central

    Steinberg, Rebecca M.; Walker, Deena M.; Juenger, Thomas E.; Woller, Michael J.; Gore, Andrea C.

    2009-01-01

    Perinatal exposures to endocrine-disrupting chemicals such as polychlorinated biphenyls (PCBs) can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally-exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture Aroclor (A) 1221 (0, 0.1, 1 or 10 mg/kg) on embryonic days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed towards females. In the F1 generation, additional effects were found including a significant alteration of serum luteinizing hormone (LH) in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been perinatally exposed to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared to F2 decendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant consequences on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans. PMID:18305224

  14. Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

    NASA Technical Reports Server (NTRS)

    Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

    2002-01-01

    During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

  15. Somatomotor and sensory urethral control of micturition in female rats.

    PubMed

    Cruz, Yolanda; Pasteln, Csar; Balog, Brian M; Zaszczurynski, Paul J; Damaser, Margot S

    2014-12-01

    In rats, axons of external urethral sphincter (EUS) motoneurons travel through the anastomotic branch of the pudendal nerve (ABPD) and anastomotic branch of the lumbosacral trunk (ABLT) and converge in the motor branch of the sacral plexus (MBSP). The aim of the present study was to determine in female rats the contribution of these somatomotor pathways and urethral sensory innervation from the dorsal nerve of the clitoris on urinary continence and voiding. EUS electromyographic (EMG) activity during cystometry, leak point pressure (LPP), and voiding efficiency (VE) were assessed in anesthetized virgin Sprague-Dawley female rats before and after transection of the above nerve branches. Transection of the MBSP eliminated EUS EMG, decreased LPP by 50%, and significantly reduced bladder contraction duration, peak pressure, intercontraction interval, and VE. Transection of the ABPD or ABLT decreased EUS EMG discharge and LPP by 25% but did not affect VE. Transection of the dorsal nerve of the clitoris did not affect LPP but reduced contraction duration, peak pressure, intercontraction interval, and VE. We conclude that somatomotor control of micturition is provided by the MBSP with axons travelling through the ABPD and ABLT. Partial somatomotor urethral denervation induces mild urinary incontinence, whereas partial afferent denervation induces voiding dysfunction. ABPD and ABLT pathways could represent a safeguard ensuring innervation to the EUS in case of upper nerve damage. Detailed knowledge of neuroanatomy and functional innervation of the urethra will enable more accurate animal models of neural development, disease, and dysfunction in the future. PMID:25339694

  16. Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats

    PubMed Central

    Pyter, Leah M.; Bih, Sarah El Mouatassim; Sattar, Husain; Prendergast, Brian J.

    2014-01-01

    Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization, or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250 ?g/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1?], CD11b, I?B?, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24 h post-treatment. In the absence of LPS, hippocampal Il-1? and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1? and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, I?B? was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences. PMID:24457042

  17. Plasma amino acid profiles at various reproductive stages in female rats

    PubMed Central

    OKAME, Rieko; NAKAHARA, Keiko; MURAKAMI, Noboru

    2015-01-01

    We measured the plasma levels of amino acids at various reproductive stages in female rats, including the estrous cycle, pregnancy and lactation, and compared the resulting amino acid profiles using two- or three-dimensional figures. These figures revealed that the amino acid profiles of pregnant and lactating dams differed considerably from those during the estrous cycle or in male rats. The plasma levels of individual amino acids were almost the same between proestrus, estrus, metestrus and diestrus, and their profiles did not differ significantly. However, the amino acid profiles changed during pregnancy and lactation in dams. The plasma Ser level decreased significantly in mid and late pregnancy, whereas Tyr, Gly and His decreased significantly in the late and end stages of pregnancy, and Trp and Lys significantly decreased and increased at the end of pregnancy, respectively. Much larger changes in amino acid profiles were observed during lactation, when the levels of many amino acids increased significantly, and none showed a significant decrease. Plasma Pro, Ser and Gly levels increased continuously from day 1 until day 15 of lactation, whereas Asn and Met increased significantly from days 1 and 5 respectively until the end of lactation. These results suggest that the profiles of plasma amino acids show characteristic changes according to reproductive stage and that it may be necessary to consider such differences when performing amino acid-based diagnosis. PMID:25787929

  18. Prior access to a sweet is more protective against cocaine self-administration in female rats than male rats

    PubMed Central

    Cason, Angie M.; Grigson, Patricia S.

    2013-01-01

    It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson & Twining, 2002). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior. PMID:23474135

  19. Quantitative alterations in the liver and adrenal gland in pregnant rats induced by Pyralene 3000

    SciTech Connect

    Vreci, M.; Sek, S.; Lorger, J.; Bavdek, S.; Pogacnik, A.

    1995-06-01

    Polychlorinated biphenyls (PCBs) are among the most widespread environmental pollutants known in the world. The half-life of PCBs is very long and, therefore, once released into the environment, they accumulate in food chains and tissues of various mammals, including man. Their presence can cause numerous toxic effects, e.g., hepatotoxicity, immunotoxicity, dermatotoxicity, neurotoxicity, and disorders of the reproductive system, among others. These effects depend on the distribution route in the organism, the rate of metabolism and excretion. Their characteristics are closely associated with the number and position of the chlorine atoms in the molecule. Previous studies of trichlorobiphenyl distributions in various tissues demonstrated that low chlorinated trichlorobiphenyls do no accumulate in endocrine organs, whereas higher chlorinated biphenyls, such as hexa- and octachlorobiphenyl, are deposited and retained in the adrenal gland. A selective distribution of radioabelled tetrachlorobiphenyl to the zona fasciculata, accompanied by morphometric evidence of the hypertrophy of the zona fasciculata, was also noted. The purpose of this study was to examine changes in the tissue structure of the pregnant rat liver and adrenal gland induced experimentally by Pyralene 3000 administration. We chose this commercial low chlorinated PCB because it was in use in Slovenia and, discharged from the electroindustrial plants, caused a serious incidence of environmental pollution in the region of Bela Krajina. Our further aim was to research the transplacental influences of Pyralene 3000 in rats. 17 refs., 1 fig., 3 tabs.

  20. The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development

    NASA Astrophysics Data System (ADS)

    Ladd, B.; Nguon, K.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation during the same period are not affected. This study suggests that while pregnancy can proceed under altered gravity, exposure to hypergravity affects pregnant dams, pregnancy outcome and the developing fetus as well as nursing dams and neonates and raises an important question whether the mammalian system possess a gravisensing ability.

  1. LHRH and LH in peripubertal female rats following prenatal and/or postnatal ethanol exposure

    SciTech Connect

    Morris, D.L.; Harms, P.G.; Petersen, H.D.; McArthur, N.H.

    1989-01-01

    The effects of pre- and postnatal exposure to ethanol (ETHO) on LHRH and LH were investigated. Pregnant and/or lactating dams were fed ETHOD during: (1) gestation, (2) lactation, or (3) gestation-lactation. Female offspring were decapitated at 30 or 40 days-of-age; trunk blood was collected for plasma LH RIA; and hypothalamic tissues were collected for LHRH RIA. Hypothalamic LHRH content of all ETOH-exposed groups was less than that of non-ETOH-fed controls at 30 and 40 days-of-age. Plasma LH concentrations of all ETOH-exposed groups were less than those of non-ETOD-fed controls at 30 and 40 days-of-age. Also, at 30 and 40 days-of-age, the plasma LH concentrations of the animals exposed to ETOH during lactation and gestation-lactation were less than those of the animals exposed to ETOH during gestation. These data suggest that ETOH exposure during gestation and/or lactation negatively affects hypothalamic LHRH content of femal rat offspring. Decreased hypothalamic LHRH content with corresponding lowered plasma LH concentration suggests that ETOH influences development or maturation of hypothalamic LHRH neurons by possibly decreasing their number or synthesizing capability.

  2. Intrauterine growth restriction transiently delays alveolar formation and disrupts retinoic acid receptor expression in the lung of female rat pups

    PubMed Central

    Yang, Yan; Fitzhugh, Melanie; Metcalfe, Drew; Oman, Jake; Hale, Merica; Dong, Li; Wang, Zheng-Ming; Yu, Xing; Callaway, Christopher W.; O'Brien, Elizabeth; McKnight, Robert A.; Lane, Robert H.; Albertine, Kurt H.

    2014-01-01

    Background We showed that intrauterine growth restriction (IUGR) increases distal airspace wall thickness at birth (postnatal age 0; P0) in rat pups (saccular stage of lung development). However, that report did not assess whether the saccular phenotype persisted postnatally or occurred in males or females. Nor did that report identify a potential molecular pathway for the saccular phenotype at P0. We hypothesized that IUGR persistently delays alveolar formation and disrupts retinoic acid receptor (RAR) mRNA and protein levels in the lung of rat pups in postnatal age- and sex-specific manners. Methods IUGR was induced in pregnant rats by bilateral uterine artery ligation. Alveolar formation and expression of RAR?, ?, and ? were quantified at P0, P6 (alveolar stage), and P21 (postalveolarization). Results IUGR increased distal airspace wall thickness in female pups at P0 only. IUGR did not affect male pups at any age. IUGR transiently increased lung RAR? protein abundance, which inhibits alveolar formation, at P0 in female pups. Serum retinol concentration was normal at all ages. Conclusions IUGR alone is not sufficient to persistently delay postnatal alveolar formation or disrupt expression RARs. We speculate that for IUGR to delay alveolar formation postnatally, a second insult is necessary. PMID:23419538

  3. Fetal translocation and metabolism of PAH obtained from coal fly ash given intratracheally to pregnant rats

    SciTech Connect

    Srivastava, V.K.; Chauhan, S.S.; Srivastava, P.K.; Kumar, V.; Misra, U.K.

    1986-01-01

    Polycyclic aromatic hydrocarbons (PAH) were extracted from coal fly ash collected from the electrostatic precipitator of a thermal power plant. The PAH extract was given intratracheally daily to pregnant rats (2 mg/100 g body weight) on d 18 and 19 of gestation. In addition of d 19 of gestation rats were also given (/sup 4/H)benzo(a)pyrene intratracheally. Rats were sacrificed on d 20 of gestation, and the distribution of (/sup 3/H)benzo(a)pyrene radioactivity and PAH of coal fly ash was studied in maternal lung, liver, and placenta, as well as in the liver and lung of the fetus. The radioactivity of intratracheally given benzo(a)pyrene was found in liver (68%), placenta (4%), fetal lung (1.9%), and fetal liver (1.4%) of maternal lung. Intratracheally administered PAH of coal fly ash were translocated to maternal liver and placenta, as well as to the liver and lung of the fetus. PAH of coal fly ash were also metabolized to several minor and major metabolites by maternal lung, liver, and placenta, as well as by the maternal fetal liver and lung. Some of the PAH metabolites in lung and liver were common; however, the major metabolite of liver, M-16, was different from the major metabolite M-16 of lung. The major PAH metabolite of placenta, M-15, and fetal liver, F-12, were common PAH metabolites. M-2 and M-6 of the placenta and F-5 and F-10 of the fetal lung were also common.

  4. Vulnerability to (+)-Methamphetamine Effects and the Relationship to Drug Disposition in Pregnant Rats during Chronic Infusion

    PubMed Central

    White, Sarah J.; Laurenzana, Elizabeth M.; Gentry, William Brooks; Hendrickson, Howard P.; Williams, David Keith; Ward, Keith W.; Owens, Samuel Michael

    2009-01-01

    Chronic (+)-methamphetamine (METH) use during pregnancy increases the health risk for both mother and fetus. To provide insights into these risks, the relationship between changes in METH disposition and METH-induced pharmacological effects were studied in Sprague-Dawley rat dams and litters. Timed-pregnant rats (n = 56) were given saline or METH (5.617.8 mg/kg/day) by continuous sc infusion from gestational day (GD) 7 (before organogenesis) until GD21 (02 days before delivery). By GD11, all rats in the 17.8-mg/kg/day group died or were sacrificed for humane reasons. There were significant (p < 0.05) dose- and gestational time-dependent decreases in maternal body weight in the 10- to 13.2-mg/kg/day groups, which slowly recovered to near normal by GD21. Continued METH dosing in the surviving groups did not affect the mean pups/litter weight at the end of the experiment on GD21. While maternal and fetal METH and (+)-amphetamine serum concentrations were similar on GD21, brain concentrations were significantly greater in the dams (p < 0.05). Importantly, brain-to-serum ratios in the dams were 9:1 and 3:1 in the pups. METH systemic clearance (ClS) in dams significantly (p < 0.05) decreased from 52 14 ml/min/kg on GD10 to 28 6 ml/min/kg on GD21 in all dose groups, indicating late-gestational stage reductions in METH ClS. Overall, these findings suggest that there were two periods of increased susceptibility for dams and fetuses during chronic METH treatment. First was the period after the start of METH dosing in which neuroadaptation and tolerance to METH occurs in the adult. The second was at the end of pregnancy when METH clearance was significantly reduced. PMID:19520673

  5. The effects of N-acetyl-l-cysteine on the female reproductive performance and nephrotoxicity in rats.

    PubMed

    Helal, Mona A M

    2016-03-01

    This study was designed to investigate whether the treatment with the N-acetyl-l-cysteine prior to the administration of chemotherapy drug would prevent from nephrotoxicity and the loss of reproductive performance induced from chemotherapy treatment. Female rats were divided into five equal groups of six each: 1/control group; 2/rats i.p administered saline solution; 3/rats i.p administered holoxan (50 mg/kg b.wt); 4/rats i.p administered N-acetyl-l-cysteine (160 mg/kg b.wt); 5/rats i.p administered holoxan and N-acetyl-l-cysteine at the same doses. After medications, females rats were allowed to mate with males and the pregnant rats were sacrificed on day 18 of gestation. Premating treatment with holoxan showed reduction (p < 0.05) in reproductive performance. Whereas administration of N-acetyl-l-cysteine prior to treatment with holoxan and then concurrently with it modulated significantly fertility index, progesterone level, decreasing postimplantation loss, resorbed fetuses and improved fetal growth. Additionally, holoxan elevated the renal nicotinamide dinucleotide phosphate (NADPH) oxidase activity, oxidative stress, renal functions and caused histological changes in renal tissue. N-Acetyl-l-cysteine treatment reduced (p < 0.05) renal tissue NADPH oxidase, nitric oxide, malondialdehyde and improved super oxide dismutase (SOD) depletion, elevated levels phosphate, total protein and calcium as well as prevented renal histological damages. N-Acetyl-l-cysteine can confer protection against nitrosative and oxidative stresses in renal tissue induced by holoxan by suppressing NADPH oxidase activation, malondialdehyde, nitric oxide and restoring SOD activity which led to the reduction of reactive oxygen species production and subsequently might effectively improve the gonadal hormone disturbance and reproductive functions. PMID:26837610

  6. Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in pregnant rats and the placental transfer to fetuses.

    PubMed Central

    Takahashi, O; Oishi, S

    2000-01-01

    We studied the disposition of bisphenol A (BPA) in pregnant female F344/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36 microg/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the maximum 6 hr after the administration. The maximal concentration of BPA in fetuses (9 microg/g) was also attained 20 min after the administration. BPA levels then gradually reduced in a similar manner to maternal blood. These results suggest that the absorption and distribution of BPA in maternal organs and fetuses are extremely rapid and that the placenta does not act as a barrier to BPA. PMID:11049811

  7. 2-HYDROXYESTRADIOL ENHANCES BINGE ONSET IN FEMALE RATS AND REDUCES PREFRONTAL CORTICAL DOPAMINE IN MALE RATS

    PubMed Central

    R.K., Babbs; E.L., Unger; R.L.W., Corwin

    2013-01-01

    Women are more likely to suffer from a bingeing-related eating disorder, which is surprising, since estradiol reduces meal size and is associated with reduced binge frequency. This apparent contradiction may involve the estradiol metabolite, 2-hydroxyestradiol. We previously reported that female rats had faster escalations in shortening intake during the development of bingeing than did males, but acute administration of 2-hydroxyestradiol increased the intake of vegetable shortening to a greater extent in male rats once bingeing was established. Here, we report two separate studies that follow up these previous findings. In the first, we hypothesized that chronic exposure to 2-hydroxyestradiol would promote escalation of bingeing during binge development in ovariectomized female rats. In the second, we hypothesized that acute exposure to 2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex after bingeing was established in male rats. In study 1, non-food-deprived female rats were separated into 3 groups: ovariectomized (OVX) with chronic 2-hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and intact with vehicle (I). Each group was given access to an optional source of dietary fat (shortening) on Mon, Wed, and Fri for four weeks. 2-hydroxyestradiol supplementation prevented OVX-induced weight gain and enhanced escalation of shortening intake over the four-week period (ps < 0.05). Additionally, in week 4, rats in the E group ate significantly more shortening than I controls, less chow than either the O or I group, and had a higher shortening to chow ratio than O or I (ps < 0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing male rats (p < 0.05). Together, these studies indicate that 2-hydroxyestradiol can exacerbate bingeing as it develops and can suppress dopamine signaling in the prefrontal cortex once bingeing is established. PMID:23116652

  8. 2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal cortical dopamine in male rats.

    PubMed

    Babbs, R K; Unger, E L; Corwin, R L W

    2013-01-01

    Women are more likely to suffer from a bingeing-related eating disorder, which is surprising, since estradiol reduces meal size and is associated with reduced binge frequency. This apparent contradiction may involve the estradiol metabolite, 2-hydroxyestradiol. We previously reported that female rats had faster escalations in shortening intake during the development of bingeing than did males, but acute administration of 2-hydroxyestradiol increased the intake of vegetable shortening to a greater extent in male rats once bingeing was established. Here, we report two separate studies that follow up these previous findings. In the first, we hypothesized that chronic exposure to 2-hydroxyestradiol would promote escalation of bingeing during binge development in ovariectomized female rats. In the second, we hypothesized that acute exposure to 2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex after bingeing was established in male rats. In study 1, non-food-deprived female rats were separated into 3 groups: ovariectomized (OVX) with chronic 2-hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and intact with vehicle (I). Each group was given access to an optional source of dietary fat (shortening) on Mon, Wed, and Fri for 4 weeks. 2-hydroxyestradiol supplementation prevented OVX-induced weight gain and enhanced escalation of shortening intake over the four-week period (ps<0.05). Additionally, in week 4, rats in the E group ate significantly more shortening than I controls, less chow than either the O or I group, and had a higher shortening to chow ratio than O or I (ps<0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing male rats (p<0.05). Together, these studies indicate that 2-hydroxyestradiol can exacerbate bingeing as it develops and can suppress dopamine signaling in the prefrontal cortex once bingeing is established. PMID:23116652

  9. Pancreatic functions in high salt fed female rats

    PubMed Central

    Lasheen, Noha N

    2015-01-01

    Salt consumption has been increased worldwide and the association of high salt diets with enhanced inflammation and target organ damage was reported. Little data were available about the effect of high salt diet on exocrine function of pancreas, while the relation between high salt intake and insulin sensitivity was controversial. This study was designed to investigate the effect of high salt diet on exocrine and endocrine pancreatic functions, and to elucidate the possible underlying mechanism(s). Twenty adult female Wistar rats were randomly divided into two groups; control group; fed standard rodent diet containing 0.3% NaCl, and high salt fed group; fed 8% NaCl for 8 weeks. On the day of sacrifice, rats were anesthized by i.p. pentobarbitone (40 μg/kg B.W.). Nasoanal length was measured and fasting blood glucose was determined from rat tail. Blood samples were obtained from abdominal aorta for determination of plasma sodium, potassium, amylase, lipase, aldosterone, insulin, transforming growth factor-β (TGF-β1), and interleukin 6 (IL6). Pancreata of both groups were histologically studied. Compared to control group, 8-week high salt fed group showed: significant elevation in body weight, body mass index, Lee index, plasma sodium, TGF-β1 and IL6, however, plasma aldosterone, amylase, lipase, and insulin levels were significantly decreased. A nonsignificant increase in plasma potassium and nonsignificant changes in fasting blood glucose and HOMA-IR were detected between groups. Pancreatic fibrosis was observed in test group. High salt diet for 8 weeks caused pancreatic fibrosis evidenced by decline of both exocrine and endocrine functions of pancreas in Wistar rats. PMID:26216433

  10. Zinc Insufficiency Mediates Ethanol-Induced Alveolar Macrophage Dysfunction in the Pregnant Female Mouse

    PubMed Central

    Konomi, Juna V.; Harris, Frank L.; Ping, Xiao-Du; Gauthier, Theresa W.; Brown, Lou Ann S.

    2015-01-01

    Aims: (a) Establish the minimum number of weeks of chronic ethanol ingestion needed to perturb zinc homeostasis, (b) Examine intracellular zinc status in the alveolar macrophages (AMs) when ethanol ingestion is combined with pregnancy, (c) Investigate whether in vitro zinc treatment reverses the effects of ethanol ingestion on the AM. Methods: C57BL/6 female mice were fed a liquid diet (25% ethanol-derived calories) during preconception and pregnancy. The control group was pair-fed to the ethanol group. In the isolated AMs, we measured intracellular AM zinc levels, zinc transporter expression, alternative activation and phagocytic index. Zinc acetate was added to some cells prior to analysis. Results: Intracellular zinc levels in the AM decreased within 3 weeks of ethanol ingestion. After ethanol ingestion prior to and during pregnancy, zinc transporter expression and intracellular zinc levels were decreased in the AMs when compared with controls. Bacterial clearance was decreased because the AMs were alternatively activated. In vitro additions of zinc reversed these effects of ethanol. Conclusion: Ethanol ingestion prior to and during pregnancy perturbed AM zinc balance resulting in impaired bacterial clearance, but these effects were ameliorated by in vitro zinc treatments. PMID:25371044

  11. Appearance of circulating and tissue /sup 14/C-lipids after oral /sup 14/C-tripalmitate administration in the late pregnant rat

    SciTech Connect

    Argiles, J.; Herrera, E.

    1989-02-01

    Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.

  12. Blood boron concentrations in pregnant rats fed boric acid throughout gestation.

    PubMed

    Price, C J; Strong, P L; Murray, F J; Goldberg, M M

    1997-01-01

    Timed-mated Sprague-Dawley rats (28 to 32/group) were exposed to boric acid (BA) in the diet from Gestational Day (GD) 0 to 20. Dietary concentrations of added BA (0%, 0.025%, 0.050%, 0.075%, 0.100%, or 0.200%) yielded average daily intakes equivalent to 0, 3, 6, 10, 13, or 25 mg boron/kg body weight/d. Dams and their fetuses were evaluated for evidence of maternal or developmental toxicity, as reported previously. At termination on GD 20, maternal whole blood was collected in heparinized Vacutainer tubes, stored frozen (-20 degrees C), and subsequently prepared by a high-temperature alkaline ashing procedure for analysis of boron by inductively coupled plasma optical emission spectrometry. Increasing dietary concentrations of BA were positively associated with whole blood boron concentrations in confirmed pregnant rats, specifically 0.229 +/- 0.143, 0.564 +/- 0.211, 0.975 +/- 0.261, 1.27 +/- 0.298, 1.53 +/- 0.546, or 2.82 +/- 0.987 micrograms boron/g whole blood (mean +/- SD) for the control through high-dose groups. Maternal blood boron concentrations were positively correlated with indices of maternal dietary intake of boron and with embryo/fetal toxicity observed at 0.100% and 0.200% BA in the diet reported previously. Thus, blood boron concentrations of 1.27 +/- 0.298 and 1.53 +/- 0.546 micrograms boron/g were associated with the no-observed-adverse-effect level (10 mg boron/kg/d) and lowest-observed-adverse-effect level (13 mg boron/kg/d) for developmental toxicity reported previously. PMID:9407594

  13. Effect of sub-lethal doses of Bacillus thuringiensis subsp. Aizawai and deltamethrin with regard to fertility and organ toxicity in pregnant albino rats.

    PubMed

    Lemos, Ana Janaina J M; Siqueira, Herbert A A; Wanderley-Teixeira, Valria; Maia, Frederico C L; Teixeira, lvaro A C; Silva, Edson J; Oliveira, Jos V

    2013-07-01

    Products with Bacillus thuringiensis (Bt) and synthetic insecticides have been widely used against important vectors of human diseases. However, few studies have addressed the application of these substances on the female reproduction apparatus during pregnancy at doses that do not cause clinical symptoms of intoxication. Seventy pregnant albino rats were analyzed with regard to fertility and histopathology of the kidneys, liver and lungs as well as the morphology of the neonates. The rats were submitted to three sub-lethal doses of the biological insecticide XenTari() WG (B. thuringiensis subsp. Aizawai) and the synthetic insecticide deltamethrin (Decis() 25CE). After the confirmation of copulation, the insecticides were administered orally for either seven days or during the entire pregnancy. The analysis revealed histopathological alterations in all organs analyzed in both treatments. No miscarriages occurred and the neonates did not exhibit signs of malformation of the head, limbs, thorax or abdomen. However, there were a smaller number of pups in the groups that received higher doses of the insecticides in comparison to the control group. Both insecticides produced similar lesions in the kidneys, liver and lungs and reduced the fertility of rats when administered at sub-lethal doses with no clinical signs of intoxication. Thus, this study suggests that sublethal doses of both insecticides can provide chronic toxicity in humans. PMID:22436576

  14. Prenatal Testosterone Induces Sex-Specific Dysfunction in Endothelium-Dependent Relaxation Pathways in Adult Male and Female Rats1

    PubMed Central

    Chinnathambi, Vijayakumar; Yallampalli, Chandrasekhar; Sathishkumar, Kunju

    2013-01-01

    ABSTRACT Prenatal testosterone (T) exposure impacts postnatal cardiovascular function, leading to increases in blood pressure with associated decreased endothelium-dependent vascular relaxation in adult females. Endothelial function in males is not known. Furthermore, which of the endothelial pathways contributes to endothelial dysfunction and if there exists sex differences are not known. The objective of this study was to characterize the relative contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the impaired endothelium-dependent vasodilation in prenatal T-exposed adult males and females. Offspring of pregnant rats treated with T propionate or its vehicle were examined. Telemetric blood pressure levels and endothelium-dependent vascular reactivity were assessed with wire myography. Levels of nitric oxide synthase (NOS3) and Kcnn3 and Kcnn4 channel expression were examined in mesenteric arteries. Mean arterial pressure was significantly higher in T males and females than in controls. Endothelium-dependent acetylcholine relaxation was significantly lower in both T males and females. EDHF-mediated relaxation was specifically blunted in T males (Emax = 48.64% 3.73%) compared to that in control males (Emax = 81.71% 3.18%); however, NO-mediated relaxation was specifically impaired in T females (Emax = 36.01% 4.29%) compared with that in control females (Emax = 54.56% 6.37%). Relaxation to sodium nitroprusside and levcromakalim were unaffected with T-treatment. NOS3 protein was decreased in T females but not in T males. Kcnn3 expression was decreased in both T males and females compared to controls. These findings suggest that prenatal T leads to an increase in blood pressure in the adult offspring, associated with blunting of endothelial cell-associated relaxation and that the effects are sex-specific: EDHF-related in males and NO-related in females. PMID:23966325

  15. The disposition of /sup 14/C-trimethyltin in the pregnant rat and fetus

    SciTech Connect

    Lipscomb, J.C.; Paule, M.G.; Slikker, W. Jr.

    1989-03-01

    Trimethyltin (TMT) is a potent neurotoxicant. For unknown reasons, age at exposure to TMT may dramatically influence the severity of TMT-induced neuropathology. We have demonstrated previously that radiolabel derived from (/sup 14/C)-TMT given to pregnant dams on gestational day (GD) 17 is found in fetal brain and blood. The present study was designed to determine the distribution of radiolabel derived from (14C)-TMT to brain and other tissue in fetuses from dams dosed on either GD 12 or 17 with 7.0 mg/kg TMT chloride. Radioactivity in GD 12 and GD 17 maternal whole blood peaked 1 hour after IP treatment. Whole blood elimination half-lives were 12-15 days. Peak radiolabel concentrations in GD 12 maternal and fetal brain were only 11-30% of those from GD 17 animals, however, peak fetal brain concentrations of radiolabel were not different from their respective maternal brain concentrations. Radiolabel concentrations in liver, kidney, and adrenal of GD 17 dams were higher than those in corresponding GD 12 tissues. Combined urinary and fecal elimination of radiolabel for two weeks after dosing accounted for 31 and 22% of the GD 12 and 17 doses, respectively. It appears that gestational age influences the distribution and elimination of TMT in the rat.

  16. Fate of orally administered radioactive fatty acids in the late-pregnant rat.

    PubMed

    López-Luna, Pilar; Ortega-Senovilla, Henar; López-Soldado, Iliana; Herrera, Emilio

    2016-03-01

    To investigate the biodisponibility of placental transfer of fatty acids, rats pregnant for 20 days were given tracer amounts of [(14)C]palmitic (PA), oleic (OA), linoleic (LA), α-linolenic (LNA), or docosahexaenoic acid (DHA) orally and euthanized at 0.5, 1.0, 2.0, or 8.0 h thereafter. Maternal plasma radioactivity in lipids initially increased only to decline at later times. Most of the label appeared first as triacylglycerols (TAG); later, the proportion in phospholipids (PhL) increased. The percentage of label in placental lipids was also always highest shortly after administration and declined later; again, PhL increased with time. Fetal plasma radioactivity increased with time, with its highest value at 8.0 h after DHA or LNA administration. DHA initially appeared primarily in the nonesterified fatty acids (NEFA) and PA, OA, LA, and LNA as TAG followed by NEFA; in all cases, there was an increase in PhL at later times. Measurement of fatty acid concentrations allowed calculation of specific (radio)activities, and the ratio (fetal/maternal) of these in the plasmas gave an index of placental transfer activity, which was LNA > LA > DHA = OA > PA. It is proposed that a considerable proportion of most fatty acids transferred through the placenta are released into the fetal circulation in the form of TAG. PMID:26714850

  17. Clinostat rotation induces apoptosis in luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Yang, Hyunwon; Bhat, Ganapathy K.; Sridaran, Rajagopala

    2002-01-01

    Recent studies have shown that microgravity induces changes at the cellular level, including apoptosis. However, it is unknown whether microgravity affects luteal cell function. This study was performed to assess whether microgravity conditions generated by clinostat rotation induce apoptosis and affect steroidogenesis by luteal cells. Luteal cells isolated from the corpora lutea of Day 8 pregnant rats were placed in equal numbers in slide flasks (chamber slides). One slide flask was placed in the clinostat and the other served as a stationary control. At 48 h in the clinostat, whereas the levels of progesterone and total cellular protein decreased, the number of shrunken cells increased. To determine whether apoptosis occurred in shrunken cells, Comet and TUNEL assays were performed. At 48 h, the percentage of apoptotic cells in the clinostat increased compared with that in the control. To investigate how the microgravity conditions induce apoptosis, the active mitochondria in luteal cells were detected with JC-1 dye. Cells in the control consisted of many active mitochondria, which were evenly distributed throughout the cell. In contrast, cells in the clinostat displayed fewer active mitochondria, which were distributed either to the outer edge of the cell or around the nucleus. These results suggest that mitochondrial dysfunction induced by clinostat rotation could lead to apoptosis in luteal cells and suppression of progesterone production.

  18. Re-Adaptation to 1-G of Pregnant Rats Following Exposure to Spaceflight or Centrifugation

    NASA Technical Reports Server (NTRS)

    Johnson, K. E.; Ronca, A. E.; Alberts, J. R.

    2003-01-01

    Late-pregnant rat dams were flown on a 9-day Space Shuttle mission or exposed to 1.5, 1.75 or 2-g centrifugation and compared with 1 .O-g vivarium controls. Exposure to altered gravity began on the 11th day and recovery occurred on the 20th day of the dams' 22-day pregnancy. In the 1 st experiment, comparisons were made between Flight (FLT), Synchronous (SYN; identically-housed) and Vivarium (VIV) controls. In the 2nd experiment, comparisons were made between dams centrifuged at 2-G, 1.75-G, 1.5-G, Rotational controls (1.08-G) or Stationary controls (1 G). Within three hours of recovery from either spaceflight or centrifugation, the dams' locomotor behavior was videotaped for 2 min. FLT dams showed dramatically reduced movement relative to both SYN and VIV control conditions, with significantly greater amounts of locomotor activity observed in SYN as compared to VIV dams. Significantly greater locomotor activity was observed in SYN as compared to VIV controls. In the second experiment, no differences were observed between dams exposed either 1, 1.5, 1.75, or 2-G. In both studies, the dams showed similar patterns of hindlimb rearing. Together, these findings provide quantitative evidence for decreased locomotor activity during re-adaptation to 1-g following spaceflight, but not centrifugation.

  19. Effects of Extended Exposure to the Antibacterial Triclosan in the the Adult Female Rat

    EPA Science Inventory

    Triclosan (TCS), an antibacterial, has been shown to have endocrine disrupting activity in the rat. We reported previously that TCS advanced puberty in the female rat in the female pubertal assay and potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth i...

  20. TCDD, dietary iron and hepatic iron distribution in female rats

    SciTech Connect

    Al-Bayati, Z.A.F.; Stohs, S.J.; Al-Turk, W.A.

    1987-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a prototype for a large group of halogenated aromatic hydrocarbons, and is the most potent of these compounds. TCDD is an environmental pollutant with exceptional toxicity for certain mammalian and avian species. The liver is one of the principal target organs affected by TCDD in the rat and other laboratory species. TCDD induces many functional, biochemical and pathological changes, including altered lipid metabolism in the liver. Ferrous iron plays an important role in the initiation of lipid peroxidation. A proposed mechanism for the production of liver injury in chronic iron overload is that organelle damage leading to cell death occurs as a result of membrane lipid peroxidation initiated and promoted by intracellular iron. The presence of iron in subcellular fractions in vitro may catalyze lipid peroxidation and produce membrane damage. There is evidence for the occurrence of hepatic lipid peroxidation after TCDD administration. The purpose of this study was to determine if TCDD induced lipid peroxidation was associated with an increase in the iron content of liver and its subcellular fractions. The effect of TCDD administration on the iron content of whole homogenate, microsomes, mitochondria, and cytosol of livers of female rats fed defined diets containing deficient, normal and excessive levels of iron for 17, 24 and 31 days was investigated.

  1. Cutaneously applied 4-hydroxytamoxifen is not carcinogenic in female rats.

    PubMed

    Sauvez, F; Drouin, D S; Attia, M; Bertheux, H; Forster, R

    1999-05-01

    Tamoxifen is widely used to treat oestrogen-dependent carcinoma of the breast. Previous long-term studies have shown that oral administration of tamoxifen induces hepatoproliferative lesions and hepatocellular tumours in rats. 4-hydroxytamoxifen is an active metabolite of tamoxifen undergoing clinical evaluation for the treatment of various non-malignant breast diseases by topical application. In the present study, 4-hydroxytamoxifen was administered daily by cutaneous application for 101 weeks to groups of 50 female Sprague-Dawley rats at 20, 140 or 1000 microg/kg/day. The product was applied with no occlusive bandage and oral ingestion was avoided by application of an Elizabethan collar for 6 h after administration. Treatment with 4-hydroxytamoxifen was clinically well tolerated and induced changes such as decreased food consumption and body weight gain, uterine and ovarian atrophy, mucification of vaginal epithelium and reduced mammary development, all of which were attributed to its pharmacological action. Mortality was significantly lower in the treated animals. The number of animals with palpable masses was similarly reduced. The incidence of mammary tumours and hypophyseal tumours was markedly lower in 4-hydroxytamoxifen-treated animals. The incidence of chronic tubulo-interstitial nephropathies, a common cause of mortality, was also lowered. There was no evidence of a carcinogenic action of 4-hydroxytamoxifen on the liver, genital organs or skin. Plasma levels of 4-hydroxytamoxifen were stable over the duration of the study and were proportional to the administered dose, exceeding clinical plasma levels by 60-fold at the high dose-level. In conclusion, 4-hydroxytamoxifen is not carcinogenic in the rat and reduces the incidence of spontaneous mammary and hypophyseal tumours. PMID:10334202

  2. Life history of female preferences for male faces: a comparison of pubescent girls, nonpregnant and pregnant young women, and middle-aged women.

    PubMed

    Kościński, Krzysztof

    2011-12-01

    Although scientific interest in facial attractiveness has developed substantially in recent years, few studies have contributed to our understanding of the ontogeny of facial preferences. In this study, attractiveness of 30 male faces was evaluated by four female groups: girls at puberty, nonpregnant and pregnant young women, and middle-aged women. The main findings are as follows: (1) Preference for sexy-looking faces was strongest in young, nonpregnant women. (2) Biologically more mature girls displayed more adultlike preferences. (3) The intragroup consistency for postmenopausal women was relatively low. (4) In terms of the preference pattern, pregnant women were more similar to perimenopausal women than they were to their nonpregnant peers. (5) Preference for youthful appearance decreased with the age of the women. I argue that the life history of female preferences for male faces is, to a large extent, hormone-driven and underpinned by a set of evolutionary adaptations. PMID:22388946

  3. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

    PubMed Central

    Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

    2013-01-01

    BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status. PMID:23949616

  4. DIFFERENT MOLECULAR MECHANISMS UNDERLIE ETHANOL-INDUCED BONE LOSS IN CYCLING AND PREGNANT RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic ethanol (EtOH) consumption can result in osteopenia. In the current study we examined the modulation of EtOH-induced bone-loss during pregnancy. Non-pregnant and pregnant dams were intragastrically infused either control or EtOH-containing diets throughout gestation (GD5 through 20 or an equ...

  5. Female rats are more susceptible to central nervous system oxygen toxicity than male rats

    PubMed Central

    Held, Heather E.; Pilla, Raffaele; Ciarlone, Geoffrey E.; Landon, Carol S.; Dean, Jay B.

    2014-01-01

    Abstract Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS‐OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS‐OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio‐telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (−42, −49, and −57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (−60, −86, and −73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (−0.4 ± 1.5 g) or FB (−1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS‐OT than males. PMID:24771690

  6. Female rats are more susceptible to central nervous system oxygen toxicity than male rats.

    PubMed

    Held, Heather E; Pilla, Raffaele; Ciarlone, Geoffrey E; Landon, Carol S; Dean, Jay B

    2014-01-01

    Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males. PMID:24771690

  7. Follicle Development of Xenotransplanted Sheep Ovarian Tissue into Male and Female Immunodeficient Rats

    PubMed Central

    Tahaei, Leila Sadat; Eimani, Hussein; Hajmusa, Ghazaleh; Fathi, Rouhollah; Rezazadeh Valojerdi, Mojtaba; Shahverdi, Abdolhossein; Eftekhari-Yazdi, Poopak

    2015-01-01

    Background This study aimed to assess follicle survival after xenotransplantation of sheep ovarian tissue into male and female immunodeficient rats. We evaluated the effects of gonadotropin treatment on follicular development in the transplanted tissue. Materials and Methods In this experimental study, sheep ovarian cortical strips were transplanted into the neck back muscles of 8 male and 8 female immunodeficient, castrated rats. Fourteen days after surgery, each rat was treated with human menopausal gonadotropin (hMG) for 9 weeks. One day after the last injection, ovarian tissues were removed and fixed for histology assessment. Histology analyses were performed before and after grafting. Estradiol (E2) levels were measured before and after gonadectomy, and at the end of the experiment. The control group consisted of 7 male and 7 female noncastrated/non-grafted rats and the sham group comprised 7 male and 7 female castrated/ non-grafted rats for comparison of serum E2 concentrations. Results The percentage of primordial follicles decreased after transplantation in male (25.97%) and female (24.14%) rats compared to the control group (ovarian tissue nongrafted; 37.51%). Preantral follicles increased in the male (19.5%) and female (19.49%) transplanted rats compared to the control group (11.4%). Differences in antral follicles between male (0.06 0.0%) and female (0.06 0.0%) rats were not noticeable compared to control (1.25 0.0%) rats. We observed a significantly higher percent of mean E2 secretion in grafted males compared to grafted females (P?0.05). Conclusion Despite significant differences in E2 secretion between xenografted male and female rats, we observed no statistical differences in terms of follicular development. PMID:26644859

  8. EFFECTS OF EPICHLOROHYDRIN ON MALE AND FEMALE REPRODUCTION IN LONG-EVANS RATS

    EPA Science Inventory

    Male and female Long-Evans rats were treated with epichlorohydrin (ECH) by oral gavage (males: 12.5, 25, and 50 mg/kg/day; females: 25, 50, and 100 mg/kg/day) for 21 and 14 days respectively, prior to mating trials with untreated animals. Treated females were further dosed until ...

  9. Immunization of Wistar female rats with 255-Gy-irradiated Toxoplasma gondii: Tissue parasitic load and lactogenic quantification.

    PubMed

    Camossi, Lucilene Granuzzio; Fornazari, Felipe; Richini-Pereira, Virgnia Bodelo; Costa da Silva, Rodrigo; Cardia, Daniel Fontana Ferreira; Langoni, Helio

    2015-07-01

    Toxoplasma gondii is one of the most significant parasite, due its importance in veterinary medicine and in public health, considered a food-borne pathogens, there is no available drug treatments to eliminate it from animal tissue, this reinforce the search for a vaccine against this parasite. This study was aimed to evaluate the dynamic of the distribution of T. gondii in tissues of female Wistar rats and their milk, after the immunization by oral rote with irradiated tachyzoites. One week after pregnancy confirmation, rats was challenged by gavage with T. gondii bradyzoites, oocysts or tachyzoites of T. gondii. Forty-eight pregnant rats were grouped as follows: immunized and challenged with bradyzoites (BZ*); non-immunized and challenged with bradyzoites (BZ); immunized and challenged with oocysts (OC*); non-immunized and challenged with oocysts (OC); immunized and challenged with tachyzoites (TZ*); non-immunized and challenged with tachyzoites (TZ); only immunized (I); control group (C). After parturition, milk samples were collected for 3 weeks and then rats were sacrificed and the tissues and milk samples were researched for T. gondii parasite load determined by the quantitative PCR (qPCR). It was verified that the immunization with irradiated tachyzoites of T. gondii induced the reduction of parasitic load in muscle samples in rats challenged by bradyzoites and oocysts, although not enabled the development of sterile immunity. The detection of parasite DNA in milk was found throughout the lactation period, from immunized and non-immunized rats, however no differences were found in the parasite load caused by immunization. PMID:25936982

  10. Effect of ethionine on the rough endoplasmic reticulum from male and female rat liver.

    PubMed

    Czosnek, H H; Ascarelli, A; De Groot, N; Hergenhahn, M; Hochberg, A A

    1977-12-01

    Ethionine causes a decrease in the amount of rough endoplasmic reticulum in rat liver, the effect being greater in female than in male rats. Rough endoplasmic reticulum isolated from rat liver 24 hr after ethionine injection and stripped of its ribosomes partially lost its in vitro ribosome binding capacity. However, no differences were detected between the binding affinities of ribosomes, isolated from either untreated animals or intoxicated rats, to stripped rough membranes derived from normal rats. Structural changes occur in the rough endoplasmic reticulum of the ethionine treated rats, while the ribosomes are still bound to the membrane. PMID:593275

  11. Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats

    PubMed Central

    Kraemer, Bernhard; Wallwiener, Christian; Rajab, Taufiek K.; Brochhausen, Christoph; Wallwiener, Markus; Rothmund, Ralf

    2014-01-01

    Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (P < 0.01). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (P < 0.01). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) (P < 0.05) and group 4 (47%) (P < 0.05). There was no difference between group 3 (60%) and group 6 (P = 0.2). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models. PMID:24809049

  12. Standardised models for inducing experimental peritoneal adhesions in female rats.

    PubMed

    Kraemer, Bernhard; Wallwiener, Christian; Rajab, Taufiek K; Brochhausen, Christoph; Wallwiener, Markus; Rothmund, Ralf

    2014-01-01

    Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (P < 0.01). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (P < 0.01). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) (P < 0.05) and group 4 (47%) (P < 0.05). There was no difference between group 3 (60%) and group 6 (P = 0.2). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models. PMID:24809049

  13. Gestational treatment of folic acid attenuates blood-brain barrier leakage in pregnant- and prepubertal rats after pentylenetetrazole-induced seizure.

    PubMed

    Seker, Fatma Burcu; Yorulmaz, Hatice; Kaptan, Engin; Caglayan, Berrak; Oztas, Baria

    2016-02-01

    Objectives Folic acid (FA) is physiologically important in mammals and is a common vitamin supplement used during pregnancy and lactation. Numerous studies have reported that FA significantly improves endothelial function. The blood-brain barrier (BBB) plays an important role in maintaining the microenvironment required for neuronal function, but its unique structure is damaged by epileptic seizures. The aim of this study was to evaluate the potential protective role of FA on BBB leakage, as well as on the reactive astrogliosis in pregnant rats and their prepubertal offspring during pentylenetetrazole (PTZ)-induced epileptic seizure. Methods Pregnant rats were treated with FA (5mg/kg) and PTZ on gestational days 0-19 and 19, respectively. The pups were treated with PTZ at puberty. Evans blue was used to evaluate BBB integrity. Reactive astrogliosis was defined using immunohistochemical analysis for glial fibrillary acidic protein (GFAP). Mean arterial blood pressure (MABP) was measured at the femoral artery. Results A moderate decrease in BBB leakage was observed in FA-treated pregnant and prepubertal animals (P<0.05). MABP was decreased significantly in pregnant rats (P<0.05). The epilepsy-induced increase in MABP was less prominent in pregnant animals (P<0.05). GFAP intensity decreased in PTZ-treated pregnant animals (P<0.01) and FA-treated prepubertal rats. Discussion Our findings suggest that FA, which is used as a maternal vitamin to promote normal fetus development, may be beneficial against seizure-induced neuronal damage by decreasing BBB leakage and reactive astrogliosis in pregnant and prepubertal rats. PMID:25222769

  14. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats.

    PubMed

    Ehrlich, David E; Neigh, Gretchen N; Bourke, Chase H; Nemeth, Christina L; Hazra, Rimi; Ryan, Steven J; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney A; Rainnie, Donald G; Stowe, Zachary N; Owens, Michael J

    2015-10-01

    Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436

  15. A Novel Telometric Metric for In-Situ Measurement of Intrauterine Pressure (IUP) in Pregnant and Parturient Rats

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; LaFramboise, M. N.; Hills, E. M.; Daly, M. E.; Mills, N. A.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    During labor and birth, considerable forces exerted on fetuses help instigate certain adaptive postpartum responses (viz., breathing and suckling). To make precise, reliable measures of the forces experienced by rat fetuses during parturition, we developed a novel method for measuring intrauterine pressure (IUP) in late pregnant rats. A small (1.25 x 4cm) telemetric blood pressure sensor is fitted within a fluid-filled balloon, similar in size to a full term rat fetus. The balloon is surgically implanted in the uterus on Gestational Day 19 of the rats' 22-day pregnancy. During birth, dams are able to deliver their pups and the balloon. IUP arsenals are recorded during labor (G22 or 23) and birth. Data derived from a group of implanted rats indicated that pressures on the balloon increased across the period of birth, reaching 18 mmHg during labor, 25 mmHg during pup births and 39 mmHg just prior to delivery of the balloon. These data are within the range reported for conventional IUP measurement techniques. Dams are simultaneously videotaped, enabling us to analyze behavioral expressions of labor contractions and to integrate in-situ and behavioral findings.

  16. The expression of orexigenic and anorexigenic factors in middle-aged female rats that had been subjected to prenatal undernutrition.

    PubMed

    Tungalagsuvd, Altankhuu; Matsuzaki, Toshiya; Iwasa, Takeshi; Munkhzaya, Munkhsaikhan; Yiliyasi, Mayila; Kawami, Takako; Kato, Takeshi; Kuwahara, Akira; Irahara, Minoru

    2016-04-01

    Fetal growth retardation, which affects short- and long-term fetal brain development, is associated with metabolic, hematological, and thermal disturbances, which can increase the risk of metabolic syndrome later in life. Orexigenic and anorexigenic factors regulate food intake and energy expenditure. We studied how the expression of these factors was affected by food deprivation (FD) in middle-aged female rats that had been subjected to prenatal undernutrition. Eight pregnant rats were divided into two groups, the normal nutrition (NN) (n=4) group and the undernutrition (UN) (n=4) group, which received 50% (approximately 11g) of the daily food intake of the normal nutrition rats from day 13 of pregnancy to delivery. The pups from these dams were defined as the maternal NN (mNN) and maternal UN (mUN) groups, respectively. After weaning, all of the pups were housed and allowed ad libitum access to food and water. At the age of 6 months, both groups of pups were sub-divided into three groups. One group was allowed to consume normal amounts of food (Fed), and the other two groups were subjected to 24h or 48h FD (n=7-8 per group). The rats' serum leptin levels and hypothalamic mRNA expression levels of various orexigenic or anorexigenic factors were measured. In both the mNN and mUN rats, the serum leptin levels of the 24h and 48h FD groups tended to be lower than those of the Fed group, and the serum leptin levels of the 24h FD mUN rats and the Fed mUN rats differed significantly. The hypothalamic neuropeptide Y (NPY) mRNA expression levels of the 24h and 48h FD groups were significantly higher in the mUN rats than in the mNN rats. In addition, among the mUN rats the hypothalamic NPY mRNA expression levels of the 48h FD group were significantly higher than those of the Fed group. In both the mNN and mUN rats, prepro-orexin mRNA expression was lower in the 48h FD group than in the corresponding Fed group. Among the mUN rats, the 48h FD group exhibited significantly lower hypothalamic proopiomelanocortin (POMC) mRNA expression than the Fed group, and a similar tendency was seen among the mNN rats. Among the mNN rats, the 24h FD group displayed significantly higher hypothalamic leptin receptor (OBRb) mRNA levels than the Fed group. However, no such differences were seen among the mUN rats. As a result, the hypothalamic OBRb mRNA expression levels of the mUN rats in the 24h and 48h FD groups were lower than those of the corresponding mNN rat groups. These findings indicate that rats that are subjected to prenatal undernutrition exhibit upregulated expression of orexigenic factors and are more sensitive to FD in middle age, which might increase their risk of developing metabolic disorders in later life. PMID:26702900

  17. Testosterone and imipramine have antidepressant effects in socially isolated male but not female rats

    PubMed Central

    Carrier, Nicole; Kabbaj, Mohamed

    2012-01-01

    Rationale Affective disorders are twice as likely to occur in women as they are in men suggesting a critical role for gonadal hormones in their etiology. In particular, testosterone has been shown to have protective effects in men. Objective To investigate antidepressant effects and interactions between testosterone and imipramine in socially isolated male and female rats. Methods A chronic social isolation model was used to induce an anxiety and depressive-like state in adult gonadectomized (Gnx) male and ovariectomized (Ovx) female rats receiving chronic testosterone and imipramine treatments. Their anxiety and depression-like behaviors were examined using the light-dark box, elevated plus maze, open field, sucrose preference and novelty induced hypophagia tests. Results In socially isolated rats, the anxiolytic and antidepressant effects of testosterone and imipramine were limited to male rats. Additionally, testosterone enhanced the neurogenic effect of imipramine on hippocampal cell proliferation in male rats. Although female rats exhibited signs of anxiety and depressive-like behaviors following social isolation, testosterone and/or imipramine administration had no anxiolytic or antidepressant effects in Ovx females. Conclusions Testosterone and imipramine had anxiolytic and antidepressant effects in socially isolated male, but not female rats. Testosterone enhanced the effect of imipramine on cell proliferation in the hippocampus of male rats. PMID:22426002

  18. Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet

    PubMed Central

    Gao, Haijun; Tanchico, Daren T; Yallampalli, Uma; Balakrishnan, Meena P; Yallampalli, Chandra

    2015-01-01

    Gestational protein restriction causes hypertension in the adult offspring. Very little is known about the food intake regulation and ghrelin signaling in pregnant dams fed a low-protein (LP) diet. We hypothesized that diet intake and ghrelin signaling are altered in pregnant rats fed the low-protein diet. SpragueDawley rats were fed a control (CT) or LP diet from Day 3 of pregnancy. Diet intake and body weight were monitored daily. Expression of ghrelin production-related genes in the stomach and appetite-related genes in the hypothalamus was analyzed by real-time PCR. Plasma levels of total and active ghrelin, growth hormone and leptin were measured by ELISA. Main results include: (1) Daily diet intake was greater in the LP group than in the CT group in early pregnancy, but substantially lower in late pregnancy; (2) Daily gain in body weight was substantially lower in the LP group in late pregnancy; (3) Expression of ghrelin production-related genes in the stomach and plasma total ghrelin levels were increased in LP group in late pregnancy; (4) Plasma active ghrelin levels were elevated in the LP group at mid-late pregnancy, but growth hormone and leptin levels were uncorrelated with active ghrelin in late pregnancy; and (5) Hypothalamic expression of ghrelin-stimulated genes in LP rats was unassociated with the changes in both plasma ghrelin levels and the diet intake. Taken together, the appetite in LP rats is greater in early pregnancy but reduced at late pregnancy, possibly due to ghrelin insensitivity in appetite regulation. PMID:25907788

  19. Development of a physiologically based pharmacokinetic model of 2-methoxyethanol and 2-methoxyacetic acid disposition in pregnant rats.

    PubMed

    Hays, S M; Elswick, B A; Blumenthal, G M; Welsch, F; Conolly, R B; Gargas, M L

    2000-02-15

    An accurate description of developing embryos' exposure to a xenobiotic is a desirable component of mechanism-based risk assessments for humans exposed to potential developmental toxicants during pregnancy. 2-Methoxyethanol (2-ME), a solvent used in the manufacture of semiconductors, is embryotoxic and teratogenic in all species tested including nonhuman primates. 2-Methoxyacetic acid (2-MAA) is the primary metabolite of 2-ME and the proximate embryotoxic agent. The objective of the work described here was to adapt an existing physiologically based pharmacokinetic (PBPK) model for 2-ME and 2-MAA kinetics during midorganogenesis in mice to rats on gestation days (GD) 13 and 15. Blood and tissue data were analyzed using the extrapolated PBPK model that was modified to simulate 2-ME and 2-MAA kinetics in maternal plasma and total embryo tissues in pregnant rats. The original mouse model was simplified by combining the embryos and placenta with the richly perfused tissue compartment. The model includes a description of the growth of the developing embryo and changes in the physiology of the dam during pregnancy. Biotransformation pathways of 2-ME to either ethylene glycol (EG) or to 2-MAA were described as first-order processes based on the data collected from rats by Green et al., (Occup. Hyg. 2, 67-75, 1996). Tissue partition coefficients (PCs) for 2-ME and 2-MAA were determined for a variety of maternal tissues and the embryos. Model simulations closely reflected the biological measurement of 2-ME and 2-MAA concentrations in blood and embryo tissue following gavage or iv administration of 2-ME or 2-MAA. The PBPK model for rats as described here is well suited for extrapolation to pregnant women and for assessment of 2-MAA dosimetry under various conditions of possible human exposure to 2-ME. PMID:10662606

  20. Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat

    EPA Science Inventory

    Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...

  1. A cognitive rehabilitation paradigm effective in male rats lacks efficacy in female rats

    PubMed Central

    Langdon, Kristopher D; Granter-Button, Shirley; Harley, Carolyn W; Moody-Corbett, Frances; Peeling, James; Corbett, Dale

    2014-01-01

    Cognitive dysfunction, as a consequence of dementia, is a significant cause of morbidity lacking efficacious treatment. Females comprise at least half of this demographic but have been vastly underrepresented in preclinical studies. The current study addressed this gap by assessing the protective efficacy of physical exercise and cognitive activity on learning and memory outcomes in a rat model of vascular dementia. Forty ovariectomized Sprague-Dawley rats (?6 months old) were exposed to either a diet high in saturated fats and refined sugars or standard laboratory chow and underwent either chronic bilateral carotid occlusion or Sham surgery. Learning and memory abilities were evaluated using standard cognitive outcomes over the ensuing 6 months, followed by histologic analyses of hippocampal CA1 neurons. In Experiment 1, we confirmed hypoperfusion-induced cognitive dysfunction using a 2 2 (Surgery Diet) experimental design, without alterations in hippocampal architecture. In Experiment 2, hypoperfused animals were either exposed to alternating days of physical (wheel running) and cognitive activity (modified HebbWilliams maze) or sedentary housing. In contrast to males, this combination rehabilitation paradigm did not improve cognition or histopathologic outcomes in hypoperfused animals. These findings, highlighting differences between female and male animals, show the necessity of including both sexes in preclinical experimentation. PMID:25052554

  2. Studies on Apoptotic Changes in Combined Toxicity of Citrinin and Endosulfan in Pregnant Wistar Rats and Their Fetuses

    PubMed Central

    Singh, N. D.; Sharma, A. K.; Dwivedi, P.; Telang, A. G.; Kumar, M.; Patil, R. D.

    2012-01-01

    Background: Citrinin (mycotoxin) and endosulfan (pesticide) both environmental contaminants easily enter the food chain and are caoomon causes of various toxicities. Materials and Methods: In the present investigation, citrinin (CIT) (10 mg/kg feed) and endosulfan (1 mg/kg body weight) were administered orally alone and in combination to pregnant Wistar rats from gestational day 6 to 20 to study their effect to cause apoptosis in the pregnant Wistar rats and their fetuses. Apoptosis was assessed in dams by agarose gel electrophoresis, flow cytometry and electron microscopy, while in the fetuses it was assessed by flow cytometry only. Result: Citrinin and endosulfan in the combination group caused apoptosis in an additive manner as there was increased number of apoptotic cells as compared to the individual toxin and control groups. The fetuses also showed increased number of apoptotic cells in the combination groups, which also indicated that both the toxins crossed the placental barrier. Conclusion: So it was concluded that apoptosis played a significant role in the pathogenesis of endosulfan and citrinin toxicity. PMID:22778511

  3. Effect of Post-Weaning Individual Housing on Autonomic Responses in Male Rats to Sexually Receptive Female Rats

    PubMed Central

    Inagaki, Hideaki; Kuwahara, Masayoshi; Tsubone, Hirokazu

    2013-01-01

    Post-weaning individual housing induces significant alterations in the reward system of adult male rats presented with sexually receptive female rats. In this study, we examined the effects of post-weaning individual housing on autonomic nervous activity in adult male rats during encounters with sexually receptive female rats to assess whether different affective states depending on post-weaning housing conditions are produced. Changes in heart rate and spectral parameters of heart rate variability indicated that in post-weaning individually housed male rats, both sympathetic and parasympathetic activity increased with no change in the sympathovagal balance, while in post-weaning socially housed male rats, both sympathetic and parasympathetic activity decreased with a predominance of parasympathetic activity. These two patterns of shifts in sympathovagal balances closely resembled changes in autonomic nervous activity with regard to classical appetitive conditioning in male rats. The autonomic changes in male rats housed individually after weaning corresponded to changes associated with the reward-expecting state evoked by the conditioned stimulus, and the autonomic changes observed in male rats housed socially after weaning corresponded to changes associated with the reward-receiving state evoked by the unconditioned stimulus. These results suggest that different affective states were induced in adult male rats during sexual encounters depending on male–male social interactions after weaning. The remarkable change caused by post-weaning individual housing may be ascribed to alteration of the reward system during sexual encounters induced by deficiency of intermale social communication after weaning. PMID:23903058

  4. Changes in geometrical and biomechanical properties of immature male and female rat tibia

    NASA Technical Reports Server (NTRS)

    Zernicke, Ronald F.; Hou, Jack C.-H.; Vailas, Arthur C.; Nishimoto, Mitchell; Patel, Sanjay

    1990-01-01

    The differences in the geometry and mechanical properties of immature male and female rat tibiae were detailed in order to provide comparative data for spaceflight, exercise, or disease experiments that use immature rats as an animal model. The experiment focuses on the particularly rapid period of growth that occurs in the Sprague-Dawley rat between 40 and 60 d of age. Tibial length and middiaphysical cross-sectional data were analyzed for eight different groups of rats according to age and sex, and tibial mechanical properties were obtained via three-point bending tests to failure. Results indicate that, during the 15 d period of rapid growth, changes in rat tibial geometry are more important than changes in bone material properties for influencing the mechanical properties of the tibia. Male tibiae changed primarily in structural properties, while in the female rats major changes in mechanical properties of the tibia were only attributable to changes in the structural properties of the bone.

  5. Release of mercury from dental amalgam fillings in pregnant rats and distribution of mercury in maternal and fetal tissues.

    PubMed

    Takahashi, Y; Tsuruta, S; Hasegawa, J; Kameyama, Y; Yoshida, M

    2001-06-21

    Mercury vapor released from a single amalgam restoration in pregnant rats and mercury concentrations in maternal and fetal rat tissues were studied. Dental treatment was given on day 2 of pregnancy. Mercury concentration in air sample drawn from the metabolism chamber with the rat was measured serially for 24 h on days 2, 8 and 15 of pregnancy. An average mercury concentration in the air samples from the rats given amalgam restorations was 678.6+/-167.5 ng/day on day 2. The average mercury concentration in the air samples tended to decline as time elapsed but a marked amount (423.2+/-121.5 ng/day) was observed even on day 15. The amount of mercury in the air samples increased 7--20-fold after chewing. The placement of the single amalgam restoration (3.8--5.5 mg in weight) increased the levels of mercury approximately three to 6 times in the maternal brain, liver, lung, placenta and 20 times in the kidneys. The highest mercury concentration among fetal organs was found in the liver, followed by the kidneys and brain. Mercury concentrations in maternal organs and fetal liver were significantly higher than those of the controls, and concentrations in maternal whole blood, erythrocytes and plasma, and in fetal whole blood were also significantly higher. Mercury concentrations in the fetal brain, liver, kidneys and whole blood were lower than those of the maternal tissues. PMID:11516521

  6. Osteoprotective Effect of Alfacalcidol in Female Rats with Systemic Chronic Inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have shown that alfacalcidol (a hydroxylated form of vitamin D) mitigates glucocorticoid-induced bone loss. This study was undertaken to explore the mechanism and bone microarchitecture of alfacalcidol in rats with systemic chronic inflammation. Thirty female rats (3-month-old) assigned to ...

  7. EFFECT OF CONAZOLE FUNGICIDES ON REPRODUCTIVE DEVELOPMENT IN THE FEMALE RAT

    EPA Science Inventory

    Three triazole fungicides were evaluated for effects on female rat reproductive development. Rats were exposed via feed to propiconazole (P) (100, 500, or 2500 ppm), myclobutanil (M) (100, 500, or 2000 ppm), or triadimefon (T) (100, 500, or 1800 ppm) from gestation day 6 to postn...

  8. Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Our previous study demonstrated that green tea polyphenols (GTP) benefit bone health in female rats with chronic inflammation, because of GTPs antioxidant capacity. The current study further evaluates whether GTP can restore bone microstructure along with related mechanism in rats wit...

  9. The role of oxytocin and vasopressin in conditioned mate guarding behavior in the female rat.

    PubMed

    Holley, Amanda; Bellevue, Shannon; Vosberg, Daniel; Wenzel, Kerstin; Roorda, Sieger; Pfaus, James G

    2015-05-15

    We have shown previously that female rats given their first copulatory experiences with the same male rat display mate guarding behavior in the presence of that male provided a female competitor is also present. Females given access to the familiar male show more Fos induction within regions of the brain that contain oxytocin (OT) and vasopressin (AVP) cell bodies, notably the supraoptic (SON) and paraventricular nuclei (PVN) relative to females given sexual experience with different males. The present experiments examined whether the Fos induction we previously observed within the SON and PVN occurred within OT and/or AVP neurons, and whether exogenous administration of OT or AVP prior to female rats first sexual experience could potentiate the acquisition of mate guarding behavior. Female rats that display conditioned mate guarding had significantly more double-labeled Fos/OT neurons in both SON and PVN, and significantly more Fos/AVP neurons in the PVN. Peripheral administration of OT or AVP prior to their first sexual experience with the familiar male facilitated different aspects of mate guarding: OT augmented affiliative behaviors and presenting responses whereas AVP augmented interference behavior. These results indicate that female rats' first experiences with sexual reward when paired with the same male induce changes to bonding networks in the brain. Moreover peripheral administration of OT or AVP during their first sexual experience can augment different aspects of mate guarding behavior. PMID:25724299

  10. Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

    PubMed Central

    Ishii, Yukihito; Motohashi, Yu; Muramatsu, Makoto; Katsuda, Yoshiaki; Miyajima, Katsuhiro; Sasase, Tomohiko; Yamada, Takahisa; Matsui, Tohru; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    AIM: To investigate the histological features of the liver in spontaneously diabetic Torii (SDT) fatty rats compared with age-matched Sprague-Dawley (SD) rats. METHODS: Female SDT Leprfa (SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters, such as serum glucose, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the non-fasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis, inflammation, and fibrosis was examined in the liver. RESULTS: SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose, TG, and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically, severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age, and fibrosis started to occur at 32 wk of age. Furthermore, Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis, inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats, and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION: Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity. PMID:26290633

  11. Remodeling and angiotensin II responses of the uterine arcuate arteries of pregnant rats are altered by low- and high-sodium intake.

    PubMed

    St-Louis, Jean; Sicotte, Benot; Beausjour, Annie; Brochu, Michle

    2006-02-01

    Lowering and increasing sodium intake in pregnant rats evoke opposite changes in renin-angiotensin-aldosterone system (RAAS) activity and are associated with alterations of blood volume expansion. As augmented uterine blood flow during gestation is linked to increased circulatory volume, we wanted to determine if low- and high-sodium intakes affect the mechanical properties and angiotensin II (AngII) responses of the uterine vasculature. Non-pregnant and pregnant rats received a normal sodium (0.22% Na+) diet. On the 15th day of gestation some animals were moved to a low-sodium (0.03%) diet, whereas others were given NaCl supplementation as beverage (saline, 0.9% or 1.8%) for 7 days. All rats were killed after 7 days of treatment (eve of parturition). Uterine arcuate arteries (>100 microm) were set up in wire myographs under a tension equivalent to 50 mmHg transmural pressure. The pregnancy-associated increase in diameter of the uterine arteries was significantly attenuated on the low-sodium diet and 1.8% NaCl supplementation. The arcuate arteries of non-pregnant rats on the low-sodium diet showed markedly increased responses to AngII and phenylephrine (Phe). Pregnancy also resulted in heightened responses to AngII and Phe that were significantly reduced for the former agent in rats on the low-sodium diet. Sodium supplementation of non-pregnant rats did not affect the reactivity of the uterine arteries to AngII, but significantly reduced the effect of Phe (1 micromol/l). High salt also significantly diminished the elevated responses to AngII in the arteries of pregnant animals. It was observed that altered sodium intake affects the mechanical and reactive properties of the uterine arcuate arteries more importantly in pregnant than in non-pregnant rats. Low-salt intake similarly affected the reactivity of the uterine arcuate arteries to AngII and Phe, whereas high-salt intake more specifically affected AngII responses. These results showed that perturbations of sodium intake have major impacts on the structure and functions of the uterine arterial circulation, indicating RAAS involvement in uterine vascular remodeling and function during gestation. PMID:16452726

  12. Sorbitol accumulation in male and female rats consuming starch or fructose diets with or without copper

    SciTech Connect

    Lewis, C.G.; Fields, M.; Beal, T. )

    1989-02-09

    The present study was designed to examine the relationship between the sex of the rats, tissue sorbitol accumulation and copper deficiency in rats consuming dietary fructose. Rats were provided with a diet containing either 62.7% fructose or starch, and either 6.0 or 0.6 {mu}g copper/g for three weeks. Hepatic copper concentration of all rats consuming the copper-deficient diets was about 40% of copper sufficient rats. Hepatic, renal and thymic sorbitol concentrations were significantly elevated in males consuming the fructose, copper-deficient diet when compared to all other dietary groups regardless of the sex of the rat. Hepatic, renal the thymic fructose concentrations were significantly higher in rats eating fructose as compared to female rats. Hepatic glucose concentration was higher in males and females consuming the fructose, copper-deficient diet when compared to all other dietary groups. Renal glucose concentration was elevated in males as compared to females. These results demonstrate that the pathology and complications of copper deficiency in the male rat consuming fructose closely parallel aberration in tissue sorbitol accumulation.

  13. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats.

    PubMed

    Souza, M F; Couto-Pereira, N S; Freese, L; Costa, P A; Caletti, G; Bisognin, K M; Nin, M S; Gomez, R; Barros, H M T

    2014-06-01

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse. PMID:24878606

  14. Bone turnover in passive smoking female rat: relationships to change in bone mineral density

    PubMed Central

    2011-01-01

    Background Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat. Methods Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats. Results BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats. Conclusion Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat. PMID:21663694

  15. Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats.

    PubMed

    Yengkopiong, Jada Pasquale; Lako, Joseph Daniel Wani

    2015-09-01

    Genetic modifier loci influence the inheritance of diseases and lead to variability in phenotype progression. We report the influence of modifier loci in female Wistar Kyoto (WKY) rats on cellular pathogenesis of nephronophthisis inherited from Lewis polycystic kidney (LPK) rats. The loci modified cellular expression and progression of nephronophthisis in the backcross 1 (BC1) progeny. Mating experiments to produce BC1 progeny were carried out between three male LPK and seven female WKY rats. Fifteen female rats from the F1 generation were mated with the male LPK rats to produce the BC1 progeny. The rats with cystic kidney disease were identified and histology of the kidneys was carried out. Mapping studies and linkage analysis were carried out to identify the modifier loci. The BC1 progeny were less affected than the LPK strain with respect to disease severity and progression of the kidneys to end stage renal disease. It was found that the mean values of all the disease phenotypes of the mutant BC1 progeny were significantly different from those of the LPK rats, and these segregated with the genotypes of the markers located on chromosomes 5q34-q36 and 7q11-q34, giving maximum LOD scores greater than 3 (p < 0.001). PMID:26619107

  16. Change of genes in calcium transport channels caused by hypoxic stress in the placenta, duodenum, and kidney of pregnant rats.

    PubMed

    Yang, Hyun; An, Beum-Soo; Choi, Kyung-Chul; Jeung, Eui-Bae

    2013-02-01

    Preeclampsia is a pregnancy-specific disease characterized by concurrent development of hypertension, proteinuria, and oxidative stress in the placenta. In this study, we induced hypoxic stress in rats during pregnancy to reproduce physiological conditions associated with preeclampsia. The maternal weight of hypoxic pregnant rats was lower than that of normoxic animals. The level of calcium ions were also increased in urine collected from the hypoxic animals. In contrast, urinary concentrations of sodium, chloride, and potassium ions declined in hypoxic rats, and developed to proteinuria. The expression of genes known as two biomarkers, sFLT1 (for preeclampsia) and HIF-1alpha (for hypoxia), were highly induced in the placenta, duodenum, and kidney by hypoxic stress. The overexpression of sFLT1 and HIF-1alpha demonstrated that our experimental conditions closely mimicked ones that are associated with preeclampsia. In the present study, we measured the expression of calcium transporters (TRPV5, TRPV6, PMCA1, NCKX3, NCX1, and CaBP-9k) in the placenta, duodenum, and kidney under hypoxic conditions on Gestational Day 19.5 in rats. Placental TRPV5, TRPV6, and PMCA1 expression was up-regulated in the hypoxic rats, whereas the levels of NCX1 and CaBP-9k were unchanged. In addition, NCKX3 expression was increased in the placenta of hypoxic rats. Duodenal expression of CaBP-9k, TRPV5, TRPV 6, and PMCA1 was decreased in the hypoxic rats, whereas levels of NCXs were not altered. Renal expression of NCKX3 and TRPV6 was increased, whereas NCX1 was decreased in the hypoxic rats compared to the normoxic controls. Taken together, these results indicate that physiological changes observed in the hypoxic rats were similar to ones associated with preeclampsia. Expression of calcium transport genes in the placenta, duodenum, and kidney perturbed by hypoxic stress during pregnancy may cause calcium loss in the urine, and thereby induce calcium-deficient characteristics of preeclampsia. PMID:23255337

  17. Sex differences in fear-induced feeding cessation: prolonged effect in female rats.

    PubMed

    Petrovich, Gorica D; Lougee, Mariel A

    2011-10-24

    Fear inhibits food intake. Cessation of eating in anticipation of danger is an adaptive response that prepares an organism for an imminent threat, but it could become maladaptive when persistent. To begin to examine the underlying mechanisms, we developed an animal model for fear-cue induced inhibition of feeding. In that preparation, food-deprived rats stop eating when presented with a tone that signals a foot-shock based on prior associations. Here, we examined whether there are sex differences in adult male and female rats. We found that female rats showed sustained fear-cue induced feeding inhibition compared to males during the extinction. During the first of four extinction tests with tone presentations, both male and female rats showed similar, robust cessation of eating. Rats of both sexes that previously received tone-shock pairings ate significantly less than the control rats that received tones without shocks during training. Male rats extinguished this behavior during the second test, while females continued to show the effect during the second and third tests, and extinguished during the fourth test. The findings provide a novel framework for investigation of sex differences in the control of feeding and the underlying brain substrates. The animal model may also be informative for understanding human eating and associated disorders. In particular, the potential contribution of fear in the maintenance of low food intake in anorexia nervosa is hypothesized. PMID:21745485

  18. The Effects of Aerobic Exercise on Cocaine Self-Administration in Male and Female Rats

    PubMed Central

    Smith, Mark A.; Walker, Katherine L.; Cole, Kathryn T.; Lang, Kimberly C.

    2013-01-01

    Rationale In drug self-administration procedures, extended-access test sessions allow researchers to model maladaptive patterns of excessive and escalating drug intake that are characteristic of human substance-abusing populations. Objectives The purpose of the present study was to examine the ability of aerobic exercise to decrease excessive and escalating patterns of drug intake in male and female rats responding under extended-access conditions. Methods Male and female Long-Evans rats were obtained at weaning and divided into sedentary (no running wheel) and exercising (running wheel) groups immediately upon arrival. After six weeks, rats were surgically implanted with intravenous catheters and allowed to self-administer cocaine under positive reinforcement contingencies. In Experiment 1, cocaine self-administration was examined during 23-hour test sessions that occurred every four days. In Experiment 2, the escalation of cocaine intake was examined during daily 6-hour test sessions over 14 consecutive days. Results In Experiment 1, sedentary rats self-administered significantly more cocaine than exercising rats during uninterrupted 23-hour test sessions, and this effect was apparent in both males and females. In Experiment 2, sedentary rats escalated their cocaine intake to a significantly greater degree than exercising rats over the 14 days of testing. Although females escalated their cocaine intake to a greater extent than males, exercise effectively attenuated the escalation of cocaine intake in both sexes. Conclusions These data indicate that aerobic exercise decreases maladaptive patterns of excessive and escalating cocaine intake under extended-access conditions. PMID:21567123

  19. Female rats are more susceptible to the deleterious effects of paradoxical sleep deprivation on cognitive performance.

    PubMed

    Hajali, Vahid; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Shabani, Mohammad

    2012-03-17

    Paradoxical sleep deprivation (PSD) may alter subsequent learning and memory capacity. There are differences in both the intensity and direction of responses of the male and female species to the same environmental stimuli and experimental conditions. In the present study, we examined the extent of the effects of PSD for 72h on spatial learning and memory, anxiety-like behavior, corticosterone levels, and the body weight in male as well as in intact and ovariectomized (OVX) female Wistar rats. Multiple platform method was used for PSD induction. Spatial learning and memory and anxiety-like behavior were determined using Morris water maze (MWM) task and open field test, respectively. The data showed that PSD could not significantly affect subsequent spatial learning and short-term memory in male rats, while it significantly impaired the performance of the intact and OVX female rats. The PSD-intact and -OVX female rats showed more memory impairment than the PSD-male animals. Those impairments do not appear to be due to elevated stress level, since the plasma corticosterone did not significantly change following PSD induction. The open field data showed that PSD significantly reduced anxiety-like behavior in all experimental groups. In addition, PSD had a reducing effect on the mean body weight of female groups. Such results suggest that the female rats are more vulnerable to the deleterious effects of sleep loss on cognitive performance. PMID:22192378

  20. Isoflurane anesthesia interferes with the expression of cocaine-induced sensitization in female rats.

    PubMed

    Siegal, Nora; Dow-Edwards, Diana

    2009-10-16

    Repeated cocaine administration results in a progressive sensitization of behavior which typically occurs more readily in female rats than in males. Our recent studies of rats undergoing surgical procedures revealed that following anesthesia, females sensitized less than males receiving identical repeated cocaine injections. Since isoflurane acts primarily by increasing the effects of the inhibitory neurotransmitter gamma-amino butyric acid (GABA) and reducing the effects of the excitatory amino acid glutamate, these amino acids may play more prominent roles in sensitization to cocaine in females than previously understood. In order to examine the effects of isoflurane on cocaine-sensitization, we administered cocaine (15 mg/kg i.p) or saline to adult male and female Sprague-Dawley rats for 9 days; on day 10, half of the rats were subjected to isoflurane anesthesia and the other half did not receive anesthesia. On day 11, rats were given their last dose of either cocaine or saline. We recorded behaviors for 1h on days 1, 9 and 11. Locomotor activity and stereotyped behaviors were quantified using photo beam monitors and the scoring of video tapes, respectively. Results indicated that a single exposure to isoflurane significantly dampens the stereotypic behavior associated with repeated cocaine administration in females but not in males. They further suggest that either GABA or glutamate play more prominent roles in cocaine-sensitization behavior in females than in males. PMID:19660521

  1. Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.

    PubMed

    Golcu, Doruk; Gebre, Rahiwa Z; Sapolsky, Robert M

    2014-08-01

    The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. PMID:24907696

  2. [The diuretic effect of a bath. Study in healthy pregnant females and patients with edema and gestosis].

    PubMed

    Schnizer, W; Mesrogli, M; Seichert, N; Schps, P; Knorr, H; Schneider, J; Wassmann, M

    1989-01-01

    The effect of a 40 minute thermoneutral bath on diuretic function and blood volume in a total of 27 pregnant women (13 healthy and 14 pregnant women with edema rsep. EPH-gestosis) was investigated. In both groups water immersion led to a significant increase of urine flow, natriuresis, kaliuresis, osmotic and free water clearance. Plasma volume increased about 8-9%. The patients with gestosis showed a higher creatinine clearance. The same group also showed a higher osmotic clearance and relatively more sodium excretion. Regarding the flushing effect of bath, two mechanism of water immersion that originated in hydrostatic pressure have to be discussed-activation of renal functions and mobilisation of interstitial fluid. PMID:2800772

  3. 14-C-NAPHTHYL, 14-C-METHYL AND 14-C-CARBONYL CARBARYL DISTRIBUTION IN THE PREGNANT MOUSE AND RAT

    EPA Science Inventory

    The distribution of carbaryl labeled with 14C in the ring, methyl or carbonyl groups was determined in pregnant mice and rats. Three identical concurrent experiments were performed using each of the three radiolabeled compounds in each of the species so that the different moietie...

  4. Characterization of biliary conjugates of 4,4'-methylenedianiline in male versus female rats

    SciTech Connect

    Chen, Kan; Cole, Richard B.; Santa Cruz, Vicente; Blakeney, Ernest W.; Kanz, Mary F.; Dugas, Tammy R.

    2008-10-15

    4,4'-Methylenedianiline (4,4'-diaminodiphenylmethane; DAPM) is an aromatic diamine used in the production of numerous polyurethane foams and epoxy resins. Previous studies in rats revealed that DAPM initially injures biliary epithelial cells of the liver, that the toxicity is greater in female than in male rats, and that the toxic metabolites of DAPM are excreted into bile. Since male and female rats exhibit differences in the expression of both phase I and phase II enzymes, our hypothesis was that female rats either metabolize DAPM to more toxic metabolites or have a decreased capacity to conjugate metabolites to less toxic intermediates. Our objective was thus to isolate, characterize, and quantify DAPM metabolites excreted into bile in both male and female bile duct-cannulated Sprague Dawley rats. The rats were gavaged with [{sup 14}C]-DAPM, and the collected bile was subjected to reversed-phase HPLC with radioisotope detection. Peaks eluting from HPLC were collected and analyzed using electrospray MS and NMR spectroscopy. HPLC analysis indicated numerous metabolites in both sexes, but male rats excreted greater amounts of glutathione and glucuronide conjugates than females. Electrospray MS and NMR spectra of HPLC fractions revealed that the most prominent metabolite found in bile of both sexes was a glutathione conjugate of an imine metabolite of a 4'-nitroso-DAPM. Seven other metabolites were identified, including acetylated, cysteinyl-glycine, glutamyl-cysteine, glycine, and glucuronide conjugates. While our prior studies demonstrated increased covalent binding of DAPM in the liver and bile of female compared to male rats, in these studies, SDS-PAGE with autoradiography revealed 4-5 radiolabeled protein bands in the bile of rats treated with [{sup 14}C]-DAPM. In addition, these bands were much more prominent in female than in male rats. These studies thus suggest that a plausible mechanism for the increased sensitivity of female rats to DAPM toxicity may be decreased conjugation of reactive DAPM metabolites, leading to greater levels of protein adduct formation.

  5. Exercise training attenuates acute hyperalgesia in streptozotocin-induced diabetic female rats

    PubMed Central

    Rossi, Denise M.; Valenti, Vitor E.; Navega, Marcelo T.

    2011-01-01

    OBJECTIVES: We investigated the effects of chronic (eight weeks) low- to moderate-intensity swimming training on thermal pain sensitivity in streptozotocin-induced diabetic female rats. METHODS: Female Wistar rats (n = 51) were divided into the following groups: trained streptozotocin-induced diabetic rats [hyperglycemic trained (HT)], sedentary streptozotocin-induced diabetic rats [hyperglycemic sedentary (HS)], normoglycemic trained rats (NT) and normoglycemic sedentary rats (NS). Diabetes was induced by a single injection of streptozotocin (50 mg/kg, i.p.). One day after the last exercise protocol (60 min/day, five days/week for eight weeks) in the trained groups or after water stress exposure (ten min/twice a week) in the sedentary groups, the rats were subjected to a hot plate test. RESULTS: After eight weeks of swimming training, streptozotocin-induced diabetic rats presented a significantly lower body mass (trained: 219.5±29 g, sedentary: 217.8±23 g) compared with the normoglycemic groups (trained: 271±24 g, sedentary: 275.7±32 g). Interestingly, we did not find differences in blood glucose levels (mg/dl) between the trained and sedentary groups of the hyperglycemic or normoglycemic rats (HT: 360.2±66.6, HS: 391.7±66.7, NT: 83.8±14.0, NS: 77.5±10.1). In the hot plate test, the rats from the HT group presented a significantly lower latency than the other rats (HT: 11.7±7.38 s, HS: 7.02±7.38 s, NT: 21.21±7.64 s, NS: 22.82±7.82 s). CONCLUSION: Low-to-moderate swimming training for a long duration reduces thermal hyperalgesia during a hot plate test in streptozotocin-induced diabetic female rats. PMID:22179169

  6. The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study

    PubMed Central

    Nikoui, Vahid; Ostadhadi, Sattar; Takzare, Nasrin; Nabavi, Seyyed Mohammad-Ali; Bakhtiarian, Azam

    2013-01-01

    Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5?mL of normal saline. Clomipramine was injected at 40?mg/kg and 80?mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60?mg/kg and 120?mg/kg, respectively. The sixth group received a combination of 40?mg/kg clomipramine and 60?mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80?mg/kg and 120?mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P ? 0.001). This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity. PMID:24298213

  7. Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague-Dawley Rat.

    PubMed

    Breckenridge, Charles B; Sawhney Coder, Pragati; Tisdel, Merrill O; Simpkins, James W; Yi, Kun Don; Foradori, Chad D; Handa, Robert J

    2015-10-01

    Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post-weaning (G/L/PW cohort) to F1 generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen-primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F1 females received the vehicle or ATZ from PND 21-133 or from PND 120-133. Slight reductions in fertility and the percentage of F1 generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F1 generation offspring. The onset of puberty was delayed in of the F1 generation G/L/PW females at doses of 25 and 50 mg/kg/day. F1 generation females in the PW high-dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F1 generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F1 generation females exposed from gestation through to PND 133 or only for two weeks from PND 120-133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults. PMID:26439775

  8. Endothelial-Derived Hyperpolarization Factor (EDHF) Contributes to PlGF-Induced Dilation of Mesenteric Resistance Arteries from Pregnant Rats

    PubMed Central

    Mandal, Maurizio; Gokina, Natalia; Barron, Carolyn; Osol, George

    2011-01-01

    The aim of this study was to investigate the cellular mechanism involved in the potent vasodilatory action of PlGF on mesenteric resistance arteries from pregnant rats. PlGF (3 nM) induced a vasodilation of 64 3.8% that was completely abolished by endothelial denudation. Significant dilation (28 4.0%) remained, however, in the presence of nitric oxide synthase and cyclooxygenase inhibition, and was associated with significant reductions in vascular smooth muscle cell calcium. Absence of dilation in potassium-depolarizing solution (30 mM) confirmed its dependence on endothelial-derived hyperpolarization factor. Subsequent studies established that vasodilation was abolished by pharmacologic inhibition of SKCa (apamin) and BKCa (iberiotoxin) but not IKCa (tram-34) potassium channels. In summary, PlGF acts through the release of a combination of endothelium-derived relaxation factors. Based on the results of potassium channel blockade, we suggest that it induces endothelial hyperpolarization via SKCa channel activation; this, in turn, leads to the release of a diffusible mediator that activates vascular smooth muscle BKCa channels, hyperpolarization and vasodilation. This is the first study to identify the mechanism for PlGF/VEGFR-1 resistance artery dilation in the pregnant state, whose attenuation likely contributes to the systemic hypertension characteristic of pre-eclampsia. PMID:21985802

  9. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C.

    PubMed

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

  10. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C

    PubMed Central

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

  11. The accumulation and histological effects of organometallic fungicides Propineb and Maneb in the kidneys of fetus and female rats during pregnancy.

    PubMed

    Guven, K; Deveci, E; Akba, O; Onen, A; de Pomerai, D

    1998-10-15

    Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb and 250 ppm maneb, from the sixth day of gestation up to birth. We found that the body weights of both one-day old litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the kidneys of fetus and fungicide-treated pregnant females showed a variety of histopathological effects. Moreover, the analysis of zinc (Zn) and manganese (Mn) concentrations (using inductively coupled plasma-atomic emission spectrometry) in the kidneys of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the kidney were higher than those of controls. However, the renal metal concentrations were significantly increased in the litters subjected to the fungicides during gestation, indicating that high levels of the trace metals in the organ of fetus may well be due to the fungicides easily passing the placental barrier. PMID:9817080

  12. Nonpreventive Role of Aerobic Exercise Against Cisplatin-induced Nephrotoxicity in Female Rats

    PubMed Central

    Noroozi, Jalaledin; Zeynali, Farzaneh; Nematbakhsh, Mehdi; Pezeshki, Zahra; Talebi, Ardeshir

    2015-01-01

    Background: Cisplatin (CP) is a chemotherapy drug and nephrotoxicity is a major concern for CP therapy. CP-induced nephrotoxicity is gender-dependent, and the effect of aerobic exercise in females has not been reported yet while it has a beneficial effect in males. Hence, this study was designed to determine the protective role of aerobic exercise against CP-induced nephrotoxicity in female rats. Methods: Twenty-eight adult female rats were divided into four groups. Groups I and II had aerobic exercise on a treadmill for 8 weeks. Then, the exercise protocol was continued for another week in group I and stopped in group II. All animals in these groups received CP (2.5 mg/kg/day; i.p.) for 1-week. Groups III and IV were treated with CP and vehicle, respectively, without exercise. Finally, the animals were sacrificed for biochemical measurements and tissue histopathology investigations. Results: CP alone without exercise increased serum levels of blood urea nitrogen (BUN) and creatinine (Cr), kidney weight, and kidney tissue damage score (KTDS); while exercise could not attenuate these parameters in female rats. Exercise in females increased the serum levels of BUN and Cr and KTDS and weight loss (P < 0.05). Kidney nitrite levels reduce significantly in group I in compared to positive and negative control groups. Exercise also did not have beneficial effects on malondialdehyde levels in plasma and kidney. Conclusions: Aerobic exercise cannot reduce CP-induced nephrotoxicity in female rats. Increasing the damage in female rats may be related to female sex hormone estrogen or gender differences in renal hemodynamic and renin-angiotensin system activity in the presence of exercise. In general, it is recommended that the females under CP chemotherapy avoid exercising during treatment. PMID:26288702

  13. Long-term programming of enhanced aggression by peripuberty stress in female rats.

    PubMed

    Cordero, M Isabel; Ansermet, Franois; Sandi, Carmen

    2013-11-01

    Human literature has linked adverse early life experiences with an increased risk to develop violent behaviors in both boys and girls. We have previously shown that male rats submitted to stress during the peripuberty period display as adults abnormal aggressive behavior against both male intruders and female partners. In the present study, we examined whether the same stress protocol would affect the development of aggressive behaviors in female rats. We evaluated the behavior of these peripuberty stressed female rats when confronted, at adulthood, with either female or male intruders, and during their cohabitation with male partners. Given that estrus cycle influences mood and aggressive behaviors, female aggressive behavior was assessed at different estrus cycle phases: estrus and diestrus, and during pregnancy and lactancy. Additionally, we evaluated postpartum plasma levels of vasopressin, oxytocin and corticosterone, hormones associated with aggression and the regulation of social behavior. Compared to control females, females submitted to stressful events during puberty exhibited higher and more sustained rates of aggression during adulthood independently on the estrus cycle or the sex of the intruder, and they had higher levels of plasma vasopressin. Significant correlations between plasma levels of vasopressin and corticosterone and aggressive behavior were also found. Strikingly, our results showed opposite intragroup correlations suggesting a different role of these hormones on aggression depending on life experiences. We provide here an animal model, devoid of cultural influences strongly supporting a role for biological factors in the development of aggressive behaviors following exposure to stressful events at puberty in females. PMID:23942011

  14. In Utero and Lactational Exposures to Low Doses of Polybrominated Diphenyl Ether-47 Alter the Reproductive System and Thyroid Gland of Female Rat Offspring

    PubMed Central

    Talsness, Chris E.; Kuriyama, Sergio N.; Sterner-Kock, Anja; Schnitker, Petra; Grande, Simone Wichert; Shakibaei, Mehdi; Andrade, Anderson; Grote, Konstanze; Chahoud, Ibrahim

    2008-01-01

    Background Polybrominated diphenyl ethers (PBDEs) are capable of disrupting thyroid hormone homeostasis. PBDE-47 (2,2?,4,4?-tetrabromodiphenyl ether) is one of the most abundant congeners found in human breast adipose tissue and maternal milk samples. Objectives We evaluated the effects of developmental exposure to low doses of PBDE-47 on the female reproductive system. Methods Pregnant Wistar rats were administered vehicle (peanut oil) or PBDE-47 [140 or 700 ?g/kg body weight (bw)] on gestation day (GD) 6, or 5 mg 6-n-propyl-2-thiouracil (PTU)/L in the drinking water from GD7 through postnatal day (PND) 21. Results In female offspring sacrificed on PND38, there was a significant decrease in ovarian weight after exposure to PTU or 140 ?g/kg PBDE-47. Alterations in folliculogenesis were apparent: we observed a decrease in tertiary follicles and serum estradiol concentrations in the offspring exposed to either PTU or 700 ?g/kg PBDE-47. PTU exposure also resulted in a decrease in primordial follicles. On PND100, persistent effects on the thyroid glands included histologic and morphometric changes after exposure to either PTU or PBDE-47. No relevant changes in reproductive indices were observed after mating the exposed F1 females with nontreated males. Conclusions Administration of PBDE-47 at doses relevant to human exposure led to changes in the rat female reproductive system and thyroid gland. PMID:18335096

  15. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    PubMed

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy. PMID:7699389

  16. ACUTE CADMIUM EXPOSURE AND OVARIAN STEROIDOGENESIS IN CYCLING AND PREGNANT RATS

    EPA Science Inventory

    The purpose of this study was to evaluate the effect(s) of acute in vivo cadmium exposure on steroidogenesis in rat ovaries during different reproductive states. prague-Dawley rats were injected subcutaneously on the day of diestrus, or on day 7 or 16 of gestation with a single d...

  17. A calcium-deficient diet in pregnant, nursing rats induces hypomethylation of specific cytosines in the 11?-hydroxysteroid dehydrogenase-1 promoter in pup liver.

    PubMed

    Takaya, Junji; Iharada, Anna; Okihana, Hiroyuki; Kaneko, Kazunari

    2013-11-01

    Prenatal undernutrition affects offspring phenotype via changes in the epigenetic regulation of specific genes. We hypothesized that pregnant females that were fed a calcium (Ca)-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and altered epigenetic gene regulation. Female Wistar rats ate either a Ca-deficient or control diet from 3 weeks before conception to 21 days after parturition. Pups were allowed to nurse from their original mothers and then euthanized on day 21. Methylation of individual cytosine-guanine dinucleotides in the phosphoenolpyruvate carboxykinase (Pck1), peroxisome proliferator-activated receptor ? (Ppara), glucocorticoid receptor (Nr3c1), 11?-hydroxysteroid dehydrogenase-1 (Hsd11b1), and 11?-hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters was measured in liver tissue using pyrosequencing. For each gene, quantitative real-time polymerase chain reaction was used to assess mRNA levels in liver tissue. Overall Hsd11b1 methylation was lower in the Ca-deficient group than in the control group; however, overall methylation of each other gene did not differ between groups. Serum corticosterone levels in male pups from Ca-deficient dams were higher than those in control pups. Expression of Pck1 and Nr3c1 was lower in the Ca-deficient group than in the control group. A Ca-deficient diet for a dam during gestation and early nursing may alter glucocorticoid metabolism and lead to higher intracellular glucocorticoid concentrations in the hepatic cells of her offspring; moreover, this abnormal glucocorticoid metabolism may induce the metabolic complications that are associated with Ca deficiency. These findings indicated that prenatal nutrition affected glucocorticoid metabolism in offspring in part by affecting the epigenome of offspring. PMID:24176236

  18. Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury

    PubMed Central

    Geddes, Rastafa I.; Peterson, Bethany L.; Stein, Donald G.; Sayeed, Iqbal

    2016-01-01

    Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone’s effects in the same model of brain injury but with pre-pubescent females. Methods Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1–7, and underwent behavioral testing from PID 9–27. Brains were evaluated for lesion size at PID 28. Results Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Conclusion Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI. PMID:26799561

  19. Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats.

    PubMed

    Lalanza, Jaume F; Sanchez-Roige, Sandra; Cigarroa, Igor; Gagliano, Humberto; Fuentes, Silvia; Armario, Antonio; Capdevila, Llus; Escorihuela, Rosa M

    2015-01-01

    Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non-handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders. PMID:26538081

  20. Long-term moderate treadmill exercise promotes stress-coping strategies in male and female rats

    PubMed Central

    Lalanza, Jaume F.; Sanchez-Roige, Sandra; Cigarroa, Igor; Gagliano, Humberto; Fuentes, Silvia; Armario, Antonio; Capdevila, Lluís; Escorihuela, Rosa M.

    2015-01-01

    Recent evidence has revealed the impact of exercise in alleviating anxiety and mood disorders; however, the exercise protocol that exerts such benefit is far from known. The current study was aimed to assess the effects of long-term moderate exercise on behavioural coping strategies (active vs. passive) and Hypothalamic-Pituitary-Adrenal response in rats. Sprague-Dawley male and female rats were exposed to 32-weeks of treadmill exercise and then tested for two-way active avoidance learning (shuttle-box). Two groups were used as controls: a non-handled sedentary group, receiving no manipulation, and a control group exposed to a stationary treadmill. Female rats displayed shorter escape responses and higher number of avoidance responses, reaching criterion for performance earlier than male rats. In both sexes, exercise shortened escape latencies, increased the total number of avoidances and diminished the number of trials needed to reach criterion for performance. Those effects were greater during acquisition in female rats, but remained over the shuttle-box sessions in treadmill trained male rats. In females, exercise did not change ACTH and corticosterone levels after shuttle-box acquisition. Collectively, treadmill exercise improved active coping strategies in a sex-dependent manner. In a broader context, moderate exercise could serve as a therapeutic intervention for anxiety and mood disorders. PMID:26538081

  1. The influence of dietary restriction on the development of diabetes and pancreatitis in female WBN/Kob-fatty rats.

    PubMed

    Akimoto, Toshio; Terada, Misao; Shimizu, Akira; Sawai, Nobuhiko; Ozawa, Hitoshi

    2010-01-01

    Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr(fa)) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis. PMID:21030790

  2. The effects of vitamin D3 on lipogenesis in the liver and adipose tissue of pregnant rats.

    PubMed

    Kang, Eun-Jin; Lee, Jae-Eon; An, Sung-Min; Lee, Jae Ho; Kwon, Hyeog Soong; Kim, Byoung Chul; Kim, Seon Jong; Kim, Joo Man; Hwang, Dae Youn; Jung, Young-Jin; Yang, Seung Yun; Kim, Seung Chul; An, Beum-Soo

    2015-10-01

    Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitaminD3(VD3), an active hormonal form of nutritional vitaminD3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism?associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase(FAS), stearoyl-CoA desaturase1(SCD1) and acetyl-CoA carboxylase1(ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c(SREBP-1c), peroxisome proliferator-activated receptor-?(PPAR-?) and insulin-induced gene2(INSIG2) were differentially regulated by VD3 in a tissue?specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity?related pregnancy complications such as pre-eclampsia, gestational diabetes, hypertension and issues with labor. PMID:26239543

  3. Selenium and vitamin E modulates radiation-induced liver toxicity in pregnant and nonpregnant rat: effects of colemanite and hematite shielding.

    PubMed

    Genel, Osman; Naziroglu, Mustafa; Celik, Omer; Yalman, Kadir; Bayram, Dilek

    2010-06-01

    The levels of liver lipid peroxidation, glutathione peroxidase, reduced glutathione, and vitamins A and E were used to follow the level of oxidative damage caused by ionizing radiation in pregnant rats. The possible protective effects of selenium and vitamin E supplemented to rats housed in concrete-protected cages using hematite and colemanite were tested and compared to untreated controls. Ninety-six rats were randomly divided into four main equal groups namely control (A), normal concrete (B), concrete containing colemanite (C), and concrete containing hematite (D). Except group A, all groups exposed to 7 Gy radiation. The four main groups were divided into four subgroups each as follows: subgroups 1 (n = 6): nonpregnant control rats. Subgroups 2 (n = 6): selenium and vitamin E combination was intraperitoneally (i.p.) given to the nonpregnant rats for 20 days. Subgroups 3 (n = 6): pregnant control rats. Subgroups 4 (n = 6): selenium and vitamin E combination was i.p. given to the pregnant rats for concessive 20 days. Lactate dehydrogenate, alkaline phosphates, and lipid peroxidation values were higher in subgroups 1 and 3 than in no radiation group although glutathione peroxidase and vitamin E levels in liver were lower in radiation group than in no radiation group. Lactate dehydrogenate activity and lipid peroxidation levels were found to be decreased in subgroups 2 and 4 protected with concrete containing hematite and colemanite when compared to subgroup 1 and 3 with normal concrete. The radiation doses in rats housed by concrete without colemanite and hematite exposed radiation clearly showed liver degeneration. In conclusion, selenium and vitamin E supplementations and housing by concrete with colemanite was found to offer protection against gamma-irradiation-induced liver damage and oxidative stress in rats, probably by exerting a protective effect against liver necrosis via its free radical scavenging and membrane stabilizing. Protective effects of colemanite in the liver seem to be more important than in hematite. PMID:19763408

  4. Knowledge of malaria prevention among pregnant women and female caregivers of under-five children in rural southwest Nigeria

    PubMed Central

    Adebayo, Ayodeji M.; Cadmus, Eniola O.

    2015-01-01

    Introduction. The morbidity and mortality from malaria are still unacceptably high in the developing countries, especially among the vulnerable groups like pregnant women and under-five children, despite all control efforts. The knowledge about the preventive measures of malaria is an important preceding factor for the acceptance and use of malaria preventive measures like Insecticide Treated Nets (ITN) by community members. Therefore, this study assessed the knowledge of malaria prevention among caregivers of under-five children and pregnant women in a rural community in Southwest Nigeria. Methodology. This is part of a larger malaria prevention study in rural Southwest Nigeria. A descriptive cross-sectional survey was conducted among pregnant women and caregivers of under-five children in Igbo-Ora, a rural town in Southwest Nigeria using a semi-structured, interviewer-administered questionnaire. Information was obtained on knowledge of malaria prevention, and overall composite scores were computed for knowledge of malaria prevention and ITN use. Data were analyzed using SPSS version 16. Associations between variables were tested using a Chi-square with the level of statistical significance set at 5%. Results. Of the 631 respondents, 84.9% were caregivers of under-five children and 67.7% were married. Mean age was 27.7 6.3 years with 53.4% aged between 20 and 29 years. Majority (91.1%) had at least primary school education and 60.2% were traders. Overall, 57.7% had poor knowledge of malaria prevention. A good proportion (83.5%) were aware of the use of ITN for malaria prevention while 30.6% had poor knowledge of its use. Respondents who were younger (<30 years), had at least primary education and earn <10,000/per month had significantly poor knowledge of ITN use in malaria prevention. Majority (60.0%) respondents had poor attitude regarding use of ITNs. Conclusion. This study showed that the knowledge of malaria prevention is still low among under-five caregivers and pregnant women in rural Southwest Nigeria despite current control measures. There is a need for concerted health education intervention to improve the knowledge of rural dwellers regarding malaria prevention, including the use of ITN. This will go a long way to improving the reported low level of ownership and utilization of ITN in the rural areas. PMID:25755925

  5. Triazophos induced oxidative stress and histomorphological changes in liver and kidney of female albino rats.

    PubMed

    Sharma, Dharmender; Sangha, Gurinder Kaur

    2014-03-01

    Organophosphate (OP) pesticides toxic manifestations have been associated with enhanced generation of reactive oxygen species (ROS) which culminates into oxidative stress (OS). Triazophos (TZ), a broad spectrum OP, was used in the present study to investigate toxic effects on liver and kidney of female albino rats at three sub-chronic dose levels of 1/10th, 1/20th and 1/40th of LD50 for 30 days. Activity levels of different OS parameters viz: catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation (LPO) were differentially altered in liver and kidney of TZ treated rats as compared to control rats. Histomorphological studies further revealed number of abnormalities as infiltration, vacuolization, enlarged sinusoids and necrosis in liver of TZ treated rats, while renal histoarchitecture of 1/10th and 1/20th of LD50 TZ treated rats showed high degeneration of glomeruli. Enhanced apoptosis was also observed in hepatocytes at dose levels of 1/10th and 1/20th of LD50 TZ treated female rats. The results infer that exposure of female albino rats to TZ leads to number of pathophysiological conditions in the liver and kidney at dose dependent manner. PMID:24759054

  6. The Effect of Route of Administration in Thymoquinone Toxicity in Male and Female Rats

    PubMed Central

    AbuKhader, M. M.

    2012-01-01

    The maximum tolerated dose for intraperitoneal injection and oral ingestion of thymoquinone was determined in male and female Wistar rats. A range of dose levels of thymoquinone: 20, 30 and 40 mg/kg body weight for intraperitoneal injection and 200, 300 and 500 mg/kg body weight for oral ingestion were tested for acute toxicity in rats. The results showed that the maximum tolerated dose for intraperitoneal injection was 22.5 mg/kg in male rats and 15 mg/kg in females, whereas for oral ingestion it was 250 mg/kg in both male and female rats. There were different signs of toxicity shown in rats which received intraperitoneal injection from those that received oral ingestion of thymoquinone. Rats which received intraperitoneal injection of thymoquinone showed toxicity signs which were related to acute pancreatitis. Meanwhile, rats which received oral ingestion of thymoquinone showed transient toxicity signs. Two deaths were reported at dose of 500 mg/kg as a result of bowel obstruction complications. The data presented in this study indicate that the route of administration of thymoquinone could have an influence on thymoquinone toxicity outcome in both genders. PMID:23440704

  7. Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis.

    PubMed

    Gualberto, Erivan Clementino; Theodoro, Letcia Helena; Longo, Marielln; Novaes, Vivian Cristina Noronha; Nagata, Maria Jos Hitomi; Ervolino, Edilson; Garcia, Valdir Gouveia

    2016-01-01

    The aim of this study was to compare the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of experimentally induced periodontitis in female rats that were systemically treated with or without nicotine. Female rats (n?=?180) were divided into two groups: vehicle administration (Veh) and nicotine administration (Nic). Mini-pumps containing either vehicle or nicotine were implanted in the rats 30days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7days, the ligature was removed, and the rats were randomly divided into three treatment subgroups: SRP (only SRP), DL (SRP plus diode laser), and aPDT (SRP plus aPDT). The aPDT consisted of phenothiazine photosensitizer deposition followed by diode laser irradiation. Ten rats from each subgroup were euthanized at 7, 15, and 30days after treatment. Alveolar bone loss (ABL) in the furcation region was evaluated using histological, histometric, and immunohistochemical analyses. The rats that were treated with nicotine showed more ABL compared to those treated with vehicle. In both the Veh and Nic groups, SRP plus aPDT treatment resulted in reduced ABL, smaller numbers of both TRAP- and RANKL-positive cells, and higher numbers of PCNA-positive cells compared to SRP treatment alone. aPDT was an effective adjunctive therapy for the treatment of periodontitis in female rats regardless of whether they received nicotine. PMID:26545755

  8. /sup 20/neon ion- and x-ray-induced mammary carcinogenesis in female rats

    SciTech Connect

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to /sup 20/Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for /sup 20/Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that /sup 20/Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

  9. Influence of ascorbic acid (AA) on iron (Fe) utilization in copper (Cu) deficient male and female rats

    SciTech Connect

    Johnson, M.A. )

    1989-02-09

    Interactions between Cu status (-Cu: 1.0 mg Cu/kg diet or +Cu: 5.8 mg Cu/kg diet) and AA (0 or 1% of the diet) were compared in male and female weanling rats. Food intakes were controlled so that final body weights were similar on day 23 when rats were killed. On day 17 rats were given an oral dose of 4 uCi of Fe-59 and feces were collected for 5 days. Heart weights (g/100 g body weight) were increased in both male and female -Cu rats. Among -Cu rats, AA increased heart weight by 25% in females but by only 6% in males. Similarly, among -Cu rats AA increased liver weight (g/100 g body weight) by 16% in females but not at all in males. Hematocrits (%) were similar among +Cu rats but were decreased in -Cu rats to a greater in male than in female rats. However, among -Cu rats AA decreased hematocrits from 34.1 to 26.4% in females but from only 30.0 to 26.8% in males. Compared to -Cu rats, +Cu rats apparently absorbed 2-times more Fe-59 and retained 2.5- times more absorbed Fe-59 in their whole blood. Among -Cu rats, AA decreased the absorption of Fe-59 and whole blood Fe-59 to a greater extent in female than in male rats. These results suggest that female rats may be somewhat more sensitive to the adverse effects of AA during Cu deficiency than are male rats.

  10. Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats.

    PubMed

    Coldren, K Max; Brown, Randall; Hasser, Eileen M; Heesch, Cheryl M

    2015-12-15

    Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptor-denervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 ± 3%) and mean arterial pressure (MAP; 26 ± 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml(-1)·h(-1); 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 ± 2%) and arginine-vasopressin (AVP)-IR (21 ± 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy. PMID:26400184

  11. Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring.

    PubMed

    Lucas, A; Baker, B A; Desai, M; Hales, C N

    1996-10-01

    Epidemiological studies in human show that size in early life is related to blood cholesterol concentrations in adult life, raising the hypothesis that early nutrition programs later lipid metabolism, affecting risk for later vascular disease. Here, we tested the hypothesis that nutrition during pregnancy or lactation in the rat programs lipid metabolism in the offspring, studied in adult life (mean 6 months). Rats (n 35) from normally-fed dams (controls) were compared with (1) rats (n 22) from dams protein-restricted in pregnancy and lactation; (2) rats (n 9) born to normally-fed mother crossed to protein-restricted lactating dams and (3) those (n 9) born of protein-restricted dams and crossed to normally-fed lactating animals. In these latter three groups the offspring showed long-term reduction in plasma cholesterol, HDL-cholesterol and triacylglycerol concentrations compared with controls. The effects were predominantly in males. These findings suggest that in the rat the sensitive period for nutritional programming of cholesterol and triacylglycerol metabolism is both pre- and postnatal (pre-weaning) and that rats may be 'indirectly' programmed by altering the maternal nutritional milieu during gestation or lactation. Whilst it has been hypothesized that early human undernutrition programs risk for vascular disease, one aspect of undernutrition, low maternal protein intake, in this rat model programmed lower plasma cholesterol and triacylglycerol concentrations. PMID:8942366

  12. Lead exposure and latent learning ability of adult female rats.

    PubMed

    Rodrigues, A L; Rubin, M A; Souza, D O; de Mello, C F

    1993-11-01

    The present report investigates the effects of lead exposure during the pre- and postnatal period on the latent learning ability in a maze. Rats were submitted to lead acetate intoxication by giving their dams 0.5, 1.0, or 4.0 mM lead acetate or deionized water. Rats were weaned at 21 days, and the treatment was continued by giving the same solution of lead acetate in the drinking water until behavioral testing. Under a nonappetitive condition, rats were exposed either to an open field or to a maze apparatus. They were thereafter deprived of food and tested in the maze apparatus. Lead treatment induced an increase in locomotor activity in the open field during training sessions, and animals failed to habituate to the environment. Nevertheless, both lead-treated and control rats that had been previously exposed to the maze performed better than those exposed to the open field. These results suggest that rats intoxicated with lead are able to learn about the environment when no immediate reinforcement is involved. PMID:8297324

  13. Brain activation by an olfactory stimulus paired with juvenile play in female rats.

    PubMed

    Paredes-Ramos, P; McCarthy, M M; Bowers, J M; Miquel, M; Manzo, J; Coria-Avila, G A

    2014-06-22

    We have previously shown that reward experienced during social play at juvenile age can be paired with artificial odors, and later in adulthood facilitate olfactory conditioned partner preferences (PP) in female rats. Herein, we examined the expression of FOS immunoreactivity (FOS-IR) following exposure to the odor paired with juvenile play (CS+). Starting at day P31 females received daily 30-min periods of social play with lemon-scented (paired group) or unscented females (unpaired group). At day P42, they were tested for play-PP with two juvenile males, one bearing the CS+ (lemon) and one bearing a novel odor (almond). Females were ovariectomized, hormone-primed and at day P55 tested for sexual-PP between two adult stud males scented with lemon or almond. In both tests, females from the paired group displayed conditioned PP (play or sexual) toward males bearing the CS+. In the present experiments females were exposed at day P59 to the CS+ during 60 min and their brains processed for FOS-IR. One group of female rats (Play+Sex) underwent play-PP and sexual-PP, whereas a second group of females (Play-only) underwent exclusively play-PP but not sexual-PP. Results showed that in the Play-only experiment exposure to the CS+ induced more FOS-IR in the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, and ventral tegmental area as compared to females from the unpaired group. In the Play+Sex experiment, more FOS-IR was observed in the piriform cortex, dorsal striatum, lateral septum, nucleus accumbens shell, bed nucleus of the stria terminalis and medial amygdala as compared to females from the unpaired group. Taken together, these results indicate mesocorticolimbic brain areas direct the expectation and/or choice of conditioned partners in female rats. In addition, transferring the meaning of play to sex preference requires different brain areas. PMID:24835545

  14. Female rats exhibit greater susceptibility to early alcohol-induced liver injury than males.

    PubMed

    Iimuro, Y; Frankenberg, M V; Arteel, G E; Bradford, B U; Wall, C A; Thurman, R G

    1997-05-01

    It is known that women develop hepatic injury more rapidly and with exposure to less ethanol than men; however, mechanisms remain unclear. The purpose of this study was to determine if an enteral alcohol delivery model could be used to study susceptibility of females to alcohol-induced liver injury. Male and female Wistar rats (age- or weight-matched) were given ethanol (11-12 g.kg-1.day-1) continuously for up to 4 wk via intragastric feeding, and control rats received a high-fat diet without ethanol. There were no significant differences in body weight among the groups studied. Furthermore, mean ethanol concentrations, their cyclic pattern in urine, and rates of ethanol elimination were also not different between the genders under these conditions. Ethanol treatment elevated serum aspartate aminotransferase levels in male rats to 126 +/- 10 IU/l after 4 wk. In females, however, values increased more rapidly and reached significantly higher values at 4 wk (168 +/- 18 IU/l). Steatosis, inflammation, and necrosis assessed histologically also developed more rapidly and were more severe in females than males. Steatosis due to ethanol exposure, which was localized in centrilobular areas in males, was panlobular in the female. Moreover, endotoxin in plasma, intercellular adhesion molecule 1 expression in hepatic sinusoidal-lining cells, and the number of infiltrating inflammatory cells in the liver were 2-2.5-fold greater in females than males. These changes possibly account for increased hepatic injury due to ethanol in the female. PMID:9176229

  15. Environmental enrichment attenuates nicotine behavioral sensitization in male and female rats.

    PubMed

    Hamilton, Kristen R; Elliott, Brenda M; Berger, Sarah Shafer; Grunberg, Neil E

    2014-08-01

    Environmental enrichment decreases nicotine reactivity in male rats, but these effects have not been examined in females. This research was conducted to examine the effects of enrichment on nicotine behavioral sensitization (i.e., nicotine reactivity) in male and female rats. One hundred forty-four Sprague-Dawley rats (72 male, 72 female) were raised in isolation, social enrichment (groups of three rats [SE]), or combined physical enrichment and social enrichment (groups of three rats with novel toys [PESE]) housing conditions. As adults, they received daily subcutaneous injections of saline or nicotine (0.1, 0.5, or 1.0 mg/kg) for 12 days; locomotor activity was measured on drug days 1, 5, 9, and 12. Before drug administration, PESE and SE decreased activity in males; only PESE decreased activity in females, F(2, 120) = 6.51, p < .01. In the drug phase, nicotine behavioral sensitization occurred, F(8.46, 341.04) = 20.71, p < .001, and was greater in females than males, F(8.340, 319.715) = 2.072, p < .05. Enrichment decreased nicotine behavioral sensitization in both sexes, F(16.91, 341.04) = 2.48, p < .01. In conclusion, nicotine behavioral sensitization occurred in male and female rats and was attenuated by environmental enrichment. This research has implications for treatment and prevention strategies in humans. Programs that incorporate aspects of social and environmental stimulation may have enhanced effectiveness in preventing and reducing cigarette smoking and may have implications for relapse prevention. PMID:24956172

  16. Cognitive differences between male and female rats following exposure to 56Fe particles

    NASA Astrophysics Data System (ADS)

    Rabin, Bernard; Shukitt-Hale, Barbara; Carrihill-Knoll, Kirsty; Luskin, Katharine; Long, Lauren; Joseph, James

    On exploratory class missions astronauts will be exposed to types and doses of radiation (HZE particles) that are not experienced in low earth orbit. While it is likely that the crew will consist of both male and female astronauts, there has been little research on the effects of exposure to HZE particles on cognitive performance in female subjects. While previous research has shown that exposure to HZE particles disrupts cognitive performance in male rats it remains to be established whether or not similar effects will occur with female subjects because estrogen may act as a neuroprotectant. Ovariectomized (OVX) female rats were obtained from Taconic Farms. Thirty mm segments of silastic tubing containing either 180 pg l7-estradiol/mL in sesame oil or vehicle alone were implanted subcutaneously in the neck. Three days following surgery the rats were exposed to 56Fe particles (1000 MeV/n, 0-200 cGy) at the NSRL. Following irradiation the rats were shipped to UMBC for behavioral testing. The results indicated that the pattern of decrements in cognitive performance differed between male and female rats. In addition, for female rats, there were differences in performance as a function of the presence or absence of estradiol. In the vehicle implanted subjects exposure to 56Fe particles did not affect operant responding on an ascending fixed-ratio schedule; whereas irradiation did disrupt responding in OVX animals given estradiol. These results suggest that estrogen may not be protective following exposure to HZE particles. This research was supported by Grant NNX08AM66G from NASA.

  17. Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and Augments Fetal Growth and Venous Remodeling.

    PubMed

    Gizurarson, Sveinbjorn; Sigurdardottir, Elisabet Run; Meiri, Hamutal; Huppertz, Berthold; Sammar, Marei; Sharabi-Nov, Adi; Mandal, Maurizio; Osol, George

    2016-01-01

    Reduced first-trimester concentrations of placental protein 13 (PP13) are associated with subsequent development of preeclampsia, a major pregnancy disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood pressure and augments expansive remodeling of the uteroplacental vasculature in pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was associated with a reversible blood pressure reduction that returned to normal on day 15. In addition, PP13 caused venous expansion that is larger in the venous branches closer to the placenta. Then, it increased placental and pup weights. Similar administration of a truncated PP13 variant (DelT221) that is unable to bind carbohydrates (a rare spontaneous mutation associated with a high frequency of severe early preeclampsia among Blacks in South Africa) produced a hypotensive effect similar to the full-length molecule, but without venous remodeling and increased placental and pup weights. These results indicate the importance of PP13 carbohydrate binding for inducing vascular remodeling and improving reproductive outcome. Future studies are needed to determine whether beneficial effects would be evident in animal models of preeclampsia or in women predisposed to the development of preeclampsia. PMID:26314825

  18. Data supporting the cardiac mitochondria calcium handling in female normotensive and spontaneously hypertensive rats.

    PubMed

    Ciocci Pardo, Alejandro; Rinaldi, Gustavo J; Mosca, Susana M

    2016-06-01

    In association with the published article "Mitochondrial calcium handling in normotensive and spontaneously hypertensive rats: correlation with systolic blood pressure levels" [1], this data article contains information about calcium handling of cardiac mitochondria isolated from female of both rats strains (WKY and SHR). Dataset of mitochondrial permeability transition pore (mPTP) resistance to opening Ca(2+)-mediated, Ca(2+) retention capacity (CRC), time constants and mitochondrial membrane potential (ΔΨm) are showed. PMID:26977446

  19. Data supporting the cardiac mitochondria calcium handling in female normotensive and spontaneously hypertensive rats

    PubMed Central

    Ciocci Pardo, Alejandro; Rinaldi, Gustavo J.; Mosca, Susana M.

    2016-01-01

    In association with the published article “Mitochondrial calcium handling in normotensive and spontaneously hypertensive rats: correlation with systolic blood pressure levels” [1], this data article contains information about calcium handling of cardiac mitochondria isolated from female of both rats strains (WKY and SHR). Dataset of mitochondrial permeability transition pore (mPTP) resistance to opening Ca2+-mediated, Ca2+ retention capacity (CRC), time constants and mitochondrial membrane potential (ΔΨm) are showed. PMID:26977446

  20. Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats

    PubMed Central

    Doperalski, N.J.; Sandhu, M.S.; Bavis, R.W.; Reier, P.J.; Fuller, D.D.

    2008-01-01

    Female sex hormones influence the neural control of breathing and may impact neurologic recovery from spinal cord injury. We hypothesized that respiratory recovery after C2 spinal hemisection (C2HS) differs between males and females and is blunted by prior ovariectomy (OVX) in females. Inspiratory tidal volume (VT), frequency (fR), and ventilation (VE) were quantified during quiet breathing (baseline) and 7% CO2 challenge before and after C2HS in unanesthetized adult rats via plethysmography. Baseline breathing was similarly altered in all rats (reduced VT, elevated fR) but during hypercapnia females had relatively higher VT (i.e. compared to pre-injury) than male or OVX rats (p < 0.05). Phrenic neurograms recorded in anesthetized rats indicated that normalized burst amplitude recorded ipsilateral to C2HS (i.e. the crossed phrenic phenomenon) is greater in females during respiratory challenge (p < 0.05 vs. male and OVX). We conclude that sex differences in recovery of VT and phrenic output are present at 2 weeks post-C2HS. These differences are consistent with the hypothesis that ovarian sex hormones influence respiratory recovery after cervical spinal cord injury. PMID:18586119

  1. Triazophos-induced oxidative stress and histomorphological changes in ovary of female Wistar rats.

    PubMed

    Sharma, Dharmender; Sangha, Gurinder Kaur; Khera, Kuldeep Singh

    2015-01-01

    Triazophos (TZ), a non-systemic broad spectrum organophosphate (OP), is being extensively used against a wide range of pests in agricultural practices. The present study was carried out to investigate the toxic effects of triazophos (TZ) in female Wistar rats. Three sub-chronic dose levels of TZ corresponding to 1/10th, 1/20th and 1/40th of LD50 were given for 30 days to adult female Wistar rats through oral intubation. During the treatment period estrous cycle was significantly altered. Activity levels of different oxidative stress (OS) parameters viz. catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation (LPO) were differentially altered in the ovary of treated rats. Estradiol levels were significantly high while progesterone levels were significantly reduced in plasma of 1/10th and 1/20th of LD50 TZ-treated rats. Histomorphological studies of ovary revealed increased follicular atresia and increased ovarian surface epithelial height in 1/10th and 1/20th of LD50 TZ-treated rats. Enhanced apoptosis and necrosis were also observed in ovarian granulosa cells at dose-dependent manner. Results infer that TZ exposure may lead to the number of pathophysiological conditions in female rats and severity increases at high doses. PMID:25619906

  2. Exposure to repeated maternal aggression induces depressive-like behavior and increases startle in adult female rats

    PubMed Central

    Bourke, Chase H.; Neigh, Gretchen N.

    2011-01-01

    The stress response is a multifaceted physiological reaction that engages a wide range of systems. Animal studies examining stress and the stress response employ diverse methods as stressors. While many of these stressors are capable of inducing a stress response in animals, a need exists for an ethologically relevant stressor for female rats. The purpose of the current study was to use an ethologically relevant social stressor to induce behavioral alterations in adult female rats. Adult (postnatal day 90) female Wistar rats were repeatedly exposed to lactating Long Evans female rats to simulate chronic stress. After six days of sessions, intruder females exposed to defeat were tested in the sucrose consumption test, the forced swim test, acoustic startle test, elevated plus maze, and open field test. At the conclusion of behavioral testing, animals were restrained for 30 minutes and trunk blood was collected for assessment of serum hormones. Female rats exposed to maternal aggression exhibited decreased sucrose consumption, and impaired coping behavior in the forced swim test. Additionally, female rats exposed to repeated maternal aggression exhibited an increased acoustic startle response. No changes were observed in female rats in the elevated plus maze or open field test. Serum hormones were unaltered due to repeated exposure to maternal aggression. These data indicate the importance of the social experience in the development of stress-related behaviors: an acerbic social experience in female rats precipitates the manifestation of depressive-like behaviors and an enhanced startle response. PMID:22093902

  3. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    PubMed Central

    Rice, K. M.; Fannin, J. C.; Gillette, C.; Blough, E. R.

    2014-01-01

    Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging. PMID:25610649

  4. Effects of Obesity on Bone Mass and Quality in Ovariectomized Female Zucker Rats

    PubMed Central

    Feresin, Rafaela G.; Johnson, Sarah A.; Elam, Marcus L.; Arjmandi, Bahram H.

    2014-01-01

    Obesity and osteoporosis are two chronic conditions that have been increasing in prevalence. Despite prior data supporting the positive relationship between body weight and bone mineral density (BMD), recent findings show excess body weight to be detrimental to bone mass, strength, and quality. To evaluate whether obesity would further exacerbate the effects of ovariectomy on bone, we examined the tibiae and fourth lumbar (L4) vertebrae from leptin receptor-deficient female (Leprfa/fa) Zucker rats and their heterozygous lean controls (Leprfa/+) that were either sham-operated or ovariectomized (Ovx). BMD of L4 vertebra was measured using dual-energy X-ray absorptiometry, and microcomputed tomography was used to assess the microstructural properties of the tibiae. Ovariectomy significantly (P < 0.001) decreased the BMD of L4 vertebrae in lean and obese Zucker rats. Lower trabecular number and greater trabecular separation (P < 0.001) were also observed in the tibiae of lean- and obese-Ovx rats when compared to sham rats. However, only the obese-Ovx rats had lower trabecular thickness (Tb.Th) (P < 0.005) than the other groups. These findings demonstrated that ovarian hormone deficiency adversely affected bone mass and quality in lean and obese rats while obesity only affected Tb.Th in Ovx-female Zucker rats. PMID:25309751

  5. Characterization of diet-dependent metabolic serotypes: proof of principle in female and male rats.

    PubMed

    Shi, Honglian; Vigneau-Callahan, Karen E; Shestopalov, Alexander I; Milbury, Paul E; Matson, Wayne R; Kristal, Bruce S

    2002-05-01

    Our research seeks to identify a serum profile, or serotype, that reflects substantial changes in food intake. Earlier studies demonstrated that a number of low-molecular-weight, redox-active compounds of metabolome were sufficiently stable analytically and biologically to identify biomarkers of dietary restriction (DR, restriction of total food intake) in rats. A second initial requirement is to demonstrate feasibility, i.e., that concentration changes in selected serum metabolites can contain sufficient information to classify rats by diet. The current study distinguished 101 (female) and 112 (male) chromatographically identifiable compounds that differ between ad libitum (AL) consumption and DR 6-mo-old rats. In a cohort of female rats, both hierarchical cluster analysis (HCA) and principal component analyses (PCA) could distinguish dietary groups with 100% efficiency (101 metabolites). Repeating the classification studies using the 63 biologically and analytically most robust metabolites decreased noise without affecting categorical separation. In a cohort of male rats, PCA, but not HCA, distinguished the original dietary groups with 100% accuracy (112 metabolites). A subset of 52 of the 112 metabolites enabled both HCA and PCA to group the male rats with 100% accuracy. These data demonstrate that quantitative analysis of selected serum metabolites can yield sufficient information by which to classify the dietary intake of a group of rats, identify such markers chromatographically and set the stage for validation of these metabolic serotypes in independent datasets. PMID:11983833

  6. Exercise pressor reflex function in female rats fluctuates with the estrous cycle.

    PubMed

    Koba, Satoshi; Yoshinaga, Kenshi; Fujita, Sayaka; Miyoshi, Michio; Watanabe, Tatsuo

    2012-09-01

    In women, sympathoexcitation during static handgrip exercise is reduced during the follicular phase of the ovarian cycle compared with the menstrual phase. Previous animal studies have demonstrated that estrogen modulates the exercise pressor reflex, a sympathoexcitatory mechanism originating in contracting skeletal muscle. The present study was conducted in female rats to determine whether skeletal muscle contraction-evoked reflex sympathoexcitation fluctuates with the estrous cycle. The estrous cycle was judged by vaginal smear. Plasma concentrations of estrogen were significantly (P < 0.05) higher in rats during the proestrus phase of the estrus cycle than those during the diestrus phase. In decerebrate rats, either electrically induced 30-s continuous static contraction of the hindlimb muscle or 30-s passive stretch of Achilles tendon (a maneuver that selectively stimulates mechanically sensitive muscle afferents) evoked less renal sympathoexcitatory and pressor responses in the proestrus animals than in the diestrus animals. Renal sympathoexcitatory response to 1-min intermittent (1- to 4-s stimulation to relaxation) bouts of static contraction was also significantly less in the proestrus rats than that in the diestrus rats. In ovariectomized female rats, 17?-estradiol applied into a well covering the dorsal surface of the lumbar spinal cord significantly reduced skeletal muscle contraction-evoked responses. These observations demonstrate that the exercise pressor reflex function and its mechanical component fluctuate with the estrous cycle in rats. Estrogen may cause these fluctuations through its attenuating effects on the spinal component of the reflex arc. PMID:22723635

  7. Development of multi-route physiologically-based pharmacokinetic models for ethanol in the adult, pregnant, and neonatal rat.

    PubMed

    Martin, Sheppard A; McLanahan, Eva D; El-Masri, Hisham; LeFew, William R; Bushnell, Philip J; Boyes, William K; Choi, Kyoungju; Clewell, Harvey J; Campbell, Jerry L

    2012-09-01

    Biofuel blends of 10% ethanol (EtOH) and gasoline are common in the USA, and higher EtOH concentrations are being considered (15-85%). Currently, no physiologically-based pharmacokinetic (PBPK) models are available to describe the kinetics of EtOH-based biofuels. PBPK models were developed to describe life-stage differences in the kinetics of EtOH alone in adult, pregnant, and neonatal rats for inhalation, oral, and intravenous routes of exposure, using data available in the open literature. Whereas ample data exist from gavage and intravenous routes of exposure, kinetic data from inhalation exposures are limited, particularly at concentrations producing blood and target tissue concentrations associated with developmental neurotoxicity. Compared to available data, the three models reported in this paper accurately predicted the kinetics of EtOH, including the absorption, peak concentration, and clearance across multiple datasets. In general, model predictions for adult and pregnant animals matched inhalation and intravenous datasets better than gavage data. The adult model was initially better able to predict the time-course of blood concentrations than was the neonatal model. However, after accounting for age-related changes in gastric uptake using the calibrated neonate model, simulations consistently reproduced the early kinetic behavior in blood. This work provides comprehensive multi-route life-stage models of EtOH pharmacokinetics and represents a first step in development of models for use with gasoline-EtOH blends, with additional potential applicability in investigation of the pharmacokinetics of EtOH abuse, addiction, and toxicity. PMID:22954395

  8. Salt Loading Exacerbates Diastolic Dysfunction and Cardiac Remodeling in Young Female Ren2 Rats

    PubMed Central

    Whaley-Connell, Adam T.; Habibi, Javad; Aroor, Annayya; Ma, Lixin; Hayden, Melvin R.; Ferrario, Carlos M.; DeMarco, Vincent G.; Sowers, James R.

    2013-01-01

    Objective Recent data would suggest pre-menopausal insulin resistant women are more prone to diastolic dysfunction than men, yet it is unclear why. We and others have reported that transgenic (mRen2)27 (Ren2) rats overexpressing the murine renin transgene are insulin resistant due to oxidative stress in insulin sensitive tissues. As increased salt intake promotes inflammation and oxidative stress, we hypothesized that excess dietary salt would promote diastolic dysfunction in transgenic females under conditions of excess tissue Ang II and circulating aldosterone levels. Materials/methods For this purpose we evaluated cardiac function in young female Ren2 rats or age-matched Sprague-Dawley (SD) littermates exposed to a high (4%) salt or normal rat chow intake for three weeks. Results Compared to SD littermates, at 10 weeks of age, female Ren2 rats fed normal chow showed elevations in left ventricular (LV) systolic pressures, LV and cardiomyocyte hypertrophy, and displayed reductions in LV initial filling rate accompanied by increases in 3-nitrotyrosine content as a marker of oxidant stress. Following 3 weeks of a salt diet, female Ren2 rats exhibited no further changes in LV systolic pressure, insulin resistance, or markers of hypertrophy but exaggerated increases in type 1 collagen, 3-nitrotryosine content, and diastolic dysfunction. These findings occurred in parallel with ultrastructural findings of pericapillary fibrosis, increased LV remodeling, and mitochondrial biogenesis. Conclusion These data suggest that a diet high in salt in hypertensive female Ren2 rats promotes greater oxidative stress, maladaptive LV remodeling, fibrosis, and associated diastolic dysfunction without further changes in LV systolic pressure or hypertrophy. PMID:24075738

  9. The effects of simazine, a chlorotriazine herbicide, on pubertal development in the female Wistar rat.

    PubMed

    Zorrilla, Leah M; Gibson, Emily K; Stoker, Tammy E

    2010-07-01

    Chlorotriazine herbicides, such as atrazine and its metabolites, have been shown to target the neuroendocrine regulation of male and female reproductive development. However, no studies have evaluated the effects of the chlorotriazine simazine on pubertal development in the female rat. Here we report the effects of a 21- and 41-day exposure to simazine on pubertal development and estrous cyclicity in the female rat using the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program, Pubertal Development and Thyroid Function in Intact/Juvenile Peripubertal Female Rats (Tier 1) protocol. In the first study, Wistar rats were exposed orally to 0, 12.5, 25, 50, or 100mg/kg of simazine from postnatal day 22 to 42. In the second study, rats were exposed from PND 22 until the first day of estrus after PND 62 to 0, 12.5, 25, 50, 100 or 200mg/kg of simazine. In the 21-day exposure, vaginal opening (VO) was delayed, the number of normal cycles was significantly decreased, and the day of first estrus was delayed compared to controls. In the 41-day exposure, VO and the day of first estrus was delayed, but the number of normal estrous cycles was not different than controls. In addition, both studies showed a significant decrease in serum prolactin (PRL) following simazine exposure. This data clearly demonstrates that simazine delays the onset of puberty in the female rat and decreases serum PRL similar to other chlorotriazines. The extended dosing period after VO provides a sufficient time period to monitor the effects of a toxicant on estrous cyclicity, an important measure for reproductive competence. PMID:20381603

  10. Embryo-transfer of the F2 Postnatal Calorie Restricted Female Rat Offspring into a Control Intra-uterine Environment Normalizes the Metabolic Phenotype

    PubMed Central

    Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Lee, Paul W.N.; Devaskar, Sherin U.

    2014-01-01

    Objective Postnatal calorie and growth restriction (PNGR) in the first generation (F1) rat female offspring causes a lean and glucose tolerant phenotype associated with hypoinsulinemia and reduced glucose-stimulated insulin secretion (GSIS). Despite the absence of gestational hyperglycemia in the F1 PNGR female, naturally born second generation (F2) PNGR female adult offspring reportedly exhibit obesity, hyperglycemia with insulin resistance. The objective of this study was to determine the role of the intrauterine environment on the heritability of the trans-generational phenotypic expression in the F2 PNGR female adult offspring. Materials/Methods We performed embryo transfer (ET) of the F2 embryos from the procreating F1 pregnant PNGR or control (CON) females to gestate in control recipient rat mothers. Employing stable isotopes glucose metabolic kinetics was determined. Results Birth weight, postnatal growth pattern and white adipose tissue in female F2 ET-PNGR were similar to ET-CON. Similarly, no differences in basal glucose and insulin concentrations, GSIS, glucose futile cycling and glucose clearance were seen. When compared to F2 ET-CON, F2 ET-PNGR showed no overall difference in glucose or hepatic glucose production (HGP) AUCs with minimal hyperglycemia (p<0.04) as a result of unsuppressed endogenous HGP (p<0.02) observed only during the first phase of IVGTT. Conclusions We conclude that the lean, glucose tolerant and hypoinsulinemic phenotype with reduced GSIS in the F1 generation is near normalized when the embryo-transferred F2 offspring gestates in a normal metabolic environment. This observation supports a role for the intra-uterine environment in modifying the heritability of the trans-generational PNGR phenotype. PMID:23021963

  11. Female rats are resistant to developing the depressive phenotype induced by maternal separation stress.

    PubMed

    Dimatelis, J J; Vermeulen, I M; Bugarith, K; Stein, D J; Russell, V A

    2016-02-01

    Many stress-related psychiatric disorders are more common in women than in men. We aimed to determine how female rats respond to maternal separation (MS; removal of the dam from the litter for 3h/day from postnatal day (P) 2-14)). A subset of MS females were also exposed to chronic constant light for 3weeks during adolescence (P42-63) to investigate whether the antidepressant effect of light treatment, previously observed in male rats, could be seen in female rats. Ultrasonic vocalizations (22kHz) were recorded and the forced swim test was conducted immediately after light exposure (P65-67) and 33days later (P98-99) to determine depressive-like behaviour. Key proteins in the MAPK signal transduction pathway (MKP-1, phospho-ERK, total ERK) and a synaptosomal marker (synaptophysin) were measured in the ventral hippocampus. We found that MS decreased the duration of 22kHz vocalizations at P65 which was reversed by subsequent light. Light exposure increased time spent in the inner zone of the open field and the number of 22kHz calls in response to novelty at P98. MS decreased the time females spent immobile and increased time actively swimming in the forced swim test at P67 but not at P99. MKP-1 and synaptophysin levels remained unchanged while MS decreased phospho-ERK levels in the ventral hippocampus. In contrast to clinical findings, the results suggest that female rats may be resistant to MS-induced depression-like behaviour. The behavioural effects of MS and light treatment in female rats may involve the MAPK/ERK signal transduction pathway. PMID:26344502

  12. Role of Oestrogen ? Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment.

    PubMed

    Snoeren, E M S; Antonio-Cabrera, E; Spiteri, T; Musatov, S; Ogawa, S; Pfaff, D W; gmo, A

    2015-11-01

    The present study investigated the role of oestrogen receptor (ER)? in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ER? to reduce the number of ER? in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ER? expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ER? in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ER? did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ER? less than the controls. This suggests that the ER? in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ER? in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. PMID:26314929

  13. Y are you not pregnant: identification of Y chromosome segments in female cattle with decreased reproductive efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reproductive efficiency is of economic importance in commercial beef cattle production, as failure to achieve pregnancy reduces the number of calves marketed. Identification of genetic markers with predictive merit for reproductive success would facilitate early selection of females and avoid ineff...

  14. Correlative Analysis of Behavioral and Physiological Concomitants of Labor in Pregnant Rats

    NASA Technical Reports Server (NTRS)

    Baer, L. A.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    During parturition, rats exhibit characteristic behavioral expressions of labor. Lordosis contractions, consisting of an elongation of the dams body, are observed beginning several hours prior to neonate births, whereas vertical contractions, repeated rapid lifts of the abdomen, occur immediately preceding the birth of each neonate. We analyzed underlying changes in intrauterine pressure (IUP) using a telemetric sensor that we modified for use in freely-moving rats. This technique enabled us to correlate behavioral expressions of labor contractions with IUP. A small telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day 19 of the rats' 22-day pregnancy, a unit was surgically implanted within the uterus. The dams were simultaneously videotaped, enabling us to directly correlate IUP signals with behavioral expressions of labor contractions. Earlier phases of labor, consisting predominantly of lordosis contractions were characterized by lower pressures relative to later phases during which higher pressures and vertical contractions were frequently observed.

  15. Role of Endothelin in Mediating Soluble fms-like Tyrosine Kinase-1 (sFlt-1)-induced Hypertension in Pregnant Rats

    PubMed Central

    Murphy, Sydney R.; LaMarca, B. Babbette D.; Cockrell, Kathy; Granger, Joey P.

    2010-01-01

    While soluble fms-like tyrosine kinase-1 (sFlt-1), an antagonist of vascular endothelial growth factor and placental growth factor has been implicated in the pathogenesis of hypertension during preeclampsia (PE), the mechanisms whereby enhanced sFlt-1 production leads to hypertension remain unclear. Both sFlt-1 and endothelin-1 production are elevated in women with PE and in placental ischemic animal models of PE, however, the importance of endothelin-1 and sFlt-1 interactions in control of blood pressure during pregnancy is unknown. The purpose of this study was to determine the role of endothelin-1 in mediating sFlt-1-induced hypertension in pregnant rats. To achieve this goal, sFlt-1 (3.7?g/kg/day for 6 days) was infused into normal pregnant rats (NP) and pregnant rats treated with a selective endothelin type A receptor antagonist, ABT 627 (5 mg/kg/day for 6 days). Plasma concentration of sFlt-1 increased from 73534 pg/ml in NP rats to 2498645 pg/ml, (p<0.05) with infusion of sFlt-1. Arterial pressure increased from 1001 mmHg in NP rats to 1223 mmHg, (p<0.05) in sFlt-1 infused rats. Chronic increases in plasma sFlt-1 in NP rats increased preproendothelin mRNA expression in the renal cortices ? 3 fold. In addition, chronic ETA blockade completely abolished the blood pressure response to sFlt-1 in pregnant rats (1043 vs. 1001 mmHg, p<0.05), while the ETA receptor antagonist had no effect on arterial pressure in NP rats (1052 vs. 1001mm Hg). In conclusion, this study demonstrates that endothelin-1, via endothelin type A receptor activation, plays an important role in mediating the hypertension in response to excess sFlt-1 during pregnancy. PMID:20026766

  16. DEVELOPMENTAL ATRAZINE EXPOSURE SUPPRESSES IMMUNE FUNCTION IN MALE, BUT NOT FEMALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Developmental Atrazine Exposure Suppresses Immune Function in Male, but not Female Sprague-Dawley Rats

    Andrew A. Rooney,*,1 Raymond A. Matulka,? and Robert Luebke?

    *College of Veterinary Medicine, Anatomy, Physiological Sciences and Radiology, NCSU, Raleigh, North...

  17. Environmental enrichment promotes robust functional and histological benefits in female rats after controlled cortical impact injury.

    PubMed

    Monaco, Christina M; Mattiola, Vincent V; Folweiler, Kaitlin A; Tay, Justin K; Yelleswarapu, Narayana K; Curatolo, Lauren M; Matter, Ashley M; Cheng, Jeffrey P; Kline, Anthony E

    2013-09-01

    Environmental enrichment (EE) consistently induces marked benefits in male rats after traumatic brain injury (TBI), but whether similar efficacy extends to females is not well established. Hence, the aim of this study was to reassess the effect of EE on functional and histological outcome in female rats after brain trauma. Twenty-four normal cycling adult female rats underwent verification of estrous stage prior to controlled cortical impact (CCI) or sham injury and then were assigned to EE or standard (STD) housing. Motor function was assessed with beam-balance/beam-walk and rotarod tasks on post-operative days 1-5 and every other day from 1-19, respectively. Spatial learning/memory was evaluated in a Morris water maze on days 14-19. Morphologically intact hippocampal CA(1/3) cells and cortical lesion volume were quantified 3 weeks after injury. No differences were observed between the EE and STD sham groups in any endpoint measure and thus the data were pooled. In the TBI groups, EE improved beam-balance, beam-walk, rotarod, and spatial learning performance vs. STD (p's<0.05). EE also provided significant histological protection as confirmed by increased CA(1/3) cell survival and decreased cortical lesion size vs. STD. These data demonstrate that EE confers robust benefits in female rats after CCI injury, which parallels numerous studies in males and lends further credence for EE as a preclinical model of neurorehabilitation. PMID:23333563

  18. In Utero Phthalate Effects in the Female Rat: A Model for MRKH Syndrome

    EPA Science Inventory

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly define etiology. Reproductive toxicity of phthlate esters (PEs) occurs in rat offspring exposed in utero. a phenome...

  19. Brown-colored deposits on hair of female rats chronically exposed to 60-Hz electric fields

    SciTech Connect

    Leung, F.C.; Rommereim, D.N.; Miller, R.A.; Anderson, L.E. )

    1990-01-01

    An increased incidence and severity of a brownish coloration of hair has been observed around the nose and on the ears of female rats that were chronically exposed to 60-Hz electric fields. Microscopic examination of the colored areas revealed a red-brown globular deposit on hair shafts in affected areas without signs of physical injury.

  20. 17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

    ERIC Educational Resources Information Center

    Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

    2013-01-01

    Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…

  1. REPRODUCTIVE TOXICITY ASSOCIATED WITH ACRYLAMIDE TREATMENT IN MALE AND FEMALE RATS

    EPA Science Inventory

    The present study was designed to evaluate the influence of acrylamide (ACR) on male and female reproductive function. Male rats received ACR in drinking water (50, 100, or 200 ppm) for up to 10 wk. Copulatory behavior, semen, and (for controls and 100 ppm only) fertility and fet...

  2. Effects of altered food intake during pubertal development in male and female Wistar rats

    EPA Science Inventory

    The U.S.EPA is currently validating assays that will be used in a Tier I Screening Battery to detect endocrine disrupting chemicals. A primary concern with the Protocols for the Assessment of Pubertal Development and Thyroid Function in Juvenile Male and Female Rats is that a non...

  3. THE ENDOCRINE PROFILE OF INTACT FEMALE RATS ON THE DAY OF PROESTRUS FOLLOWING EXPOSURE TO ATRAZINE

    EPA Science Inventory

    The Endocrine Profile of Intact Female Rats on the Day of Proestrus Following Exposure to Atrazine.
    RL Cooper, A Buckalew, SC Laws and TE Stoker
    Endocrinology Branch, RTD, NHEERL, ORD, U.S. EPA, RTP, NC, 27711.

    The chlorotriazine herbicide, atrazine, has been sho...

  4. PREGNANCY ALTERATIONS FOLLOWING XENOBIOTIC-INDUCED DELAYS IN OVULATION IN THE FEMALE RAT

    EPA Science Inventory

    Female rats were exposed to the formamidine pesticide chlordimeform (50 mg/kg) or sodium pentobarbital (35 mg/kg) at selected times during the estrous cycle and the effect of this treatment on pregnancy outcome was evaluated. When exposed on the afternoon of vaginal proestrus, bo...

  5. SUPPRESSION OF THE LUTEINIZING HORMONE SURGE BY CHLORDIMEFORM IN OVARIECTOMIZED, STEROID-PRIMED FEMALE RATS

    EPA Science Inventory

    The midcycle surge of luteinizing hormone (LH) from the pituitary provides the physiological trigger in the mammalian female for the process of ovulation. ccordingly, any agent that compromises the LH surge could function as a reproductive toxicant. ince ovariectomized (OVX) rats...

  6. In utero phthalate effects in the female rat: a model for MRKH syndrome##

    EPA Science Inventory

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phen...

  7. 17-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

    ERIC Educational Resources Information Center

    Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

    2013-01-01

    Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a

  8. Green Tea Polyphenols and Vitamin D3 Protect Bone Microarchitecture in Female Rats with Chronic Inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our recent study showed that green tea polyphenols (GTP) in conjunction with 1-a-OHvit-D3 (vitD3) treatment mitigates lipopolysaccharide (LPS)-induced bone mineral density loss in female rats. This study was undertaken to further explore the mechanism and bone microarchitecture of GTP plus vitD3 in...

  9. MASCULINIZATION OF FEMALE RATS BY PRENATAL TESTOSTERONE PROPIONATE IS PARTIALLY ATTENUATED BY VINCLOZOLIN

    EPA Science Inventory

    MASCULINIZATION OF FEMALE RATS BY PRENATAL TESTOSTERONE PROPIONATE IS PARTIALLY ATTENUATED BY VINCLOZOLIN
    Cynthia Wolf1,2, Gerald LeBlanc2, Andrew Hotchkiss3, Jonathan Furr1, L Earl Gray, Jr.1
    1USEPA, Reproductive Toxicology Division, RTP, NC 27711, 2Dept. Molecular and En...

  10. NEUROBEHAVIORAL EFFECTS OF TRIADIMEFON, A TRIAZOLE FUNGICIDE, IN MALE AND FEMALE RATS

    EPA Science Inventory

    Triadimefon is a widely used systemic fungicide, yet there is little published information on its effects in mammals. This study describes the effects of triadimefon in male and female rats using a functional observational battery (FOB), motor activity (measured in a figure-eight...

  11. OFFSPRING MORTALITY AND MATERNAL LUNG PATHOLOGY IN FEMALE RATS FED HEXACHLOROBENZENE

    EPA Science Inventory

    Female Sprague-Dawley CD rats were fed 0, 60, 80, 100, 120 and 140 ppm hexachlorobenzene (HCB) continuously in the diet and 2 successive litters raised. These doses were selected to range from approximately the no observable effect level to lethality in suckling offspring of trea...

  12. EFFECT OF LINDANE ON HORMONAL CONTROL OF REPRODUCTIVE FUNCTION IN THE FEMALE RAT

    EPA Science Inventory

    The effect of the gamma isomer of 1,2,3,4,5,6-hexachlorocyclohexane (Y-HCH), lindane, on reproductive funtion in the female rat was examined in two experiments. n the first experiment, chronic treatment with 0, 5, 10, 20, and 40 mg/kg lindane delayed vaginal opening and disrupted...

  13. NONYLPHENOL AND ATRAZINE INDUCE INVERSE EFFECTS ON MAMMARY GLAND DEVELOPMENT IN FEMALE RATS EXPOSED IN UTERO

    EPA Science Inventory

    Nonylphenol and Atrazine Induce Inverse Effects on Mammary Gland Development in Female Rats Exposed In Utero.
    HJ Moon1, SY Han1, CC Davis2, and SE Fenton2
    1 Department of Toxicology, NITR, Korea FDA, 5Nokbun-Dong, Eunpyung-Gu, Seoul, Korea and 2 Reproductive Toxicology Divi...

  14. Oxytocin differentially affects sucrose taking and seeking in male and female rats.

    PubMed

    Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2015-04-15

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens. PMID:25647756

  15. Suppression of liver microsomal drug-metabolizing enzyme activities in adult female rats pretreated with cannabidiol.

    PubMed

    Narimatsu, S; Watanabe, K; Matsunaga, T; Yamamoto, I; Imaoka, S; Funae, Y; Yoshimura, H

    1993-04-01

    The suppression by cannabidiol (CBD) of the liver microsomal drug-metabolizing enzyme activities in female rats was demonstrated and its mechanism was examined. Pretreatment of rats with CBD (10 mg/kg, i.p.) caused temporary decreases in contents of cytochrome P450 (P450) and b5 and NADPH-cytochrome c (P450) reductase activity compared with values from the vehicle control group. p-Nitroanisole O-demethylase, aniline hydroxylase, d-benzphetamine N-demethylase and delta 9-tetrahydrocannabinol 11-hydroxylase were also decreased by the CBD pretreatment. The latter two activities took a longer time to return to control levels than the former two. However, the CBD pretreatment, which reduced the protein level of P450 UT-2 (CYP2C11) in adult male rats, did not decrease the protein level of P450 F-1 (CYP2C6) or F-2 (CYP2C12) in liver microsomes from female rats. These results suggest that the mechanisms by which CBD suppresses liver microsomal drug-metabolizing enzyme activities are different in male and female rats. PMID:8395282

  16. Estradiol and Progesterone have Opposing Roles in the Regulation of Fear Extinction in Female Rats.

    PubMed

    Graham, Bronwyn M; Daher, Melissa

    2016-02-01

    Fear extinction, the laboratory basis of exposure therapy for anxiety disorders, fluctuates across the female rat estrous cycle, where extinction is enhanced during proestrus (high estradiol and progesterone), and impaired during metestrus (low estradiol and progesterone). During the estrous cycle increasing levels of estradiol precede and then overlap with increased levels of progesterone. We sought to isolate the impact of these hormonal changes on fear extinction by systematically treating ovariectomized female rats with estradiol alone, or in combination with progesterone. We found that estradiol alone facilitated extinction recall, whereas the effects of progesterone on estradiol-treated rats were biphasic and dependent on the time interval between progesterone administration and extinction training. Progesterone potentiated estradiol's facilitation of extinction recall when extinction training occurred 6?h after progesterone administration. However, progesterone abolished estradiol's facilitation of extinction recall when extinction training occurred 24?h after progesterone administration. Furthermore, in naturally cycling rats, blocking progesterone receptor activation during proestrus (when progesterone levels peak) prevented the impairment in extinction recall in rats extinguished during metestrus. These results suggest that in naturally cycling females whereas cyclical increases in estradiol facilitate fear extinction, cyclical increases in progesterone may lead to fear extinction impairments. As extinction training took place after the hormonal treatments had been metabolized, we propose that genomic mechanisms may at least partly mediate the impact of cyclic fluctuations in sex hormones on fear extinction. PMID:26156559

  17. Female rats express a conditioned object preference for receipt of sexual stimulation.

    PubMed

    Guterl, Sophie A; McNamara, Tanner A; Klumpp, Gracie C; Meerts, Sarah H

    2015-11-01

    Female rats alternately approach and avoid the male rat during copulation, potentially reflecting appetitive and aversive aspects of mating, respectively. We developed a novel classical conditioning procedure, conditioned object preference (COP), to test whether female rats show increased approach toward a conditioned stimulus associated directly with receipt of sexual stimulation. During conditioning, one scented object was paired with an appetitive stimulus and a different object plus scent was paired with a control stimulus on a separate day. After conditioning, preference for each object was evaluated with a choice task. Experiment 1 was conducted to verify the procedure. Rats exhibited a significant COP for 1mg/kg amphetamine, indicating that the conditioned object preference procedure is an effective tool for evaluating the rewarding nature of a treatment. In Experiment 2, paced mating to one ejaculation and experimenter-delivered artificial vaginocervical stimulation (aVCS) each induced a COP. The robust COPs for paced mating and aVCS support the notion that female rats experience a reward state during receipt of sexual stimulation. Moreover, the data suggest that any aversive aspects of receipt of sexual stimulation do not overshadow the appetitive effects. PMID:26247393

  18. Influences of chemical sympathectomy and simulated weightlessness on male and female rats

    NASA Technical Reports Server (NTRS)

    Woodman, Christopher R.; Stump, Craig S.; Stump, Jane A.; Sebastian, Lisa A.; Rahman, Z.; Tipton, Charles M.

    1991-01-01

    Consideration is given to a study aimed at determining whether the sympathetic nervous system is associated with the changes in maximum oxygen consumption (VO2max), run time, and mechanical efficiency observed during simulated weightlessness in male and female rats. Female and male rats were compared for food consumption, body mass, and body composition in conditions of simulated weightlessness to provide an insight into how these parameters may influence aerobic capacity and exercise performance. It is concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. It is noted that the mechanisms remain unclear at this time.

  19. Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study.

    PubMed

    Wolf, Cynthia J; Hotchkiss, Andrew; Ostby, Joseph S; LeBlanc, Gerald A; Gray, L Earl

    2002-01-01

    Testosterone plays a major role in male sexual development. Exposure of females to testosterone in utero can induce masculine characteristics such as anovulation, increased anogenital distance (AGD), absence of nipples, retention of male-like tissues, and agenesis of the lower vagina. In addition, high levels of androgens during fetal development can lead to toxic effects such as reduced litter size and viability. The study of the effects of testosterone administration during sexual differentiation provides a foundation for understanding the effects of environmental androgens on fetuses, a sensitive subpopulation. In the current study, we investigated the ability of a range of concentrations of testosterone propionate (TP) administered prenatally to masculinize female and alter male offspring, and measured maternal and fetal T levels. Pregnant Sprague-Dawley rats were dosed by sc injection on gestational day (GD) 14-19 (GD 1= day of plug) with either corn oil (vehicle; 0.1 ml/rat) or with 0.1 ml of TP solution at 0.1, 0.5, 1, 2, 5, or 10 mg/0.1 ml. Parturition was delayed at 2, 5, and 10 mg TP, litter size was reduced at 5 and 10 mg TP, and pup weight was significantly reduced in both sexes at 0.5 mg TP and higher doses. Viability of offspring was unaffected at any dosage level. Androgenic effects seen at 0.5 mg TP in females included increased AGD at weaning and adulthood, reduced number of areolas and nipples, cleft phallus, small vaginal orifice, and presence of prostate tissue. This dose of TP elevated maternal T levels 10x but had no effect on fetal T levels. At 1 mg TP and above, female AGD on postnatal day (PND) 2 (or postcoital day 24 [gestation length = 22(1/2)]) was increased; areolas and nipples were virtually eliminated; levator ani muscle, bulbourethral glands, and seminal vesicles (2 mg TP and above) were present; none of the females developed a vaginal orifice and many females in the 1 and 2 mg TP dose groups developed a greatly distended, fluid-filled uterus after puberty. Maternal T levels at 1 mg TP were elevated 30x, and female fetal T levels showed an 80% increase. Male offspring displayed a reduced AGD and body weight on PND 2 at 0.5 mg TP and higher doses. These effects were not evident by weaning and male offspring displayed no malformations. We conclude that gestational administration of 0.5 and 1 mg TP masculinizes female offspring without greatly affecting pup viability or pregnancy of the dam. This study provides a useful model for in utero testing of environmental androgens for their potential to induce developmental abnormalities. PMID:11752687

  20. Statistical determination of whole-body average SARs in a 2 GHz whole-body exposure system for unrestrained pregnant and newborn rats.

    PubMed

    Wang, Jianqing; Wake, Kanako; Kawai, Hiroki; Watanabe, Soichi; Fujiwara, Osamu

    2012-01-01

    A 2 GHz whole-body exposure to rats over a multigeneration has been conducted as part of bio-effect research in Japan. In this study, the rats moved freely in the cage inside the exposure system. From observation of the activity of rats in the cage, we found that the rats do not stay in each position with uniform possibility. In order to determine the specific absorption rate (SAR) during the entire exposure period with high accuracy, we present a new approach to statistically determine the SAR level in an exposure system. First, we divided the rat cage in the exposure system into several small areas, and derived the fraction of time the rats spent in each small area based on the classification of the documentary photos of rat activity. Then, using the fraction of time spent in each small area as a weighting factor, we calculated the statistical characteristics of the whole-body average SAR for pregnant rats and young rats during the entire exposure period. As a result, this approach gave the statistical distribution as well as the corresponding mean value, median value and mode value for the whole-body SAR so that we can reasonably clarify the relationship between the exposure level and possible biological effect. PMID:22127341

  1. Statistical determination of whole-body average SARs in a 2 GHz whole-body exposure system for unrestrained pregnant and newborn rats

    NASA Astrophysics Data System (ADS)

    Wang, Jianqing; Wake, Kanako; Kawai, Hiroki; Watanabe, Soichi; Fujiwara, Osamu

    2012-01-01

    A 2 GHz whole-body exposure to rats over a multigeneration has been conducted as part of bio-effect research in Japan. In this study, the rats moved freely in the cage inside the exposure system. From observation of the activity of rats in the cage, we found that the rats do not stay in each position with uniform possibility. In order to determine the specific absorption rate (SAR) during the entire exposure period with high accuracy, we present a new approach to statistically determine the SAR level in an exposure system. First, we divided the rat cage in the exposure system into several small areas, and derived the fraction of time the rats spent in each small area based on the classification of the documentary photos of rat activity. Then, using the fraction of time spent in each small area as a weighting factor, we calculated the statistical characteristics of the whole-body average SAR for pregnant rats and young rats during the entire exposure period. As a result, this approach gave the statistical distribution as well as the corresponding mean value, median value and mode value for the whole-body SAR so that we can reasonably clarify the relationship between the exposure level and possible biological effect.

  2. Corticotropin releasing factor impairs sustained attention in male and female rats.

    PubMed

    Cole, Robert D; Kawasumi, Yushi; Parikh, Vinay; Bangasser, Debra A

    2016-01-01

    Stressful life events and stress-related psychiatric disorders impair sustained attention, the ability to monitor rare and unpredictable stimulus events over prolonged periods of time. Despite the link between stress and attentional disruptions, the neurobiological basis for stress regulation of attention systems remains underexplored. Here we examined whether corticotropin releasing factor (CRF), which orchestrates stress responses and is hypersecreted in patients with stress-related psychiatric disorders, impairs sustained attention. To this end, male and female rats received central infusions of CRF prior to testing on an operant sustained attention task (SAT), where rats were trained to discriminate signaled from non-signaled events. CRF caused a dose-dependent decrease in SAT performance in both male and female rats. Females were more impaired than males following a moderate dose of CRF, particularly during the middle part of the session. This sex difference was moderated by ovarian hormones. Females in the estrous cycle stage characterized by lower ovarian hormones had a greater CRF-induced attentional impairment than males and females in other cycle stages. Collectively, these studies highlight CRF as a critical stress-related factor that can regulate attentional performance. As sustained attention subserves other cognitive processes, these studies suggest that mitigating high levels of CRF in patients with stress-related psychiatric disorders may ameliorate their cognitive deficits. PMID:26306826

  3. Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

    PubMed Central

    Lugo, Joaquin N.; Wilson, Marlene A.; Kelly, Sandra J.

    2013-01-01

    This study used a rat model of Fetal Alcohol Syndrome to investigate whether combined prenatal and postnatal ethanol exposure affects met-enkephalin levels in the brains of male and female LongEvans adult rats. Intragastric ethanol was administered to a group of rats (ET) from gestational day (GD) 1 through 22 and from postnatal day (PD) 2 through 10. The control groups consisted of a nontreated control group (NTC) and an intubated control group (IC) that received the intragastric intubation procedure but no exposure to ethanol. We measured met-enkephalin levels in the prefrontal cortex, nucleus accumbens, hypothalamus, central and basolateral nucleus of amygdala and ventral tegmental area. Met-enkephalin levels in the hypothalamus of male and female ET animals were significantly higher than those in either the NTC or IC animals. Met-enkephalin levels in the central nucleus of the amygdala of male and female ET animals were significantly lower than the levels in the NTC animals. Met-enkephalin levels in the nucleus accumbens of ET females were significantly greater than those in the IC females. These results demonstrate that the combination of prenatal and postnatal ethanol exposure affects basal met-enkephalin levels in specific regions in a sex-specific manner. These changes in met-enkephalin levels may explain how early ethanol exposure affects opioid-regulated behaviors such as social play, sexual behavior, and other social behaviors. PMID:16457985

  4. Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats

    PubMed Central

    Stoffel, Erin C.; Ulibarri, Catherine M.; Craft, Rebecca M.

    2005-01-01

    The purpose of this study was to examine how gonadal steroid hormones modulate basal nociception and morphine antinociception relative to regulating reproduction in the adult rat. Male and female SpragueDawley rats were either gonadectomized (GDX) or sham-gonadectomized (sham); GDX males were implanted subcutaneously with capsules containing testosterone (T), estradiol (E2), dihydrotestosterone (DHT), E2 and DHT, or nothing (0). GDX females received E2, T, or empty (0) capsules immediately after surgery, and vehicle or progesterone (P4) injections at 4-day intervals. Basal nociception and morphine antinociception were tested 28 days after surgery on 50C and 54C hotplate tests, and reproductive behavior and physiology were assessed shortly thereafter. There were no significant differences in baseline hotplate latencies among the male treatment groups, but morphine was significantly more potent in sham and GDX + T males than in GDX + 0 males. The ability of T to increase morphine's potency was approximated by its major metabolites E2 and DHT, given together but not alone. Baseline hotplate latencies were higher in sham females tested during diestrus than in those tested during estrus. Morphine was significantly more potent in sham females tested during proestrus and diestrus than in those tested during estrus. Baseline hotplate latencies were significantly higher, and morphine was significantly less potent in GDX + E2, GDX + E2/P4 and GDX + T females than in GDX + 0 females. All group differences in basal nociception and morphine antinociception observed on the 50C hotplate test were smaller and generally non-significant on the 54C hotplate test. Steroid manipulations produced the expected changes in reproductive behaviors and steroid-sensitive organs. These results demonstrate that in adult rats, gonadal steroid manipulations that are physiologically relevant, modulate (1) basal nociception in females but not males, and (2) morphine's antinociceptive potency in both males and females. PMID:12791435

  5. Enhanced Mesenteric Arterial Responsiveness to Angiotensin II Is Androgen Receptor-Dependent in Prenatally Protein-Restricted Adult Female Rat Offspring1

    PubMed Central

    Sathishkumar, Kunju; Balakrishnan, Meena P.; Yallampalli, Chandrasekhar

    2014-01-01

    ABSTRACT Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally protein-restricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent. PMID:25550341

  6. HIV-1 Transgenic Female Rat: Synaptodendritic Alterations of Medium Spiny Neurons in the Nucleus Accumbens

    PubMed Central

    Roscoe, Robert F.; Mactutus, Charles F.

    2015-01-01

    HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins. PMID:25037595

  7. HIV-1 transgenic female rat: synaptodendritic alterations of medium spiny neurons in the nucleus accumbens.

    PubMed

    Roscoe, Robert F; Mactutus, Charles F; Booze, Rosemarie M

    2014-12-01

    HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins. PMID:25037595

  8. Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid

    PubMed Central

    Sun, Jiarui; Zhang, Xinchen; Cao, Yinan; Zhao, Qiling; Bao, Endong; Lv, Yingjun

    2016-01-01

    Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats. PMID:26866683

  9. Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

    PubMed Central

    Zelzer, Sieglinde; Mangge, Harald; Pailer, Sabine; Ainoedhofer, Herwig; Kieslinger, Petra; Stojakovic, Tatjana; Scharnagl, Hubert; Prller, Florian; Weghuber, Daniel; Datz, Christian; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Trummer, Christian; Gostner, Johanna; Gruber, Hans-Jrgen

    2015-01-01

    Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats. PMID:26006242

  10. Synergism of estrogens and x-rays in mammary carcinogenesis in female ACI rat

    SciTech Connect

    Holtzman, S.; Stone, J.P.; Shellabarger, C.J.

    1981-08-01

    A previously demonstrated synergistic interaction between diethylstilbestrol (DES) and radiation on rate mammary carcinogenesis was extended to another estrogen, 17-ethinyl-estradiol (EE2). These newly reported results with EE2 demonstrated that the previously reported synergistic interaction between DES and radiation is not confined to just DES. Instead, these new results implied that the synergistic interaction is a synergistic interaction between the estrogenic activity of DES and radiation on rat mammary carcinogenesis. Female inbred ACI rats were used. By the end of the experiment, no neoplasia was detected in rats bearing cholesterol pellets, with an without x-ray exposure. No significant n tumor data were obtained from rats treated with 0.1 mg EE2, with and without x-rays. Approximately 50% of the rats treated with DES and approximately 90% of the rats treated with 1 mg EE2 had 1 or more mammary adenocarcinomas (MAC). X-rays synergistically increased the number of MAC per rat in the groups implanted with DES or 1 mg EE2. X-rays also increased the trend toward earlier increased incidence of rats with MAC as compared to rats treated with estrogens only. All rats treated with DES and 1 mg EE2 had pituitary tumors. The mean weight of the pituitary tumors in the groups treated with 1 mg EE2 was approximately 1.5 times that of the groups treated with DES. Mean terminal plasma prolactin levels for rats treated with 1 mg EE2 or DES were, respectively, 17.5 and 9.5 times control values.

  11. Role of orexin/hypocretin in conditioned sucrose-seeking in female rats

    PubMed Central

    Cason, Angie M.; Aston-Jones, Gary

    2014-01-01

    The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. Given that eating disorders affect women more than men, we reasoned that the orexin system may be strongly engaged in female rats, and during periods of food restriction as we recently reported in male rats. Therefore, the present study examined the involvement of the orexin system in operant responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed vs. food-restricted female subjects. Female Sprague Dawley rats were trained to self-administer sucrose pellets, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB 334867 (SB; 10-30 mg/kg) on fixed ratio (FR) sucrose self-administration, and on cue-induced reinstatement of extinguished sucrose-seeking. SB decreased sucrose self-administration in food-restricted but not in ad libitum-fed females. SB did not alter active lever responding during cue-induced reinstatement of sucrose-seeking in either feeding group. These results confirm our previous results in male rats that signaling at the OxR1 receptor is involved in the sucrose reinforcement and self-administration in food-restricted subjects. However, the finding that SB is ineffective at attenuating cue-induced reinstatement in females, but was effective in food-restricted males, leads us to conclude that food seeking induced by conditioned stimuli engages the orexin system differentially in males and females. PMID:25036612

  12. Role of orexin/hypocretin in conditioned sucrose-seeking in female rats.

    PubMed

    Cason, Angie M; Aston-Jones, Gary

    2014-11-01

    The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. Given that eating disorders affect women more than men, we reasoned that the orexin system may be strongly engaged in female rats, and during periods of food restriction as we recently reported in male rats. Therefore, the present study examined the involvement of the orexin system in operant responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed vs. food-restricted female subjects. Female Sprague Dawley rats were trained to self-administer sucrose pellets, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB 334867 (SB; 10-30 mg/kg) on fixed ratio (FR) sucrose self-administration, and on cue-induced reinstatement of extinguished sucrose-seeking. SB decreased sucrose self-administration in food-restricted but not in ad libitum-fed females. SB did not alter active lever responding during cue-induced reinstatement of sucrose-seeking in either feeding group. These results confirm our previous results in male rats that signaling at the OxR1 receptor is involved in the sucrose reinforcement and self-administration in food-restricted subjects. However, the finding that SB is ineffective at attenuating cue-induced reinstatement in females, but was effective in food-restricted males, leads us to conclude that food seeking induced by conditioned stimuli engages the orexin system differentially in males and females. PMID:25036612

  13. Diphenyl diselenide supplemented diet reduces depressive-like behavior in hypothyroid female rats.

    PubMed

    Dias, Glaecir Roseni Mundstock; de Almeida, Tielle Moraes; Sudati, Jssie Haigert; Dobrachinski, Fernando; Pavin, Sandra; Soares, Flix Alexandre Antunes; Nogueira, Cristina Wayne; Barbosa, Nilda Berenice Vargas

    2014-01-30

    Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able to reduce this effect. PMID:24239994

  14. A boundary-representation method for designing whole-body radiation dosimetry models: pregnant females at the ends of three gestational periodsRPI-P3, -P6 and -P9

    NASA Astrophysics Data System (ADS)

    Xu, X. George; Taranenko, Valery; Zhang, Juying; Shi, Chengyu

    2007-12-01

    Fetuses are extremely radiosensitive and the protection of pregnant females against ionizing radiation is of particular interest in many health and medical physics applications. Existing models of pregnant females relied on simplified anatomical shapes or partial-body images of low resolutions. This paper reviews two general types of solid geometry modeling: constructive solid geometry (CSG) and boundary representation (BREP). It presents in detail a project to adopt the BREP modeling approach to systematically design whole-body radiation dosimetry models: a pregnant female and her fetus at the ends of three gestational periods of 3, 6 and 9 months. Based on previously published CT images of a 7-month pregnant female, the VIP-Man model and mesh organ models, this new set of pregnant female models was constructed using 3D surface modeling technologies instead of voxels. The organ masses were adjusted to agree with the reference data provided by the International Commission on Radiological Protection (ICRP) and previously published papers within 0.5%. The models were then voxelized for the purpose of performing dose calculations in identically implemented EGS4 and MCNPX Monte Carlo codes. The agreements of the fetal doses obtained from these two codes for this set of models were found to be within 2% for the majority of the external photon irradiation geometries of AP, PA, LAT, ROT and ISO at various energies. It is concluded that the so-called RPI-P3, RPI-P6 and RPI-P9 models have been reliably defined for Monte Carlo calculations. The paper also discusses the needs for future research and the possibility for the BREP method to become a major tool in the anatomical modeling for radiation dosimetry.

  15. Stimulation of contraction of pregnant rat uterus in vitro by non-dechlorinated and microbially dechlorinated mixtures of polychlorinated biphenyls.

    PubMed

    Bae, J; Mousa, M A; Quensen, J F; Boyd, S A; Loch-Caruso, R

    2001-03-01

    A previous study of six polychlorinated biphenyl (PCB) congeners showed that PCBs with four or fewer chlorines and ortho substitution stimulate uterine contraction frequency in vitro, whereas congeners with a greater number of chlorines or non-ortho substitution are inactive in vitro. We tested the hypothesis that PCB mixtures stimulate uterine contractions in a manner inversely related to the degree of chlorination and the presence of chlorines in the ortho- position of the biphenyl constituents of the mixtures. Uterine strips from pregnant rats were suspended in standard muscle baths and analyzed for changes in isometric contractions in response to in vitro exposure to commercial PCB mixtures (Aroclors) and their dechlorinated products after microbial degradation. The PCB mixtures Aroclor 1242, 1248, and 1254 significantly stimulated uterine contraction frequency, and the least chlorinated mixture, Aroclor 1242, was the most potent stimulant. Microbes from Hudson River sediment dechlorinated Aroclor 1242 and Aroclor 1254 under reducing conditions to produce mixtures with an increased proportion of ortho-substituted congeners with one or two chlorine substitutions. The PCB mixtures that had undergone microbial reductive dechlorination stimulated uterine contraction frequency to a significantly greater extent than the parent mixtures. These results show that increased uterotonic activity was associated with decreased chlorination and increased ortho substitution of the biphenyl constituents of the mixtures. PMID:11333189

  16. Effect of restricted food supply to pregnant rats inhaling carbon monoxide on fetal weight, compared with cigarette smoke exposure

    SciTech Connect

    Tachi, N.; Aoyama, M.

    1986-12-01

    Although many studies have shown that cigarette smoking during gestation retarded the intrauterine fetal growth, resulting in the decreased birth weight in babies born to smoking mothers, neither causal substance nor mechanism of action to disturb fetal growth has been firmly established yet. Based on the human and animal studies, researchers have implied that fetal hypoxia induced by carbon monoxide (CO) in the cigarette smoke to be responsible for the event. A shortage in energy intake in smoking mothers also has been suspected to cause the retardation in fetal development. In the previous results (Tachi and Aoyama 1983), the weight increment in CO exposed animals was greater than that in the smoke exposed group. The phenomenon seemed to indicate that the reduction in the food intake occurs in animals which inhale the cigarette smoke, and induces the disturbance of fetal development in association with CO. In the present study, so as to evaluate the role of energy intake upon the fetal development in utero, the experiment of paired feeding with pregnant rats exposed to cigarette smoke is designed in animals which inhale the cigarette smoke, CO, or room air, following after the observation of the quantity of food taken by mothers exposed to cigarette smoke, CO, or room air.

  17. Effect of subchronic administration of methyl parathion on in vivo protein synthesis in pregnant rats and their conceptuses

    SciTech Connect

    Gupta, R.C.; Thornburg, J.E.; Stedman, D.B.; Welsch, F.

    1984-03-15

    Pregnant rats received daily po doses of the organophosphate methyl parathion (MPTH) from Day 6 through Day 15 or 19 of gestation at doses causing no (1.0 mg/kg) or minimal (1.5 mg/kg) signs of maternal toxicity. Following the dose of MPTH on Day 15 or 19, in vivo protein synthesis was measured 0.5, 1.0, and 2.0 hr after sc injection of L-(1-/sup 14/C)valine at a dose of 5 microCi/mmol/100 g body wt. The specific activity of (/sup 14/C)valine in the free amino acid pool and protein bound pool was significantly reduced in various regions of maternal brain and in maternal viscera, placenta, and whole embryos (Day 15), and in fetal brain and viscera (Day 19). The inhibitory effect of MPTH on net protein synthesis was dose dependent, greater on Day 19 than 15 of gestation and more pronounced in fetal than in maternal tissues.

  18. Stimulation of contraction of pregnant rat uterus in vitro by non-dechlorinated and microbially dechlorinated mixtures of polychlorinated biphenyls.

    PubMed Central

    Bae, J; Mousa, M A; Quensen, J F; Boyd, S A; Loch-Caruso, R

    2001-01-01

    A previous study of six polychlorinated biphenyl (PCB) congeners showed that PCBs with four or fewer chlorines and ortho substitution stimulate uterine contraction frequency in vitro, whereas congeners with a greater number of chlorines or non-ortho substitution are inactive in vitro. We tested the hypothesis that PCB mixtures stimulate uterine contractions in a manner inversely related to the degree of chlorination and the presence of chlorines in the ortho- position of the biphenyl constituents of the mixtures. Uterine strips from pregnant rats were suspended in standard muscle baths and analyzed for changes in isometric contractions in response to in vitro exposure to commercial PCB mixtures (Aroclors) and their dechlorinated products after microbial degradation. The PCB mixtures Aroclor 1242, 1248, and 1254 significantly stimulated uterine contraction frequency, and the least chlorinated mixture, Aroclor 1242, was the most potent stimulant. Microbes from Hudson River sediment dechlorinated Aroclor 1242 and Aroclor 1254 under reducing conditions to produce mixtures with an increased proportion of ortho-substituted congeners with one or two chlorine substitutions. The PCB mixtures that had undergone microbial reductive dechlorination stimulated uterine contraction frequency to a significantly greater extent than the parent mixtures. These results show that increased uterotonic activity was associated with decreased chlorination and increased ortho substitution of the biphenyl constituents of the mixtures. PMID:11333189

  19. The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Cephas, Stacy; Cleek, Tammy; Sayavongsa, Phouyong; Arnaud, Sara B.

    2003-01-01

    Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.

  20. Female rats are relatively more sensitive to reduced lipid versus reduced carbohydrate availability

    PubMed Central

    Sandoval, D A; Ryan, K K; de Kloet, A D; Woods, S C; Seeley, R J

    2012-01-01

    Objectives: Because females have blunted counterregulatory responses to hypoglycemia relative to males, we hypothesized that females would have greater sensitivity to changes in lipid availability. Design and subjects: To assess this, we examined the feeding response to glucoprivation (2-deoxyglucose; 2DG) and lipoprivation (mercaptoacetate; MA) in age-matched male and female Long-Evans rats. Results: Males versus females had significantly greater food intake after 250?mg?kg?1 of 2DG, but there were no sex differences with the 750?mg?kg?1 dose of 2DG. Glucose responses to 250?mg?kg?1 of 2DG were also significantly greater in males versus females. In contrast, females had a significant increase in food intake with all doses of MA versus saline, and had significantly greater food intake compared with males at the lowest and highest doses of MA with a trend towards significance with the intermediate dose. To determine whether estradiol (E2) is the mechanism underlying this sexual dimorphism, ovariectomized females were injected with vehicle or 2??g of E2 every fourth day to mimic the variations in across the estrous cycle. Ovariectomized females significantly increased feeding and glucose after 250?mg?kg?1 of 2DG over intact females and E2 had no effect on these responses. Although the feeding response to 2DG was not different, the glucose response to 2DG was still significantly greater in males versus ovariectomies females. However, ovariectomized females also did not increase food intake after MA, regardless of E2 treatment. Conclusions: These data collectively suggest that males are relatively more sensitive to glucose deprivation and females are relatively more sensitive to lipid deprivation. Further, these data rule out a role for cyclic changes in E2 in these sex differences. PMID:23169552

  1. Potentiation of morphine antinociception by pentobarbital in female vs. male rats.

    PubMed

    Craft, Rebecca M; Leitl, Michael D

    2006-03-01

    It has been shown previously that female rats are more sensitive than males to barbiturate anesthesia, whereas males may be more sensitive than females to opioid antinociception. The aim of the present study was to determine whether enhancement of morphine antinociception by pentobarbital, previously demonstrated in male animals and humans, occurs similarly in females. Pentobarbital (50 mg/kg i.p.) produced longer-lasting anesthetic effects (loss of muscle tone, righting reflex) in gonadally intact female rats than in males, but greater antinociceptive effects in males at some time points post-injection. There were no significant sex differences in morphine-induced anesthesia or antinociception; however, 50 mg/kg pentobarbital produced greater leftward shifts in the morphine antinociceptive dose-effect curve in gonadally intact females than males, whether pentobarbital was administered 30 vs. 120 min before morphine (times at which there were no sex differences vs. sex differences, respectively, in pentobarbital's effects when administered alone). Dose-addition analysis confirmed that pentobarbital enhancement of morphine antinociception was supra-additive in both sexes; morphine also significantly enhanced pentobarbital-induced anesthesia in both sexes. In gonadectomized males, testosterone did not significantly alter pentobarbital enhancement of morphine antinociception; in contrast, in gonadectomized females, estradiol significantly attenuated the drug interaction. Estradiol did not significantly alter the effects of pentobarbital alone or morphine alone, indicating that the attenuation of the pentobarbital's potentiation of morphine antinociception in estradiol-treated rats is specific to the drug interaction. These results suggest that barbiturate potentiation of opioid antinociception may be greater in females - particularly those in low ovarian hormone states - than in males. PMID:16473463

  2. Differential effects of central administration of relaxin-3 on food intake and hypothalamic neuropeptides in male and female rats.

    PubMed

    Calvez, J; Lenglos, C; de Ávila, C; Guèvremont, G; Timofeeva, E

    2015-09-01

    Relaxin-3 (RLN3) is an orexigenic neuropeptide that produces sex-specific effects on food intake by stronger stimulation of feeding in female compared with male rats. This study determined which hypothalamic nuclei and associated neuropeptides may be involved in the sex-specific orexigenic effects of RLN3. Relaxin-3 (800 pmol) or vehicle was injected into the lateral ventricle of female and male rats. Food and water intake were measured after the first injection, and rats were euthanized after the second injection to determine the mRNA expression of the hypothalamic neuropeptides. Food but not water intake showed sex-specific effects of RLN3. Stimulation of food intake by RLN3 was significantly higher in female than in male rats. No effect of RLN3 injection was found on c-fos mRNA expression in the arcuate, dorsomedial and ventromedial hypothalamic nuclei. Increased c-fos mRNA expression was observed in the paraventricular hypothalamic nucleus (PVN) in both sexes and in the lateral hypothalamic area (LHA) in female rats. Relaxin-3 injections led to a sex-nonspecific increase in the expression of oxytocin mRNA in the magnocellular PVN. Conversely, RLN3-induced expression of anorexigenic neuropeptide arginine vasopressin (AVP) was significantly higher in the parvocellular PVN in male compared with female rats. Finally, RLN3 administration significantly increased the expression of orexin (ORX) mRNA in the LHA in female but not in male rats. Stronger expression of anorexigenic AVP in the PVN in male rats and increased expression of ORX in the LHA in female rats may contribute to stronger orexigenic effects of RLN3 in female rats compared with male rats. PMID:26234422

  3. Behavioral and hormonal responses to stress in binge-like eating prone female rats.

    PubMed

    Calvez, Juliane; Timofeeva, Elena

    2016-04-01

    Binge eating episodes are frequently stimulated by stress. We developed a model of binge eating proneness based on individual sensitivity of young female Sprague Dawley rats to significantly increase sucrose consumption in response to stress. The rats were subjected to unpredictable intermittent 1-h access to 10% sucrose. After the stabilization of sucrose intake, rats were assessed for consistency of higher (for binge-like eating prone, BEP) or lower (for binge-like eating resistant, BER) sucrose intake in response to unpredictable episodes of foot-shock stress. The objectives of this study included demonstrating face validity of the BEP model and determining if some of the features of this model were pre-existing before exposure to intermittent access to sucrose and repeated stress. The BEP rats consumed a larger (20%>BER) amount of sucrose in a discrete (1-h) period of time compared to the BER phenotype in non-stressful conditions and significantly increased sucrose intake (50%>BER) under stress. Conversely, stress did not affect sucrose intake in BER rats. BEP rats showed higher sucrose intake compared to BER rats at the beginning of darkness as well as during the light period when they were sated and not physically hungry. Analyses of the sucrose licking microstructure revealed that BEP rats had a high motivational drive to consume sucrose in non-stressful condition and an increased hedonic value of sucrose when they were exposed to stressful conditions. BEP rats consumed sucrose much more rapidly under stressful conditions compared to BER rats. Finally, BEP rats demonstrated compulsive-like intake of sucrose (assessed in the light-dark box) and a blunted stress-induced increase in plasma corticosterone levels. Body weight and chow intake were not different between the phenotypes. Before exposure to intermittent access to sucrose and repeated stress, the BEP rats showed no clear evidence for compulsive sucrose intake. However, from the first 1-h access to sucrose, the BEP rats exhibited sucrose overeating; and from the first exposure to stress before intermittent access to sucrose, the BEP rats showed a blunted increase in corticosterone plasma levels. Innate sucrose hyperconsumption and altered reactivity of the hypothalamo-pituitary adrenal (HPA) axis to stress may be involved in the development of binge-like eating. Increased perceived hedonic value of palatable food and an increased motivation to consume this food despite aversive conditions as well as deregulated reactivity of the HPA axis may contribute to stress-induced bingeing on sucrose in BEP rats. PMID:26812591

  4. The teratogenic effects of dietary Cassava on the pregnant albino rat: a preliminary report.

    PubMed

    Singh, J D

    1981-12-01

    Cassava is a tuberous root of a shrublike plant cultivated in tropical rain forests as a staple food in South Eastern Nigeria. Reports are on record showing correlation between cassava intake and occurrence of various types of neuropathies (Money, '59; Monekosso and Wilson, '66; Osuntokun et al., '68,'69). About 0.1-2 mg of cyanide/100 gm is released from Cassava by action of hydrolase (Paula and Rangel, '46). It has been suspected by several local clinicians as a cause of congenital anomalies if consumed in excess during pregnancy. However, it remains a controversial problem and precise scientific data is lacking. This study was conducted on albino rats by giving them milled cassava powder as 50% and 80% of their diet during the first 5 days of pregnancy. Fetuses collected on day 20 from the group receiving cassava as 80% of the diet showed a low incidence of limb defects, open eye, microcephaly, and growth retardation in the rat. Interpretation of this data for the human should be made with caution. PMID:7330778

  5. Teratogenicity study on pyrethrum and rotenone (natural origin) and ronnel in pregnant rats.

    PubMed

    Khera, K S; Whalen, C; Angers, G

    1982-07-01

    Insecticidal formulations in the form of dusts or aerosols containing rotenone from the root of Derris elliptica and pyrethrum from the flower of Chrysanthemum cinerariaefolium are commonly used in homes and gardens. Ronnel (fenchlorphos), a systemic insecticide, is used to control house flies and, upon oral treatment, ectoparasites of cattle. These insecticides are extensively used and their teratologic potential has not been fully investigated. Technical grades of rotenone at 0, 2.5, 5, or 10 mg/kg, pyrethrum at 0, 50, 100, or 150 mg/kg (rotenone and pyrethrum were of natural origin) and ronnel at 0, 400, 600 or 800 mg/kg were tested. Each of these was suspended in corn oil and administered orally in single daily doses on d 6-15 of pregnancy to Wistar rats. The dams were killed on the last day of pregnancy, and all fetuses were evaluated following routine teratologic methods. Rotenone was associated with an increased number of nonpregnant rats and resorptions, at a dose of 10 mg/kg; reductions in maternal body weight gain, fetal weight, and skeletal ossification, together with an increased incidence of extra rib, were found at 5 and 10 mg/kg; but no significant effects were found at 2.5 mg/kg. Increases in the incidence of resorptions in pyrethrum-treated groups and of extra rib in ronnel-treated groups were also observed. PMID:6182301

  6. Gonadotropins in female rats androgenized by various treatments: prolactin as an index to hypothalamic damage.

    PubMed

    Mallampati, R S; Johnson, D C

    1974-01-01

    Keeping as many variables as possible constant, several indices of reproductive function were examined in female rats androgenized by different methods. The age at which vaginal opening occurred, the incidence of persistent estrus, the ovarian, uterine, adrenal, and pituitary weights, and the pituitary and serum gonadotropin (FSH, LH, prolactin) concentrations were compared in female rats treated neonatally with 10 mcg estradiol benzoate (EB), 250 mcg androstenediol-propionate, 250 mcg dehydroepiandrosterone (DHEA) or 10, 50, 250, or 1,250 mcg doses of testosterone propionate (TP). The animals were treated with EB and TP at 5 days of age, and they were killed at 40, 90, and 150 days of age. By 90 days of age, 99% of the rats treated with steroids other than DHEA were in constant estrus. None of the rats given DHEA became anovulatory. In all anovulatory females, the pituitary prolactin content increased with age, and it was higher than in animals given DHEA. Serum prolactin was linearly related to both the dose of TP given and the animal's age. The findings appear to support the belief that loss of prolactin-inhibiting control mechanisms of the hypothalamus is a consequence of aging. It is not known whether this is related to a loss of neurons or only to a loss of function. PMID:4279359

  7. Curcumin improves spatial memory and decreases oxidative damage in aged female rats.

    PubMed

    Belviranlı, Muaz; Okudan, Nilsel; Atalık, Kısmet Esra Nurullahoğlu; Öz, Mehmet

    2013-04-01

    Aging induced cognitive impairment has been well documented for many years and several antioxidant strategies have been developed against this impairment. Curcumin is the active component of curcuma longa and has shown antioxidant, antiinflamatory and neuroprotective properties. We hypothesized that curcumin would have an influence on cognitive functions in aged female rats. The purpose of the present study was to investigate the effects of curcumin supplementation on cognitive impairment evaluated by Morris water maze (MWM) as well as the oxidative stress induced by aging in female rats. Rats were randomly divided into either control or curcumin-supplemented groups. Curcumin or vehicle (corn oil) were given once daily for a period of 12 days, beginning 7 days prior to and 5 days during the behavioral tests. Behavioral assessment was performed in MWM. At the end of the behavioral test, blood samples and brain tissues were taken for the analysis of malondialdeyde (MDA), protein carbonyl and glutathione levels. During the training session, curcumin supplementation decreased latency to reach to the platform and the total distance traveled. During the probe trial, curcumin supplementation increased the number of platform crossings. In addition to the behavioral testing, biochemical results showed that MDA levels decreased in brain tissue by curcumin supplementation. It may be concluded that, curcumin supplementation improves cognitive functions by decreasing the lipid peroxidation in brain tissue of aged female rats. PMID:23609199

  8. ATP-binding cassette ABCC1 is involved in the release of sphingosine 1-phosphate from rat uterine leiomyoma ELT3 cells and late pregnant rat myometrium.

    PubMed

    Tanfin, Zahra; Serrano-Sanchez, Martin; Leiber, Denis

    2011-12-01

    Sphingosine 1-phosphate (S1P), a bioactive lipid generated by sphingosine kinases (SphK1/2), initiates different signalling pathways involved in physiological and pathological processes. We previously demonstrated that in rat myometrium at late (day 19) gestation, SphK1 increases the expression of COX2 via S1P generation and release. In rat uterine leiomyoma cells (ELT3), SphK1/S1P axis controls survival and proliferation. In the present study we demonstrate that PDBu activates SphK1 but not SphK2. SphK1 activation requires PKC and MAPK ERK1/2. S1P produced by PDBu is released in the medium. PDBu-induced S1P export is abolished by Ro-318220 and BIM (PKC inhibitors), by U0126 and PD98059 (MEK inhibitors), SKI-II (SphKI/2 inhibitor) and SphK1-siRNA, suggesting the involvement of PKC, ERK and SphK1 respectively. The release of S1P is insensitive to inhibitors of ATP Binding Cassette (ABC)A1 and ABCB1 transporters, but is abolished when ABCC1 transporters are inhibited by MK571 or down-regulated by ABCC1-siRNA. PDBu increases COX2 expression that is blocked by the inhibition of PKC, ERK1/2, SphK1, and when cells are treated with MK571 or transfected with ABCC1-siRNA. The induction of COX2 by the S1P release due to PDBu or by exogenous S1P involves S1P2 receptors coupled to Gi. In myometrium from rat at late gestation, the release of S1P is also strongly reduced when SphK and ABCC1 are inhibited. The data reveal that in rat leiomyoma cells and late pregnant rat myometrium, the release of S1P involves a similar signalling pathway and occurs through ABCC1. PMID:21803151

  9. Raloxifene Prevents Skeletal Fragility in Adult Female Zucker Diabetic Sprague-Dawley Rats

    PubMed Central

    Hill Gallant, Kathleen M.; Gallant, Maxime A.; Brown, Drew M.; Sato, Amy Y.; Williams, Justin N.; Burr, David B.

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n?=?24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies. PMID:25243714

  10. Effects of acute ethanol administration of female rat liver as a function of aging

    SciTech Connect

    Rikans, L.E.; Snowden, C.D. )

    1989-01-01

    Female Fischer 344 rats, aged 4, 14, and 25 months, received 4.0 g/kg of ethanol by intraperitoneal (i.p.) injection. Blood alcohol concentrations 2.5, 6 and 16 hr after ethanol injection were similar in the three age groups. Hepatic glutathione (GSH) levels were diminished 6 hr after ethanol injection, and there were no age-dependent differences in the depleted levels (3.2 {plus minus} 0.1, 3.5 {plus minus} 0.2, and 3.0 {plus minus} 0.5 {mu}g GSH/g liver). However, GSH contents in livers of young-adult rats approached control levels after 16 hr, whereas they remained depressed in older rats. Serum levels of hepatic enzymes were significantly elevated 6 hr after ethanol administration. The increases were greater in middle-aged and old rats than in young-adult rats. The results suggest that middle-aged and old rats are more susceptible than young rats to the acute toxicity of ethanol.

  11. Motor activity effects in female Fischer 344 rats exposed to isopropanol for 90 days.

    PubMed

    Burleigh-Flayer, H; Gill, M; Hurley, J; Bevan, C; Gardiner, T; Kapp, R; Tyler, T; Wright, G

    1998-01-01

    In a previous subchronic neurotoxicity study, increases in motor activity were observed for female rats after 9 and 13 weeks of exposure to 5000 ppm of isopropanol vapor. The present study was conducted to evaluate the reproducibility of these effects and, if reproducible, to assess the potential for reversibility following cessation of exposure. Two groups, each containing 30 female Fischer 344 rats, were exposed to concentrations of zero (control) and 5000 ppm of isopropanol vapor for 6 h per day, 5 days per week. Fifteen of the animals in the control and 5000 ppm groups were exposed for 9 weeks (designated as the 9-week subgroup), while the other 15 animals in each group were exposed for 13 weeks (designated as the 13-week subgroup). Motor activity was assessed for both subgroups prior to exposure and following 4, 7 and 9 weeks of exposure. Motor activity was also measured for rats in the 13-week subgroup following 11 and 13 weeks of exposure. These motor activity measurements were made 18-20 h following the end of the last exposure for that week. In addition, to evaluate the reversibility of motor activity effects, measurements were made on three occasions during the week following the final exposure for rats in both the 9-week and 13-week subgroups and weekly thereafter for five additional weeks for rats in the 13-week subgroup. Increases in cumulative test session motor activity counts were observed following 4, 7 and 9 weeks of exposure for rats in the 9-week subgroup. Increases in cumulative test session motor activity counts were also observed following 4, 7, 9, 11 and 13 weeks of exposure for rats in the 13-week subgroup. Reversibility of this effect was observed for rats in the 9-week subgroup within 2 days following the last exposure. Reversibility was also noted for rats in the 13-week subgroup but not until Study Week 15 (2 weeks following the last exposure). Minor changes were observed in the shape of the motor activity habituation curves for isopropanol-exposed animals in the 9-week and 13-week subgroups at ca. 50% of the measurement intervals beginning at Study Week 4. While most of these statistical changes were observed in conjunction with increases in cumulative test session motor activity, some were observed following time points where recovery of the cumulative test session motor activity counts had occurred. No change in the shape of the motor activity habituation curve was observed at 42 days following the last exposure, indicating that complete recovery of motor activity effects had occurred. Thus, repeated exposure of female rats to 5000 ppm of isopropanol produced reversible increases in motor activity. PMID:9804438

  12. Methamphetamine enhances paced mating behaviors and neuroplasticity in the medial amygdala of female rats.

    PubMed

    Holder, Mary K; Mong, Jessica A

    2010-08-01

    Methamphetamine (METH) is a psychomotor stimulant strongly associated with increases in sexual drive and behavior in women and men. Even though men and women are equally as likely to be addicted to or use METH, studies of sexual behavior often focus on male users. The paucity in studies examining the effect of METH in women is of great concern, when one considers the high correlation with sexually transmitted diseases such as HIV/AIDS and unplanned pregnancies. In fact, why METH so profoundly increases sexual drive is unknown. We have demonstrated that repeated exposure to METH enhances both receptivity and proceptivity in hormonally primed female rats. The current study examined whether a repeated exposure to METH enhanced female-initiated sexual behaviors in hormonally primed rats. In a paced mating paradigm, METH treatment significantly decreased the female's return latency following a mount (57%) and an ejaculation (44%), and the likelihood to leave the male following an intromission (37%) compared to controls. The METH-induced changes in paced mating behavior were accompanied by a 60% increase in spinophilin levels in the medial amygdala following hormonal priming and METH treatment. Taken together, these findings suggest that METH increases female sexual motivation and behavior in the rat potentially via changes in the neural substrate that require repeated exposure to the drug. PMID:20399784

  13. Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis in adult female rats.

    PubMed

    Liu, Te; Li, Na; Zhu, Jian; Yu, Guangyan; Guo, Kun; Zhou, Liting; Zheng, Dongchun; Qu, Xiaofeng; Huang, Jian; Chen, Xin; Wang, Shuyue; Ye, Lin

    2014-07-01

    Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely present in the environment and some products with phthalate plasticizer. It has become a serious problem in recent years. The effect of DEHP on female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on hypothalamus-pituitary-ovarian axis in adult female rats. Compared with control rats, the DEHP-treated rats showed: (1) lower body weight; (2) lower organ coefficient of ovary; (3) higher GnRH level in the hypothalamus; (4) higher mRNA and protein levels of GnRHR in the pituitary; and (5) lower serum sex hormone levels. Our data reveal that DEHP exposure may lead to the disruption of estrogen biosynthesis pathways in female rats and imbalance of hypothalamus-pituitary-ovarian axis. DEHP may impose negative influence on the development and function of the reproductive system in female rats. PMID:24675100

  14. Response of liver to lipopolysaccharide treatment in male and female rats.

    PubMed

    Depboylu, Bilge; Giri?, Murat; Olga, Vakur; Do?ru-Abbaso?lu, Semra; Uysal, Mjdat

    2013-07-01

    Gender is considered to be an important factor in endotoxin-induced tissue damage. Our aim was to examine the role of sex on the prooxidant-antioxidant status, necrotic and apoptotic events in the liver of lipopolysaccharide (LPS)-treated rats. We determined levels of lipid peroxides, non-enzymatic and enzymatic antioxidants, and expressions of apoptosis-related proteins, antiapoptotic B cell lymphoma-2 (Bcl-2) and proapoptotic Bax, caspase-3 activity and apoptotic cell numbers in the liver. Hepatic histopathology and serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were also investigated. Male and female Wistar rats (180-200 g) were injected with LPS (10 mg/kg, i.p.) and examinations were performed 6 h after the injection. Significant increases in hepatic thiobarbituric acid reactive substances and diene conjugate levels were observed in male and female rats following LPS treatment. However, there were no changes in hepatic glutathione, vitamin E and vitamin C levels together with superoxide dismutase, glutathione peroxidase and glutathione transferase activities. LPS treatment caused significant increases in serum ALT and AST activities and lymphocyte infiltration and necrotic changes in the livers. Bcl-2 and Bax expressions, caspase-3 activity and apoptotic cell numbers were also found to be increased in both groups. In conclusion, no sex-dependent difference was observed in the changed hepatic prooxidant-antioxidant status of rats following LPS treatment. Besides, the process leading to apoptosis and necrosis in the liver showed a similar pattern in both gender of rats. PMID:22884257

  15. Effects of high frequency noise on female rat's multi-organ histology.

    PubMed

    Xue, Laijun; Zhang, Dajun; Wang, Ting; Shou, Xi

    2014-01-01

    To investigate the pathological damage of high-frequency stable noise exposure on the brain, heart, liver, and spleen of female rat's. Controlled animal intervention study. Twenty female Sprague-Dawley rats were randomly divided into experimental and control groups with 10 rats in each group. Rats in the experimental group were exposed to continuous high-frequency stable noise for 2 weeks (3 h/day)followed by the pathological damages in the rat's brain, heart, liver, and spleen were compared with those of the control group. After 2 weeks' continuous exposure to high-frequency stable noise, compared with the control group, the most prominent histopathologic changes in the brain tissue structures of the experimental group included loose disorder, hyperemia, edema, blood vessels expand, glial cell hyperplasia, mild atypia in some areas (hyperchromatic nuclei, irregular karyotype), and no degeneration and necrosis. There were dilatation and congestion of central vein, hepatic sinus, and interlobular veins of liver tissue. The structure of hepatic lobule was destroyed by inflammatory cell infiltration, as well as lymphoid nodule formation. There was hyperemia in spleen, but the structure was clear. There was extravasated blood, and the splenic sinuses were highly expanded by a blood clot. Hyperplasias of the lymphoid of white pulp were also active. There was dilation and congestion in myocardial interstitial vascular, and there was mild degeneration and hyperemia in myocardial cells. No hemorrhage and myocardial necrosis were observed. High-frequency stable noise can cause pathological damage in brain, liver, spleen, and heart tissues of female rat at a various degree. PMID:25033787

  16. Estrogenic activity of a hydro-alcoholic extract of Bambusa arundinaceae leaves on female wistar rats

    PubMed Central

    Jawaid, Talha; Awasthi, Akanksha; Kamal, Mehnaz

    2015-01-01

    To study the estrogenic activity of the hydro-alcoholic extract of Bambusa arundinaceae leaves (HEBA) in female Wistar rats. The dried powdered leaves were extracted with hydroalcoholic mixture (60%), and the resultant extract was subjected for phytochemical analyses to identify different phytoconstituents. HEBA were administered to ovariectomized rats for 7 days at three different doses (viz., 200, 300, 400 mg/kg body weight, p.o.) and their estrogenic activity were compared with each of daily treatment with 0.2 mg/kg body weight, i.p. conjugated equine estrogen as a positive control or olive oil as a negative control. Estrogenic activity was evaluated by doing uterotropic assay, vaginal cytology and measurement of vaginal opening in female Wistar rats. Oral administration of HEBA in ovariectomized immature and mature female Wistar rats in a dose of 400 mg/kg b.w. resulted in significant increase in the uterine wet weight (in mg) (224.82 ± 7.01) and (912.25 ± 27.22) when compared with ovariectomized control rats (111.52 ± 3.17) and (506.67 ± 21.39). HEBA (400 mg/kg b.w., p.o.) treated rats, showing only cornified epithelial cells which was an indication of the presence of the estrogen and also showed 100% vaginal opening. It was observed that HEBA possess significant estrogenic activity at 400 mg/kg b.w., p.o. which was evident by uterotropic assay, measurement of vaginal opening, and histopathological changes. PMID:25709965

  17. Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats

    PubMed Central

    Maeng, Lisa Y.; Cover, Kara K.; Landau, Aaron J.; Milad, Mohammed R.; Lebron-Milad, Kelimer

    2015-01-01

    Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that neural mechanisms for certain behavioral tasks and response behaviors are different in females and males. Using females in research studies can represent a challenge because of the variation of gonadal hormones during their estrous cycle. This protocol describes well-established procedures that are useful in investigating the role of estrogen in fear extinction memory consolidation in female rats. Phase of the estrous cycle and exogenous estrogen administration prior to extinction training can influence extinction recall 24 hr later. The vaginal swabbing technique for estrous phase identification described here aids the examination and manipulation of naturally cycling gonadal hormones. The use of this basic rodent model may further delineate the mechanisms by which estrogen can modulate fear extinction memory in females. PMID:25741747

  18. Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

    PubMed

    Fournier, Sbastien; Gulemetova, Roumiana; Baldy, Ccile; Joseph, Vincent; Kinkead, Richard

    2015-04-01

    Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ?30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ?57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (?12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia. PMID:25652536

  19. Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.

  20. Effect of valproic acid on /sup 65/Zn distribution in the pregnant rat

    SciTech Connect

    Keen, C.L.; Peters, J.M.; Hurley, L.S.

    1989-04-01

    The effect of valproic acid on the distribution of gavaged /sup 65/Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of /sup 65/Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher /sup 65/Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake.

  1. Lack of hydroxylated fullerene toxicity after intravenous administration to female Sprague-Dawley rats.

    PubMed

    Monteiro-Riviere, Nancy A; Linder, Keith E; Inman, Alfred O; Saathoff, John G; Xia, Xin-Rui; Riviere, Jim E

    2012-01-01

    Hydroxylated fullerenes (C??OH(x)) or fullerols are water-soluble carbon nanoparticles that have been explored for potential therapeutic applications. This study assesses acute in vivo tolerance in 8-wk-old female Sprague-Dawley rats to intravenous (iv) administration of 10 mg/kg of well-characterized C??(OH)??. Complete histopathology and clinical chemistries are assessed at 8, 24, and 48 h after dosing. Minor histopathology changes are seen, primarily in one animal. No clinically significant chemistry changes were observed after treatment. These experiments suggest that this fullerol was well tolerated after iv administration to rats. PMID:22524592

  2. Lack of Hydroxylated Fullerene Toxicity after Intravenous Administration to Female Sprague-Dawley Rats

    PubMed Central

    Monteiro-Riviere, Nancy A.; Linder, Keith E.; Inman, Alfred O.; Saathoff, John G.; Xia, Xin-Rui; Riviere, Jim E.

    2012-01-01

    Hydroxylated fullerenes (C60OHx) or fullerols are water-soluble carbon nanoparticles that have been explored for potential therapeutic applications. This study assessed acute in vivo tolerance in 8 week old female Sprague Dawley rats to intravenous administration (IV) of 10 mg/kg of well-characterized C60(OH)30. Complete histopathology and clinical chemistries were assessed at 8, 24, and 48 hr after dosing. Minor histopathology changes were seen, primarily in one animal. No clinically significant chemistry changes were observed after treatment. These experiments suggest that this fullerol was well tolerated after IV administration to rats. PMID:22524592

  3. High salt diet increases the pressor response to stress in female, but not male ETB-receptor-deficient rats.

    PubMed

    Speed, Joshua S; D'Angelo, Gerard; Wach, Paul A; Sullivan, Jennifer C; Pollock, Jennifer S; Pollock, David M

    2015-03-01

    Acute stress in both rodents and humans causes a transient rise in blood pressure associated with an increase in plasma endothelin-1 (ET-1). High salt (HS) intake also increases ET-1 production, and interestingly, blunts the pressor response to acute air jet stress in rats. We previously reported that female rats lacking functional ETB receptors everywhere except sympathetic nerves (ETB def) had a greater degree of hypertension in response to a HS diet compared to their male counterparts when measured by the tail cuff method. However, we now report that salt-induced hypertension is not different between sexes when measured by telemetry. Therefore, additional experiments were designed to test the hypothesis that female ETB def rats are more sensitive to acute stress when on a HS diet. The pressor response, measured by telemetry, to acute air jet stress was similar between male transgenic control (Tg control) and ETB def rats following chronic HS intake. In contrast, female ETB def rats had a significantly greater pressor response (about twofold higher) than female or male Tg control or male ETB def rats maintained on HS, a finding that cannot be explained by increased vascular reactivity to ET-1 in female rats as we observed that male ETB def rats had a greater pressor response to i.v. infusion of ET-1 compared to females. Furthermore, HS feeding exacerbated the pressor response to ET-1 in both male and female ETB def rats. Given our previous studies demonstrating that the ETA receptor functions to reduce the pressor response to acute stress, these findings further support a role for the ET receptor system in the pressor response to acute stress and that female rats have reduced ETA receptor activity when on a HS diet compared to males. PMID:25802361

  4. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual interactions than for social interactions. PMID:26794592

  5. Comparison of male and female rats in avoidance of a moving object: more thigmotaxis, hypolocomotion and fear-like reactions in females.

    PubMed

    Svoboda, J; Telenský, P; Blahna, K; Bureš, J; Stuchlík, A

    2012-01-01

    Although male rats generally outperform females in many spatial tasks, sometimes gender differences are not present. This preliminary study examined gender effects in the Enemy avoidance task, in which a rat on a stable circular arena avoids approaching a small mobile robot while collecting randomly dispersed small pellets. Whenever distance between robot and the rat dropped below 25 cm, animal was punished by a mild footshock. Female rats showed thigmotaxis, hypolocomotion and avoidance of robot in the habituation phase, when approaches were not punished. No statistically significant differences in avoidance learning under reinforcement training sessions were observed; but females still spent significantly more time at periphery of the arena and foraged less than males. We conclude that females were able to perform at the same level as males under reinforcement despite different behavioral strategy. The thigmotaxic behavior appears to function as innate escape strategy in female rats triggered by the stressing effect of the moving robot rather then the presence of shocks. PMID:23098661

  6. Estradiol and striatal dopamine receptor antagonism influence memory system bias in the female rat.

    PubMed

    Quinlan, Matthew G; Almey, Anne; Caissie, Meghen; LaChappelle, Ivonne; Radiotis, George; Brake, Wayne G

    2013-11-01

    Estradiol (E2) has been shown to influence learning and memory systems used by female rats to find a reward. Rats with high levels of E2 tend to use allocentric, or place, memory while rats with low levels of E2 use egocentric, or response, memory. It has been shown that systemic dopamine receptor antagonism interacts with E2 to affect which memory system is used. Here, dopamine antagonists were administered directly into either the dorsal striatum or nucleus accumbens to determine where in the brain this interaction takes place. Seventy-four young adult, female, Sprague-Dawley rats were trained and tested in a modified plus-maze. All rats were ovariectomized, received a subcutaneous low E2 implant, and were implanted with bilateral cannulae into either the dorsal striatum or the nucleus accumbens. Additionally, high E2 rats received daily injections of E2 in a sesame oil solution while low E2 rats received daily injections of vehicle. After reaching criterion levels of performance in a plus-maze task, rats were administered microinjections of either a dopamine D1 receptor (SCH 23390; 0.1 ?g/ml and 0.01 ?g/ml) or D2 receptor (raclopride; 2 ?g/ml and 0.5 ?g/ml) antagonist or a vehicle control (saline) in a counterbalanced manner. High E2 rats exhibited a trend towards a place memory bias while low E2 rats showed a response memory bias. Dorsal striatal administration of a D1, but not D2, dopamine receptor antagonist caused a switch in the memory system used by both high and low E rats. There was no significant effect of dopamine receptor antagonism in the nucleus accumbens group. Thus, E2 determined which memory system controlled behavior in a plus-maze task. Moreover, this effect was modulated by dopamine D1R antagonism in the dorsal but not ventral striatum suggesting that memory systems are, in part, mediated by E2 and dopamine in this region. PMID:24036396

  7. The toxicity mechanism of sodium fluoride on fertility in female rats.

    PubMed

    Zhou, Yongjiang; Qiu, Yiwen; He, Junlin; Chen, Xuemei; Ding, Yubing; Wang, Yingxiong; Liu, Xueqing

    2013-12-01

    Recognition of the harmful effects of sodium fluoride (NaF) on human reproduction is increasing, especially as it relates to female reproduction. However, the mechanism by which NaF interferes with female reproduction is unclear. The aims of the present study were to investigate the effects of fluoride exposure on female fertility and to elucidate the mechanisms underlying these effects. Female Sprague-Dawley rats were divided into three groups: one control group and two NaF-treated groups (100 and 200 mg/L in the drinking water for 12 weeks). Several parameters were evaluated, including: (i) fluoride concentrations; (ii) estrogen (E2) and progesterone (P) concentrations; (iii) estrogen receptor alpha protein (ER?); (iv) progesterone receptor (PgR) protein; (v) follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) protein. The results indicated that administration of NaF lead to significant decreases in E2 and P levels in the serum and in the expression of FSHR protein. In addition, fluoride exposure significantly increased Er? and PgR protein expression levels and LHR protein expression. These results suggest that the reproductive hormone reduction and the abnormalities of related receptor proteins expression are important factors underlying the decreased fertility observed in female rats that have been exposed to NaF. PMID:24071475

  8. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. PMID:22484141

  9. Early maternal separation increases symptoms of activity-based anorexia in male and female rats.

    PubMed

    Hancock, Stephanie; Grant, Virginia

    2009-07-01

    Running activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing the release of stress hormones known to exert anorexic effects. HPA axis reactivity is strongly influenced by early postnatal manipulations, including removal of pups from the dam for short (handling) or prolonged (maternal separation) durations during the preweaning period. The authors examined the effects of handling and maternal separation on food intake, body weight loss, and running rates of young adult male and female rats in the activity-based anorexia (ABA) paradigm. Postnatal treatment did not affect adaptation to a 1-hr restricted feeding schedule before the introduction of wheel running. During the ABA paradigm, maternally separated animals lost weight faster, ate less, ran more, and required fewer days to reach removal criterion compared with handled rats. Females were particularly vulnerable. These findings indicate that early postnatal treatment and sex influence ABA. PMID:19594284

  10. Metabolic response to starvation in late pregnant rats. II. Fetal response.

    PubMed

    Nowacka, M; Grski, J

    1988-01-01

    Effect of prolonged maternal fasting on the fetal liver and heart glycogen and triglyceride content and on concentration of glucose, urea, uric acid and alpha amino-nitrogen in the amniotic fluid has been studied in rats. The animals were divided into four groups: fed (control), fasted for one day (from 20 to 21 day of pregnancy), fasted for two days (from 19 to 21 day) and fasted for three days (from 18 to 21 day). Maternal fasting for two and three days resulted in reduction in fetal growth. The fetal liver glycogen content was reduced already after one day of fasting, stabilized after two days and then further decreased after three days. The fetal heart glycogen content was reduced only after three days of fasting. The fetal liver triglyceride content increased gradually during the first two days of fasting and then stabilized. The content of triglycerides in the heart was elevated after two and three days of food deprivation. The amniotic fluid glucose concentration decreased after one day of fasting and then stabilized. Fasting did not effect the concentration of the nitrogenous compounds in the amniotic fluid. It is concluded that maternal fasting affects markedly metabolism of energy substrates stored in the fetal liver and the heart and the composition of the amniotic fluid. PMID:3257056

  11. [Studies on nutritional effects of traditional Chinese tonics with strengthened nutrients on pregnant women and rats].

    PubMed

    Ling, C D; Zhang, Z J; Chen, Z L

    1996-05-01

    Clinical and Experimental studies on a mixture made of traditional Chinese tonics (such as Fructus Lycii, Rhizoma Dioscoreae and Arillus Longannae, etc.) and strengthened nutrients (such as iron, zinc and Calcium, etc.) were conducted in order to explore its nutritional and health promoting effects. (1) One hundred and three primiparous women were divided randomly into observed group and control group, results showed that the serum levels of iron, zinc, hemoglobin of observed group were all raised after treatment, these parameters and the concentration of iron in umbilical cord blood as well as body weight of new-born baby of the observed group were higher than that of control group (P < 0.05 or P < 0.01). (2) Results of experimental rats showed that the utilization rate, hemoglobin level, fetal growth and developing parameters of test group were all higher than that of control group significantly (P < 0.05 or P < 0.01). These results suggested that the nutrient mixture has a good nutritional and health promoting effect on pregnancy. PMID:9387716

  12. Effect of 6-mercaptopurine on /sup 65/Zn distribution in the pregnant rat

    SciTech Connect

    Amemiya, K.; Hurley, L.S.; Keen, C.L.

    1989-04-01

    The effect of 6-mercaptopurine (6-MP) on the distribution of gavaged /sup 65/Zn in maternal and embryonic tissues of Sprague-Dawley rats was examined 24 hr after injection of the drug on day 13 of pregnancy. 6-MP injection resulted in a significantly higher retention of counts of /sup 65/Zn in maternal liver and lower counts in maternal plasma, uterus, placenta, and embryo than in controls. Compared to controls, gel chromatography of maternal liver from 6-MP injected dams showed higher counts associated with a protein peak of molecular weight 6,000-8,000, the approximate molecular weight of the zinc-binding protein metallothionein. These results support the idea that the zinc deficiency, which is observed in day 21 fetuses from dams injected with 6-MP during midgestation, may be the result of a drug-induced sequestering of zinc into maternal liver followed by a decrease in maternal plasma zinc and subsequent reduction in fetal zinc uptake. We suggest that this 6-MP-associated redistribution of zinc into maternal liver may be due to induction of maternal metallothionein synthesis by the drug.

  13. Acute iron overload leads to hypothalamic-pituitary-gonadal axis abnormalities in female rats.

    PubMed

    Rossi, Emilly M; Marques, Vinicius B; Nunes, Dieli de O; Carneiro, Maria T W D; Podratz, Priscila L; Merlo, Eduardo; dos Santos, Leonardo; Graceli, Jones B

    2016-01-01

    Iron plays a critical role in a mammal's physiological processes. However, iron tissue deposits have been shown to act as endocrine disrupters. Studies that evaluate the effect of acute iron overload on hypothalamic-pituitary-gonadal (HPG) axis health are particularly sparse. This study demonstrates that acute iron overload leads to HPG axis abnormalities, including iron accumulation and impairment in reproductive tract morphology. Female rats were treated with iron-dextran (Fe rats) to assess their HPG morphophysiology. The increasing serum iron levels due to iron-dextran treatment were positively correlated with higher iron accumulation in the HPG axis and uterus of Fe rats than in control rats. An increase in the production of superoxide anions was observed in the pituitary, uterus and ovary of Fe rats. Morphophysiological reproductive tract abnormalities, such as abnormal ovarian follicular development and the reduction of serum estrogen levels, were observed in Fe rats. In addition, a significant negative correlation was obtained between ovary superoxide anion and serum estrogen levels. Together, these data provide in vivo evidence that acute iron overload is toxic for the HPG axis, a finding that may be associated with the subsequent development of the risk of reproductive dysfunction. PMID:26536400

  14. Metyrapone Blocks Maternal Food Restriction-Induced Changes in Female Rat Offspring Lung Development

    PubMed Central

    Li, Yishi; Corral, Julia; Saraswat, Aditi; Husain, Sumair; Dhar, Ankita; Sakurai, Reiko; Khorram, Omid; Torday, John S.

    2014-01-01

    Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant production in the intrauterine growth-restricted (IUGR) offspring through unknown mechanisms. Since pulmonary surfactant production is regulated by maternal and fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would block the effects of MFR on surfactant production in the offspring. Three groups of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50% reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR offspring weighed significantly more, had reduced alveolar number, increased septal thickness, and decreased surfactant protein and phospholipid synthesis. These MFR-induced effects were normalized by the antiglucocorticoid MTP, suggesting that the stress of MFR causes hypercorticoidism, altering lung structure and function in adulthood. PMID:24023031

  15. Prolactin potentiates the activity of acid-sensing ion channels in female rat primary sensory neurons.

    PubMed

    Liu, Ting-Ting; Qu, Zu-Wei; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Hu, Wang-Ping

    2016-04-01

    Prolactin (PRL) is a polypeptide hormone produced and released from the pituitary and extrapituitary tissues. It regulates activity of nociceptors and causes hyperalgesia in pain conditions, but little is known the molecular mechanism. We report here that PRL can exert a potentiating effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRL dose-dependently increased the amplitude of ASIC currents with an EC50 of (5.89 ± 0.28) × 10(-8) M. PRL potentiation of ASIC currents was also pH dependent. Second, PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRL receptor antagonist, and removed by intracellular dialysis of either protein kinase C inhibitor GF109203X, protein interacting with C-kinase 1(PICK1) inhibitor FSC-231, or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Four, PRL exacerbated nociceptive responses to injection of acetic acid in female rats. Finally, PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behavior in intact female rats than OVX female and male rats and thus modulation of PRL may be gender-dependent. These results suggest that PRL up-regulates the activity of ASICs and enhances ASIC mediated nociceptive responses in female rats, which reveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia. PMID:26188144

  16. Tonic and reflex cardiovascular autonomic control in trained-female rats.

    PubMed

    Sanches, I C; Sartori, M; Jorge, L; Irigoyen, M C; De Angelis, K

    2009-10-01

    The effects of exercise training on cardiovascular and autonomic functions were investigated in female rats. After an aerobic exercise training period (treadmill: 5 days/week for 8 weeks), conscious female Wistar (2 to 3 months) sedentary (S, N = 7) or trained rats (T, N = 7) were cannulated for direct arterial pressure (AP) recording in the non-ovulatory phases. Vagal (VT) and sympathetic tonus (ST) were evaluated by vagal (atropine) and sympathetic (propranolol) blockade. Baroreflex sensitivity was evaluated by the heart rate responses induced by AP changes. Cardiopulmonary reflex was measured by the bradycardic and hypotensive responses to serotonin. Resting bradycardia was observed in T (332 +/- 7 bpm) compared with S animals (357 +/- 10 bpm), whereas AP did not differ between groups. T animals exhibited depressed VT and ST (32 +/- 7 and 15 +/- 4 bpm) compared to S animals (55 +/- 5 and 39 +/- 10 bpm). The baroreflex and cardiopulmonary bradycardic responses were lower in T (-1.01 +/- 0.27 bpm/mmHg and -17 +/- 6 bpm) than in the S group (-1.47 +/- 0.3 bpm/mmHg and -41 +/- 9 bpm). Significant correlations were observed between VT and baroreflex (r = -0.72) and cardiopulmonary (r = -0.76) bradycardic responses. These data show that exercise training in healthy female rats induced resting bradycardia that was probably due to a reduced cardiac ST. Additionally, trained female rats presented attenuated bradycardic responses to baro- and cardiopulmonary receptor stimulation that were associated, at least in part, with exercise training-induced cardiac vagal reduction. PMID:19784478

  17. 17?-Oestradiol Modulates Glucocorticoid, Neural and Behavioural Adaptations to Repeated Restraint Stress in Female Rats

    PubMed Central

    Lunga, P.; Herbert, J.

    2009-01-01

    Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17?-oestradiol on hypothalamic-pituitary-adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17?-oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17?-oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17?-oestradiol-treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin-releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17?-oestradiol treatment at the higher dose (120 ?g/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17?-oestradiol-treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17?-oestradiol-replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non-stressed control rats with or without 17?-oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17?-oestradiol-treated rats. After repeated restraint stress, 17?-oestradiol-replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17?-oestradiol-treated ovariectomized rats, but stress-induced anxiety behaviour is reduced. PMID:15344916

  18. Metabolic Effects of Sleeve Gastrectomy in a Female Rat Model of Diet-Induced Obesity

    PubMed Central

    Brinckerhoff, Tatiana Z.; Bondada, Sandhya; Lewis, Catherine E.; French, Sam; DeUgarte, Daniel A.

    2011-01-01

    Background While females disproportionately undergo bariatric surgery, rodent models investigating mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients as it avoids the malabsorption associated with intestinal bypass. Objectives We sought to evaluate the impact of sleeve gastrectomy on young female rats with diet-induced obesity. Settings David Geffen School of Medicine at UCLA Methods Sprague Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, animals underwent either sleeve gastrectomy or sham surgery. Animals were sacrificed four weeks after surgery. A chemistry panel was performed, and serum adipokines and gut hormones were assayed. Homeostasis model assessment score (HOMA) was calculated. Liver histology was graded for steatosis. Two-sample t-test was used to compare groups. Results Sleeve gastrectomy was associated with significant weight loss (56% vs. ?46%; p<0.001), lower leptin levels (1.31.2 vs. 3.52.3 ng/ml; p<0.01), and higher adiponectin levels (0.43 0.19 vs. 0.17 0.14 ng/ml; p<0.004) when compared to sham animals. There were no significant differences in fasting ghrelin. Furthermore, we did not observe evidence of insulin resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, further gender-specific studies are warranted given that the majority of bariatric surgeries are performed in females. Conclusion Sleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin via mechanisms independent of ghrelin in a female model of diet-induced obesity. PMID:22093377

  19. Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats

    PubMed Central

    2013-01-01

    Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female SpragueDawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. PMID:24345032

  20. Alpha-difluoromethylornithine modifies FSH secretion and puberty onset in the female rat.

    PubMed

    Thyssen, S M; Libertun, C

    1996-01-01

    FSH secretion is high in immature female rats from Postnatal Day 5 to 18 and decreases thereafter. This is a relatively steroid-independent event of cerebral origin and of importance for puberty onset. Polyamines, a group of ubiquitous amines, play an essential role in tissue growth and differentiation, body weight increment, brain organization, and molecular mechanisms of hormonal action. Polyamine levels as well as the activity of ornithine decarboxylase, the limiting enzyme in polyamines biosynthesis, are highest during development. Inhibition of their synthesis during this period by alpha- difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, impairs normal brain development. The present study tested the hypothesis that polyamines play a role during brain organization of reproduction. DFMO was administered following different schedules in female newborn rats, and the effect on pituitary secretion, puberty onset, and fertility was evaluated. In three groups (daily injections from Day 1 to 9, or from Day 1 to 6, or injections on alternative days from Day 1 to 9), a delay in vaginal opening and first estrous was observed. When vaginal opening was plotted against body weight, it was evident that in groups daily injected with DFMO vaginal opening occurred at a lower body weight. In the group treated on alternate days, a delay occurred but at a higher body weight than in controls. In this group, serum FSH levels on Day 10 and 20, but not on Day 30, were higher in DFMO rats. In the group treated from Day 1 to 6 daily, DFMO increased serum FSH on Postnatal Day 20. After vaginal opening, estrous cyclicity in control and DFMO injected rats was similar. There was no significant effect of treatment on fertility and litter weight or number of offspring at birth. It is concluded that DFMO, an inhibitor of ornithine decarboxylase, administered during the first week of life in female rats is followed by prolonged high FSH serum levels and delayed puberty, but once puberty occurs, fertility is normal. PMID:8594622

  1. Physiological, biochemical and histological alterations induced by administration of imidacloprid in female albino rats.

    PubMed

    Vohra, Prerna; Khera, Kuldeep Singh; Sangha, Gurinder Kaur

    2014-03-01

    Imidacloprid, a neonicotinoid the newest class of major insecticide has outstanding potency and systemic action for crop protection against piercing and sucking insects pests and also highly effective for control of flea on cats and dogs. The effect of oral administration of two doses of imidacloprid 10 and 20mg/kg/day for 60 days on biochemical parameters, histopathology and protein profile of female albino rat was assessed. Average feed intake was significantly reduced (P<0.01) at 20mg/kg/day. Relative weight of heart and spleen decreased significantly (P<0.05) at higher dose level. Non significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), alkaline phosphatase (AKP) activity was observed in both the imidacloprid treated groups. There was significant decrease (P<0.01, P<0.05) in acetyl cholinesterase (AChE) activity in plasma and brain of both the imidacloprid treated groups. Microscopically, liver tissue of rats treated with higher dose of imidacloprid showed marked dilation and congestion of central vein and degeneration of hepatocytes. The exposure to imidacloprid produced histopathological changes that could be correlated with changes in the biochemical profile of female albino rats. The blood plasma proteins were examined by SDS PAGE. There was no diagnostic difference in the pattern of plasma protein profile of control and treated rats. Based on the present physiological, biochemical and histological studies it is evident that imidacloprid did not produce any significant effects at 10mg/kg/day dose but induced toxicological effects at 20mg/kg/day to female rats. PMID:24759051

  2. TITLE Disposition and kinetics of Tetrabromobisphenol A in female Wistar Han rats

    PubMed Central

    Knudsen, Gabriel A.; Sanders, J. Michael; Sadik, Abdella M.; Birnbaum, Linda S.

    2014-01-01

    Tetrabromobisphenol A (TBBPA) is the brominated flame retardant with the largest production volume worldwide. NTP 2-year bioassays found TBBPA dose-dependent increases in uterine tumors in female Wistar Han rats; evidence of reproductive tissues carcinogenicity was equivocal in male rats. To explain this apparent sex-dependence, the disposition and toxicokinetic profile of TBBPA were investigated using female Wistar Han rats, as no data were available for female rats. In these studies, the primary route of elimination following [14C]-TBBPA administration (25, 250 or 1,000 mg/kg) was in feces; recoveries in 72 h were 95.7±3.5%, 94.3±3.6% and 98.8±2.2%, respectively (urine: 0.2-2%; tissues: <0.1). TBBPA was conjugated to mono-glucuronide and —sulfate metabolites and eliminated in the bile. Plasma toxicokinetic parameters for a 250 mg/kg dose were estimated based on free TBBPA, as determined by UV/radiometric-HPLC analyses. Oral dosing by gavage (250 mg/kg) resulted in a rapid absorption of compound into the systemic circulation with an observed Cmax at 1.5 h post-dose followed by a prolonged terminal phase. TBBPA concentrations in plasma decreased rapidly after an IV dose (25 mg/kg) followed by a long elimination phase. These results indicate low systemic bioavailability (F<0.05), similar to previous reports using male rats. Elimination pathways appeared to become saturated leading to delayed excretion after a single oral administration of the highest dose (1,000 mg/kg); no such saturation or delay was detected at lower doses. Chronic high exposures to TBBPA may result in competition for metabolism with endogenous substrates in extrahepatic tissues (e.g., SULT1E1 estrogen sulfation) resulting in endocrine disruption. PMID:24977115

  3. Properties of voltage-activated [Ca2+]i transients in single smooth muscle cells isolated from pregnant rat uterus

    PubMed Central

    Shmigol, A V; Eisner, D A; Wray, Susan

    1998-01-01

    The intracellular calcium concentration ([Ca2+]i) was measured at 35 °C using the fluorescent indicator indo-1 in patch-clamped, single uterine myocytes from pregnant rats to investigate the relationship between depolarization, Ca2+ current (ICa) and [Ca2+]i. Membrane depolarization activated ICa and produced a [Ca2+]i transient. The rapid increase in [Ca2+]i occurred at the same time as the inward ICa. Both ICa and the increase in [Ca2+]i were abolished by nifedipine (10 μm). When the membrane potential was held at -80 mV the threshold depolarization for an increase in [Ca2+]i was about -55 to -50 mV. As the magnitude of the depolarization was increased to about 0 mV there was an increase in the size of both ICa and the increase in [Ca2+]i. As the magnitude of the depolarization was further increased both ICa and the [Ca2+]i increase declined. When the depolarizing pulses were applied at 3 Hz to mimic normal action potentials then the individual [Ca2+]i transients did not fully relax and a tetanic rise of [Ca2+]i was observed. Under these conditions, there was not a simple relationship between the magnitude of the Ca2+ response and Ca2+ entry. When pairs of depolarizing pulses were applied, the increase in [Ca2+]i produced by the second pulse was larger (in relation to the magnitude of the L-type Ca2+ current) than that produced by the first pulse. This facilitation was abolished by both ryanodine and cyclopiazonic acid suggesting a role for release from intracellular stores. We conclude that the L-type Ca2+ current is the major source of Ca2+ ions entering the cell to produce the [Ca2+]i transient on depolarization. The magnitude of the increase in [Ca2+]i may, however, be amplified by Ca2+-induced Ca2+ release. PMID:9714861

  4. Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats

    PubMed Central

    Habibi, Javad; Hayden, Melvin R.; Ferrario, Carlos M.; Sowers, James R.; Whaley-Connell, Adam T.

    2014-01-01

    Background/Aims It is increasingly recognized that there is sexual dimorphism in kidney disease progression; however, this disparity is lost in the presence of diabetes where women progress at a similar rate to men. The renin-angiotensin-aldosterone system (RAAS) is known to regulate diabetes-induced kidney injury, and recent literature would suggest that gender differences exist in RAAS-dependent responses in the kidney. In this regard, these gender differences may be overcome by excessive salt intake. Thereby, we hypothesized that salt would promote proteinuria in transgenic female rats under conditions of excess tissue angiotensin (Ang) II and circulating aldosterone. Materials and Methods We utilized young female transgenic (mRen2)27 (Ren2) rats and Sprague-Dawley (SD) littermates and fed a high-salt diet (4%) over 3 weeks. Results Compared to SD and Ren2 controls, female Ren2 rats fed a high-salt diet displayed increases in proteinuria, periarterial and interstitial fibrosis as well as ultrastructural evidence of basement membrane thickening, loss of mitochondrial elongation, mitochondrial fragmentation and attenuation of basilar canalicular infoldings. These findings occurred temporally with increases in transforming growth factor-? but not indices of oxidant stress. Conclusions Our current data suggest that a diet high in salt promotes progressive kidney injury as measured by proteinuria and fibrosis associated with transforming growth factor-? under conditions of excess tissue Ang II and circulating aldosterone. PMID:24847333

  5. Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats

    PubMed Central

    Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

    2014-01-01

    Background: Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. Objectives: The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. Patients and Methods: The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P < 0.05). Results: The results of the present study showed that agitation, disparity, and floppy eyelids in group E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. Conclusions: The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats . PMID:25593890

  6. Antiarthritic activity of a polyherbal formulation against Freund's complete adjuvant induced arthritis in Female Wistar rats

    PubMed Central

    Petchi, R. Ramesh; Parasuraman, S.; Vijaya, C.; Gopala Krishna, S. V.; Kumar, M. Kiran

    2015-01-01

    Objectives: To formulate a polyherbal formulation and evaluate its antiarthritic activity against Freund's complete adjuvant induced arthritis in Female Wistar rats. Materials and Methods: Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including arthritis. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. Arthritis was induced in female Wistar rats using Freund's complete adjuvant (FCA), and the antiarthritic effect of polyherbal formulation was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, blood samples were collected for biochemical and hematological analysis. The radiological examination was carried out before terminating the study. Results: Polyherbal formulation showed significant antiarthritic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of indomethacin. The antiarthritic activity of polyherbal formulation is supported by biochemical and hematological analysis. Conclusion: The polyherbal formulation showed signinicant antiarthritic activity against FCA-induced arthritis in female Wistar rats. PMID:26229343

  7. Diallyl sulfide inhibits diethylstilbesterol-induced DNA adducts in the breast of female ACI rats.

    PubMed

    Green, M; Wilson, C; Newell, O; Sadrud-Din, S; Thomas, R

    2005-09-01

    Diethylstilbestrol (DES) is metabolized to reactive intermediates that produce DNA adducts and ultimately cancer. Diallyl sulfide (DAS) has been shown to inhibit the metabolism of several procarcinogens. The ability of DES to produce DNA adducts in microsomal, mitochondrial, and nuclear in vitro metabolic systems and in the breast of female ACI rats, as well as ability of DAS to inhibit DNA adducts were investigated. Microsomes, mitochondria, and nuclei isolated from breast tissue of female ACI rats were used to catalyze oxidation reactions. Female ACI rats were treated i.p. as follows: (1) corn oil, (2) 200mg/kg DES, (3) 200mg/kg DES/200mg/kg of DAS, (4) 200mg/kg DES/400mg/kg DAS. DES produced DNA adducts in each metabolic system. The relative adduct levels were 2.1 x 10(-4), 6.2 x 10(-6), and 2.9 x 10(-7) in microsomal, mitochondrial, and nuclear reactions, respectively. DAS inhibited DNA adducts in each metabolic system. The percent inhibition ranged from 86% in microsomes to 93% in nuclei. DES produced DNA adducts in mtDNA and nDNA. DAS completely inhibited the DES-induced mtDNA adducts and caused a dose dependent decrease in nDNA adduct formation. These findings suggest that DAS could inhibit DES-induced breast cancer by inhibiting its metabolism. PMID:15989972

  8. Detecting Early Biomechanical Effects of Zoledronic Acid on Femurs of Osteoporotic Female Rats

    PubMed Central

    Palacio, Evandro Pereira; Müller, Sérgio Swain; Sardenberg, Trajano; Mizobuchi, Roberto Ryuiti; Galbiatti, José Antônio; Durigan, Alcides; Savarese, Aniello; Ortolan, Érika Veruska Paiva

    2012-01-01

    Aim. To investigate the biomechanical effects of zoledronic acid (ZA) on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O) (n = 40) and sham surgery (S) (n = 40). At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1 mg/kg of ZA or distilled water (DW) was intraperitoneally administered: OZA (n = 20), ODW (n = 20), SZA (n = 20), and SDW (n = 20). The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N), yield point (N), and stiffness coefficient (N/mm) of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1 mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy. PMID:23304634

  9. Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams

    NASA Technical Reports Server (NTRS)

    Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    From pregnancy to weaning there is a progressive elevation of plasma oxytocin (OT) levels associated with nursing activity, irrespective of litter size. In the present study, we analyzed the effects of continuous 1.5G, 1.75G and 2.0G hypergravity exposure on OT plasma concentration in prepartum (Gestation Day 20) (G20) and lactating (Postnatal day) (P10) rat dams. For this study, litter size was controlled with a yoking procedure established in our lab where individual control litters were yoked-matched to individual hypergravity litters. We reviewed all data at hypergravity irrespective of gravitational level and compared the values with the controls in both G20 (HG, n=15;SC, n=9) and P10 (HG, n=21;SC, n=16). Results showed that over time, we did observe the expected OT increase in both groups. In G20 dams, measurement of OT concentrations showed no significance. However, at P10, measurements of OT concentrations suggest a reduction of about 20% compared to established controls in our laboratory, 0.9+/-0.09 ng/ml for the controls and 0.7+/-0.06 ng/ml for centrifuged animals (p<0.02). These data suggest that exposure to centrifugation may reduce OT levels during lactation. When these plasma samples were obtained, the dams were removed from the litters, and values were not adjusted for the size of the litters. The reduction in OT with centrifugation may reflect a decrease in nursing activity or a decreased responsiveness of the mammary hypothalamic axis. In addition, we have analyzed data on plasma prolactin concentrations and mammary gland development, which may give additional insight to the results of our OT measurements.

  10. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    SciTech Connect

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-09-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17{beta}-estradiol (E{sub 2}). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E{sub 2}-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E{sub 2} pellets, co-exposure to quercetin did not protect rats from E{sub 2}-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E{sub 2}-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E{sub 2} group relative to those in the E{sub 2} group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F{sub 2{alpha}} (8-iso-PGF{sub 2{alpha}}) levels as a marker of oxidant stress showed that quercetin did not decrease E{sub 2}-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E{sub 2}-induced oxidant stress and may exacerbate breast carcinogenesis in E{sub 2}-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E{sub 2} and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E{sub 2} and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E{sub 2}-induced breast tumors in female ACI rats.

  11. Cypermethrin induced pathological and biochemical changes in reproductive organs of female rats.

    PubMed

    Sangha, G K; Kaur, Kamalpreet; Khera, K S

    2013-01-01

    Cypermethrin, a synthetic pyrethroid, has broad spectrum use in domestic agriculture, and veterinary applications due to its high bioefficacy, enhanced stability and low mammalian toxicity. The present investigation was performed to investigate the sub acute effects of cypermethrin (25EC) in female rats. Cypermethrin (25EC) at a dose of 50 mg kg(-1) body weight (1/5th LD50) was orally given to female rats for 4 weeks. Control rats received similar amount of ground nut oil. Significant decrease in ovarian weight (15.4%) was observed after four weeks of cypermethrin administration while the uterine weight (68.2%) and thickness of myometrium increased at 2 and 4 weeks. Cypermethrin caused degenerative changes in ovary as evidenced by increased follicular atresia and decreased concentration of proteins (38%), lipids (20%), phospholipids (18%) and cholesterol (37%). Acid (49.2%) and alkaline phosphatase (41%) activities were increased while lactate dehydrogenase (37.9%) and 3beta-HSDH (31.3%) decreased in treated rat ovary. PMID:24006814

  12. Differential motivational profiles following adolescent sucrose access in male and female rats.

    PubMed

    Reichelt, Amy C; Abbott, Kirsten N; Westbrook, R Fred; Morris, Margaret J

    2016-04-01

    Adolescents are the highest consumers of sugar sweetened drinks. Excessive consumption of such drinks is a likely contributor to the development of obesity and may be associated with enduring changes in the systems involved in reward and motivation. We examined the impact of daily sucrose consumption in young male and female rats (N=12 per group) across the adolescent period on the motivation to perform instrumental responses to gain food rewards as adults. Rats were or were not exposed to a sucrose solution for 2h each day for 28days across adolescence [postnatal days (P) 28-56]. They were then trained as adults (P70 onward) to lever press for a palatable 15% cherry flavored sucrose reward and tested on a progressive ratio (PR) schedule to assess motivation to respond for reinforcement. Female rats exposed to sucrose had higher breakpoints on the PR schedule than controls, whereas male rats exposed to sucrose had lower breakpoints than controls. These results show that consumption of sucrose during adolescence produced sex-specific behavioral changes in responding for sucrose as adults. PMID:26826605

  13. Proliferative retinopathy and neovascularization of the anterior segment in female type 2 diabetic rats

    PubMed Central

    2013-01-01

    Background To examine the presence of diabetic retinopathy in a female rat model of type 2 diabetes fed on a high-fat diet (HFD). Methods Wistar rats were injected with streptozotocin (STZ) at the age of two days and fed on an HFD from eight weeks onwards. Five diabetic animals were euthanized at 110weeks of disease, together with a control group of age-matched, non-diabetic animals. A group of diabetic animals at 57weeks of disease was included for comparison. Cross sections of the rats corneas, iris and retinas were histologically examined and analysed by immunohistochemistry and immunofluorescence, using glial-fibrillary-acidic-protein (GFAP), the vascular endothelial growth factor (VEGF) and the Von Willebrand factor (vWF). The trypsine digestive technique was used for the pericytes count. Results Neovascularization was only found in the retinas, irises and corneas of the diabetic animals of 110weeks of disease. There was also a significantly lower number of pericytes in these animals than in the controls. Conclusion The female rat model of type 2 diabetes fed on an HFD may prove useful in evaluating the mechanisms involved in diabetic retinopathy, together with strategies to reduce its severity. PMID:24499599

  14. Reproductive experience and the response of female Sprague-Dawley rats to fear and stress.

    PubMed

    Rima, Brandi N; Bardi, Massimo; Friedenberg, Julia M; Christon, Lillian M; Karelina, Kate E; Lambert, Kelly G; Kinsley, Craig H

    2009-10-01

    The present work examines the relationship between reproductive experience (comprising breeding, parturition, and lactation) and the behavioral and hormonal processes of fear and stress in the female laboratory rat. Previous research has indicated that reproductive experience functions to decrease the female's stress response in potentially harmful environments, thereby providing her with numerous survival benefits, including decreased fearfulness, increased aggression, and refined hunting skills. This study was designed to determine how nulliparous (no reproductive experience), primiparous (1 reproductive experience) and multiparous (at least 2 reproductive experiences) rats respond to a Pavlovian paradigm of learned fear, involving the pairing of a neutral stimulus (conditioned stimulus) with an aversive stimulus (unconditioned stimulus). We report evidence that reproductive experience is linked with fear-response and anxiety-like behaviors. Our findings indicate that reproductive experience has an additive effect: primiparous mothers showed a different response to the paradigm of conditioned fear not only compared with those of nulliparous rats as well as multiparous mothers. Assessing the complex interconnections among the behavioral and physiologic measures recorded in this study, multidimensional scaling confirmed a clear separation among the 3 groups of rats in terms of the behavioral and physiologic responses to the experimental paradigm, supporting the conclusion that reproductive experience influences the maternal mind. PMID:19887027

  15. Immunotoxicity evaluation of jet a jet fuel in female rats after 28-day dermal exposure.

    PubMed

    Mann, Cynthia M; Peachee, Vanessa L; Trimmer, Gary W; Lee, Ji-Eun; Twerdok, Lorraine E; White, Kimber L

    2008-01-01

    The potential for jet fuel to modulate immune functions has been reported in mice following dermal, inhalation, and oral routes of exposure; however, a functional evaluation of the immune system in rats following jet fuel exposure has not been conducted. In this study potential effects of commercial jet fuel (Jet A) on the rat immune system were assessed using a battery of functional assays developed to screen potential immunotoxic compounds. Jet A was applied to the unoccluded skin of 6- to 7-wk-old female Crl:CD (SD)IGS BR rats at doses of 165, 330, or 495 mg/kg/d for 28 d. Mineral oil was used as a vehicle to mitigate irritation resulting from repeated exposure to jet fuel. Cyclophosphamide and anti-asialo GM1 were used as positive controls for immunotoxic effects. In contrast to reported immunotoxic effects of jet fuel in mice, dermal exposure of rats to Jet A did not result in alterations in spleen or thymus weights, splenic lymphocyte subpopulations, immunoglobulin (Ig) M antibody-forming cell response to the T-dependent antigen, sheep red blood cells (sRBC), spleen cell proliferative response to anti-CD3 antibody, or natural killer (NK) cell activity. In each of the immunotoxicological assays conducted, the positive control produced the expected results, demonstrating the assay was capable of detecting an effect if one had occurred. Based on the immunological parameters evaluated under the experimental conditions of the study, Jet A did not adversely affect immune responses of female rats. It remains to be determined whether the observed difference between this study and some other studies reflects a difference in the immunological response of rats and mice or is the result of other factors. PMID:18338284

  16. Effects of radiofrequency radiation exposure on blood-brain barrier permeability in male and female rats.

    PubMed

    Sirav, Bahriye; Seyhan, Nesrin

    2011-12-01

    During the last several decades, numerous studies have been performed aiming at the question of whether or not exposure to radiofrequency radiation (RFR) influences the permeability of the blood-brain barrier (BBB). The objective of this study was to investigate the effect of RFR on the permeability of BBB in male and female Wistar albino rats. Right brain, left brain, cerebellum, and total brain were analyzed separately in the study. Rats were exposed to 0.9 and 1.8GHz continuous-wave (CW) RFR for 20min (at SARs of 4.26mW/kg and 1.46mW/kg, respectively) while under anesthesia. Control rats were sham-exposed. Disruption of BBB integrity was detected spectrophotometrically using the Evans-blue dye, which has been used as a BBB tracer and is known to be bound to serum albumin. Right brain, left brain, cerebellum, and total brain were evaluated for BBB permeability. In female rats, no albumin extravasation was found in in the brain after RFR exposure. A significant increase in albumin was found in the brains of the RF-exposed male rats when compared to sham-exposed male brains. These results suggest that exposure to 0.9 and 1.8GHz CW RFR at levels below the international limits can affect the vascular permeability in the brain of male rats. The possible risk of RFR exposure in humans is a major concern for the society. Thus, this topic should be investigated more thoroughly in the future. PMID:22047463

  17. Use of novel inhalation kinetic studies to refine physiologically-based-pharmacokinetic models for ethanol in non-pregnant and pregnant rats

    EPA Science Inventory

    Ethanol (EtOH) exposure induces a variety of concentration-dependent neurological and developmental effects in the rat. Physiologically-based pharmacokinetic (PBPK) models have been used to predict the inhalation exposure concentrations necessary to produce blood EtOH concentrat...

  18. Female rats exposed to stress and alcohol show impaired memory and increased depressive-like behaviors.

    PubMed

    Gomez, J L; Luine, V N

    2014-01-17

    Exposure to daily life stressors is associated with increases in anxiety, depression, and overall negative affect. Alcohol or other psychoactive drugs are often used to alleviate stress effects. While females are more than twice as likely to develop mood disorders and are more susceptible to dependency than males, they are infrequently examined. In this study, female rats received no stress/no alcohol control (CON), alcohol alone (ALC), stress alone (STR), or stress plus alcohol (STR+ALC). Stress consisted of restraint for 6h/day/7days, and alcohol was administered immediately following restraint via gastric gavage at a dose of 2.0g/kg. Dependent measures included tests utilizing object recognition (OR), Y-maze, elevated plus maze (EPM), forced swim (FST), blood alcohol content, corticosterone levels, and body weights. ALC, STR+ALC, but not stress alone, impaired memory on OR. All treatments impaired spatial memory on the Y-maze. Anxiety was not affected on the EPM, but rats treated with alcohol or in combination with stress showed increased immobility on the FST, suggestive of alcohol-induced depression. Previously, we found alcohol reversed deleterious effects of stress on memory and mood in males, but current results show that females reacted negatively when the two treatments were combined. Thus, responses to alcohol, stress and their combination suggest that sex specific treatments are needed for stress-induced behavioral changes and that self-medicating with alcohol to cope with stress maybe deleterious in females. PMID:24096191

  19. Reproductive suppression in female Damaraland mole-rats Cryptomys damarensis: dominant control or self-restraint?

    PubMed

    Clarke, F M; Miethe, G H; Bennett, N C

    2001-05-01

    Colonies of Damaraland mole-rats Cryptomys damarensis exhibit a high reproductive skew. Typically one female breeds and the others are anovulatory. Two models, the dominant control model (DCM) and the self-restraint model (SRM), have been proposed to account for this reproductive suppression. The DCM proposes that suppression is under the control of the dominant breeder and is imposed by mechanisms such as aggression, pheromones and interference with copulation, whereas the SRM does not involve aggression directed towards non-breeders and may function in order to minimize inbreeding. We investigated potential proximate mechanisms involved in the suppression of females in a series of experiments. Socially induced stress through aggression did not appear to be responsible for anovulation. Nor did breeders actively interfere with subordinate copulation. Females were physiologically suppressed when housed in intact colonies. However, as predicted by the DCM, they did not become reproductively active when removed from the presence of breeders. We found no evidence that pheromonal cues block ovulation. We suggest that the SRM is the basic model found in the Damaraland mole-rat and that self-restraint functions in order to minimize inbreeding by restricting reproduction until an unrelated male is present. This would explain the rapid onset of reproductive activation in females when paired with an unrelated male, as demonstrated in this study. PMID:11370962

  20. Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: sexual dimorphism and diergism at the spinal cord level.

    PubMed

    Nacka-Aleksi?, Mirjana; Djiki?, Jasmina; Pilipovi?, Ivan; Stoji?-Vukani?, Zorica; Kosec, Duko; Bufan, Biljana; Arsenovi?-Ranin, Nevena; Dimitrijevi?, Mirjana; Leposavi?, Gordana

    2015-10-01

    Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-?+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-?+:IL-17+IL-10+ cell ratio was shifted towards IL-17+IFN-?+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1? and IL-6, but downregulated TGF-? mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. PMID:25944279

  1. Female's DHT controls sex differences in the rat bed nucleus of the accessory olfactory tract.

    PubMed

    Collado, P; Segovia, S; Calés, J M; Pérez Laso, C; Rodriquez Zafra, M; Guillamón, A; Valencia, A

    1992-04-01

    In the present study the regulatory action of the non-aromatic androgen dihydrotestoterone (DHT) on the volume of the sexually dimorphic bed nucleus of the accessory olfactory tract (BAOT) was investigated. Postnatal treatment with DHT (180 micrograms day-1) between days 6 and 20 (D6-D20) induced, in gonadally intact male rats, a drastic reduction in the overall volume to levels typical in control females. Conversely, the postnatal administration of the anti-androgen cyproterone acetate (CA) to the females from D6-D20 produced an increment in the BAOT volume not dissimilar to that found in control males. These findings reveal that sexual organization in this vomeronasal structure is dependent on the presence of DHT in females during postnatal development. PMID:1387557

  2. Prenatal stress reduces estradiol-induced prolactin release in male and female rats.

    PubMed

    Kinsley, C H; Bridges, R S

    1987-01-01

    Prenatal stress is a potent disruptor of the normal course of sexual differentiation, affecting both males and females. In the present study, we wished to examine a sexually dimorphic endocrine response, estradiol (E2)-induced prolactin (Prl) release, in prenatally-stressed (P-S) males and females. Sprague-Dawley female rats were timed-mated (+ sperm = Day 1). From gestation days 15-22 one group of females was subjected to a thrice-daily regimen of heat and restraint stress (0830, 1230, and 1630 hr) consisting of placing the rats into a Plexiglas restraint tube over which were poised two 100 W floodlights. Control females remained undisturbed throughout pregnancy. At parturition all offspring were cross-fostered to untreated, recently-parturient dams and weaned at 25 days of age. Separate groups of P-S and Control males and females were gonadectomized and, for males, paired testes weights and body weights were recorded. Four days later the animals were implanted with Silastic capsules containing E2, and fitted with intra-atrial cannulae. The following day, blood samples were taken at 0900, 1300, 1500, and 1700 hr for a total of five days. Beginning with the 1700 hr sample on Day 2, and with the exception of the 1500 hr sample on Day 3, P-S males had significantly lower plasma Prl values than Control males through Day 4, and at the 1500 hr sample on Day 5. Moreover, at no point did P-S males exhibit a significant daily afternoon increase in Prl values, whereas Control males did so on Days 2 and 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3671531

  3. Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens

    PubMed Central

    Lund, Trent D; West, Timothy W; Tian, Lilyan Y; Bu, Lihong H; Simmons, Daniel L; Setchell, Kenneth DR; Adlercreutz, Herman; Lephart, Edwin D

    2001-01-01

    Background In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen). This study examined the influence of phytoestrogens (estrogen-like plant compounds) on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB), and cyclooxygenase-2 (COX-2) levels were determined. Results Female rats receiving lifelong exposure to a high-phytoestrogen containing diet (Phyto-600) acquired the maze faster than females fed a phytoestrogen-free diet (Phyto-free); in males the opposite diet effect was identified. In a separate experiment, at 80 days-of-age, animals fed the Phyto-600 diet lifelong either remained on the Phyto-600 or were changed to the Phyto-free diet until 120 days-of-age. Following the diet change Phyto-600 females outperformed females switched to the Phyto-free diet, while in males the opposite diet effect was identified. Furthermore, males fed the Phyto-600 diet had significantly higher phytoestrogen concentrations in a number of brain regions (frontal cortex, amygdala & cerebellum); in frontal cortex, expression of CALB (a neuroprotective calcium-binding protein) decreased while COX-2 (an inducible inflammatory factor prevalent in Alzheimer's disease) increased. Conclusions Results suggest that dietary phytoestrogens significantly sex-reversed the normal sexually dimorphic expression of VSM. Specifically, in tasks requiring the use of reference, but not working, memory, VSM was enhanced in females fed the Phyto-600 diet, whereas, in males VSM was inhibited by the same diet. These findings suggest that dietary soy derived phytoestrogens can influence learning and memory and alter the expression of proteins involved in neural protection and inflammation in rats. PMID:11801187

  4. Pudendal denervation affects the structure and function of the striated, urethral sphincter in female rats.

    PubMed

    Heidkamp, M C; Leong, F C; Brubaker, L; Russell, B

    1998-01-01

    Our aim was to examine the effects of denervation on urethral anatomy and urine voiding pattern. Rats usually void at one end of their cage, which gives a behavioral index of continence. The voiding preference for denervated rats was decreased to 88.8 + 4.7%, n = 32, P < 0.001, compared to improvements with time for unoperated (117 +/- 10%, n = 16) or sham-operated rats (105 +/- 8%, n = 5). The volume of urine or the frequency of voidings between denervated, unoperated or sham-operated rats did not differ significantly. Urethral sections were analyzed immunochemically and quantified morphometrically. Smooth muscle volume remained constant but skeletal muscle volume decreased after denervation, from 43 +/- 2% to 36 +/- 3% (P < 0.05, n = 5). Fiber diameter decreased from 14.3 +/- 1.4 microm to 8.5 +/- 0.7 microm (P < 0.005). We concluded that pudendal nerve transection in female rats causes behavioral alterations in voiding and muscular atrophy of the striated sphincter. PMID:9694137

  5. Blood risk factor metabolites associated with heart disease and myocardial fatty acids in copper-deficient male and female rats

    SciTech Connect

    Fields, M.; Lewis, C.; Beal, T. ); Berlin, E.; Kliman, P.G.; Peters, R.C. )

    1989-07-01

    Intact and castrated males and intact and ovariectomized female rats were fed a copper-deficient diet in order to establish whether the protection provided in females against cardiovascular pathology and mortality is due to endogenous sex hormones, and different levels of blood lipids and/or myocardial fatty acids. Seventy-three male and female rats were assigned to a copper-deficient diet (0.6 {mu}g of copper/g diet) containing 62% fructose for 8 weeks. Twelve of the male rats underwent castration and 12 of the females were ovariectomized. All animals exhibited high levels of plasma cholesterol, triglycerides, and uric acid, which were neither affected by the sex of the rat nor by the surgical treatment. The composition of fatty acids of the myocardium was similar in males and females. Except for those animals that were sacrificed by us, all other male rats died of heart pathology. In contrast, none of the female rats exhibited heart pathology and none died of the deficiency. It is suggested that heart pathology and mortality in copper deficiency are sex related and not due to high levels of plasma cholesterol, triglycerides, and uric acid or to differences in myocardial fatty acid composition.

  6. The Effects of Boron on Arsenic-Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats.

    PubMed

    Kucukkurt, Ismail; Ince, Sinan; Demirel, Hasan Huseyin; Turkmen, Ruhi; Akbel, Erten; Celik, Yasemin

    2015-12-01

    The aim of the present study was to investigate the possible protective effects of boron, an antioxidant agent, against arsenic-induced oxidative stress in male and female rats. In total, 42 Wistar albino male and female rats were divided into three equal groups: The animals in the control group were given normal drinking water, the second group was given drinking water with 100 mg/L arsenic, and the third group was orally administered drinking water with 100 mg/kg boron together with arsenic. At the end of the 28-day experiment, arsenic increased lipid peroxidation and damage in the tissues of rats. However, boron treatment reversed this arsenic-induced lipid peroxidation and activities of antioxidant enzymes in rats. Moreover, boron exhibited a protective action against arsenic-induced histopathological changes in the tissues of rats. In conclusion, boron was found to be effective in protecting rats against arsenic-induced lipid peroxidation by enhancing antioxidant defense mechanisms. PMID:26184899

  7. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    SciTech Connect

    Seppen, Jurgen

    2012-11-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

  8. N-acetylcysteine attenuates nicotine-induced kindling in female periadolescent rats.

    PubMed

    Okamura, Adriana Mary Nunes Costa; Gomes, Patrícia Xavier L; de Oliveira, Gersilene V; Araújo, Fernanda Yvelize R de; Tomaz, Viviane S; Chaves Filho, Adriano José Maia; de Sousa, Francisca Cléa F; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Macêdo, Danielle

    2016-06-01

    Kindling is a form of behavioral sensitization that is related to the progression of several neuropsychiatric disorders such as bipolar disorder. We recently demonstrated that female periadolescent rats are more vulnerable to nicotine (NIC)-induced kindling than their male counterparts. Furthermore, we evidenced that decreases in brain antioxidative defenses may contribute to this gender difference. Here we aimed to determine the preventive effects of the antioxidant N-acetyl cysteine (NAC) against NIC-kindling in female periadolescent rats. To do this female Wistar rats at postnatal day 30 received repeated injections of NIC 2mg/kg, i.p. every weekday for up to 19days. NAC90, 180 or 270mg/kg, i.p. was administered 30min before NIC. The levels of glutathione (GSH), superoxide dismutase (SOD) activity, lipid peroxidation (LP) and nitrite were determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The development of kindling occurred at a median time of 16.5days with 87.5% of NIC animals presenting stage 5 seizures in the last day of drug administration. NAC270 prevented the occurrence of kindling. NIC-kindled animals presented decreased levels of GSH and increased LP in the PFC, HC and ST, while SOD activity was decreased in the ST. NAC180 or 270 prevented the alterations in GSH induced by NIC, but only NAC270 prevented the alterations in LP. Nitrite levels increased in the ST of NAC270 pretreated NIC-kindled animals. Taken together we demonstrated that NAC presents anti-kindling effects in female animals partially through the restoration of oxidative alterations. PMID:26812248

  9. Ovariectomy Results in Variable Changes in Nociception, Mood and Depression in Adult Female Rats

    PubMed Central

    Li, Li-Hong; Wang, Zhe-Chen; Yu, Jin; Zhang, Yu-Qiu

    2014-01-01

    Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way. PMID:24710472

  10. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    PubMed

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-?-erythroidine, a selective ?4?2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of ?1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking ?4?2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on ?4?2-nAChR.-Tie, K., Zhang, X., Tan, Y., Deng, Y., Li, J., Ni, Q., Wang, H., Chen, L. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring. PMID:26499267

  11. THE EFFECTS OF ATRAZINE ON FEMALE WISTAR RATS: AN EVALUATION OF THE PROTOCOL FOR ASSESSING PUBERTAL DEVELOPMENT AND THYROID FUNCTION

    EPA Science Inventory

    Female rats were dosed by oral gavage from postnatal day (PND) 22 through PND 41 with 0, 12.5, 25, 50, 100 or 200 mg ATR /kg. Half of the females in each treatment group were killed on PND 41 and organ weights (e.g., liver, kidney, adrenal, ovary, uterus and pituitary) and serum ...

  12. Effects of Prenatal Dexamethasone on the Rat Pituitary Gland and Gonadotropic Cells in Female Offspring.

    PubMed

    Ristić, Nataša; Severs, Walter; Nestorović, Nataša; Jarić, Ivana; Manojlović-Stojanoski, Milica; Trifunović, Svetlana; Pendovski, Lazo; Milosević, Verica

    2016-01-01

    Glucocorticoids have a strong influence on growth and maturation of fetal organ systems, but overexposure to exogenous glucocorticoids may retard fetal growth and alter developmental processes in sensitive tissues. The aim of this study was to specifically determine whether prenatal exposure to dexamethasone (Dx) altered normal development and function of pituitary gonadotropic cells in neonatal, infant and peripubertal female offspring. On day 16 of pregnancy, rat dams received 1.0 mg Dx/kg body weight (BW) s.c., followed by 0.5 mg Dx/kg BW on days 17 and 18 of gestation. Control gravid females received the same volume of saline. Female offspring were sacrificed on days 5, 16 and 38 after delivery. The volume of the pituitary gland estimated using Cavalieri's principle was significantly reduced (p < 0.05). Using a fractionator-physical disector method, we found reduced total numbers of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells (p < 0.05), accompanied by a decrease (p < 0.05) in serum concentrations of FSH and LH, while the relative intensity of FSH and LH immunofluorescence remained unchanged in neonatal, infant and peripubertal female offspring prenatally exposed to Dx. The data document that overexposure to Dx during fetal development evokes developmental programming of the female reproductive system at the pituitary cellular level, which may be associated with impaired reproductive function. PMID:26950885

  13. Intestinal Mucus Layer Preservation in Female Rats Attenuates Gut Injury After Trauma-Hemorrhagic Shock

    PubMed Central

    Sheth, Sharvil U.; Lu, Qi; Twelker, Kate; Sharpe, Susan M.; Qin, Xiaofa; Reino, Diego C.; Lee, Marlon A.; Xu, Da-Zhong; Deitch, Edwin A.

    2010-01-01

    Background We tested the hypothesis that females are more resistant to trauma-hemorrhagic shock (T/HS)-induced gut injury than males, and this is related to better preservation of their intestinal mucus layer, which is influenced in turn by the estrus cycle stage at the time of injury. Methods Male, proestrus and diestrus female rats underwent a laparotomy (trauma) and 90 minutes of shock (~35 mm Hg). At 3 hours after reperfusion, terminal ileum was harvested and stained with Carnoys Alcian Blue for mucus assessment, hematoxylin and eosin, and periodic acid schiff for villous and goblet cell morphology and injury. Ileal permeability was measured in separate intestinal segments using the ex vivo everted gut sac technique. Results When compared with males, proestrus female rats were significantly more resistant to T/HS-induced morphologic gut injury, as reflected in both a lower incidence of villous injury (14% vs. 22%; p < 0.05) and a lesser grade of injury (1.0 vs. 2.8; p < 0.05) as well as preservation of gut barrier function (17.9 vs. 32.2; p < 0.05). This resistance to gut injury was associated with significant preservation of the mucus layer (87% vs. 62%; p < 0.05) and was influenced by the estrus cycle stage of the female rats. There was a significant inverse correlation between mucus layer coverage and the incidence (r2 = 0.9; p < 0.0001) and magnitude (r2 = 0.89; p < 0.0001) of villous injury and gut permeability (r2 = 0.74; p < 0.001). Conclusions The resistance of female rats to T/HS-induced intestinal injury and dysfunction was associated with better preservation of the intestinal mucus barrier and was to some extent estrus cycle-dependent. Preservation of the mucus barrier may protect against shock-induced gut injury and subsequent distant organ injury by limiting the ability of luminal contents such as bacteria and digestive enzymes from coming into direct contact with the epithelium. PMID:20154538

  14. Development of motor coordination and cerebellar structure in male and female rat neonates exposed to hypergravity

    NASA Astrophysics Data System (ADS)

    Nguon, K.; Ladd, B.; Baxter, M. G.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that the developing rat cerebellum is affected by exposure to hypergravity. In the present study, we explored the hypothesis that the changes in cerebellar structure in hypergravity-exposed rat neonates may affect their motor coordination. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravitational loading. To test this hypothesis, we compared motor behavior, cerebellar structure, and protein expression in rat neonates exposed to 1.5 1.75G on a 24-ft centrifuge daily for 22.5 h starting on gestational day (G) 10, through birth on G22/G23 and through postnatal day (P) 21. Exposure to hypergravity impacted the neurodevelopmental process as indicated by: (1) impaired righting response on P3, more than doubling the righting time at 1.75G, and (2) delayed onset of the startle response by one day, from P9 in controls to P10 in hypergravity-exposed pups. Hypergravity exposure resulted in impaired motor functions as evidenced by performance on a rotarod on P21; the duration of the stay on the rotarod recorded for 1.75G pups of both sexes was one tenth that of the stationary control (SC) pups. These changes in motor behavior were associated with cerebellar changes: (1) cerebellar mass on P6 was decreased by 7.5% in 1.5G-exposed male pups, 27.5% in 1.75G-exposed male pups, 17.5% in 1.5G-exposed female pups, and 22.5% in 1.75G female pups and (2) changes in the expression of glial and neuronal proteins. The results of this study suggest that perinatal exposure to hypergravity affects cerebellar development as evidenced by decreased cerebellar mass and altered cerebellar protein expression; cerebellar changes observed in hypergravity-exposed rat neonates are associated with impaired motor behavior. Furthermore, the response to hypergravity appears to be different in male and female neonates. If one accepts that the hypergravity paradigm is a useful animal model with which to predict those biological processes in the CNS affected by microgravity, and because males and females were shown to respond differently to hypergravity, it can be surmised that males and females may respond differently to the microgravity encountered in space.

  15. Striated muscle and nerve fascicle distribution in the female rat urethral sphincter.

    PubMed

    Kim, Ronald J; Kerns, James M; Liu, Shirley; Nagel, Ted; Zaszczurynski, Paul; Lin, Dan Li; Damaser, Margot S

    2007-02-01

    The anatomical basis for urinary continence depends on a thorough understanding of the tissues in the urethra. The objective of this study was to evaluate the morphology and neuroanatomy of urethral striated muscle, called the rhabdosphincter or external urethral sphincter, in normal female rats. Urethras from 12 female rats were dissected from the bladder, fixed, embedded in paraffin or epon, and sectioned every 1 mm. Striated muscle content was taken as the ratio of the striated muscle area to net urethral area. Nerve fascicles containing myelinated axons near the rhabdosphincter were counted and mapped. Both striated muscle content and number of nerve fascicles peak in the proximal third of the urethra, with a secondary peak at the distal end of the urethra. This secondary peak may correspond to an analog of the combined compressor urethrae/urethrovaginal sphincter located in the distal urethra in human. The rhabdosphincter has a variable distribution along the length of the urethra. In the middle and distal thirds of the urethra, the dorsal striated muscle fibers between the urethra and vagina become more sparse. The majority of nerve fascicles are contained in the lateral quadrants of the urethra, similar to the lateral distribution of somatic nerves in humans. In conclusion, this study demonstrates the normal distribution of the striated musculature and neuroanatomy in the urethra, with similarities to the human. It thus supports and extends the usefulness of the rat as an experimental model for studying urinary incontinence. PMID:17441207

  16. Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats

    NASA Technical Reports Server (NTRS)

    Allen, Matthew R.; Bloomfield, Susan A.

    2003-01-01

    This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.

  17. In utero exposure to the environmental androgen trenbolone masculinizes female Sprague-Dawley rats.

    PubMed

    Hotchkiss, A K; Furr, J; Makynen, E A; Ankley, G T; Gray, L E

    2007-11-01

    Recently, the occurrence of environmental contaminants with androgenic activity has been described from pulp and paper mill effluents and beef feedlot discharges. A synthetic androgen associated with beef production is trenbolone acetate, which is used to promote growth in cattle. A primary metabolite, 17beta Trenbolone (TB), has been characterized as a potent androgen in both in vitro and in vivo studies with rats. The current study was designed to characterize the permanent morphological and functional consequences of prenatal TB exposure on female rats compared with those produced in an earlier study with testosterone propionate (TP). Female rat offspring were exposed to 0mg/day, 0.1mg/day, 0.5mg/day, 1.0mg/day, or 2.0mg/day TB on gestational days 14-19. The 0.5mg/day, 1.0mg/day, or 2.0mg/day TB groups displayed increases in neonatal anogenital distance (AGD) which persisted in the high dose group. Puberty was delayed in the high dose group and there were increased incidences of external genital malformations and the presence of male prostatic tissue in the 0.5mg/day, 1.0mg/day, or 2.0mg/day groups. These changes were associated with amniotic fluid concentrations of TB that compare favorably with concentrations known to be active in both in vitro systems and in fish. PMID:17931805

  18. Oral administration of leaf extracts of Momordica charantia affect reproductive hormones of adult female Wistar rats

    PubMed Central

    Adewale, Osonuga Odusoga; Oduyemi, Osonuga Ifabunmi; Ayokunle, Osonuga

    2014-01-01

    Objective To determine the effect of graded doses of aqueous leaf extracts of Momordica charantia on fertility hormones of female albino rats. Methods Twenty adult, healthy, female Wistar rats were divided into four groups: low dose (LD), moderate dose (MD) and high dose (HD) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. Result Estrogen levels reduced by 6.40 nmol/L, 10.80 nmol/L and 28.00 nmol/L in the LD, MD and HD groups respectively while plasma progesterone of rats in the LD, MD and HD groups reduced by 24.20 nmol/L, 40.8 nmol/L and 59.20 nmol/L respectively. Conclusion Our study has shown that the antifertility effect of Momordica charantia is achieved in a dose dependent manner. Hence, cautious use of such medication should be advocated especially when managing couples for infertility. PMID:25183143

  19. Percutaneous absorption of triadimefon in the adult and young male and female rat

    SciTech Connect

    Knaak, J.B.; Yee, K.; Ackerman, C.R.; Zweig, G.; Wilson, B.W.

    1984-03-15

    The percutaneous absorption of /sup 14/C-phenoxy ring labeled triadimefon was studied in adult and young male and female Sprague-Dawley rats. Triadimefon was applied (41.1 to 46.4 micrograms/cm2) in 0.2 ml of acetone to areas comprising 3% of the body surface (7.0 to 14.5 cm2). Thirty-six animals were treated at the initiation of each study. Groups of three animals were subsequently killed at 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hr after treatment. Skin from the treated area as well as blood, heart, liver, kidneys, remaining carcass, urine, and feces were analyzed for /sup 14/C by scintillation counting techniques. Based on /sup 14/C counts, triadimefon was lost more rapidly from the skin of young animals (t 1/2, 20 to 25 hr) than from the skin of adult animals (t 1/2, 29 to 53 hr). Recovery studies indicated that adult males, adult females, young males, and young females, respectively, absorbed 53, 82, 57, and 52% of the dose. The rest of the dose based on material balance was presumably lost by evaporation. Approximately 2.5 to 3.9% of the dose penetrated the skin in one hour and was available for absorption. The rate of entry triadimefon into blood was 2 to 2.5 times faster for young than that observed in adult animals. Elimination of it from blood was faster in the case of the young animals. Triadimefon was absorbed through the skins of the adult male, adult female, young male, and young female rats, respectively, at rates of 0.20, 0.50, 0.58, and 0.48 micrograms/hr/cm2 of skin.

  20. Antispasmodic Effects of Aqueous and Hydroalcoholic Punica granatum Flower Extracts on the Uterus of Non-pregnant Rats

    PubMed Central

    Ahangarpour, Akram; Heidari, Razieh; Abdolahzadeh, Mahsa; Oroojan, Ali Akbar

    2012-01-01

    Background Punica granatum Linn. (PG) is native to the Mediterranean region. Its flower exhibited antioxidant activity. The present study attempt to investigate the effect of these extract on uterine contraction and its possible mechanism(s). Methods Thirty five female Wistar rats (200–300 g) at estrous phases of cycle was examined in this study; pieces of virgin adult rat uterus (1.5 cm) were suspended in an organ bath containing 10 ml of De Jalon solution at 29 °C. Tissue contractility was isometrically recorded. KCl (60 mM), BaCl2 (4 mM) and oxytocin (10 mU/ml) were applied to the tissue in the presence and absence of aqueous and hydroalcoholic extracts of the plant (0.05, 0.1, 0.2, 0.4 and 0.8 mg/ml). Propranolol (1 µM) and naloxane (1 µM) were added in KCl induced contractions. The results were analyzed by ANOVA and p < 0.05 were considered as significant. Results Cumulative concentration of extracts reduced uterine contractions induced by KCl dose-dependently (p < 0.01). Extracts in a dose dependent (p < 0.05) reduced uterine contractions decreased dose-dependently after of addition oxytocin. The extracts added cumulatively to the organ bath reduced contractions but they did not affect uterine contractions induced by BaCl2 except the last dose. Spasmolytic effects of the extracts were not affected by propranolol or naloxane in KCl induced contractions. Conclusion Extracts diminished K+-induced contraction in uterus, therefore it seems that substances that decrease K+-induced contraction can also block voltage dependent calcium channel. The extracts did not have any effect on β-adrenoceptors or potassium channels. PMID:23926538

  1. Training-induced Increase in Bone Mineral Density between Growing Male and Female Rats.

    PubMed

    Joo, W; Singh, H; Ahles, C P; Lee, Y; Colazas, W; Lee, L C; Prakash, A; Jaque, S V; Sumida, K D

    2015-11-01

    The purpose of this study was to determine the existence of sex differences in the resistance training-induced elevation in bone mineral density (BMD) and bone strength (Fmax) during the growth period in rats. 16 male (M) and 16 female (F) rats (approx. 8 weeks old) were randomly divided into sedentary control (MC=8, FC=8), and resistance-trained (RT) groups (M-RT=8, F-RT=8). The RT groups were conditioned to climb a vertical ladder 4 consecutive times (per exercise session) with weights attached to their tail 3 days per week for a total of 6 weeks. After 6 weeks, there were no interaction effects (sexexercise). The main effect of sex indicated no difference in tibial BMD (in g/cm(2)) for males (0.2260.005) compared to females (0.2210.004). However, Fmax (in Newtons) was significantly greater for males (131.35.3) compared to females (89.93.0). The main effect of exercise indicated that tibial BMD and Fmax were significantly greater for RT groups (0.2340.004?g/cm(2) and 120.97.4 Newtons) compared to controls (0.2120.003?g/cm(2) and 100.35.1 Newtons). The results indicate that during growth, there were no sex differences in the training-induced elevation in BMD and bone mechanical properties. PMID:26212247

  2. Inner capillary diameter of hypothalamic paraventricular nucleus of female rat increases during lactation

    PubMed Central

    2013-01-01

    Background The role of the endothelial cell (EC) in blood flow regulation within the central nervous system has been little studied. Here, we explored EC participation in morphological changes of the anterior hypothalamic paraventricular nucleus (PVN) microvasculature of female rats at two reproductive stages with different metabolic demand (virginity and lactation). We measured the inner capillary diameter (ICD) of 800 capillaries from either the magnocellular or parvocellular regions. The space occupied by neural (somas, dendrites and axons) and glial, but excluding vascular elements of the neurovascular compartment was also measured in 100-μm2 sample fields of both PVN subdivisions. Results The PVN of both groups of animals showed ICDs that ranged from 3 to 10 microns. The virgin group presented mostly capillaries with small ICD, whereas the lactating females exhibited a significant increment in the percentage of capillaries with larger ICD. The space occupied by the neural and glial elements of the neurovascular compartment did not show changes with lactation. Conclusions Our findings suggest that during lactation the microvasculature of the PVN of female rats undergoes dynamic, transitory changes in blood flow as represented by an increment in the ICD through a self-cytoplasmic volume modification reflected by EC changes. A model of this process is proposed. PMID:23302443

  3. Effects of perinatal ethinyl estradiol exposure in male and female Wistar rats.

    PubMed

    Mandrup, Karen Riiber; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Axelstad, Marta; Dreisig, Karin; Hadrup, Niels; Vinggaard, Anne Marie; Hass, Ulla; Boberg, Julie

    2013-12-01

    Perinatal exposure to endocrine disrupting chemicals with estrogenic activity can adversely affect reproductive development, but few studies evaluating estrogen-sensitive endpoints have been performed in Wistar rats. Therefore, time-mated Wistar rats (n=10) were gavaged during gestation and lactation with 0, 5, 15 or 50?g/kg bw/day of ethinyl estradiol. This potent estrogen was found to induce an increased number of nipples and reduced ovary weight in female offspring. Malformations of female genitalia were found in young as well as adult offspring, as an increased AGD was seen at birth and a deeper urethral slit length was seen in adulthood. In prepubertal male offspring, estrogen-regulated gene expression in ventral prostate was increased dose-dependently and a decreased ventral prostate weight was seen at 15?g/kg. Female external sexual characteristics and prostate development were found to be targets for exposure to estrogenic compounds and may be of interest in studies on estrogenic environmental compounds. PMID:24036065

  4. Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

    PubMed Central

    Mossa, Abdel-Tawab H.; Ibrahim, Faten M.; Mohafrash, Samia M. M.; Abou Baker, Doha H.; El Gengaihi, Souad

    2015-01-01

    The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity. PMID:26265923

  5. Development of, and recovery from, activity-based anorexia in female rats.

    PubMed

    Dixon, Deann P; Ackert, Allison M; Eckel, Lisa A

    2003-11-01

    Activity-based anorexia occurs in rats maintained on a restricted-feeding schedule while given free access to running wheels. These conditions induce high levels of wheel running and rapid weight loss. Although this procedure was developed as an animal model of anorexia nervosa, it has been studied primarily in male rats. Our goal was to examine the development of, and recovery from, activity-based anorexia in female rats. Food intake, wheel running, body weight, and phase of the estrous cycle were monitored daily prior to, during, and after a period of restricted feeding in which access to food was limited to 2 h/day. Food intake, body weight, and estrous cyclicity were also monitored in a control group housed without access to running wheels. Prior to food restriction, rats with wheels displayed high levels of wheel running and consumed more food than rats without wheels. Despite that both groups consumed similar amounts of food during the restricted-feeding phase, only rats with wheels developed symptoms of activity-based anorexia, including increased wheel running, rapid weight loss, and disruptions in estrous cyclicity. Recovery from activity-based anorexia was associated with hypoactivity and hyperphagia. Resumption of estrous cycles occurred when the weight lost during food restriction was regained. Hyperphagia, but not hypoactivity, was maintained following resumption of estrous cycles; however, this hyperphagia was limited to nonestrous phases. Our findings suggest that recovery from activity-based anorexia is mediated primarily by an increase in orexigenic signaling that promotes pronounced hyperphagia, and that the increase in satiogenic signaling during estrus abolishes this compensatory hyperphagia. PMID:14637226

  6. Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet

    PubMed Central

    Mangge, Harald; Prller, Florian; Zelzer, Sieglinde; Aindhofer, Herwig; Pailer, Sabine; Kieslinger, Petra; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Cvirn, Gerhard; Gruber, Hans-Jrgen

    2015-01-01

    Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increasedand hyperthyroid animals significantly decreasedETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition. PMID:26184174

  7. 17?-Estradiol Attenuates Poststroke Depression and Increases Neurogenesis in Female Ovariectomized Rats

    PubMed Central

    Cheng, Yifan; Su, Qiaoer; Shao, Bei; Cheng, Jianhua; Wang, Hong; Wang, Liuqing; Lin, Zhenzhen; Ruan, Linhui; ZhuGe, Qichuan; Jin, Kunlin

    2013-01-01

    Studies have linked neurogenesis to the beneficial actions of specific antidepressants. However, whether 17?-estradiol (E2), an antidepressant, can ameliorate poststroke depression (PSD) and whether E2-mediated improvement of PSD is associated with neurogenesis are largely unexplored. In the present study, we found that depressive-like behaviors were observed at the first week after focal ischemic stroke in female ovariectomized (OVX) rats, as measured by sucrose preference and open field test, suggesting that focal cerebral ischemia could induce PSD. Three weeks after middle cerebral artery occlusion (MCAO), rats were treated with E2 for consecutive 14 days. We found that E2-treated rats had significantly improving ischemia-induced depression-like behaviors in the forced-swimming test and sucrose preference test, compared to vehicle-treated group. In addition, we also found that BrdU- and doublecortin (DCX)-positive cells in the dentate gyrus of the hippocampus and the subventricular zone (SVZ) were significantly increased in ischemic rats after E2 treatment, compared to vehicle-treated group. Our data suggest that focal cerebral ischemia can induce PSD, and E2 can ameliorate PSD. In addition, newborn neurons in the hippocampus may play an important role in E2-mediated antidepressant like effect after ischemic stroke. PMID:24307996

  8. Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

    PubMed

    Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

    2016-01-15

    Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. PMID:26431763

  9. Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats

    PubMed Central

    Ferguson, Sherry A.; Law, Charles Delbert; Kissling, Grace E.

    2014-01-01

    The developing central nervous system may be particularly sensitive to bisphenol A (BPA)-induced alterations. Here, pregnant Sprague Dawley rats (n = 11–12/group) were gavaged daily with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE2) on gestational days 6–21. The BPA doses were selected to be below the no-observed-adverse-effect level (NOAEL) of 5 mg/kg/day. On postnatal days 1–21, all offspring/litter were orally treated with the same dose. A naïve control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually elicited lordosis were assessed. No significant differences existed between the vehicle and naïve control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) at weaning in female siblings of these subjects (He, Z., Paule, M. G. and Ferguson, S. A. (2012) Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol. Teratol. 34, 331–337). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their behaviors were within the range of control males. Conversely, BPA treatment did not alter any measured endpoint. Similar to our previous reports (Ferguson, S. A., Law, C. D. Jr and Abshire, J. S. (2011) Developmental treatment with bisphenol A or ethinyl estradiol causes few alterations on early preweaning measures. Toxicol. Sci. 124, 149–160; Ferguson, S. A., Law, C. D. and Abshire, J. S. (2012) Developmental treatment with bisphenol A causes few alterations on measures of postweaning activity and learning. Neurotoxicol. Teratol. 34, 598–606), the BPA doses and design used here produced few alterations. PMID:24798382

  10. Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

    PubMed

    Pic-Taylor, Aline; da Motta, Luciana Gueiros; de Morais, Juliana Alves; Junior, Willian Melo; Santos, Alana de Fátima Andrade; Campos, Leandro Ambrósio; Mortari, Marcia Renata; von Zuben, Marcus Vinicius; Caldas, Eloisa Dutra

    2015-09-01

    Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated. PMID:26049017

  11. Delay of the Onset of Puberty in Female Rats by Prepubertal Exposure to T-2 Toxin

    PubMed Central

    Yang, Rong; Wang, Yi-Mei; Zhang, Li-Shi; Zhang, Li; Zhao, Zeng-Ming; Zhao, Jun; Peng, Shuang-Qing

    2015-01-01

    Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children. PMID:26569305

  12. Attenuation of bleomycin-induced Hprt mutant frequency in female and male rats by calorie restriction.

    PubMed

    Aidoo, A; Desai, V G; Lyn-Cook, L E; Chen, J J; Feuers, R J; Casciano, D A

    1999-11-29

    Calorie restriction modulates spontaneous and chemically induced tumors and increases maximal life span in experimental animals; however, the mechanism by which calorie restriction exerts its ameliorating effects is not fully elucidated, although reduced levels of reactive oxygen species (ROS) by calorie restriction has generated much interest. In the present study, we have determined whether or not calorie restriction would affect the mutagenic response in rats treated with bleomycin (BLM) a radiomimetic drug that is associated with DNA damage by a free radical mechanism. Fourteen weeks after weaning, the rats were divided into two groups; ad libitum (AL)-fed and 40% calorie restriction. Both AL and calorie-restricted animals were injected with 2.5, 5.0 and 10.0 mg BLM/kg, or with phosphate-buffered saline (PBS), and they were killed 4 weeks post drug treatment. Lymphocytes from the spleens were seeded in 96-well microtiter plates to determine mutant frequency in the hypoxantine guanine phosphoribosyl transferase (Hprt) gene. The mutant frequency in the BLM-treated rats was higher in AL males (P=0.001), and AL females (P=0.0174) than in their calorie-restricted counterparts. The difference in mutagenic response relative to AL males and AL females appeared unrelated to a low percent cloning efficiency seen in the males, since the mean absolute number of Hprt mutant clones was higher in the AL males compared to the females. A reduction in animal weight by calorie restriction was significant in both sexes (P<0.001), but the dose effect appeared non-significant. The results indicate that calorie intake of 60% reduced the mutagenic response of BLM, a compound known to induce oxidative DNA damage, and suggest a possible decrease in ROS as a function of calorie restriction. PMID:10592326

  13. Delay of the Onset of Puberty in Female Rats by Prepubertal Exposure to T-2 Toxin.

    PubMed

    Yang, Rong; Wang, Yi-Mei; Zhang, Li-Shi; Zhang, Li; Zhao, Zeng-Ming; Zhao, Jun; Peng, Shuang-Qing

    2015-01-01

    Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 ?g/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children. PMID:26569305

  14. Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats

    SciTech Connect

    Trabace, L.; Zotti, M.; Morgese, M.G.; Tucci, P.; Colaianna, M.; Schiavone, S.; Avato, P.; Cuomo, V.

    2011-09-01

    Carvacrol is the major constituent of essential oils from aromatic plants. It showed antimicrobial, anticancer and antioxidant properties. Although it was approved for food use and included in the chemical flavorings list, no indication on its safety has been estimated. Since the use of plant extracts is relatively high among women, aim of this study was to evaluate carvacrol effects on female physiology and endocrine profiles by using female rats in proestrus and diestrus phases. Serotonin and metabolite tissue content in prefrontal cortex and nucleus accumbens, after carvacrol administration (0.15 and 0.45 g/kg p.o.), was measured. Drug effects in behavioral tests for alterations in motor activity, depression, anxiety-related behaviors and endocrine alterations were also investigated. While in proestrus carvacrol reduced serotonin and metabolite levels in both brain areas, no effects were observed in diestrus phase. Only in proestrus phase, carvacrol induced a depressive-like behavior in forced swimming test, without accompanying changes in ambulation. The improvement of performance in FST after subchronic treatment with fluoxetine (20 mg/kg) suggested a specific involvement of serotonergic system. No differences were found across the groups with regard to self-grooming behavior. Moreover, in proestrus phase, carvacrol reduced only estradiol levels without binding hypothalamic estradiol receptors. Our study showed an estrous-stage specific effect of carvacrol on depressive behaviors and endocrine parameters, involving serotonergic system. Given the wide carvacrol use not only as feed additive, but also as cosmetic essence and herbal remedy, our results suggest that an accurate investigation on the effects of its chronic exposure is warranted. - Highlights: > Carvacrol induced a depressive-like phenotype in rats, depending on ovarian cyclicity. > Carvacrol selectively reduced serotonin content in female rats in proestrus phase. > Carvacrol reduced serotonin levels in areas belonging to the emotional circuit. > Carvacrol reduced plasma estradiol levels only during the proestrus phase.

  15. Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

    SciTech Connect

    Takaku, Tomoyuki Nagahori, Hirohisa; Sogame, Yoshihisa

    2014-06-15

    A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000 mg/kg). The data on flumioxazin concentration in pregnant rats (30 mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose of 1000 mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-{sup 14}C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000 mg/kg in rats was low (12.3%) by summing up {sup 14}C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000 mg/kg po was 0.86 μg/mL and 0.68 μg/mL, respectively, which is much lower than K{sub m} (202.4 μg/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000 mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30 mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments. - Highlights: • A PBPK model of flumioxazin in pregnant humans was developed. • Simulated flumioxazin concentration in pregnant humans was relatively low. • The results would be useful for further in vitro toxicology experiments.

  16. Central estrogen action sites involved in prepubertal restraint of pulsatile luteinizing hormone release in female rats

    PubMed Central

    UENOYAMA, Yoshihisa; TANAKA, Akira; TAKASE, Kenji; YAMADA, Shunji; PHENG, Vutha; INOUE, Naoko; MAEDA, Kei-ichiro; TSUKAMURA, Hiroko

    2015-01-01

    The present study aimed to determine estrogen feedback action sites to mediate prepubertal restraint of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release in female rats. Wistar-Imamichi strain rats were ovariectomized (OVX) and received a local estradiol-17? (estradiol) or cholesterol microimplant in several brain areas, such as the medial preoptic area (mPOA), paraventricular nucleus, ventromedial nucleus and arcuate nucleus (ARC), at 20 or 35 days of age. Six days after receiving the estradiol microimplant, animals were bled to detect LH pulses at 26 or 41 days of age, representing the pre- or postpubertal period, respectively. Estradiol microimplants in the mPOA or ARC, but not in other brain regions, suppressed LH pulses in prepubertal OVX rats. Apparent LH pulses were found in the postpubertal period in all animals bearing estradiol or cholesterol implants. It is unlikely that pubertal changes in responsiveness to estrogen are due to a change in estrogen receptor (ER) expression, because the number of ER?-immunoreactive cells and mRNA levels of Esr1, Esr2 and Gpr30 in the mPOA and ARC were comparable between the pre- and postpubertal periods. In addition, kisspeptin or GnRH injection overrode estradiol-dependent prepubertal LH suppression, suggesting that estrogen inhibits the kisspeptin-GnRH cascade during the prepubertal period. Thus, estrogen-responsive neurons located in the mPOA and ARC may play key roles in estrogen-dependent prepubertal restraint of GnRH/LH secretion in female rats. PMID:26004302

  17. Increased number of neurons in the cervical spinal cord of aged female rats.

    PubMed

    Portiansky, Enrique L; Nishida, Fabian; Barbeito, Claudio G; Gimeno, Eduardo J; Goya, Rodolfo G

    2011-01-01

    In the brain, specific signaling pathways localized in highly organized regions called niches allow the persistence of a pool of stem and progenitor cells that generate new neurons in adulthood. Much less is known about the spinal cord where a sustained adult neurogenesis is not observed. Moreover, there is scarce information concerning cell proliferation in the adult mammalian spinal cord and virtually none in aging animals or humans. We performed a comparative morphometric and immunofluorescence study of the entire cervical region (C1-C8) in young (5 mo.) and aged (30 mo.) female rats. Serum prolactin (PRL), a neurogenic hormone, was also measured. Gross anatomy showed a significant age-related increase in size of all of the cervical segments. Morphometric analysis of cresyl violet stained segments also showed a significant increase in the area occupied by the gray matter of some cervical segments of aged rats. The most interesting finding was that both the total area occupied by neurons and the number of neurons increased significantly with age, the latter increase ranging from 16% (C6) to 34% (C2). Taking the total number of cervical neurons the age-related increase ranged from 19% (C6) to 51% (C3), C3 being the segment that grew most in length in the aged animals. Some bromodeoxyuridine positive-neuron specific enolase negative (BrdU(+)-NSE(-)) cells were observed and, occasionally, double positive (BrdU(+)-NSE(+)) cells were detected in some cervical segments of both young and aged rats groups. As expected, serum PRL increased markedly with age. We propose that in the cervical spinal cord of female rats, both maturation of pre-existing neuroblasts and/or possible neurogenesis occur during the entire life span, in a process in which PRL may play a role. PMID:21799890

  18. Increased Number of Neurons in the Cervical Spinal Cord of Aged Female Rats

    PubMed Central

    Portiansky, Enrique L.; Nishida, Fabian; Barbeito, Claudio G.; Gimeno, Eduardo J.; Goya, Rodolfo G.

    2011-01-01

    In the brain, specific signaling pathways localized in highly organized regions called niches allow the persistence of a pool of stem and progenitor cells that generate new neurons in adulthood. Much less is known about the spinal cord where a sustained adult neurogenesis is not observed. Moreover, there is scarce information concerning cell proliferation in the adult mammalian spinal cord and virtually none in aging animals or humans. We performed a comparative morphometric and immunofluorescence study of the entire cervical region (C1-C8) in young (5 mo.) and aged (30 mo.) female rats. Serum prolactin (PRL), a neurogenic hormone, was also measured. Gross anatomy showed a significant age-related increase in size of all of the cervical segments. Morphometric analysis of cresyl violet stained segments also showed a significant increase in the area occupied by the gray matter of some cervical segments of aged rats. The most interesting finding was that both the total area occupied by neurons and the number of neurons increased significantly with age, the latter increase ranging from 16% (C6) to 34% (C2). Taking the total number of cervical neurons the age-related increase ranged from 19% (C6) to 51% (C3), C3 being the segment that grew most in length in the aged animals. Some bromodeoxyuridine positive-neuron specific enolase negative (BrdU+-NSE?) cells were observed and, occasionally, double positive (BrdU+-NSE+) cells were detected in some cervical segments of both young and aged rats groups. As expected, serum PRL increased markedly with age. We propose that in the cervical spinal cord of female rats, both maturation of pre-existing neuroblasts and/or possible neurogenesis occur during the entire life span, in a process in which PRL may play a role. PMID:21799890

  19. The Roles of Dopamine and ?1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats.

    PubMed

    Perry, Adam N; Westenbroek, Christel; Jagannathan, Lakshmikripa; Becker, Jill B

    2015-11-01

    Cocaine dependence is characterized by compulsive drug taking and reduced involvement in social, occupational, or recreational activities. Unraveling the diverse mechanisms contributing to the loss-of-interest in these 'non-drug' pursuits is essential for understanding the neurobiology of addiction and could provide additional targets for treating addiction. The study objectives were to examine changes in cocaine-induced dopamine (DA) overflow in the nucleus accumbens (NAc) over the course of self-administration and determine the roles of ?1- and ?-adrenergic receptors (AR) in the loss-of-interest in food rewards following the development of an addicted phenotype in male and female rats. Subjects were given access to cocaine and palatable food pellets in a choice self-administration paradigm to identify 'addicted' cocaine-preferring (CP) individuals and resistant pellet-preferring (PP) individuals based on their patterns of self-administration over 7 weeks. Cocaine-induced DA overflow in the NAc was examined with microdialysis early and late during self-administration (weeks 2 and 7). Subjects were treated in counter-balanced order with propranolol (?-AR antagonist), terazosin (?1-AR antagonist), or vehicle for an additional 3 weeks of self-administration. CP rats displayed increased motivation for cocaine and attenuated motivation for pellets following the development of cocaine preferences. In females, the estrous cycle affected pellet, but not cocaine, self-administration. CP rats displayed attenuated cocaine-induced DA overflow in the NAc. Propranolol enhanced cocaine reinforcement and reduced pellet intake, whereas terazosin enhanced motivation for pellets and reversed preferences in a subset of CP rats. The implications of these results for the treatment of addiction are discussed. PMID:25900120

  20. Protective effects of probiotic Lactobacillus plantarum BJ0021 on liver and kidney oxidative stress and apoptosis induced by endosulfan in pregnant rats.

    PubMed

    Bouhafs, Leila; Moudilou, Elara N; Exbrayat, Jean Marie; Lahouel, Mesbah; Idoui, Tayeb

    2015-01-01

    Endosulfan (EDS) is one of the most widely organochlorine insecticide used in many parts of the world, although it is currently banned or severely restricted in use in some countries. EDS causes a variety of negative effects in non-target species including humans. Therefore, the aim of the present study was to investigate the possible protective effects of Lactobacillus plantarum BJ0021 on toxicity, oxidative stress, and apoptosis induced by EDS intoxication on liver and kidneys of pregnant rats. This pesticide induced a significant increase in total cholesterol, alanine-amino transferase (ALAT), aspartate-amino transferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), urea and creatinine in serum, while urinary urea and creatinine were lower than those of the control group. In the liver and kidney, lipid peroxidation increased significantly, the antioxidant levels, such as superoxide dismutase (SOD) and catalase (CAT) were markedly depressed and TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) revealed more apoptotic cells. In contrast, co-administration of L. plantarum BJ0021 to EDS-treated animals ameliorated most of these biochemical parameters, but the activity of antioxidant enzymes (SOD, CAT) did not modify and the number of apoptotic nuclei remained significantly raised in kidney compared to control. In conclusion, the administration of L. plantarum BJ0021 decreased apoptosis and might play a protective role in reducing toxicity of EDS in pregnant rats. PMID:26287934

  1. [Early indicators of kidney injury in male and female rats after oral administration of cadmium].

    PubMed

    Ozierenski, B; Plass, R; Lewerenz, H J

    1989-01-01

    The effect of cadmium on the urinary excretion of glucose, creatinine and enzymes has been studied in adult male and female rats given the substance (70, 140 and 280 mg/kg food) for 4 weeks. Renal function tests and gel electrophoresis of urinary proteins were conducted simultaneously. Sex-dependent differences were demonstrated with regard to sensitivity of several kidney parameters and their predictive character of a possible chronic nephrotoxicity. These results were compared with hematological and general biological examinations of cadmium toxicity. PMID:2797117

  2. Evaluation of reproductive function of female rats exposed to radiofrequency fields (27. 12 MHz) near a shortwave diathermy device

    SciTech Connect

    Brown-Woodman, P.D.; Hadley, J.A.; Richardson, L.; Bright, D.; Porter, D.

    1989-04-01

    In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

  3. Multi-Generational Drinking of Bottled Low Mineral Water Impairs Bone Quality in Female Rats

    PubMed Central

    Zeng, Hui; Wang, Lingqiao; Wang, Dahua; Luo, Jiaohua; Zhang, Liang; Huang, Yujing; Chen, Ji-an; Shu, Weiqun

    2015-01-01

    Background Because of reproductions and hormone changes, females are more sensitive to bone mineral loss during their lifetime. Bottled water has become more popular in recent years, and a large number of products are low mineral water. However, research on the effects of drinking bottled low mineral water on bone health is sparse. Objective To elucidate the skeletal effects of multi-generational bottled water drinking in female rats. Methods Rats continuously drank tap water (TW), bottled natural water (bNW), bottled mineralized water (bMW), or bottled purified water (bPW) for three generations. Results The maximum deflection, elastic deflection, and ultimate strain of the femoral diaphysis in the bNW, bMW, and bPW groups and the fracture strain in the bNW and bMW groups were significantly decreased. The tibiae calcium levels in both the bNW and bPW groups were significantly lower than that in the TW group. The tibiae and teeth magnesium levels in both the bNW and bPW groups were significantly lower than those in the TW group. The collagen turnover markers PICP (in both bNW and bPW groups) were significantly lower than that in the TW group. In all three low mineral water groups, the 1,25-dihydroxy-vitamin D levels were significantly lower than those in the TW group. Conclusion Long-term drinking of low mineral water may disturb bone metabolism and biochemical properties and therefore weaken biomechanical bone properties in females. Drinking tap water, which contains adequate minerals, was found to be better for bone health. To our knowledge, this is the first report on drinking bottled low mineral water and female bone quality on three generation model. PMID:25803851

  4. Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats.

    PubMed

    Sinclair, Elaine B; Culbert, Kristen M; Gradl, Dana R; Richardson, Kimberlei A; Klump, Kelly L; Sisk, Cheryl L

    2015-12-01

    Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague-Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial prefrontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex than in nucleus accumbens. These data confirm that PF activates brain regions responsible for encoding the incentive salience and hedonic properties of PF, and suggest that binge eating proneness is associated with enhanced responses to PF in brain regions that exert executive control over food reward. PMID:26459117

  5. Adolescent pre-treatment with oxytocin protects against adult methamphetamine-seeking behavior in female rats.

    PubMed

    Hicks, Callum; Cornish, Jennifer L; Baracz, Sarah J; Suraev, Anastasia; McGregor, Iain S

    2016-03-01

    The neuropeptide oxytocin (OT), given acutely, reduces self-administration of the psychostimulant drug methamphetamine (METH). Additionally, chronic OT administration to adolescent rats reduces levels of alcohol consumption in adulthood, suggesting developmental neuroplasticity in the OT system relevant to addiction-related behaviors. Here, we examined whether OT exposure during adolescence might subsequently inhibit METH self-administration in adulthood. Female Sprague-Dawley rats were administered vehicle or OT (1 mg/kg, i.p.) once daily from postnatal days (PND) 28 to 37 (adolescence). At PND 62 (adulthood), rats were trained to self-administer METH (intravenous, i.v.) in daily 2-hour sessions for 10 days under a fixed ratio 1 (FR1) reinforcement schedule, followed by determination of dose-response functions (0.01-0.3 mg/kg/infusion, i.v.) under both FR1 and progressive ratio (PR) schedules of reinforcement. Responding was then extinguished, and relapse to METH-seeking behavior assessed following priming doses of non-contingent METH (0.1-1 mg/kg, i.p.). Finally, plasma was collected to determine pre-treatment effects on OT and corticosterone levels. Results showed that OT pre-treatment did not significantly inhibit the acquisition of METH self-administration or FR1 responding. However, rats pre-treated with OT responded significantly less for METH under a PR reinforcement schedule, and showed reduced METH-primed reinstatement with the 1 mg/kg prime. Plasma OT levels were also significantly higher in OT pre-treated rats. These results confirm earlier observations that adolescent OT exposure can subtly, yet significantly, inhibit addiction-relevant behaviors in adulthood. PMID:25402719

  6. Renoprotective effect of hydroalcoholic extract of Rheum ribes root in diabetic female rats

    PubMed Central

    Hamzeh, Shokri; Farokhi, Farah; Heydari, Reza; Manaffar, Ramin

    2014-01-01

    Objective: Medical plants, as rich sources of natural antioxidants with antidiabetic effects, are used worldwide to diminish a variety of symptoms and many diseases. R. ribes L., which belongs to the family of polygonaceae, can provide symptomatic relief and assist in the prevention of the secondary complications of the diabetes. Material and Methods: 36 female adult rats were randomly divided into 6 groups of 6. Normal Control groups treated with normal saline. Positive control groups treated with hydroalcohlic extract of R. ribes root (150 mg/kg) daily by gavages for 4 consecutive weeks. Diabetes was inducedby injection of 120 mg/kg alloxan monohydrate intraperitoneally. Two diabetic groups were treated with different doses of R. ribes root extract. The sixth diabetic groups were treated with glibenclamide (0.6 mg/kg). At the end of 28 days, blood samples were collected and their kidney tissues were processed for light microscopy. Results: The results showed that hydro-alcoholic extract of R. ribes decreased the level of glucose, cholesterol, triglyceride, urea and creatinine in diabetic rats (p<0.05) in compared with diabetic rats, while the level of HDL increased at the same group (p<0.05). Histopathological changes of kidney samples were comparable with respective control. In diabetic rats, kidney sections showed atrophy of glomerular capillaries with increased Bowman's space and acute tubular necrosis. The groups that were treated with R. ribes root were improved towards normal condition. Conclusion: It is interesting to note that hydroalcohlic extract of R. ribes root improves renal dysfunction in alloxan-induced diabetic rats through controlling blood glucose and renal protective effects. PMID:25386403

  7. Behavioural response of sexually nave and experienced male rats to the smell of 6-methyl-5-hepten-2-one and female rat faeces.

    PubMed

    Nielsen, Birte L; Jerme, Nathalie; Saint-Albin, Audrey; Rampin, Olivier; Maurin, Yves

    2013-08-15

    Sexually experienced male rats display penile erections when exposed to faeces from mammalian females in oestrus (Rampin et al., Behav Brain Res, 172:169, 2006), suggesting that specific odours indicate female receptiveness across species. However, it is unknown to what extent the sexual response observed results from an odorous conditioning acquired during sexual experience. We tested the behavioural response of male Brown Norway rats both when sexually nave and experienced to four odours, including oestrous rat faeces and 6-methyl-5-hepten-2-one (methylheptenone; a molecule found in higher concentrations during oestrus in female rats, foxes and horses). Odour had a significant effect on the sexual response of the nave rats, with oestrus faeces provoking significantly more erections than herb odour, and with methylheptenone and di-oestrus faeces being intermediate. This indicates that sexually nave male rats have an unconditioned ability to detect oestrous mediated via odour. After gaining sexual experience, the response to methylheptenone, di- and oestrus faeces was significantly higher than that observed with herb odour. These results strongly suggest that methylheptenone is part of the odorous bouquet of oestrus and contributes to the olfactory determination of female receptiveness. PMID:23911690

  8. The effects of chronic restraint on the morphology of ventral CA1 neurons in female Long Evans rats.

    PubMed

    Rico, Alexander Morales; Mendoza, Anayeli López; Durán, Dolores Adriana Bravo; Torres, Héctor de la Luz; Mendoza, Guadalupe Arias; Gómez, Adriana Berenice Silva

    2015-01-01

    Women are more likely than men to develop psychopathology as a result of stress, but there is little research regarding the effects of a stressful condition and its treatment in female non-human animals, perhaps because of inherent hormonal activity. Recent studies have demonstrated that there are structural and functional differences between the dorsal and ventral hippocampus, but the effects of stress on the morphology of CA1 and CA3 neurons have been studied primarily in the dorsal hippocampus. This study assessed the effects of stress induced by restricted movement on the morphology of ventral hippocampal CA1 neurons in male and female rats. Male and female Long Evans (LE) rats were subjected to restraint stress for 6 h every day for 25 days. One group of rats was used to study the dendritic morphology of CA1 ventral hippocampal neurons using the Golgi-Cox stain. A second group of rats was used to analyze learning and memory using the Morris water maze. Stressed female rats exhibited a decrease in the density of basilar dendritic spines, an increase in the number of apical dendritic intersections and deficits in spatial memory. There were no apparent effects of stress on male rats. Our data support previous findings of a dimorphic response to chronic stress and indicate that the ventral hippocampus is not particularly susceptible to the effects of stress. PMID:25287136

  9. Differential effects of cadmium on the hepatic microsomal cytochrome P-450 system in male and female rats.

    PubMed

    Schnell, R C; Pence, D H

    1981-09-01

    Cadmium (Cd) produced a marked sex-related difference with respect to inhibition of the hepatic microsomal monooxygenase enzyme system in the rat. Following in vivo cadmium (2 mg/kg i.p.) treatment, significant decreases in the levels of cytochrome P-450, significant reductions in the magnitudes of spectral binding (aniline or ethylmorphine), and significant inhibitions of microsomal metabolism (aniline and ethylmorphine) were observed with microsomes isolated from male but not female rats. Of these parameters only aniline metabolism was significantly altered in females. Following the in vitro addition of Cd (10(-6) M to 10(-3) M) to hepatic microsomes isolated from untreated male or female rats, sex-related changes were also observed in these parameters. Significant, concentration-dependent reductions were observed in cytochrome P-450 levels of both sexes but the males showed greater sensitivity to the cadmium effect. With respect to binding spectra, cadmium addition produced a concentration dependent inhibition of aniline only in the male rat. Ethylmorphine binding was inhibited only at the higher cadmium concentrations in both sexes. With respect to drug metabolism, cadmium addition inhibited both aniline and ethylmorphine metabolism in male rats and only aniline metabolism in female rats. These results showed that there are sex-related differences in the interaction of the hepatic microsomal monooxygenase enzyme system with cadmium both after in vitro addition as well as in vivo treatment with the metal. PMID:7302968

  10. QRFP in Female Rats: Effects on High Fat Food Intake and Hypothalamic Gene Expression across the Estrous Cycle

    PubMed Central

    Primeaux, Stefany D.

    2011-01-01

    Pyroglutamylated arginine-phenylalanineamide peptide (QRFP) is a neuropeptide involved in feeding behavior. Central administration of QRFP selectively increases the intake of a high fat diet in male rats. QRFP administration also stimulates the hypothalamic-pituitary-gonadal axis via gonadotrophin-releasing hormone in male and female rats. Prepro-QRFP mRNA is expressed in localized regions of the mediobasal hypothalamus which are abundant in neurotransmitters, neuropeptides and receptor systems important for food intake regulation and reproductive behaviors. The current experiments were conducted to investigate the effects of centrally administered QRFP-26 on the intake of a high fat diet (HFD, 60% kcal from fat) in female rats and to investigate alterations in hypothalamic prepro-QRFP and its receptors, GPR130a and GPR103b, mRNA levels over the estrous cycle. In Experiment 1, female rats were administered QRFP-26 (intracerebroventricular; 0.3nmol, 0.5nmol, 1.0nmol) in rats consuming either a HFD or a low fat diet. All doses of QRFP-26 selectively increased the intake of the HFD in female rats. These data suggest that QRFP-26 regulates the intake of energy dense foods in female rats, which is similar to previous findings in male rats. In Experiment 2, hypothalamic levels of prepro-QRFP mRNA and its receptors were assessed during diestrus, proestrus, or estrus. The level of prepro-QRFP mRNA in the ventromedial/arcuate nucleus (VMH/ARC) of the hypothalamus was increased during proestrus, which suggests that endogenous estrogen levels regulate QRFP expression in the VMH/ARC. These data suggest that QRFP may play a role in coordinating feeding behaviors with reproductive function when energy demand is increased. PMID:21473894

  11. Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

    PubMed Central

    Dixon, Darlene; Alison, Roger; Bach, Ute; Colman, Karyn; Foley, George L.; Harleman, Johannes H.; Haworth, Richard; Herbert, Ronald; Heuser, Anke; Long, Gerald; Mirsky, Michael; Regan, Karen; Van Esch, Eric; Westwood, F. Russell; Vidal, Justin; Yoshida, Midori

    2014-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. PMID:25516636

  12. Enhanced learning deficits in female rats following lifetime pb exposure combined with prenatal stress.

    PubMed

    Cory-Slechta, Deborah A; Stern, Sander; Weston, Doug; Allen, Joshua L; Liu, Sue

    2010-10-01

    Pb (lead) exposure and stress are co-occurring risk factors (particularly in low socioeconomic communities) that also act on common biological substrates and produce common adverse outcomes, including cognitive impairments. This study sought to determine whether lifetime Pb exposure combined with prenatal stress would enhance the cognitive deficits independently associated with each of these risk factors and to explore associated mechanisms of any observed impairments. Learning was evaluated using a multiple schedule of repeated learning and performance in female rats subjected to lifetime Pb exposure (0 or 50 ppm Pb in drinking water beginning in dams 2 months prior to breeding; blood Pb levels ?10 ?g/dl), to prenatal restraint stress on gestational days 16 and 17, or to both. Blood Pb, corticosterone levels, brain monoamines, and hippocampal nerve growth factor levels were also measured. Sequence-specific learning deficits produced by Pb, particularly the number of responses to correctly learn response sequences, were further enhanced by stress, whereas performance measures were unimpaired. Statistical analyses indicated significant relationships among corticosterone levels, frontal cortex dopamine (DA), nucleus accumbens dopamine turnover, and total responses required to learn sequences. This study demonstrates that Pb and stress can act together to produce selective and highly condition-dependent deficits in learning in female rats that may be related to glucocorticoid-mediated interactions with mesocorticolimbic regions of brain. These findings also underscore the critical need to evaluate toxicants in the context of other risk factors pertinent to human diseases and disorders. PMID:20639260

  13. Dietary supplementation of female rats with elk velvet antler improves physical and neurological development of offspring.

    PubMed

    Chen, Jiongran; Woodbury, Murray R; Alcorn, Jane; Honaramooz, Ali

    2012-01-01

    Elk velvet antler (EVA) has a traditional use for promotion of general health. However, evidence of EVA effects at different lifestages is generally lacking. This paper investigated the effects of long-term maternal dietary EVA supplementation on physical, reflexological and neurological development of rat offspring. Female Wistar rats were fed standard chow or chow containing 10% EVA for 90 days prior to mating and throughout pregnancy and lactation. In each dietary group, 56 male and 56 female pups were assessed for physical, neuromotor, and reflexologic development postnatally. Among the examined physical developmental parameters, incisor eruption occurred one day earlier in pups nursing dams receiving EVA. Among neuromotor developmental parameters, duration of supported and unsupported standing was longer for pups nursing EVA supplemented dams. Acquisition of neurological reflex parameters (righting reflex, negative geotaxis, cliff avoidance acoustic startle) occurred earlier in pups nursing dams receiving EVA. Longterm maternal EVA supplementation prior to and during pregnancy and lactation accelerated certain physical, reflexologic, and neuromotor developmental milestones and caused no discernible adverse effects on developing offspring. The potential benefits of maternal EVA supplementation on postnatal development warrants further investigation to determine whether EVA can be endorsed for the promotion of maternal and child health. PMID:22550542

  14. Maternal separation exaggerates spontaneous recovery of extinguished contextual fear in adult female rats.

    PubMed

    Xiong, Gui-Jing; Yang, Yuan; Wang, Li-Ping; Xu, Lin; Mao, Rong-Rong

    2014-08-01

    Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD. PMID:24746487

  15. Maternal separation increases methamphetamine-induced damage in the striatum in male, but not female rats.

    PubMed

    Hensleigh, Emily; Pritchard, Laurel M

    2015-12-15

    Methamphetamine abuse impacts the global economy through costs associated with drug enforcement, emergency room visits, and treatment. Previous research has demonstrated early life stress, such as childhood abuse, increases the likelihood of developing a substance abuse disorder. However, the effects of early life stress on neuronal damage induced by binge methamphetamine administration are unknown. We aimed to elucidate the effects of early life stress on methamphetamine induced dopamine damage in the striatum. Pups were separated from dams for 3h per day during the first two weeks of development or 15 min for control. In adulthood, rats received either subcutaneous 0.9% saline or 5.0mg/kg METH injections every 2h for a total of four injections. Rectal temperatures were taken before the first injection and 1h after each subsequent injection. Seven days after treatment, rats were euthanized and striatum was collected for quantification of tyrosine hydroxylase (TH) and dopamine transporters (DAT) content by Western blot. Methamphetamine significantly elevated core body temperature in males and decreased striatal DAT and TH content, and this effect was potentiated by early life stress. Females did not exhibit elevated core body temperatures or changes in DAT or TH in either condition. Results indicate maternal separation increases methamphetamine induced damage, and females are less susceptible to methamphetamine induced damage. PMID:25535855

  16. Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

    PubMed

    Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

    2015-01-01

    Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. PMID:25281318

  17. Immediate early gene activity-regulated cytoskeletal-associated protein regulates estradiol-induced lordosis behavior in female rats.

    PubMed

    Christensen, Amy; Dewing, Phoebe; Micevych, Pavel

    2015-01-01

    Sensory feedback is an important component of any behavior, with each instance influencing subsequent activity. Female sexual receptivity is mediated both by the steroid hormone milieu and interaction with the male. We tested the influence of repeated mating on the level of sexual receptivity in ovariectomized rats treated with estradiol benzoate (EB) once every fourth day to mimic the normal phasic changes of circulating estradiol. Females were divided into two groups: nave, which were tested for lordosis behavior once, and experienced rats, which were tested for lordosis after each EB injection. To monitor the effect of mating, the number of neurons expressing the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) were counted in the mediobasal hypothalamus. Females were unreceptive following the first EB treatment, but the mating induced Arc expression. In nave rats, each subsequent EB injection increased the levels of sexual receptivity. This ramping was not observed in experienced rats, which achieved only a moderate level of sexual receptivity. However, experienced females treated with EB and progesterone were maximally receptive and did not have Arc expression. To test whether the expression of Arc attenuated lordosis, Arc antisense oligodeoxynucleotides (asODN) were microinjected into experienced females' arcuate nuclei. Arc expression was attenuated, and the experienced EB-treated females achieved maximal sexual receptivity. These results demonstrate that Arc expression in the hypothalamus might influence future sexual receptivity and provides evidence of learning in the arcuate nucleus. The loss of Arc results in unrestrained sexual receptivity. PMID:25088303

  18. Immediate Early Gene Activity-Regulated Cytoskeletal-Associated Protein Regulates Estradiol-Induced Lordosis Behavior in Female Rats

    PubMed Central

    Christensen, Amy; Dewing, Phoebe; Micevych, Pavel

    2016-01-01

    Sensory feedback is an important component of any behavior, with each instance influencing subsequent activity. Female sexual receptivity is mediated both by the steroid hormone milieu and interaction with the male. We tested the influence of repeated mating on the level of sexual receptivity in ovariectomized rats treated with estradiol benzoate (EB) once every fourth day to mimic the normal phasic changes of circulating estradiol. Females were divided into two groups: nave, which were tested for lordosis behavior once, and experienced rats, which were tested for lordosis after each EB injection. To monitor the effect of mating, the number of neurons expressing the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) were counted in the mediobasal hypothalamus. Females were unreceptive following the first EB treatment, but the mating induced Arc expression. In nave rats, each subsequent EB injection increased the levels of sexual receptivity. This ramping was not observed in experienced rats, which achieved only a moderate level of sexual receptivity. However, experienced females treated with EB and progesterone were maximally receptive and did not have Arc expresion. To test whether the expression of Arc attenuated lordosis, Arc antisense oligodeoxynucleotides (asODN) were microinjected into experienced females arcuate nuclei. Arc expression was attenuated, and the experienced EB-treated females achieved maximal sexual receptivity. These results demonstrate that Arc expression in the hypothalamus might influence future sexual receptivity and provides evidence of learning in the arcuate nucleus. The loss of Arc results in unrestrained sexual receptivity. PMID:25088303

  19. Preliminary assessment of the oral toxicity of 1,5-diazido-3-nitrazapentane, 2- and 6-week feeding study, male and female rats. Final report

    SciTech Connect

    Haight, E.A.; Harvey, J.G.; Bell, P.A.

    1993-02-01

    A 2 and 6 week gavage feeding of DANPE caused testicular hypospermatogenesis in male rats and pneumonitis in female rats. A NOAEL was not achieved in male rats but was achieved in female rats at the 56.00 mg/kg/day dose level.... 1,5-Diazido-3-Nitrazapentane (DANPE), Gavage, Testicular hypospermatogenesis, Insterstitual Inflammation No-observed-Adverse-Effect-Level(NOAEL), Feeding study.

  20. Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced pre-eclamptic syndrome in pregnant rats.

    PubMed Central

    Richer, C.; Boulanger, H.; Es-Slami, S.; Giudicelli, J. F.

    1996-01-01

    1. In pregnant rats, chronic NO-synthase inhibition induces the development of a pre-eclamptic syndrome, characterized by an increase in maternal blood pressure, a loss of vascular refractoriness to pressor stimuli, a reduction in litter size and a decrease in pups (and maternal) weight. We investigated whether a NO-donor, molsidomine, administered during NO synthase inhibition, could restore a normal pregnancy. 2. Pregnant rats were given daily, starting from day 14 of gestation, saline (controls), or L-NAME (50 mg kg-1 d-1), or molsidomine (15 or 30 mg kg-1 d-1), or the L-NAME + molsidomine combinations. Maternal blood pressure and body weight, litter size, pups weight and vascular reactivity to pressor stimuli (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were investigated. 3. L-NAME alone, as compared to controls, increased maternal blood pressure, reduced litter size (-59%), increased foetal reabsorptions (+ 625%) and decreased foetal weight (-10%). Vascular reactivity to pressor stimuli was enhanced. 4. Molsidomine alone, as compared to controls, dose-dependently decreased maternal blood pressure but had no effect vascular reactivity and, whatever the dose, on foetal outcome. 5. The L-NAME-molsidomine combinations dose (of molsidomine)-dependently limited the rise in maternal blood pressure induced by L-NAME alone but unexpectedly, dose-dependently and significantly worsened pregnancy evolution, e.g., at 30 mg kg-1 d-1: litter size (-80%), foetal reabsorptions (+ 1025%), foetal weight (-24%). Vascular reactivity to pressor stimuli was paradoxically further enhanced. 6. Thus, in a chronic NO deprivation-induced model of pre-eclampsia in rats, molsidomine, possibly because of its hypotensive action, worsens the foetal outcome, which questions the usefulness of NO-donors in pre-eclamptic women. PMID:8982513

  1. Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure

    NASA Technical Reports Server (NTRS)

    Tang, L. Y.; Jee, W. S.; Ke, H. Z.; Kimmel, D. B.

    1992-01-01

    This experiment contains the crucial data for the lose, restore, and maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses anabolic agents to restore bone mass and architecture (+ phase) and then switches to an agent with the established ability to maintain bone mass, to keep the new bone (+/- phase). The purpose of this study was to learn whether switching to an agent known chiefly for its ability to maintain existing bone mass preserves new bone induced by PGE2 in osteopenic, estrogen-depleted rats. The current study had three phases, the bone loss (-), restore (+), and maintain (+/-) phases. We ovariectomized (OX) or sham ovariectomized (sham-OX) 5.5-month-old female rats (- phase). The OX rats were treated 5 months postovariectomy with 1-6 mg PGE2 per kg/day for 75 days to restore lost cancellous bone mass (+ phase), and then PGE2 treatment was stopped and treatment began with 1 or 5 micrograms/kg of risedronate, a bisphosphonate, twice a week for 60 days (+/- phase). During the loss (-) phase, the cancellous bone volume of the proximal tibial metaphysis in the OX rat fell to 19% of initial and 30% of age-matched control levels. During the restore (+) phase, the cancellous bone volume in OX rats doubled. When PGE2 treatment was stopped, however, and no special maintenance efforts were made during the maintain (+/-) phase, the PGE2-induced cancellous bone disappeared. In contrast, the PGE2-induced cancellous bone persisted when the PGE2 treatment was followed by either a 1 or 5 micrograms treatment of risedronate per kg given twice a week for 60 days during the maintain (+/-) phase. The tibial shaft demonstrated very little cortical bone loss during the loss (-) phase in OX rats. The tibial shaft cortical bone fell some 8%. During the restore (+) phase, new cortical bone in OX rats increased by 22%. When PGE2 treatment was stopped and nothing was given during the maintain (+/-) phase, however, all but the PGE2-induced subperiosteal bone disappeared. In contrast, when PGE2 treatment was stopped and 1 micron risedronate per kg twice a week for 60 days was administered during the maintenance (+/-) phase, the PGE2-induced subperiosteal bone and some of the subendocortical bone and marrow trabeculae persisted.(ABSTRACT TRUNCATED AT 400 WORDS).

  2. The effect of piroctone olamine on reproduction of male and female rats.

    PubMed

    Allgood, G S; Miller, J M; Schardein, J L

    1991-01-01

    The purpose of this study was to determine the effect of piroctone olamine, an antidandruff active, on reproductive performance, fertility, parturition, and neonatal viability and growth. Piroctone olamine was administered orally by gavage to three groups of 35 male Sprague-Dawley rats each beginning 64 days prior to mating and continuing until euthanized and to three groups of 35 female Sprague-Dawley rats each beginning 14 days prior to mating and continuing until euthanized. Animals in the treated groups received piroctone olamine in a combination of 1.0% methylcellulose and polyethylene glycol 400 as a single daily dose at levels of 0, 10, 100, and 250 mg/kg/day, at a volume of 2.5 ml/kg. The control group received the vehicle only. Ten randomly selected females/group were mated and underwent a uterine examination on Gestation Day 13; the remaining females were allowed to deliver. Because earlier studies reported hematological effects, blood samples were collected from all parental animals during acclimation and prior to euthanasia for hematological and blood chemistry (Gestation Day 13 females) characterization. The parental animals were necropsied and tissues were grossly examined. Systemic effects induced by the test article were seen at the mid- and high-dose levels but only among the male rats. These effects were reduced body weight and decreased liver weights. Hematological findings representative of anemia occurred at the high-dose level, as did rales in several animals. Offspring growth was inhibited for the high-dose group as evidenced by significantly reduced mean weight values throughout lactation. The remaining parameters assessed, including mating ability and reproductive performance, were not affected by treatment at any dosage level tested. In summary, the no observable effect level of piroctone olamine with respect to systemic toxicity was considered to be 10 mg/kg/day. Neonatal growth was not affected at 100 mg/kg/day or less, and the no observable effect level with respect to reproductive parameters, including fertility, was 250 mg/kg/day. PMID:2019350

  3. STRAIN COMPARISON IN PREGNANT RATS OF ENDOCRINE RESPONSE TO BROMODICHLOROMETHANE: A DRINKING WATER DISINFECTION BY-PRODUCT

    EPA Science Inventory

    Bromodichloromethane (BDCM), a trihalomethane, is a by-product of the chlorination of drinking water. In an epidemiological study, consumption of drinking water with high levels of BDCM was associated with an increased risk of spontaneous abortion in pregnant women (Waller et al....

  4. Contextual fear cues inhibit eating in food-deprived male and female rats.

    PubMed

    Reppucci, Christina J; Kuthyar, Meghana; Petrovich, Gorica D

    2013-10-01

    Previously we have shown that food-deprived male and female rats inhibit food consumption when presented with a discrete conditioned stimulus that signals danger. Here, in a series of three experiments, we examined whether contextual conditioned stimuli can exert the same effect. Experiment 1 paired a distinct context with footshocks, to examine food intake in food-deprived rats upon re-exposure to the context. Experiment 2 used a discrimination protocol with two alternating contexts; rats were given food in one, and received footshocks in the other. This protocol allowed us to monitor food consumption during training in a context never associated with footshocks, and to evaluate consumption at test in a context that had been previously paired with footshocks. Experiments 1 and 2 compared experimental groups to controls that never received footshocks. Experiment 3 used a within-subjects design to assess the specificity of the inhibition by the contextual cues, separate from any generalized effects due solely to the prior experience of footshocks. Our results demonstrate that similar to discrete cues, contextual cues previously associated with aversive events can inhibit feeding in food-deprived animals. These findings are important for our understanding of environmental contributions to the control of food intake. PMID:23770208

  5. Imidacloprid induced histological and biochemical alterations in liver of female albino rats.

    PubMed

    Toor, Harmandeep Kaur; Sangha, Gurinder Kaur; Khera, Kuldeep Singh

    2013-01-01

    Imidacloprid is a neonicotinoid insecticide being used extensively for crop protection and pet flea control programmes. The effect of repeated oral administration of two doses of imidcloprid (1/10th and 1/50th of LD50 of imidacloprid) on liver of female albino rat was assessed. Histological examination of liver revealed that imidacloprid (1/10th of LD50) treatment resulted in dilations of central vein and sinusoids between hepatocytes however imidacloprid (1/50th of LD50) treatment did not induce histopathological changes in liver. Non significant decrease in alkaline phosphatase (AKP) activity was observed in imidacloprid treated rats. Liver aspartate aminotransferase level showed significant increase in higher dose of imidacloprid. Additionally, significant increases in plasma levels of aspatate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) were observed in the treated rats. The results suggest that the higher doses of imidacloprid at 1/10th of LD50 is hepatotoxic as compared to lower dose of 1/50th of LD50 of imidacloprid. PMID:24238282

  6. Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating in Female Rats.

    PubMed

    Micioni Di Bonaventura, Maria Vittoria; Vitale, Giovanni; Massi, Maurizio; Cifani, Carlo

    2012-01-01

    Purpose. The present study evaluated the effect of Hypericum perforatum dry extract in an experimental model of binge eating (BE). Methods. BE for highly palatable food (HPF) was evoked in female rats by three 8-day cycles of food restriction/re-feeding and acute stress on the test day (day 25). Stress was induced by preventing access to HPF for 15?min, while rats were able to see and smell it. Hypericum perforatum dry extract was given by gavage. Results. Only rats exposed to both food restrictions and stress exhibited BE. The doses of 250 and 500?mg/kg of Hypericum perforatum extract significantly reduced the BE episode, while 125?mg/kg was ineffective. The same doses did not affect HPF intake in the absence of BE. The dose of 250?mg/kg did not significantly modify stress-induced increase in serum corticosterone levels, suggesting that the effect on BE is not due to suppression of the stress response The combined administration of 125?mg/kg of Hypericum perforatum together with Salidroside, active principle of Rhodiola rosea, produced a synergic effect on BE. Conclusions. The present results indicate for the first time that Hypericum perforatum extracts may have therapeutic properties in bingeing-related eating disorders. PMID:22997570

  7. Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats.

    PubMed

    Miller, I; Serchi, T; Cambier, S; Diepenbroek, C; Renaut, J; Van der Berg, J H J; Kwadijk, C; Gutleb, A C; Rijntjes, E; Murk, A J

    2016-03-14

    Hexabromocyclododecane (HBCD) is a brominated flame retardant known for its low acute toxicity as observed in animal experiments. However, HBCD exposure can affect liver functioning and thyroid hormone (TH) status. As exact mechanisms are unknown and only limited toxicological data exists, a gel-based proteomic approach was undertaken. In a eu- and hypothyroid female rat model, rats were exposed to 3 and 30mg/kgbw/day HBCD for 7 days via their diet, and exposure was related to a range of canonical endpoints (hormone status, body weight) available for these animals. Alterations in the liver proteome under HBCD exposure were determined in comparison with patterns of control animals, for both thyroid states. This revealed significantly changed abundance of proteins involved in metabolic processes (gluconeogenesis/glycolysis, amino acid metabolism, lipid metabolism), but also in oxidative stress responses, in both euthyroid and hypothyroid rats. The results provide a more detailed picture on the mechanisms involved in these alterations, e.g. at the protein level changes of the proposed influence of HBCD on the lipid metabolism. Present results show that proteomic approaches can provide further mechanistic insights in toxicological studies. PMID:26795019

  8. Salvia officinalis L. induces alveolar bud growing in adult female rat mammary glands

    PubMed Central

    Monsefi, Malihezaman; Abedian, Mehrnaz; Azarbahram, Zahra; Ashraf, Mohammad Javad

    2015-01-01

    Objectives: In traditional medicine Salvia officinalis (sage) has been used as menstrual cycle regulator. In the present study the effects of sage extract on breast tissue were examined. Materials and Methods: Fourteen female rats were divided into two groups: 1) Distilled water-treated rats (Con) that were gavaged with 1ml distilled water and 2) Saliva officinalis hydroalcoholic extract (SHE)-treated rats that were gavaged with 30mg/kg/body weight of sage extract for 30 days. The estrus cycle changes were monitored by daily examination of vaginal smear. Whole mounts of right pelvic breast were spread on the slide and stained by carmine. The number of alveolar buds (ABs) type 1 and 2 and lobules of mammary gland were scored. Tissue sections of left pelvic mammary gland were prepared and its histomorphometrical changes were measured. Blood samples were taken from dorsal aorta and estradiol and progesterone concentrations were measured using radioimmunoassay. Results: Estrous cycles decreased significantly in SHE-treated animals. The number of alveolar buds and lobules in mammary gland whole mount of SHE-treated group were higher than the Con group. The number and diameter of ducts in histological section of mammary gland in SHE-treated group increased as compared to the Con group. Conclusion: Sage promotes alveologenesis of mammary glands and it can be used as a lactiferous herb. PMID:26693413

  9. Amelioration of Collagen-Induced Arthritis in Female Dark Agouti Rats by Glucosamine Treatment

    PubMed Central

    Haleagrahara, Nagaraja; Tudawe, Dulanthi; Chakravarthi, Srikumar; Kutty Radhakrishnan, Ammu

    2013-01-01

    The present study assessed the therapeutic efficacy of glucosamine hydrochloride against collagen-induced arthritis in female Dark Agouti rats (DA). Arthritis was induced by intradermaly injecting a collagen and complete Freund's adjuvant suspension at multiple sites in the rat at a dose of 4 mg/kg of body weight and thereafter followed by two more boosters of the same dose, after the 1st week and 2nd week of primary immunization. After 21 days from the day of primary immunization, the arthritic group rats were given oral supplementation of glucosamine hydrochloride at a dose of 300 mg/kg of body weight until day 45. The arthritic group treated with glucosamine hydrochloride from day 21 to day 45 showed significant reduction in arthritic histopathological changes of the joints, reduction in paw thickness and also a significant decrease in C-reactive protein and TNF-alpha in the serum. Treatment with 300 mg/kg of glucosamine hydrochloride was able to reverse the arthritic changes, hence suggesting that glucosamine has a therapeutic effect against collagen-induced arthritis. PMID:23476804

  10. Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

    PubMed Central

    2013-01-01

    Background Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood. Methods At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data. Results As expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered. Conclusions In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels. PMID:24499555

  11. Effects of High-Butterfat Diet on Embryo Implantation in Female Rats Exposed to Bisphenol A.

    PubMed

    Martinez, Alan M; Cheong, Ana; Ying, Jun; Xue, Jingchuan; Kannan, Kurunthachalam; Leung, Yuet-Kin; Thomas, Michael A; Ho, Shuk-Mei

    2015-12-01

    Bisphenol A (BPA) is an endocrine disruptor associated with poor pregnancy outcomes in human and rodents. The effects of butterfat diets on embryo implantation and whether it modifies BPA's actions are currently unknown. We aimed to determine the effects of butterfat diet on embryo implantation success in female rats exposed to an environmentally relevant dose of BPA. Female Sprague-Dawley rats were exposed to dietary butterfat (10% or 39% kcal/kg body weight [BW]) in the presence or absence of BPA (250 ?g/kg BW) or ethinylestradiol (0.1 ?g/kg BW) shortly before and during pregnancy to assess embryo implantation potentials by preimplantation development and transport, in vitro blastulation, outgrowth, and implantation. On gestational day (GD) 4.5, rats treated with BPA alone had higher serum total BPA level (2.3-3.7 ng/ml). They had more late-stage preimplantation embryos, whereas those receiving high butterfat (HBF) diet had the most advanced-stage embryos; dams cotreated with HBF and BPA had the most number of advanced embryos. BPA markedly delayed embryo transport to the uterus, but neither amount of butterfat had modifying effects. An in vitro implantation assay showed HBF doubled the outgrowth area, with BPA having no effect. In vivo, BPA reduced the number of implanted embryos on GD8, and cotreatment with HBF eliminated this adverse effect. HBF diet overall resulted in more and larger GD8 embryos. This study reveals the implantation disruptive effects of maternal exposure to an environmentally relevant dose of BPA and identifies HBF diet as a modifier of BPA in promoting early embryonic health. PMID:26510865

  12. Acute and chronic psychostimulant treatment modulates the diurnal rhythm activity pattern of WKY female adolescent rats.

    PubMed

    Jones, Cathleen G; Yang, Pamela B; Wilcox, Victor T; Burau, Keith D; Dafny, Nachum

    2014-05-01

    The psychostimulants considered the gold standard in the treatment of attention deficit hyperactivity disorder, one of the most common childhood disorders, are also finding their way into the hands of healthy young adults as brain augmentation to improve cognitive performance. The possible long-term effects of psychostimulant exposure in adolescence are considered controversial, and thus, the objective of this study was to investigate whether the chronic exposure to the psychostimulant amphetamine affects the behavioral diurnal rhythm activity patterns of female adolescent Wistar-Kyoto (WKY) rat. The hypothesis of this study is that change in diurnal rhythm activity pattern is an indicator for the long-term effect of the treatment. Twenty-four rats were divided into two groups, control (N=12) and experimental (N=12), and kept in a 12:12-h light/dark cycle in an open-field cage. After 5-7days of acclimation, 11days of consecutive non-stop behavioral recordings began. On experimental day 1 (ED1), all groups were given an injection of saline. On ED2 to ED7, the experimental group was injected with 0.6mg/kg amphetamine followed by 3days of washout from ED8 to ED10, and amphetamine re-challenge on ED11 similar to ED2. The locomotor movements were counted by the computerized animal activity monitoring system, and the cosinor statistical test analysis was used to fit a 24-h curve of the control recording to the activity pattern after treatment. The horizontal activity, total distance, number of stereotypy, vertical activity, and stereotypical movements were analyzed to find out whether the diurnal rhythm activity patterns were altered. Data obtained using these locomotor indices of diurnal rhythm activity pattern suggest that amphetamine treatment significantly modulates the locomotor diurnal rhythm activity pattern of female WKY adolescent rats. PMID:24482155

  13. Molecular Mechanisms Underlying the Rapid Arrhythmogenic Action of Bisphenol A in Female Rat Hearts

    PubMed Central

    Gao, Xiaoqian; Liang, Qian; Chen, Yamei

    2013-01-01

    Previously we showed that bisphenol A (BPA), an environmental estrogenic endocrine disruptor, rapidly altered Ca2+ handling and promoted arrhythmias in female rat hearts. The underlying molecular mechanism was not known. Here we examined the cardiac-specific signaling mechanism mediating the rapid impact of low-dose BPA in female rat ventricular myocytes. We showed that protein kinase A (PKA) and Ca2+/CaM-dependent protein kinase II (CAMKII) signaling pathways are the two major pathways activated by BPA. Exposure to 1 nM BPA rapidly increased production of cAMP and rapidly but transiently increased the phosphorylation of the ryanodine receptors by PKA but not by CAMKII. BPA also rapidly increased the phosphorylation of phospholamban (PLN), a key regulator protein of sarcoplasmic reticulum Ca2+ reuptake, by CAMKII but not PKA. The increase in CAMKII phosphorylation of PLN was mediated by phospholipase C and inositol trisphosphate receptor-mediated Ca2+ release, likely from the endoplasmic reticulum Ca2+ storage. These two pathways are likely localized, impacting only their respective target proteins. The rapid impacts of BPA on ryanodine receptors and PLN phosphorylation were mediated by estrogen receptor-? but not estrogen receptor-?. BPA's rapid signaling in cardiac myocytes did not involve activation of ERK1/2. Functional analysis showed that PKA but not CAMKII activation contributed to BPA-induced sarcoplasmic reticulum Ca2+ leak, and both PKA and CAMKII were necessary contributors to the stimulatory effect of BPA on arrhythmogenesis. These results provide mechanistic insight into BPA's rapid proarrhythmic actions in female cardiac myocytes and contribute to the assessment of the consequence and potential cardiac toxicity of BPA exposure. PMID:24140712

  14. Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol.

    PubMed

    Ghanayem, B I; Long, P H; Ward, S M; Chanas, B; Nyska, M; Nyska, A

    2001-06-01

    2-butoxyethanol (BE; ethylene glycol monobutyl ether) is used extensively in the manufacture of a wide range of domestic and industrial products which may result in human exposure and toxicity. BE causes severe hemolytic anemia in male and female rats and mice. In a recent report, female F344 rats exposed to 500 ppm BE by inhalation and sacrificed moribund on day 4 of treatment exhibited disseminated thrombosis associated with infarction in several organs. In contrast, no such lesions were observed in male rats similarly exposed to BE. Additional studies were therefore undertaken to compare the effects of BE in rats of both sexes. Rats received 250 mg BE/kg/day by gavage for 1, 2 or 3 days and were sacrificed 24 or 48 hr after the last dose. Control rats received 5 ml/kg water. Progressive time-dependent hemolytic anemia--macrocytic, hypochromic, and regenerative--was observed in both sexes of rats exposed to BE. Additionally, BE caused significant morphological changes in erythrocytes, first observed 24 hr after a single dose, including stomatocytosis, macrocytosis with moderate rouleaux formation, and spherocytosis. These morphological changes became progressively more severe as BE dosing continued and included the occasional occurrence of schistocytes and ghost cells, rouleaux formation in rats of both sexes, and an increased number of red blood cells with micronuclei in female rats. Overall, the progression of hemolytic anemia and morphological changes as a function of the number of days of exposure varied with gender and suggested a faster onset of hemolysis in female rats. The range of BE-related histopathological changes noted in both sexes was comparable; however, while these lesions were observed in female rats following a single dose, similar effects were first observed in males after 3 consecutive days of exposure to BE. Pathological changes involved disseminated thrombosis in the lungs, nasal submucosa, eyes, liver, heart, bones and teeth, with evidence of infarction in the heart, eyes, teeth and bones. Hemoglobinuric nephrosis and splenic extramedullary hematopoiesis were also noted. An apparent correlation between the severity of hemolytic anemia and subsequent disseminated thrombosis in BE-treated rats is proposed. Thrombosis may be related to intravascular hemolysis, which could be triggered by procoagulant release and/or alterations in erythrocyte morphology, as well as increased rigidity. PMID:11484844

  15. Distribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats?

    PubMed Central

    Cavalcante, Judney Cley; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti

    2014-01-01

    The ventral premammillary nucleus (PMV) expresses dense collections of sex steroid receptors and receptors for metabolic cues, including leptin, insulin and ghrelin. The PMV responds to opposite sex odor stimulation and projects to areas involved in reproductive control, including direct innervation of gonadotropin releasing hormone neurons. Thus, the PMV is well positioned to integrate metabolic and reproductive cues, and control downstream targets that mediate reproductive function. In fact, lesions of PMV neurons blunt female reproductive function and maternal aggression. However, although the projections of PMV neurons have been well documented, little is known about the neuronal inputs received by PMV neurons. To fill this gap, we performed a systematic evaluation of the brain sites innervating the PMV neurons of male and female rats using the retrograde tracer subunit B of the cholera toxin (CTb). In general, we observed that males and females show a similar pattern of afferents. We also noticed that the PMV is preferentially innervated by neurons located in the forebrain, with very few projections coming from brainstem nuclei. The majority of inputs originated from the medial nucleus of the amygdala, the bed nucleus of the stria terminalis and the medial preoptic nucleus. A moderate to high density of afferents was also observed in the ventral subiculum, the arcuate nucleus and the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus. Our findings strengthen the concept that the PMV is part of the vomeronasal system and integrates the brain circuitry controlling reproductive functions. PMID:25084037

  16. Flaxseed oil during lactation changes milk and body composition in male and female suckling pups rats.

    PubMed

    Guarda, Deysla Sabino; Lisboa, Patricia Cristina; de Oliveira, Elaine; Nogueira-Neto, Jos Firmino; de Moura, Egberto Gaspar; Figueiredo, Mariana Sarto

    2014-07-01

    We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation. PMID:24727050

  17. Plastic changes induced by neonatal handling in the hypothalamus of female rats.

    PubMed

    Winkelmann-Duarte, Elisa C; Todeschin, Anelise S; Fernandes, Marilda C; Bittencourt, Lisandra C; Pereira, Gabriela A M; Samios, Vinicius N; Schuh, Artur F S; Achaval, Matilde E; Xavier, Leder L; Sanvitto, Gilberto L; Mandarim-de-Lacerda, Carlos A; Lucion, Aldo B

    2007-09-19

    Early-life events can exert profound long-lasting effects on several behaviors such as fear/anxiety, sexual activity, stress responses and reproductive functions. Present study aimed to examine the effects of neonatal handling on the volume and number of cells in the hypothalamic paraventricular nucleus (pPVN, parvocellular and mPVN, magnocellular regions) and the supraoptic nucleus (SON) in female rats at 11 and 90 days of age. Moreover, in the same areas, immunohistochemistry for oxytocin (OT) and glial fibrillary acidic protein (GFAP) were analyzed in the adult animals. Daily handling during the first 10 postnatal days reduced the number of cells in the pPVN and SON at both the 11 and 90 days. Handling decreased the number of OT-positive parvocellular cells in the PVN in adult females. No significant differences were detected on the optical density (OD) of GFAP-positive cells between the handled and nonhandled adult females. The effect of handling on cell loss was observed 24 h after the 10-day handling period and persisted into adulthood, indicating a stable morphological trace. Results suggest that neonatal handling can induce plastic changes in the central nervous system. PMID:17692831

  18. Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats.

    PubMed

    Panos, John J; O'Callaghan, James P; Miller, Diane B; Ferguson, Sherry A

    2014-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight 3/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior. PMID:25132048

  19. Fluence-to-absorbed-dose conversion coefficients for neutron beams from 0.001 eV to 100 GeV calculated for a set of pregnant female and fetus models

    NASA Astrophysics Data System (ADS)

    Taranenko, Valery; Xu, X. George

    2008-03-01

    Protection of fetuses against external neutron exposure is an important task. This paper reports a set of absorbed dose conversion coefficients for fetal and maternal organs for external neutron beams using the RPI-P pregnant female models and the MCNPX code. The newly developed pregnant female models represent an adult female with a fetus including its brain and skeleton at the end of each trimester. The organ masses were adjusted to match the reference values within 1%. For the 3 mm cubic voxel size, the models consist of 10-15 million voxels for 35 organs. External monoenergetic neutron beams of six standard configurations (AP, PA, LLAT, RLAT, ROT and ISO) and source energies 0.001 eV-100 GeV were considered. The results are compared with previous data that are based on simplified anatomical models. The differences in dose depend on source geometry, energy and gestation periods: from 20% up to 140% for the whole fetus, and up to 100% for the fetal brain. Anatomical differences are primarily responsible for the discrepancies in the organ doses. For the first time, the dependence of mother organ doses upon anatomical changes during pregnancy was studied. A maximum of 220% increase in dose was observed for the placenta in the nine months model compared to three months, whereas dose to the pancreas, small and large intestines decreases by 60% for the AP source for the same models. Tabulated dose conversion coefficients for the fetus and 27 maternal organs are provided.

  20. Parasympathetic dysfunction is associated with insulin resistance in fructose-fed female rats.

    PubMed

    Brito, J O; Ponciano, K; Figueroa, D; Bernardes, N; Sanches, I C; Irigoyen, M C; De Angelis, K

    2008-09-01

    The objective of the present study was to identify metabolic, cardiovascular and autonomic changes induced by fructose overload administered in the drinking water of rats for 8 weeks. Female Wistar rats (200-220 g) were divided into 2 groups: control (N = 8) and fructose-fed rats (N = 5; 100 mg/L fructose in drinking water for 8 weeks). The autonomic control of heart rate was evaluated by pharmacological blockade using atropine (3 mg/kg) and propranolol (4 mg/kg). The animals were submitted to an intravenous insulin tolerance test (ITT) and to blood glucose measurement. The fructose overload induced a significant increase in body weight (approximately 10%) and in fasting glycemia (approximately 28%). The rate constant of glucose disappearance (KITT) during ITT was lower in fructose-fed rats (3.25 +/- 0.7%/min) compared with controls (4.95 +/- 0.3%/min, P < 0.05) indicating insulin resistance. The fructose-fed group presented increased arterial pressure compared to controls (122 +/- 3 vs 108 +/- 1 mmHg, P < 0.05) and a reduction in vagal tonus (31 +/- 9 vs 55 +/- 5 bpm in controls, P < 0.05). No changes in sympathetic tonus were observed. A positive correlation, tested by the Pearson correlation, was demonstrable between cardiac vagal tonus and KITT (r = 0.8, P = 0.02). These data provided new information regarding the role of parasympathetic dysfunction associated with insulin resistance in the development of early metabolic and cardiovascular alterations induced by a high fructose diet. PMID:18833640

  1. Predictive blood glucose lowering efficacy by Glucokinase activators in high fat fed female Zucker rats

    PubMed Central

    Coope, G J; Atkinson, A M; Allott, C; McKerrecher, D; Johnstone, C; Pike, K G; Holme, P C; Vertigan, H; Gill, D; Coghlan, M P; Leighton, B

    2006-01-01

    Background and purpose: Glucokinase (GK) is the rate-limiting enzyme of hepatic glucose metabolism and acts as a sensor for glucose-stimulated insulin release in ?-cells. Here we examine whether the lowering of blood glucose levels in the rat by small molecule glucokinase activators (GKAs) can be predicted from in vitro enzyme potencies and plasma compound exposure. Experimental approach: We developed an insulin resistant and hyperinsulinemic animal model, the high fat fed female Zucker (fa/fa) rat (HFFZ), and measured the acute in vivo glucose-lowering efficacy of a number of GKAs in an oral glucose tolerance test. Key results: Four GKAs (at 1 to 30?mg?kg?1), with different in vitro enzyme potencies, dose-dependently improved oral glucose tolerance in HFFZ rats (1040% decrease glucose area under the curve (AUC) from vehicle control). The extent of glucose lowering, or the pharmacodynamic (PD) effect, of a GKA was directly related to the total compound concentration in the plasma; the pharmacokinetic (PK) measurement. This PK-PD relationship was extended across a series of GKAs by accounting for differences in protein binding and in the in vitro potency. Conclusions and implications: When the unbound GKA compound level is greater than the in vitro enzyme potency there was significant blood glucose lowering in vivo. This latter relationship was upheld in non-diabetic Wistar rats orally dosed with a GKA. The robust and predictive nature of the PK-PD relationship for GKAs may prove of value in testing these agents in early human clinical studies. PMID:16921397

  2. Antiovulatory and abortifacient effects of Areca catechu (betel nut) in female rats

    PubMed Central

    Shrestha, Jyoti; Shanbhag, Tara; Shenoy, Smita; Amuthan, Arul; Prabhu, Krishnananda; Sharma, Stuti; Banerjee, Samik; Kafle, Sajala

    2010-01-01

    Objectives: To study the antiovulatory and abortifacient effects of ethanolic extract of Areca catechu in female rats. Materials and Methods: For antiovulatory effect, ethanolic extract of A. catechu at 100 and 300 mg/kg doses was administered orally for 15 days. Vaginal smears were examined daily microscopically for estrus cycle. Rats were sacrificed on 16th day. Ovarian weight, cholesterol estimation, and histopathological studies were done. Abortifacient activity was studied in rats at 100 and 300 mg/kg doses administered orally from 6th to 15th day of pregnancy. Rats were laparotomised on 19th day. The number of implantation sites and live fetuses were observed in both horns of the uterus. Results: The extract of A. catechu showed a significant decrease in the duration of estrus at 100 mg/kg (P = 0.015) and 300 mg/kg doses (P = 0.002) as compared with control. Metestrus phase was also significantly reduced at 100 mg/kg (P = 0.024) and 300 mg/kg doses (P = 0.002). There was a significant increase in proestrus (P < 0.001) phase. However, diestrus phase was unchanged. Histopathological study of the ovaries showed mainly primordial, primary, and secondary follicles in the test groups as compared to control. There was also a significant (P = 0.002) decrease in ovarian weight and a significant (P = 0.021) increase in ovarian cholesterol level at 100 mg/kg dose. In the study to evaluate abortifacient effect, the mean percentage of abortion with 100 and 300 mg/kg doses were 75.5% and 72.22%, respectively, which was significantly (P = 0.008 and P = 0.006, respectively) increased when compared with control. Conclusion: The ethanolic extract of A. catechu at doses of 100 and 300 mg/kg has antiovulatory and abortifacient effects. PMID:21206624

  3. Region-, Neuron-, and Signaling Pathway-Specific Increases in Prolactin Responsiveness in Reproductively Experienced Female Rats

    PubMed Central

    Sjoeholm, Annika; Bridges, Robert S.; Grattan, David R.

    2011-01-01

    Pregnancy and lactation cause long-lasting enhancements in maternal behavior and other physiological functions, along with increased hypothalamic prolactin receptor expression. To directly test whether reproductive experience increases prolactin responsiveness in the arcuate, paraventricular, and supraoptic nuclei and the medial preoptic area, female rats experienced a full pregnancy and lactation or remained as age-matched virgin controls. At 5 wk after weaning, rats received 2.5, 100, or 4000 ng ovine prolactin or vehicle intracerebroventricularly. The brains underwent immunohistochemistry for the phosphorylated forms of signal transducer and activator of transcription 5 (pSTAT5) or ERK1/2 (pERK1/2). There was a marked increase in pSTAT5 and pERK1/2 in response to prolactin in the regions examined in both virgin and primiparous rats. Primiparous rats exhibited approximately double the number of prolactin-induced pSTAT5-immunoreactive cells as virgins, this effect being most apparent at the higher prolactin doses in the medial preoptic area and paraventricular and supraoptic nuclei and at the lowest prolactin dose in the arcuate nucleus. Dual-label immunohistochemistry showed that arcuate kisspeptin (but not oxytocin or dopamine) neurons displayed increased sensitivity to prolactin in reproductively experienced animals; these neurons may contribute to the reduction in prolactin concentration observed after reproductive experience. There was no effect of reproductive experience on prolactin-induced pERK1/2, indicating a selective effect on the STAT5 pathway. These data show that STAT5 responsiveness to prolactin is enhanced by reproductive experience in multiple hypothalamic regions. The findings may have significant implications for understanding postpartum disorders affecting maternal care and other prolactin-associated pathologies. PMID:21363933

  4. Female rats are susceptible to cardiac hypertrophy induced by copper deficiency: The lack of influence of estrogen and testosterone

    SciTech Connect

    Farquharson, C.; Robins, S.P. )

    1988-07-01

    In contrast to a previous report female rats were shown to be susceptible to copper (Cu) deficiency giving rise to restriction of growth, cardiac hypertrophy, and anemia. The severity of these effects was, however, found to be less marked than in the male rats which had similar liver Cu levels. Castration or ovariectomy of Cu-deficient rats had little effect on CH or the other parameters associated with Cu deficiency, and supplementation of the neutered animals with estrogen or testosterone was similarly without effect. The ultrastructural appearance of the hypertrophied Cu-deficient female heart was similar to that previously found in males and was characterized by a large increase in mitochondrial area with disrupted cristae. The results also indicated that in contrast to Cu-deficient males iron (Fe) was not accumulated in the liver of the Cu-deficient female rats. It may be concluded that the limited protection of female rats to the effects of Cu deficiency observed in this study unconnected with the sex steroids.

  5. 2,2,4-Trimethylpentane-induced nephrotoxicity. I. Metabolic disposition of TMP in male and female Fischer 344 rats

    SciTech Connect

    Charbonneau, M.; Lock, E.A.; Strasser, J.; Cox, M.G.; Turner, M.J.; Bus, J.S.

    1987-11-01

    2,2,4-Trimethylpentane (TMP), a component of unleaded gasoline, causes nephrotoxicity in male, but not in female, rats. In the present study, male and female Fischer 344 rats were treated with a single oral dose of (/sup 14/C)TMP (4.4 mmol/kg; 2 microCi/mmol). Radiolabeled material in kidney, liver, and plasma was determined at 4, 8, 12, 24, and 48 hr after dosing. Maximum concentration of TMP-derived radioactivity in kidney, liver, and plasma of male rats was found after 12 hr (1252, 1000, and 403 nmol eq/g, respectively), whereas those measured in females were found after 8 hr (577, 1163, and 317 nmol eq/g, respectively). A selective retention of the TMP-derived radiolabel in the kidneys of male rats was noted when peak tissue concentration was expressed as a percentage of administered dose. Kidney concentrations of TMP-derived radiolabel increased in a nonlinear, but dose-dependent, manner; the kidney to plasma ratio was greater at low doses than at higher doses. Increased retention of radiolabel material in the kidney was associated with a significant increase in renal concentration of the male-rat-specific protein, alpha 2u-globulin, 24 and 48 hr after TMP administration. Total radioactivity collected in urine 48 hr after TMP administration was similar in males and females (32 and 31% of dose). Identification and quantitation of the urinary metabolites of TMP showed that both male and female rats metabolize TMP via the same pathway and at a similar rate. Female rats, however, excreted more conjugates of 2,4,4-trimethyl-2-pentanol in urine than males. 2,4,4-Trimethyl-2-pentanol was the major metabolite present in the male rat kidney, but was absent in the female rat kidney. The renal retention of 2,4,4-trimethyl-2-pentanol appears to account for the delayed clearance observed in the disposition of (/sup 14/C)TMP-derived radiolabel.

  6. Dataset of liver proteins changed in eu- and hypothyroid female rats upon in vivo exposure to hexabromocyclododecane (HBCD).

    PubMed

    Miller, I; Serchi, T; Cambier, S; Diepenbroek, C; Renaut, J; van den Berg, J H J; Kwadijk, C; Gutleb, A C; Rijntjes, E; Murk, A J

    2016-06-01

    Female Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days. Changes in protein patterns obtained by 2D-DIGE were evaluated, and different animal groups compared taking into account their exposure and thyroid status. Proteins significantly altered in abundance in any of these comparisons were identified by mass spectrometry. These data, together with hormone data of the animals, are discussed in "Hexa-bromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. PMID:26977443

  7. Using Histopathologic Evidence to Differentiate Reproductive Senescence from Xenobiotic Effects in Middle-aged Female Sprague-Dawley Rats.

    PubMed

    Shirai, Norimitsu; Houle, Christopher; Mirsky, Michael L

    2015-12-01

    The female reproductive cycle is orchestrated by cyclical and coordinated hormonal changes under the direction of the hypothalamic-pituitary-gonadal (HPG) axis. Any disruption of the HPG axis may lead to functional and structural alterations in the female reproductive system. Test article-related disturbances in the estrous cycle can be recognized in nonclinical toxicity studies by staging the cycle based on microscopic evaluation of female reproductive organs. In chronic rat toxicity studies, an additional complication is the development of reproductive senescence, which is associated with natural alterations in the reproductive cycle leading to changes in the female reproductive system that can potentially be confused with test article effects. The current article describes the features of persistent estrus, one stage of reproductive senescence, in middle-aged Sprague-Dawley rats and discusses elements to help differentiate senescence from induced effects. PMID:26220943

  8. U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats

    PubMed Central

    Ahnstedt, Hilda; Mostajeran, Maryam; Blixt, Frank W; Warfvinge, Karin; Ansar, Saema; Krause, Diana N; Edvinsson, Lars

    2015-01-01

    Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ETB) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery occlusion (tMCAO, 120 minutes) was induced in female Wistar rats, with U0126 (30 mg/kg intraperitoneally) or vehicle administered at 0 and 24 hours of reperfusion, or with no treatment. Infarct volumes were determined and neurologic function was assessed by 6-point and 28-point neuroscores. ETB receptor-mediated contraction was studied with myograph and protein expression with immunohistochemistry. In vitro organ culture and tMCAO resulted in vascular ETB receptor upregulation and activation of ERK1/2 that was prevented by U0126. Although no effect on infarct size, U0126 improved the long-term neurologic function after experimental stroke in female rats. In conclusion, early prevention of the ERK1/2 activation and ETB receptor-mediated vasoconstriction in the cerebral vasculature after ischemic stroke in female rats improves the long-term neurologic outcome. PMID:25492115

  9. Treatment with 8-OH-DPAT attenuates the weight loss associated with activity-based anorexia in female rats.

    PubMed

    Atchley, Deann P D; Eckel, Lisa A

    2006-04-01

    Serotonin (5-HT) plays an important role in controlling food intake and regulating body weight. In addition, clinical studies suggest a possible role for 5-HT in the etiology of anorexia nervosa. Recently, we have examined the effects of pharmacological manipulation of the 5-HT system in female rats exposed to conditions that promote activity-based anorexia (ABA). In this animal model of anorexia nervosa, rats are food restricted (2 h access/day) while given the opportunity to exercise in running wheels. These conditions promote symptoms of anorexia nervosa including hypophagia, hyperactivity, progressive weight loss, and disruptions of the ovarian reproductive cycle. Previously, we demonstrated that increased 5-HT activity increased the weight loss associated with ABA in female rats. Here, we investigated whether decreased 5-HT activity would attenuate symptoms of ABA. Food-restricted female rats received injections of 8-OH-DPAT, a drug that reduces serotonergic neurotransmission, or saline vehicle 40 min prior to food access. During this restricted-feeding phase, food intake was similar between groups; however, 8-OH-DPAT prevented the hyperactivity observed in saline-treated rats. This resulted in less weight loss in 8-OH-DPAT-treated rats, suggesting that decreased activation of the 5-HT system attenuates the development of ABA. PMID:16643997

  10. Neonatal domoic acid abolishes latent inhibition in male but not female rats and has differential interactions with social isolation.

    PubMed

    Marriott, Amber L; Tasker, R Andrew; Ryan, Catherine L; Doucette, Tracy A

    2014-08-22

    Deficits in attention have long been identified as a core feature in schizophrenia and related neuropsychiatric disorders. We have investigated the combined effects of neonatal treatment with domoic acid (DOM) and social isolation rearing (both putative animal models of schizophrenia) on latent inhibition (LI), a measure of attentional processing. Daily subcutaneous injections of 20 ?g/kg DOM or saline were administered to rat pups from postnatal days (PND) 8-14. After weaning, rats were housed either alone or in groups of 4 until LI was assessed at PND 110 using a lick-suppression conditional emotional response paradigm. Neonatal treatment with DOM abolished LI behaviour in adult male rats regardless of housing condition when tested 48 h after conditioning, but this effect was not observed in female rats. Social isolation rearing also reduced LI in male rats, but not to the same extent as DOM. When tested again one week later, single-housed males treated with DOM displayed significant LI whereas saline treated or group-housed DOM males did not. No significant differences were found with females 1 week later. We conclude that neonatal DOM and social isolation both impair attentional processing in young adult male, but not female, rats although the mechanisms by which this occurs appear to be different. PMID:24954074

  11. Dehydroepiandrosterone administration increased trabecular mass and dihydrotestosterone levels in the cancellous region of the tibia in young female rats.

    PubMed

    Park, J; Aizawa, K; Akimoto, T; Iemitsu, M; Agata, U; Maeda, S; Lim, K; Omi, N

    2014-08-01

    The aim of the present study was to determine whether dehydroepiandrosterone (DHEA) administration affects bone mass and local sex hormone levels in the cancellous region of young female rats. Eleven female rats (6 weeks old) were randomly divided into 2 groups: control rats (CON, n=5) and rats treated with DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group intraperitoneally at 20?mg DHEA/kg body weight, and the CON group was treated with vehicle only (sesame oil, 0.5?ml). The rats were treated with DHEA or vehicle for 3 consecutive days, followed by 1 day of no treatment. The experimental period was 8 weeks. According to dual-energy X-ray absorptiometry and high-resolution microcomputed tomography data, the DHEA group exhibited increased trabecular bone mineral density (BMD), bone volume, and tibial thickness compared to the findings in the CON group, whereas no effect was observed on cortical BMD or morphometry. The concentrations of free testosterone and estradiol in the cancellous region of the tibia did not differ between the 2 groups, but the DHT concentration was significantly higher in the DHEA group than in the CON group. These findings suggest that an increase in local DHT levels may stimulate an increase in trabecular bone mass during growth phases in female rats. PMID:24867140

  12. Estrogen receptors mediate estradiols effect on sensitization and CPP to cocaine in female rats: Role of contextual cues

    PubMed Central

    Segarra, Annabell C; Torres-Daz, Yvonne M; Silva, Richard D; Puig-Ramos, Anabel; Menndez-Delmestre, Raissa; Rivera-Bermdez, Jos G; Amadeo, Waldo; Agosto-Rivera, Jos L

    2014-01-01

    Preclinical studies show that estradiol enhances sensitization to cocaine in females by mechanisms not fully understood. These studies consistently show that ovariectomized (OVX) rats exhibit little or no sensitization to cocaine compared to OVX rats administered estradiol. In this study we varied the dose of cocaine (10, 15, and 30 mg/kg), the length of cocaine treatment (from 5 to 10 days) and the context of cocaine injections to determine if these factors play a role on estradiol's effects on cocaine sensitization. Because OVX rats are hormonally compromised, they are not representative of the natural state of the animal, and thus the physiological context of these studies remains unclear. To address this issue, we blocked ERs in gonadally intact females by icv administration of the antiestrogen ICI-182,780. Varying the dose or length of exposure to cocaine does not alter estradiol's effect on cocaine sensitization. In contrast, a highly context-dependent sensitization protocol results in robust sensitization even in OVX rats. Interestingly, using this protocol, sensitization in OVX rats diminished with time, suggesting that estradiol is necessary for the maintenance of cocaine sensitization. Blocking brain ERs with ICI completely abolishes the development and expression of cocaine sensization in gonadally intact female rats, even when tested in a highly context-dependent sensitization protocol. Given these findings, we propose that activation of brain ERs is required for the development and maintenance of sensitization and CPP. PMID:24355096

  13. Effect of Manganese Exposure on the Reproductive Organs in Immature Female Rats

    PubMed Central

    Kim, Soo In; Jang, Yeon Seok; Han, Seung Hee; Choi, Myeong Jin; Go, Eun Hye; Cheon, Yong-Pil; Lee, Jung Sick; Lee, Sung-Ho

    2012-01-01

    Manganese (Mn2+) is a trace element that is essential for normal physiology, and is predominantly obtained from food. Several lines of evidence, however, demonstrated that overexposure to MnCl2 exerts serious neurotoxicity, immunotoxicity and developmental toxicity, particularly in male. The present study aimed to evaluate the effect of 0, 1.0, 3.3, and 10 mg/kg/day doses of MnCl2 on the reproductive organs in the immature female rats. Rats (PND 22; S.D. strain) were exposed to MnCl2 (MnCl2 ∙ 4H2O) dissolved in drinking water for 2 weeks. The animals were sacrificed on PND 35, then the tissues were immediately removed and weighed. Histological studies were performed using the uteri tissue samples. Serum LH and FSH levels were measured with the specific ELISA kits. Body weights of the experimental group animals were not significantly different from those of control group animals. However, ovarian tissue weights in 1 mg and 3.3 mg MnCl2 dose groups were significantly lower than those of control animals (p<0.05 and p<0.01, respectively). Uterine tissue weights of 3.3 mg dose MnCl2 groups were significantly lower than those of control animals (p<0.01), while the 1 mg MnCl2 dose and 10 mg MnCl2 dose failed to induce any change in uterine weight. Similarly, only 3.3 mg MnCl2 dose could induce the significant decrease in the oviduct weight compared to the control group (p<0.05). Non-reproductive tissues such as adrenal and kidney failed to respond to all doses of MnCl2 exposure. The uterine histology revealed that the MnCl2 exposure could affect the myometrial cell proliferation particularly in 3.3 mg dose and 10mg dose group. Serum FSH levels were significantly decreased in 1mg MnCl2 dose and 10 MnCl2 mg groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg MnCl2 dose induced a significant increment of serum LH level (p<0.05). The present study demonstrated that MnCl2 exposure is capable of inducing abnormal development of reproductive tissues, at least to some extent, and altered gonadotropin secretions in immature female rats. Combined with the well-defined actions of this metal on GnRH and prolactin secretion, one can suggest the Mn2+ might be a potential environmental mediator which is involved in the female pubertal process. PMID:25949103

  14. Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

    PubMed Central

    Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

    2015-01-01

    Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 56 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

  15. When Both Parents May Be a Source of Support and Problems: An Analysis of Pregnant and Parenting Female African American Adolescents' Relationships with Their Mothers and Fathers.

    ERIC Educational Resources Information Center

    Davis, Anita A.; And Others

    1997-01-01

    Studied influence of maternal versus paternal support for pregnant and parenting African American adolescents who reported supportive or problematic interactions, or both, with their parents. Found more support from mothers despite equal relationship problem levels with both parents; support of both parents was associated with lower depression

  16. Soyo-san reduces depressive-like behavior and proinflammatory cytokines in ovariectomized female rats

    PubMed Central

    2014-01-01

    Background Soyo-san is a traditional oriental medicinal formula, a mixture of 9 crude drugs, and it has been clinically used for treating mild depressive disorders. The role of pro- and anti-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. In the present study, we detected the antidepressant effect of soyo-san in the ovariectomized and repeated stressed female rats. Methods This study was designed to evaluate the antidepressant-like effect of soyo-san on the forced swimming test (FST). The rats were randomly divided into the following groups: the nonoperated and nonstressed group (non-op), the nonoperated and stressed group (non-op?+?ST), the ovariectomized and stress group (OVX) and sham operated and stressed group (sham), the ovariectomized and stressed group (OVX?+?ST), the ovariectomized, stressed and soyo-san 100mg/kg treated group (SOY100) and the ovariectomized, stressed and soyo-san 400mg/kg treated group (SOY400). The rats were exposed to immobilization stress (IMO) for 14day (2h/14day), and soyo-san (100mg/kg and 400mg/kg) was administrated during the same time. In the same animals, the levels of corticosterone and interleukin-1-beta (IL-1?) were examined in the serum. Also, the change of IL-1? expression in brain regions was examined after behavior test. Results In the FST, the lower dose (100mg/kg) of extract was effective in reducing immobility, along with an increase in swimming time. The serum levels of corticosterone and IL-1? in the SOY groups were significantly lower than those in the control group. In the brain, the expression of IL-1? positive neurons in the control group were significantly increased in the paraventricular nucleus (PVN) and hippocampus compared to the non-op. However, soyo-san groups significantly reduced the IL-1?-ir neurons in the PVN and hippocampal regions compared to the control. Conclusion The present results demonstrated that soyo-san effectively reduced behavioral and patho-physiological depression-like responses. Trial registration: Our results suggest that soyo-san may be useful for immune regulator in repeated stress-induced ovariectomized female rats. PMID:24444307

  17. Distribution of suprofen in rats of both sexes.

    PubMed

    Mori, Y; Yokoya, F; Sakai, Y; Toyoshi, K; Baba, S

    1984-05-01

    The tissue distribution of 3H-labeled DL-2-(4-(2-thienylcarbonyl) phenyl) propionic acid (suprofen) after po administration was studied in male, female, and pregnant rats by radiometry. The only tissues with concentrations comparable to plasma levels were those involved in metabolism and excretion (liver and kidney), except for the gastrointestinal tract, and all other tissue levels were very low. In pregnant rats, radioactivity crossed the blood-placenta barrier to a moderate extent and low concentrations were found in fetuses. Radioactivity disappeared from most tissues of male, female, and pregnant rats at rates similar to that from plasma and no appreciable radioactivity was found in rat tissues 24 h after dosing. PMID:6473840

  18. Female Sterilizatio