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Sample records for pregnant female rats

  1. Cadmium causes delayed effects on renal function in the offspring of cadmium-contaminated pregnant female rats.

    PubMed

    Jacquillet, G; Barbier, O; Rubera, I; Tauc, M; Borderie, A; Namorado, M C; Martin, D; Sierra, G; Reyes, J L; Poujeol, P; Cougnon, M

    2007-11-01

    In the adult rat, chronic cadmium intoxication induces nephropathy with Fanconi-like features. This result raises the question of whether intoxication of pregnant rats has any deleterious effects on renal function in their offspring. To test this hypothesis, we measured the renal function of 2- to 60-day-old postnatal offspring from female rats administered cadmium chloride by the oral route (0.5 mg.kg(-1).day(-1)) throughout their entire gestation. Investigations of rat offspring from contaminated pregnant rats showed the presence of cadmium in the kidney at gestational day 20. After birth, the cadmium kidney concentration increased from postnatal day 2 to day 60 (PND2 to PND60), presumably because of 1) milk contamination and 2) neonatal liver cadmium content release. Although the renal parameters (glomerular filtration, U/P inulin, and urinary excretion rate) were not significantly affected until PND45, renal failure appeared at PND60, as demonstrated by a dramatic decrease of the glomerular filtration rate associated with increased excretion of the main ions. In parallel, an immunofluorescence study of tight-junction protein expression of PND60 offspring from contaminated rats showed a disorganization of the tight-junction proteins claudin-2 and claudin-5, specifically expressed in the proximal tubule and glomerulus, respectively. In contrast, expression of a distal claudin protein, claudin-3, was not affected. In conclusion, in utero exposure of cadmium leads to toxic renal effects in adult offspring. These results suggest that contamination of pregnant rats is a serious and critical hazard for renal function of their offspring. PMID:17686954

  2. 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

  3. 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. PMID:27049707

  4. [Effect of tobacco smoke on permeability of capillary of pregnant and non-pregnant rats].

    PubMed

    Florek, Tewa; Ignatowicz, Ewa; Piekoszewski, Wojciech; Wachowiak, Anna; Wrzosek, Jagna

    2006-01-01

    From among 4200 chemical compounds contained in the tobacco smoke, nicotine and carbon monoxide are responsible for changes in the heart-vessel system to the greatest extent. Additionally, other toxic compounds, including the carcinogenic ones, have a significant impact on the biological activity in the tissues of blood vessels. A particularly complex picture of the detrimental impact of the tobacco smoke is presented in case of pregnant women, fetuses and newborns. The aim of the research was to assess the impact of tobacco smoke on the permeability of capillaries in different tissues of rats (lungs, brain, liver, kidneys) and testing of the potentially protective impact of rutine (3-rutinozide of quercetin). The research on the permeability of capillaries has been carried out applying Evans blue. The animals were divided into 8 research groups: pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke", and non-pregnant animals--"control", "rutine", "tobacco smoke", "rutine+tobacco smoke". In the first stage of research (pregnant, non-pregnant-- groups: "rutine" and "rutine+tobacco smoke"), the water rutine solution in a dose of 40 mg/kg of body weight was administered. The non-pregnant and pregnant animals from groups "tobacco smoke" and "rutine+tobacco smoke" were exposed to tobacco smoke via inhalation (1500 mg CO/m3 of air) for 21 days. All the animals were injected with the water Evans blue solution in a dose of 30 mg/kg of body weight. After 30 minutes, the animals were killed by cutting the abdominal aorta, and lungs, brain, liver and kidneys were taken for further testing. The cotinine in the urine was determined by the HPLC method, using norephedrine as the internal standard, after the preceding extraction by means of the liquid-liquid technique. The concentration of cotinine in case of non-pregnant and pregnant females was respectively 11.8 +/- 1.9 pg/ml of urine and 12.0 +/- 2.5 microg/ml of urine. In case of the rats, which received the rutine, the concentration of rutine in the group of non-pregnant females was 9.3 +/- 1.0 microg/ml of urine, and in the group of the pregnant ones 8.5 +/- 1.1 microg/ml of urine. In the lungs of non-pregnant animals exposed to tobacco smoke, the decreased permeability of vessels for the albumin-Evans blue complex was proven. The administration of rutine to non-pregnant and pregnant animals did not exert influence on the permeability of vessels in lungs. A similar result was obtained for the lungs of rats receiving the rutine, as well as those exposed to tobacco smoke. In the brain tissue of non-pregnant and pregnant animals, a slight decrease in the content of Evans blue was declared as a consequence of tobacco smoke impact. In the groups receiving the rutine, this flavonoid was declared to influence the blood supply of the brain tissue, and the permeability of the vascular walls. In the liver tissue of animals inhaling the tobacco smoke, the permeability of vascular walls for albumin-Evans blue complex was increased. The rutine did not affect significantly the permeability of vessels, whereas the exposure of pregnant females, which received rutine, to smoke decreased the content of Evans blue in the liver tissue. In the tissues of all tested females, no significant differences between the control groups and groups exposed to tobacco smoke as well as rutine+tobacco smoke were detected. The obtained results do not indicate, however, that in case of chronic exposure to tobacco smoke, the rutine has insignificant protective meaning. PMID:17288177

  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. Effects of local anesthetics on contractions of pregnant and non-pregnant rat myometrium in vitro.

    PubMed

    Wei, Jin-Song; Jin, Zhe-Bin; Yin, Zhi-Qiang; Xie, Qiang-Min; Chen, Ji-Qiang; Li, Zi-Gang; Tang, Hui-Fang

    2014-06-01

    In order to determine whether local anesthetics directly affect the propagation and strength of myometrial contractions, we compared the effects of bupivacaine, ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated from pregnant and non-pregnant rats. Full-thickness myometrial strips were obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and incubated in an organ bath. When spontaneous contractions became regular, strips were exposed to cumulative concentrations of the four local anesthetics ranging from 0.01 to 300 μmol/L and the amplitude and frequency of contraction were recorded. All four compounds caused a concentration-dependent inhibition of the contractility of pregnant and non-pregnant uterine muscle. In pregnant myometrium, the concentration that caused 50% inhibition (IC(50)) was 100 μmol/L for bupivacaine, 157 μmol/L for ropivacaine, > 1000 μmol/L for lidocaine, and 26.3 μmol/L for tetracaine. In non-pregnant myometrium, the IC(50) was 26.9 μmol/L for bupivacaine, 40 μmol/L for ropivacaine, 384 μmol/L for lidocaine, and 7.4 μmol/L for tetracaine. These results suggested that local anesthetics do inhibit myometrial contractions in pregnant and non-pregnant rats in a concentration-dependent manner. PMID:24901082

  7. 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 PGF2α 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 < 0.05), endothelial/pericyte and luteal cell proliferation on day 10 and 14 (p < 0.05), apoptotic cell numbers on day 19 (p < 0.05) and the expression of Flk-1 and VEGF on day 14 and 19, respectively (p < 0.05). Hyperthyroidism increased the expression of COX-2 on day 19 (P < 0.05) and the proliferative activity of endothelial/pericytes cells on day 14 (p <0.05), as well as the expression of VEGF and Flk-1 on day 19 (P < 0.05). Conclusions Hypothyroidism reduces the proliferation, apoptosis and expression of angiogenic factors and COX-2in the corpus luteum of pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period. PMID:25298361

  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. 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

  10. 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

  11. [The features of sleep homeostasis in pregnant rats].

    PubMed

    Rutskova, E M; Pigareva, M L

    2011-01-01

    To investigate the effects of short-term sleep deprivation on the sleep pattern during pregnancy, cortical and hippocampal EEG and locomotor activity were recorded within 24-hours in a "disk-over-water" paradigm in 18 Wistar rats. Rats were adapted to experimental situation and were able to move across the rotating disk without falling in water. Then a polysomnogram was recorded for 3 sequential days in the control group 1 (n = 12) without disk rotation. On the next day non-pregnant rats (experimental group 1, n = 6) were subjected to the sleep deprivation procedure with a pre-set program of disk rotation from 11:00 to 14:00 during 3 sequential days. Other 6 rats (experimental group 2) were subjected to sleep deprivation on the 5-7th day of pregnancy. EEG and locomotor activity were also constantly recorded during the sleep deprivation procedure. In control group 2 (n = 6, without sleep deprivation), a polysomnogram was recorded on the 5-7th day of pregnancy. As compared to non-pregnant rats, sleep intensity of pregnant rats increased during the first hours after the deprivation, and a considerable rebound of REM sleep took place. Sleep pattern during the off-light 12 hours remained unchanged. The results suggest that homeostatic compensation of sleep deprivation effects in rats on the first week of pregnancy is more efficient than in control non-pregnant animals. PMID:21861392

  12. [Effects of cold on triiodothyronine metabolism in the pregnant rat].

    PubMed

    Blanco, M R; Cageao, L; Rivera, O E; Belmonte, N; Zaninovich, A A

    1991-01-01

    Sixteen Wistar rats were studied in the last week of pregnancy. Another group of 6 nonpregnant animals served as control. Eight pregnant and 6 control ratas were kept in the cold room at 4 degrees C for 4 days, while 8 pregnant rats remained at 22 degrees C. After blocking the thyroid gland with potassium perchlorate to prevent iodine reutilization, a dose of 4 microCi of 125I-T3 was injected i.p. Thereafter, animals were placed in individual metabolic cages for separate 24 h collection of urine and feces. Heparinized blood samples were obtained at 4, 14, 24 and 28 h following tracer injection. Pregnant rats exposed to cold had a significant increase in T3 fractional turnover as compared to pregnants at 22 degrees C (p < 0.005) and to controls at 4 degrees C (p < 0.02). No changes were observed in space of distribution, serum concentration and body pool of T3. Degradation of this hormone, however, was significantly augmented (p < 0.05) in pregnants at 4 degrees C as compared to pregnants at 22 degrees C, although not when compared to controls at 4 degrees C. The urinary excretion of 125I was increased in pregnants in the cold (p <0.005) versus pregnants at 22 degrees C. The metabolic (p < 0.005), urinary (p < 0.001) and fecal (p < 0.05) clearances in pregnants at 4 degrees C were augmented with respect to the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7476108

  13. Multiple mating and its relationship to alternative modes of gestation in male-pregnant versus female-pregnant fish species

    PubMed Central

    Avise, John C.; Liu, Jin-Xian

    2010-01-01

    We construct a verbal and graphical theory (the “fecundity-limitation hypothesis”) about how constraints on the brooding space for embryos probably truncate individual fecundity in male-pregnant and female-pregnant species in ways that should differentially influence selection pressures for multiple mating by males or by females. We then review the empirical literature on genetically deduced rates of multiple mating by the embryo-brooding parent in various fish species with three alternative categories of pregnancy: internal gestation by males, internal gestation by females, and external gestation (in nests) by males. Multiple mating by the brooding gender was common in all three forms of pregnancy. However, rates of multiple mating as well as mate numbers for the pregnant parent averaged higher in species with external as compared with internal male pregnancy, and also for dams in female-pregnant species versus sires in male-pregnant species. These outcomes are all consistent with the theory that different types of pregnancy have predictable consequences for a parent's brood space, its effective fecundity, its opportunities and rewards for producing half-sib clutches, and thereby its exposure to selection pressures for seeking multiple mates. Overall, we try to fit these fecundity-limitation phenomena into a broader conceptual framework for mating-system evolution that also includes anisogamy, sexual-selection gradients, parental investment, and other selective factors that can influence the relative proclivities of males versus females to seek multiple sexual partners. PMID:20956296

  14. 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...

  15. Effects of coffee consumption on iron, zinc and copper status in nonpregnant and pregnant Sprague-Dawley rats.

    PubMed

    Aldrian, P S; Keen, C L; Lönnerdal, B; Dewey, K G

    1997-05-01

    To investigate the influence of coffee consumption on iron, zinc and copper status, 64 Sprague-Dawley female rats were assigned to four treatment groups: nonpregnant-given coffee, nonpregnant-given water, pregnant-given coffee and pregnant-given water. The coffee groups received a freeze-dried coffee solution (1.1% w/v) as the sole source of liquids during the 18-day study period; all groups were provided a purified diet marginal in iron ad libitum. On day 18 (of gestation in the pregnant rats), rats were intubated with 0.033 MBq59Fe after an 8 h fast and killed 4, 8, 12 or 24 h post-gavage. Fluid intake was significantly lower in the coffee groups. Coffee did not affect food consumption, weight gain, hemoglobin or hematocrit in either pregnant or nonpregnant rats. In nonpregnant rats, the percentage of 59Fe was lower in plasma and higher in the spleen and erythrocytes in the coffee group than in controls; in pregnant rats the coffee group had a higher percentage of 59Fe in the stomach (at 4 h only), blood, spleen and bone than controls. There were no significant effects of coffee on tissue concentrations of Fe, Zn or Cu in the nonpregnant group, but pregnant rats given coffee had high concentrations of Fe in the liver, bone and placenta, and low placenta Zn concentrations compared to controls. In fetuses, there were trends towards lower weight, length and percentage 59Fe, but higher liver Fe, in the coffee group than in the controls. The results suggest that coffee intake leads to (a) increased attempts at erythropoeisis, an indication of iron deficiency, in both nonpregnant and pregnant rats, and (b) impaired placental Fe transport. PMID:9205593

  16. Mortality associated with using medetomidine and ketamine for general anesthesia in pregnant and nonpregnant Wistar rats.

    PubMed

    Callahan, Lauren M; Ross, Simone M; Jones, Megan L; Musk, Gabrielle C

    2014-06-01

    Medetomidine and ketamine are injectable drugs that can be used in combination to induce general anesthesia in rats. After noticing a high incidence of morbidity and mortality in pregnant Wistar rats given medetomidine and ketamine for anesthesia, the authors further investigated the effects of this combination of anesthetic drugs in both pregnant and nonpregnant Wistar rats. The time to recumbency and the duration of general anesthesia were similar between pregnant and nonpregnant rats. Pregnancy status did not affect the rats' pulse rate, respiratory rate, rectal temperature, oxygen saturation or perfusion index during 2 h of anesthesia. Pregnant rats had significantly lower blood glucose concentrations than nonpregnant rats at all time points, though blood glucose concentrations increased in both groups. The mortality rate was ∼15% both for nonpregnant rats and for pregnant rats. Researchers using medetomidine and ketamine to anesthetize Wistar rats should carefully monitor the rats in order to minimize mortality. PMID:24845007

  17. Methodological differences account for inconsistencies in reported free VEGF concentrations in pregnant rats.

    PubMed

    Weissgerber, Tracey L; McConico, Andrea; Knudsen, Bruce E; Butters, Kim A; Hayman, Suzanne R; White, Wendy M; Milic, Natasa; Miller, Virginia M; Garovic, Vesna D

    2014-06-01

    Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8-29 pg/ml) and high (527-1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82-105%) but low for the mouse ELISA (17-22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously. PMID:24622973

  18. 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.

  19. The effects of female sexual hormones on the expression and function of α1A- and α1D-adrenoceptor subtypes in the late-pregnant rat myometrium.

    PubMed

    Bóta, Judit; Hajagos-Tóth, Judit; Ducza, Eszter; Samavati, Reza; Borsodi, Anna; Benyhe, Sándor; Gáspár, Róbert

    2015-12-15

    The aim of the study was to investigate the roles of α1-adrenoceptor subtypes in the last-day pregnant rat uterus in vitro by the administration of subtype-specific antagonists (the α1A-adrenoceptor antagonist WB 4101 and the α1D-adrenoceptor antagonist BMY 7378) after 17β-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 β-, and α2-adrenergic action. The myometrial expressions of the α1-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 17β-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 17β-estradiol and the progesterone pretreatment reduced the effect of (-)-noradrenaline. The mRNA and protein expressions of the α1A-adrenoceptors were decreased after 17β-estradiol pretreatment. (-)-Noradrenaline increased the [(35)S]GTPγS binding of the α1-adrenoceptors, which was most markedly elevated by progesterone. Pertussis toxin inhibited the [(35)S]GTPγS binding-stimulating effect of (-)-noradrenaline, indicating the role of Gi proteins in the signal mechanisms. 17β-estradiol pretreatment blocks the expression of the α1A-adrenoceptors, whereas it does not influence the expression of the α1D-adrenoceptors. Progesterone pretreatment does not have any effect on the myometrial mRNA and protein expressions of the α1-adrenoceptors, but it alters the G protein coupling of these receptors, promoting a Gi-dependent pathway. PMID:26593425

  20. The Effects of Sugammadex on Progesterone Levels in Pregnant Rats

    PubMed Central

    Et, Tayfun; Topal, Ahmet; Erol, Atilla; Tavlan, Aybars; Kılıçaslan, Alper; Uzun, Sema Tuncer

    2015-01-01

    Background: Sugammadex has been shown to decrease the efficiency of progesterone-containing oral contraceptive drugs which possess a steroid structure. Aims: The aim of the present study was to evaluate the effects of sugammadex on progesterone levels in pregnant rats as well as on the physiological course of the pregnancy. Study Design: Animal experiment. Methods: This study was approved by the Selçuk University Ethical Committee for Experimental Animal Research. Pregnant Winster Albino rats (n=26) were divided into three groups and administered with various intravenous injections on the 7th day of pregnancy. The control group (Group K, n=6) received 1.5 mL serum physiologic, the sugammadex group (Group S, n=10) received 30 mg/kg sugammadex and the sugammadex + rocuronium group (Group SR, n=10) received 30 mg/kg sugammadex and 3.5 mg/kg rocuronium. Progesterone levels were measured and the offspring were monitored for morphologic status. Results: Mean progesterone levels were 94.16±15.54 ng/mL in Group K, 87.86±12.48 ng/mL in Group S, and 94.53±16.10 ng/mL in Group SR (p>0.05). No stillbirth or miscarriage was observed in the rats. The mean number of offspring was 6.8±1.47 in Group K, 6.5±1.35 in Group S, and 6.4±1.17 in Group SR. The offspring appeared macroscopically normal. Conclusion: Sugammadex does not appear to affect the progesterone levels in pregnant rats in the first trimester and the clinical course. Successful completion of pregnancy and the absence of stillbirth or miscarriage will guide future studies about the use of sugammadex, particularly in the first trimester of the pregnancy. PMID:26167346

  1. Diminished ketosis and triglyceridemia during fasting in odd-carbon enriched pregnant rats.

    PubMed

    Kim, S; Pi-Sunyer, F X

    1977-02-01

    The lipolysis, ketosis and hypertriglyceridemia of fasted rats in late pregnancy may be related to decreased insulin secretion geared to decreased glucose availability. In odd-carbon fatty acid enriched (OCE) rats, the odd-carbon fatty acids (OCFA) mobilized during fasting provide terminal three-carbon residues which are glucogenic, thereby permitting blood glucose and insulin to be maintained close to fed levels. The present study has used OCE rats to evaluate the role of insulin in the altered fat metabolism of the fasted rats in late pregnancy. The adipose tissue of 24 female Sprague-Dawley rats was enriched to more than 25% undecanoate (c11:0) and higher OCFA by feeding them a complete diet high in triundecanoin content for six weeks. Twenty-four female controls were fed a similar diet except that the fat was exclusively corn oil. Both OCE and control rats were than mated and on day 18 of pregnancy were divided into four groups: one group was killed fed, one after a 24 h fast, and one after a 48 h fast; the fourth group was fed to day 20 of pregnancy and then killed. In the fed state, the concentrations of glucose, ketones, and cholesterol in serum, as well as that of glycogen in liver, were the same in control and OCE rats. Insulin and triglycerides were similarly elevated in the two groups. After two days of fasting, serum glucose, insulin, and liver glycogen concentrations were significantly higher in OCE than in control rats, while ketones and triglycerides were significantly lower. No significant changes occurred in serum cholesterol. The results are consistent with a predominantly insulin effect in the pregnant OCE rats in diminsihing the marked fasting lipolysis, hyperketonemia and hypertriglyceridemia observed in controls, but do not rule out inhibition of FFA release by in situ re-esterification to glycerol derived from glucose or propionic acid. PMID:832630

  2. 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

  3. 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

  4. Similar metabolic response to acute ethanol intake in pregnant and non-pregnant rats either fed or fasted.

    PubMed

    Villarroya, F; Mampel, T; Herrera, E

    1985-01-01

    Plasma ethanol concentration 3 hr after its oral administration (3 g/kg body wt) did not differ in 20 day pregnant rats with virgin controls, and in both groups values were higher when studied after 24 hr fasted than when fed. In fed animals, blood glucose and liver glycogen concentrations were lower in pregnant than in virgin rats, whereas ethanol intake in both groups enhanced blood glucose levels, it reduced liver glycogen content only in virgins. In fetuses, maternal ethanol intake enhanced blood glucose levels. In fasted animals, ethanol intake decreased blood glucose levels in pregnant and virgin animals but did not affect these levels in fetuses. Ethanol intake enhanced beta-hydroxybutyrate/acetoacetate ratio similarly in blood of pregnant and virgin rats when either fed or fasted, and it produced the same change in fetuses from fasted mothers. Results indicate that the metabolic response to acute ethanol does not differ between pregnant and non-pregnant animals, and it is proposed that fetuses passively follow the metabolic changes occurring in their mothers after receiving ethanol. PMID:4054580

  5. Effect of dietary proteins on zinc bioavailability in pregnant rats.

    PubMed

    Uenishi, K; Horio, H; Manabe, S; Sakamoto, S

    1993-12-01

    In order to clarify the effects of dietary proteins on zinc bioavailability during pregnancy, two experiments were carried out. In Experiment 1, changes in zinc retention due to pregnancy (difference in retention between pregnant and nonpregnant animals) during early-mid and late pregnancy were examined in rats fed 10 and 20% egg white diets. Total amounts of retained zinc due to pregnancy were about 1000 micrograms or slightly more, equal to the zinc content in the products of conception at term. However, extra zinc retention during late pregnancy ranged between only 20 to 40% of overall retention, suggesting that almost all zinc retained during early-mid pregnancy moved from the mothers to the fetuses near term. Zinc retention in early-mid and late periods of pregnancy was higher in pregnant than nonpregnant rats, due mainly to increases in intake and bioavailability. In Experiment 2, to examine the effects of quality and quantity of dietary proteins, pregnant rats were fed either 10 or 20% egg white (EW), whole egg (WE), casein (C) and soy protein isolate with or without methionine (SM and S, respectively) diets. Total zinc retention during pregnancy was affected by both zinc and nitrogen intakes, though the former effect was greater than the latter. Because rats fed the EW diets retained dietary zinc efficiently, a relationship between zinc retention (Y, microgram/100 g BW/21 d.) and zinc intake (X, microgram/100 g BW/21 d.) was also examined in the non-EW protein groups, resulting in the following regression equation: Y = 0.471X-1790 (n: 51, r = 0.81, p < 0.001). Dietary protein quality affected the food intake resulting in different zinc intake and retention during pregnancy. Zinc from EW diets was more available than from the other four protein diets, because similar plots for rats fed the 10 and 20% EW diets fell above this line. Reasons for efficient bioavailability of zinc in EW were discussed in connection with the forms of zinc in diets and the pancreatic or intestinal responses to ingested EW. PMID:8184411

  6. Use of novel inhalation kinetic studies to refine physiologically-based pharmacokinetic models for ethanol in non-pregnant and pregnant rats.

    PubMed

    Martin, Sheppard A; Oshiro, Wendy M; Evansky, Paul A; Degn, Laura L; Ledbetter, Allen D; Ford, Jermaine; Todd Krantz, Q; LeFew, William R; Beasley, Tracey E; El-Masri, Hisham; McLanahan, Eva D; Boyes, William K; Bushnell, Philip J

    2014-08-01

    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 concentrations (BEC) in the range associated with these effects. Previous laboratory reports often lacked sufficient detail to adequately simulate reported exposure scenarios associated with BECs in this range, or lacked data on the time-course of EtOH in target tissues (e.g. brain, liver, eye, fetus). To address these data gaps, inhalation studies were performed at 5000, 10 000, and 21 000 ppm (6 h/d) in non-pregnant female Long-Evans (LE) rats and at 21 000 ppm (6.33 h/d) for 12 d of gestation in pregnant LE rats to evaluate our previously published PBPK models at toxicologically-relevant blood and tissue concentrations. Additionally, nose-only and whole-body plethysmography studies were conducted to refine model descriptions of respiration and uptake within the respiratory tract. The resulting time-course and plethysmography data from these in vivo studies were compared to simulations from our previously published models, after which the models were recalibrated to improve descriptions of tissue dosimetry by accounting for dose-dependencies in pharmacokinetic behavior. Simulations using the recalibrated models reproduced these data from non-pregnant, pregnant, and fetal rats to within a factor of 2 or better across datasets, resulting in a suite of model structures suitable for simulation of a broad range of EtOH exposure scenarios. PMID:25144475

  7. 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...

  8. 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...

  9. Exposure to stimulatory CpG oligonucleotides during gestation induces maternal hypertension and excess vasoconstriction in pregnant rats.

    PubMed

    Goulopoulou, Styliani; Wenceslau, Camilla F; McCarthy, Cameron G; Matsumoto, Takayuki; Webb, R Clinton

    2016-04-15

    Bacterial infections increase risk for pregnancy complications, such as preeclampsia and preterm birth. Unmethylated CpG DNA sequences are present in bacterial DNA and have immunostimulatory effects. Maternal exposure to CpG DNA induces fetal demise and craniofacial malformations; however, the effects of CpG DNA on maternal cardiovascular health have not been examined. We tested the hypothesis that exposure to synthetic CpG oligonucleotides (ODNs) during gestation would increase blood pressure and cause vascular dysfunction in pregnant rats. Pregnant and nonpregnant female rats were treated with CpG ODN (ODN 2395) or saline (Veh) starting on gestationalday 14or corresponding day for the nonpregnant groups. Exposure to CpG ODN increased systolic blood pressure in pregnant (Veh: 121 ± 2 mmHg vs. ODN 2395: 134 ± 2 mmHg,P< 0.05) but not in nonpregnant rats (Veh: 111 ± 2 mmHg vs. ODN 2395: 108 ± 5 mmHg,P> 0.05). Mesenteric resistance arteries from pregnant CpG ODN-treated rats had increased contractile responses to U46619 [thromboxane A2(TxA2) mimetic] compared with arteries from vehicle-treated rats [Emax(%KCl), Veh: 87 ± 4 vs. ODN 2395: 104 ± 4,P< 0.05]. Nitric oxide synthase (NOS) inhibition increased contractile responses to U46619, and CpG ODN treatment abolished this effect in arteries from pregnant ODN 2395-treated rats. CpG ODN potentiated the involvement of cyclooxygenase (COX) to U46619-induced contractions. In conclusion, exposure to CpG ODN during gestation induces maternal hypertension, augments resistance artery contraction, increases the involvement of COX-dependent mechanisms and reduces the contribution of NOS-dependent mechanisms to TxA2-induced contractions in mesenteric resistance arteries. PMID:26873968

  10. 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

  11. Pharmacokinetics of puerarin in pregnant rats at different stages of gestation after oral administration.

    PubMed

    Cao, Li; Pu, Jie; Cao, Qing-Ri; Chen, Bo-Wen; Lee, Beom-Jin; Cui, Jing-Hao

    2013-04-01

    This study aims to observe the effects of gestational stage on the pharmacokinetics of puerarin after oral administration in rats. The pharmacokinetics of puerarin was studied in pregnant rats using a sensitive and reproducible high-performance liquid chromatography/ultraviolet method. The concentration-time curves in both normal and pregnant rats were fit into a two-compartment model. The results indicated that gestation influences the pharmacokinetics of puerarin at different levels, especially during the early stages of pregnancy. Furthermore, puerarin penetrates the placental barrier and maintains high concentrations in fetal rat plasma. Therefore, puerarin administration should be carefully considered in pregnant women. PMID:23500385

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. A Transfer of Silver Nanoparticles from Pregnant Rat to Offspring

    PubMed Central

    Lee, Yeonjin; Choi, Jonghye; Kim, Pilje; Choi, Kyunghee; Kim, Suhyon; Shon, Woochan; Park, Kwangsik

    2012-01-01

    Silver nanoparticles (size: 7.9 ± 0.95 nm, dosage: 250 mg/kg) were orally administered to pregnant rats. At 4 days after parturition, four pups were randomly selected (one pup from one dam) and silver level in liver, kidney, lung and brain was determined by ICP-MS and electron microscope. As results, silver nanoparticles highly accumulated in the tissues of the pups. Silver level in the treated group was 132.4 ± 43.9 ng/g in the kidney (12.3 fold compared to control group), 37.3 ± 11.3 ng/g in the liver (7.9 fold), 42.0 ± 8.6 ng/g in the lung (5.9 fold), and 31.1 ± 4.3 ng/g in the brain (5.4 fold). This result suggested that the possible transfer of silver nanoparticles from pregnant dams to the fetus through mainly placenta. PMID:24278602

  17. Endogenous opioids and attenuated hypothalamic-pituitary-adrenal axis responses to immune challenge in pregnant rats.

    PubMed

    Brunton, Paula J; Meddle, Simone L; Ma, Shuaike; Ochedalski, Tomasz; Douglas, Alison J; Russell, John A

    2005-05-25

    In late pregnant rats, the hypothalamic-pituitary-adrenal (HPA) axis is hyporesponsive to psychogenic stressors. Here, we investigated attenuated HPA responses to an immune challenge and a role for endogenous opioids. ACTH and corticosterone were assayed in blood samples from virgin and 21 d pregnant rats before and after endotoxin [lipopolysaccharide (LPS); 1 microg/kg, i.v.], interleukin-1beta (IL-1beta; 500 ng/kg, i.v.), or vehicle. In virgins, plasma ACTH concentrations increased 1 h after LPS and 15 min after IL-1beta, as did corticosterone, with no responses in pregnant rats. In situ hybridization revealed increased corticotrophin releasing hormone (CRH) mRNA expression in the dorsomedial parvocellular paraventricular nucleus (pPVN) and increased anterior pituitary pro-opiomelanocortin mRNA expression 4 h after IL-1beta in virgins; these responses were absent in pregnant rats. In contrast, immunocytochemistry showed that Fos expression was similarly increased in the nucleus tractus solitarius (NTS) A2 region in virgin and pregnant rats 90 min and 4 h after IL-1beta. Naloxone pretreatment (5 mg/kg, i.v.) restored ACTH and pPVN CRH mRNA responses after IL-1beta in pregnant rats but reduced the CRH mRNA response in virgins without affecting ACTH. Proenkephalin-A and mu-opioid receptor mRNA expression in the NTS was significantly increased in the pregnant rats, indicating upregulated brainstem opioid mechanisms. IL-1beta increased noradrenaline release in the PVN of virgin, but not pregnant, rats. However, naloxone infused directly into the PVN increased noradrenaline release after IL-1beta in pregnant rats. Thus, the HPA axis responses to immune signals are suppressed in pregnancy at the level of pPVN CRH neurons through an opioid mechanism, possibly acting by preterminal autoinhibition of NTS projections to the pPVN. PMID:15917452

  18. 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

  19. 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

  20. Cadmium toxicity in the thyroid gland of pregnant rats.

    PubMed

    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. PMID:1884772

  1. 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.

  2. Dual effects of melatonin on uterine myoelectrical activity of non-pregnant rats

    PubMed Central

    Şimşek, Yavuz; Parlakpınar, Hakan; Turhan, Uğur; Tağluk, Mehmet Emin; Ateş, Burhan

    2014-01-01

    Objective In this experimental study, we aimed to investigate the role of melatonin on uterine myoelectrical activity of non-pregnant rats. Material and Methods Forty-six female rats were assigned to six groups: (1) control; (0.2 mL 0.9% NaCl was injected intravenously (IV), n=6); (2) melatonin applied as 0.4 mg/kg/IV (n=8); (3) melatonin applied as 4 mg/kg/IV (n=8); (4) single dose of oxytocin (100 mU/kg) injected IV (n=8); (5) melatonin (0.4 mg/kg) plus oxytocin (100 mU/kg) (n=8); and (6) melatonin (4 mg/kg) plus oxytocin (100 mU/kg) injected IV (n=8). Each rat underwent a laparotomy, and uterine myoelectrical signals were recorded. The mean spectrum, averaged over the spectral content of signals in each group, was compared. Results Melatonin induced uterine myoelectrical activity in a dose-dependent manner. Treatment of melatonin after oxytocin suppressed the mean power of the signals. Serum melatonin concentrations were significantly higher in melatonin-treated rats. Conclusion Melatonin itself at two different dose levels was found to be equally effective in stimulating the uterine electrical signals, although oxytocin-induced uterine electrical activity was suppressed by melatonin. These findings merit further investigations on the possible beneficial role of melatonin in the treatment of conditions associated with abnormal uterine activity. PMID:24976773

  3. [One case of a pregnant femal taking realgar induceing congenital inner ear malformation].

    PubMed

    Diao, Mingfang; Sun, Jianjun; Liu, Yang

    2015-08-01

    A pregnant female taken realgar because of superstition, which caused the baby congenital deafness. Auditory test indicated that bilateral auditory brainstem response (ABR) hearing threshold level was greater than 90 dB nHL and auditory steady state response (ASSR) hearing level ranging from 0.5 kHz to 4 kHz was beyond 110 dB HL. Temporal bone CT showed that bilateral cochlear and semicircular canal malformations, with internal auditory canal broadened. PMID:26685413

  4. Predictors of stress in adolescents: an exploratory study of pregnant and of parenting females.

    PubMed

    Pasley, K; Langfield, P A; Kreutzer, J A

    1993-07-01

    A study of 152 adolescents enrolled in school-based programs for pregnant and parenting youth in Colorado in 1987-88 found no differences in overall stress levels between these two groups; however, salient predictors of stressful life events for pregnant teens were not the same as those for teen mothers. The mean age of study subjects was 16.5 years (range 14-19 years); most were living with a parent rather than the child's father. The dependent variable, level of stress, was measured through use of an abbreviated Life Events Questionnaire. Independent variables were assessed through administration of the Inventory of Social Supportive Behaviors, Rosenberg Self-Esteem Scale, and the Adolescent Coping Orientation for Problem Experiences scale. Of the 5 sources of stress measured (family, accidents, autonomy, deviance, relocation, and distress), only stress related to accidents differed significantly between pregnant and parenting adolescents. For pregnant adolescents, self-esteem was the only significant predictor of the overall level of stress; among parents, the only significant predictor was objective social support. Among adolescents, self-esteem was associated with more frequent use of social support and coping strategies. For parenting adolescents, self-esteem was correlated with the frequency of use of social support, satisfaction resulting from such use, and frequent use of coping strategies. Overall, the independent variables of social support, self-esteem, coping, and age were stronger predictors of stress in pregnant than in parenting adolescent females. This finding suggests that parenting teens may have successfully negotiated the multiple transitions involved in this new stage of the life-cycle. An important implication of this study is the need to design separate counseling components of school-based programs for pregnant versus parenting adolescents rather than to use a single curriculum. PMID:12318583

  5. Pregnant female anthropometry from ct scans for finite element model development.

    PubMed

    Loftis, Kathryn; Halsey, Michael; Anthony, Evelyn; Duma, Stefan M; Stitzel, Joel

    2008-01-01

    In this study, anthropometry data is collected from a CT scan of a pregnant abdomen at 32 weeks gestation. Over 1500 fetal losses occur each year in the United States due to motor vehicles crashes. Pregnant occupants involved in motor vehicle crashes are at risk for pregnancy-specific injuries. Masks of the fetus, uterus, placenta, and each of the abdominal organs are created by segmentation of the CT slices and three-dimensional volume renderings are formed. The volume and Hounsfield unit ranges for the masks of each abdominal organ are calculated. The total volume of the uterus in the 3rd trimester is measured as 3378 cm3. By measuring the length of bones on the fetal skeleton from CT slices and the 3D rendering, the gestational age of the fetus is estimated to be 32 weeks by comparison with literature values. Measurements of each of the abdominal organs are also obtained from the 3D rendering to create a blueprint of the pregnant anatomy. The masks developed and the anthropometric measurements taken will be used to develop a more accurate FE model of the pregnant female for use in the research and development in academia, industry, and government. PMID:19141941

  6. 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

  7. 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.

  8. Vascular dysfunction in the offspring of AT1 receptor antibody-positive pregnant rats during high-salt diet.

    PubMed

    Zhang, Xi; Zhang, Su-Li; Xiong, Hai-Yan; DU, Yun-Hui; Quan, Lin; Yang, Jie; Ma, Xiu-Rui; Liu, Hui-Rong

    2011-04-25

    Antibody against the angiotensin AT1 receptor (AT1-Ab) could disturb placental development. The placenta is the key organ between mother and fetus. Placental damage will seriously impair fetal growth and development in utero, leading to intrauterine growth restriction (IUGR). Based on the fetal origins of adult disease (FOAD) hypothesis, IUGR could increase a propensity to develop adult onset cardiovascular disease (CVD). The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats. Twenty four female rats (8-week-old, AT1-Ab negative) were randomly divided into two groups, immunized and vehicle groups. Immunized group received active immunization to establish AT1-Ab-positive model, while vehicle group was subjected to Freund's adjuvant without antigen. After 8 weeks of immunization, the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay (ELISA). Then all the female rats were mated with normal Wistar male rats and became pregnant. Immunized/vehicle group offspring rats (I offspring/V offspring) were raised to 40-week-old under standard chow feeding. Then the two groups' offspring rats were given a high-salt diet for 12 weeks (4% NaCl in chow feeding). Systolic blood pressure (SBP) was measured dynamically by noninvasive blood pressure system. The vascular ring experiment was performed to detect vascular function and reactivity. As detected by ELISA, the titers of antibody peaked at the 8th week (OD values: 2.75 ± 0.08 vs 0.33 ± 0.01, P < 0.01 vs vehicle group at the same time point). There was no significant difference of SBP between the two groups' offspring rats during the high-salt diet (P > 0.05). Isolated thoracic aortic rings of I offspring had significantly decreased constriction under norepinephrine treatment (P < 0.01 vs V offspring) and significantly decreased dilation under acetylcholine treatment (P < 0.05 vs V offspring). These results suggest that the offspring of AT1-Ab-positive pregnant rats are more susceptible to vascular functional abnormality while being fed high-salt diet. PMID:21505730

  9. 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.

  10. A Low-Protein Diet Enhances Angiotensin II Production in the Lung of Pregnant Rats but Not Nonpregnant Rats

    PubMed Central

    Gao, Haijun; Tanchico, Daren Tubianosa; Yallampalli, Uma; Yallampalli, Chandrasekhar

    2016-01-01

    Pulmonary angiotensin II production is enhanced in pregnant rats fed a low-protein (LP) diet. Here we assessed if LP diet induces elevations in angiotensin II production in nonpregnant rats and whether Ace expression and ACE activity in lungs are increased. Nonpregnant rats were fed a normal (CT) or LP diet for 8, 12, or 17 days and timed pregnant rats fed for 17 days from Day 3 of pregnancy. Plasma angiotensin II, expressions of Ace and Ace2, and activities of these proteins in lungs, kidneys, and plasma were measured. These parameters were compared among nonpregnant rats or between nonpregnant and pregnant rats fed different diets. Major findings are as follows: (1) plasma angiotensin II levels were slightly higher in the LP than CT group on Days 8 and 12 in nonpregnant rats; (2) expression of Ace and Ace2 and abundance and activities of ACE and ACE2 in lungs, kidneys, and plasma of nonpregnant rats were unchanged by LP diet except for minor changes; (3) the abundance and activities of ACE in lungs of pregnant rats fed LP diet were greater than nonpregnant rats, while those of ACE2 were decreased. These results indicate that LP diet-induced increase in pulmonary angiotensin II production depends on pregnancy. PMID:27195150

  11. 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

  12. 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

  13. 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

  14. Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats

    PubMed Central

    Rezazad, Maryam; Farokhi, Farah

    2014-01-01

    Objective: Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Materials and Methods: Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant statues (TAS), creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. Results: After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. Conclusion: These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema. PMID:25386393

  15. Effect of Transverse Aortic Constriction on Cardiac Structure, Function and Gene Expression in Pregnant Rats

    PubMed Central

    Songstad, Nils Thomas; Johansen, David; How, Ole-Jacob; Kaaresen, Per Ivar; Ytrehus, Kirsti; Acharya, Ganesh

    2014-01-01

    Background There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. Methods Pregnant (gestational day 5.5–8.5) and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC) or sham surgery. After 14.2±0.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV) pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. Results Heart weight was increased by TAC (p<0.001) but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01), however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.1±2.4 vs 17.5±2.4 mmHg/mL, p<0.001) than in non-pregnant (28.2±1.7 vs 20.9±1.5 mmHg/mL, p = 0.06). However, it did not lead to overt heart failure in any group. In pregnant rats, α-MHC gene expression was reduced by TAC. Increased in the expression of β-MHC gene was higher in pregnant (5-fold) compared to non-pregnant rats (2-fold) after TAC (p = 0.001). Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. Conclusions This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and non-pregnant rats following TAC indicated that afterload increase is less tolerated in pregnancy. PMID:24586871

  16. 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

  17. 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

  18. 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

  19. 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%).

  20. Disseminated intravascular coagulation induced by progesterone in the pregnant rat. Prevention by estogens.

    PubMed

    Stamler, F W

    1977-03-01

    Fatal disseminated intravascular coagulation (DIC) was induced in female rats by administration of progesterone in late pregnacy. This prevented parturition, with intrauterine fetal death 2 to 4 days past term and subsequent retention of dead fetuses. Concomitantly with or closely following the intrauterine death of their litters, a large proportion of pregnant rats died with histologically evident DIC. Administration of cortisone, heparin, or disoumarin did not prevent DIC, and xi-aminocaproic acid, acetylsalicylic acid, or an onion-rich diet tended to increase its incidence. Antibiotic regimens gave variable results, with significant decrease in DIC only with a combination of two wide-spectrum penicillins. Neomycin and polymyxin had little effect on susceptible Sprague-dawley derived rats, but polymxin caused a significant increase in DIC in a resistant strain of hooded rats. Fatal maternal DIC was completely prevented only by use of natural or synthetic estrogens concurrently with progesterone, although this did not alter the sequence of abnormally prolonged pregnacy with intrauterine fetal death and retention of dead fetuses. Potencies of estrogens varied greatly, but all compounds tested prevented DIC at adequate dosage levels. Diethylstilbestrol, the most potent drug tested, was completely protective at 1 mug daily given subcutaneously. beta-Estradiol was the most effective natural estrogen, giving complete protection with a 10-mug daily subcutaneous injection. Estrogens were much more potent by subcutaneous injection than by oral ingestion, and toxic side effects were sometimes noted with higher levels of the latter. For estrogen therapy to be effective, it was necessary to begin its use before the expected onset of DIC, and in no instance was there evidence of reversal of this process after signs of illness were observed. PMID:65916

  1. Safety evaluation of aqueous extracts from Aegle marmelos and Stevia rebaudiana on reproduction of female rats.

    PubMed

    Saenphet, Kanokporn; Aritajat, Salika; Saenphet, Supap; Manosroi, Jeeradej; Manosroi, Aranya

    2006-01-01

    The purpose of this study was to evaluate the safety of a Thai medicinal plant, Aegle marmelos, and a non-caloric sweetener, Stevia rebaudiana, on the reproduction of female rats. Female rats were treated orally with aqueous extract of A. marmelos (6%) and S. rebaudiana at various concentrations (0, 0.2, 1, or 10%) for 60 days (1 ml/day) before mating. The control rats received only distilled water. At the end of the treatment period, treated females were mated with untreated males and the effects on reproduction were examined at day 14 of pregnancy. No notable abnormalities were observed in any of the pregnant rats. The number of corpus lutea, implanted and dead fetuses, as well as the sizes of the fetuses in the treated rats were not significantly different from those of the controls. Based on these results, it may be concluded that aqueous extracts of A. marmelos and S. rebaudiana at the concentrations used in this study do not alter the reproduction of female rats. PMID:17547081

  2. 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

  3. Does L-arginine availability during the early pregnancy alters the immune response of Trypanosoma cruzi infected and pregnant Wistar rats?

    PubMed

    da Costa, Cássia Mariana Bronzon; de Freitas, Murilo Rodrigues Barbosa; Brazão, Vânia; dos Santos, Carla Domingues; Sala, Miguel Angel; do Prado Júnior, José Clovis; Abrahão, Ana Amélia Carraro

    2014-07-01

    Chagas disease induces a strong immune response and L-arginine is an essential amino acid which plays an important role in homeostasis of the immune system. The aims of this study were to evaluate parasitemia, corticosterone levels, production of nitric oxide (NO), fetal morphological measurements, and histology of heart and placenta. Twenty pregnant Wistar rats (180-220 g) were grouped in: pregnant control (PC), pregnant control and L-arginine supplied (PCA), pregnant infected (PI), pregnant infected and L-arginine supplied (PIA). Females were infected with 1×10(5) trypomastigotes of the Y strain (3rd day of pregnancy). Animals were supplied with 21 mg of L-arginine/kg/day during 14 days. PIA showed significant decreased levels of corticosterone and parasitemia. For control groups, any alteration in NO production was found with L-arginine supplementation; for PIA, enhanced nitrite concentrations were observed as compared to PI. Weights and lengths of fetuses were higher in L-arginine treated and infected pregnant rats as compared to untreated ones. Placental weight from the PIA group was significantly increased when compared to PI. In L-arginine treated animals, cardiac tissue showed reduced amastigote burdens. PIA and PI displayed similar placental parasitism. Based on these results, L-arginine supplementation may be potentially useful for the protection against Trypanosoma cruzi during pregnancy. PMID:24786713

  4. 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

  5. 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.

  6. 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

  7. Effect of induced thyroid dysfunction upon uterine responsiveness in strips from pregnant and nonpregnant rats.

    PubMed

    Medeiros, Y S; Calixto, J B

    1989-01-01

    The influence of thyroid dysfunction on rat myometrial responsiveness to oxytocin, acetylcholine, CaCl2 and BaCl2 was assessed in uterine strips from pregnant and nonpregnant rats. In preparations obtained from hypothyroid nonpregnant rats, oxytocin and acetylcholine concentration-response curves were significantly displaced to the left, whereas myometrial strips from hyperthyroid nonpregnant rats were only supersensitive to acetylcholine. In relation to the pregnant state, T3 treatment caused an increased myometrial sensitivity to both oxytocin and acetylcholine. In this condition, concentration-response curves for oxytocin did not differ from nonpregnant control animals, whereas acetylcholine was about 300-fold more potent at the ED50 levels compared with those in nonpregnant animals. Either in pregnant or nonpregnant state, maximal responses and ED50 to BaCl2 did not differ. In addition, thyroid dysfunction did not modify the pattern of CaCl2-induced contractions in isolated myometrial strips from pregnant rats. This data extended to the myometrium, previous evidence in the literature indicating that thyroid dysfunction may affect uterine responsiveness to agonists. PMID:2755963

  8. Effect of amino acid infusion as an index of renal vasodilatory capacity in pregnant rats.

    PubMed

    Baylis, C

    1988-05-01

    Experiments were performed in midterm pregnant and virgin Munich-Wistar rats to investigate how the chronically vasodilated kidney of a gravid animal would respond to a further acute vasodilatory stimulus, in the form of a 90-min intravenous infusion of the amino acid glycine (at 0.167 mmol.kg-1.min-1). In young adult midterm pregnant rats studied in the base-line state, glomerular filtration rate (GFR), single-nephron GFR, renal plasma flow (RPF), and glomerular plasma flow were significantly greater (by approximately 30%) than in virgins due to a gestational renal vasodilation. Despite the underlying chronic renal vasodilation of pregnancy, the kidney of the gravid rat displays a marked further renal vasodilation (with consequent further increases in GFR and RPF) in response to acute glycine loading; the percent increase in GFR and RPF was similar to that seen in the relatively vasoconstricted virgin. This ability to further acutely increase the GFR in the pregnant rat was not limited to animals maintained on a normal protein diet but was also seen in older pregnant rats subjected to the additional chronic vasodilatory stimulus of long-term high-protein feeding, although in these older animals the gestational vasodilation was blunted. PMID:3364576

  9. 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, 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 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 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. PMID:22664346

  10. True hermaphroditism in six female littermates after administration of synthetic androgens to a pregnant bitch.

    PubMed

    de Rooster, H; Vercauteren, G; Görtz, K; Saunders, J; Polis, I; Rijsselaere, T

    2006-02-01

    A pregnant bitch was treated with a synthetic testosterone mixture on approximately day 40. The female offspring (six pups) showed an increased anogenital distance, vaginal enlargement and a variable amount of vaginal discharge. The urinary orifice was found dorsally in the vestibulum, stooled on a protruding phallus-like structure. All six pups underwent a laparotomy and subsequent spaying and a modified ventral episioplasty technique to lift up the labia to a more vertical position in order to prevent urine accumulation. Histopathological examination of the genital tracts demonstrated the presence of bilateral ovotestis and remnants of the Wolffian duct system in all cases. The finding of true hermaphroditism of the offspring after exogenous androgen administration during gestation of the bitch has not yet been reported elsewhere. PMID:16420323

  11. 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...

  12. Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning

    PubMed Central

    García-Peláez, Beatriz; Vilà, Ruth; Remesar, Xavier

    2008-01-01

    Background In rats, oral oleoyl-estrone (OE) decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. Methods Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day). Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. Results Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. Conclusion The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood. PMID:18570654

  13. Antifertility activity of aqueous ethanolic extract of Hymenocardia acida stem bark in female rats

    PubMed Central

    Hyacinth, Abu Adakole; Nwocha, Uchendu Chukwuka

    2011-01-01

    Background: Hymenocardia acida is traditionally used in African herbal medicine and has numerous therapeutic benefits. But little is known about its potentially negative effects on pregnant women. Objective: The aim of the present study was to evaluate the antifertility effect of aqueous ethanolic extract of Hymenocardia acida stem bark in female Wistar rats. Materials and Methods: Four groups of rats were administered orally aqueous ethanolic extract of Hymenocardia acida at doses of 100, 200 and 400 mg/kg body weight daily for 19 days. The control group received distilled water. On day 20 of gestation, each rat was laparatomised and number of corpora lutea of pregnancy, number of live fetuses as well as the postcoitum fertility index, weights of the foetuses and placentae were determined. Results: Oral administration of the extract from days 1 to 19 of gestation showed reduction (p<0.05) in the number of corpora lutea of pregnancy and number of live fetuses. Weights of fetuses of extract treated female rats were also smaller (p<0.05) compared with the control. Anti-implantation activity of the treatment groups were 41.4%, 48.3% and 51.7% for groups II to IV respectively, whereas antifertility activity of the groups was found to be 40%, 60% and 60% in the same order. Conclusion: The results suggest that aqueous ethanolic extract of Hymenocardia acida stem bark could induce negative effects on reproductive functions in female albino rats. PMID:26396567

  14. Changes in the Immune System of Female Wistar Rats After Exposure to Immunosuppressive Treatment During Pregnancy.

    PubMed

    Kabat-Koperska, J; Kolasa-Wołosiuk, A; Wojciuk, B; Wojciechowska-Koszko, I; Roszkowska, P; Krasnodębska-Szponder, B; Paczkowska, E; Safranow, K; Gołembiewska, E; Machaliński, B; Ciechanowski, K

    2016-06-01

    This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL-17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner. PMID:27007325

  15. Transplacental passage of 26Al from pregnant rats to fetuses and 26Al transfer through maternal milk to suckling rats

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Nagai, H.; Matsuzaki, H.; Kobayashi, T.; Tada, W.; Ohki, Y.; Kakimi, S.; Kobayashi, K.

    2000-10-01

    Aluminium (Al) is toxic to the growth of fetuses and sucklings. However, the incorporation of Al into fetuses and sucklings in the periods of gestation and lactation has not been well clarified because Al lacks a suitable isotope for a tracer experiment. In this study, we used 26Al (a radioisotope of Al with half-life of 716,000 yr) as a tracer, and measured 26Al incorporation into fetuses and sucklings by accelerator mass spectrometry (AMS). To investigate Al incorporation into fetuses through transplacental passage, 26Al ( 26AlCl 3) was subcutaneously injected into pregnant rats on day 15 of gestation. 26Al was also subcutaneoulsy injected into lactating rats from day 1 to day 20 postpartum. By day 20 of gestation, 0.2% of the 26Al injected into a pregnant rat had been transferred to the fetuses, and 26Al was detected in the brain and liver of the fetuses. On day 9 postpartum, high levels of 26Al were demonstrated in the brain, liver, kidneys and blood of suckling rats. It is concluded that 26Al subcutaneously injected into pregnant rats and/or lactating rats is incorporated into their offspring through transplacental passage and/or maternal milk.

  16. 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.

  17. Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero

    PubMed Central

    Sathishkumar, K.; Elkins, Rebekah; Yallampalli, Uma; Balakrishnan, Meena; Yallampalli, Chandrasekhar

    2011-01-01

    Aims The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. We examined the effects of prenatal testosterone treatment on blood pressure in adult female rats. Further, to define the mechanisms whereby blood pressure may be raised, we examined vascular endothelial function and nitric oxide synthesis. Methods and Results Testosterone propionate (0.5mg/kg/day;SC) or vehicle was administered to pregnant Sprague-Dawley rats from gestational day 15–19. Maternal feed intake and plasma levels of steroid hormones were measured in the dams. In the female offspring, birth weight, growth rate, blood pressure, vascular reactivity, eNOS expression, and nitric oxide production were examined. In the pregnant rats, testosterone-treatment increased plasma testosterone levels by 2-fold without any significant changes in 17β-estradiol, progesterone and corticosterone levels. Testosterone-treatment did not affect maternal feed intake. The pups born to testosterone mothers were smaller in size but exhibited catch-up growth. The blood pressure in the testosterone offspring at 6 months of age was significantly higher compared to controls. Endothelium-intact mesenteric arteries from testosterone group exhibited increased contractile responses to phenylephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to control rats. Testosterone rats demonstrated decreased expression for eNOS, and reduced nitric oxide production. Conclusions Our data show that elevated plasma maternal testosterone levels: (1) causes low birth weight followed by catch-up growth and hypertension in female offspring; (2) alters endothelium-dependent vascular responses. The endothelial dysfunction is associated with decreased activity/expression of eNOS. PMID:21450421

  18. Runaway and Pregnant: Risk Factors Associated with Pregnancy in a National Sample of Runaway/Homeless Female Adolescents

    PubMed Central

    Thompson, Sanna J.; Bender, Kimberly A.; Lewis, Carol M.; Watkins, Rita

    2009-01-01

    Purpose Homeless youth are at particularly high risk for teen pregnancy; research indicates as many as 20% of homeless young women become pregnant. These pregnant and homeless teens lack financial resources and adequate health care, resulting in increased risk for low– birth-weight babies and high infant mortality. This study investigated individual and family-level predictors of teen pregnancy among a national sample of runaway/homeless youth in order to better understand the needs of this vulnerable population. Methods Data from the Runaway/Homeless Youth Management Information System (RHY MIS) provided a national sample of youth seeking services at crisis shelters. A sub-sample of pregnant females and a random sub-sample (matched by age) of nonpregnant females comprised the study sample (N= 951). Chi-square and t tests identified differences between pregnant and nonpregnant runaway females; maximum likelihood logistic regression identified individual and family-level predictors of teen pregnancy. Results Teen pregnancy was associated with being an ethnic minority, dropping out of school, being away from home for longer periods of time, having a sexually transmitted disease, and feeling abandoned by one's family. Family factors, such as living in a single parent household and experiencing emotional abuse by one's mother, increased the odds of a teen being pregnant. Conclusions The complex problems associated with pregnant runaway/homeless teens create challenges for short-term shelter services. Suggestions are made for extending shelter services to include referrals and coordination with teen parenting programs and other systems of care. PMID:18639785

  19. Toxicokinetic aspects of thiocyanate after oral exposure to cyanide in female Wistar rats in different physiological states.

    PubMed

    de Sousa, Altamir Benedito; Górniak, Silvana Lima

    2014-01-01

    Cyanide (CN) is an ion that has been well studied in toxicology and has been associated with several intoxication episodes: the ingestion of contaminated foods and water, chemical war, suicides, homicides, occupational exposures and the use of certain medicines. The aim of the present study was to determine the toxicokinetic parameters of thiocyante (SCN), the main metabolite of CN, after oral administration of potassium cyanide (KCN) to female rats at diestrus, gestational and lactational periods. Female Wistar rats were divided into three equal groups: virgins in the diestrus phase of the estrus cycle, females at the 14th day of gestation and females at the 14th day of lactation. Each group of rats received 3.0 mg of potassium cyanide per kilogram (KCN/kg body weight) by gavage, and blood was collected at several time points. We also collected amniotic fluid from pregnant rats and milk from the nursing rats to analyze thiocyanate concentration. The results showed that SCN levels were significantly increased in serum, milk and amniotic fluid after administration of KCN. In conclusion, the results of the present study evidence that the metabolism of CN varies greatly considering the physiologic state of the female rat, being females at estrus probably more exposed by these substances than at gestation and lactation because in these states there are other compartments, fetus and milk, which may capture these substances, as demonstrated by the V(d) values. PMID:23841473

  20. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. PMID:27059334

  1. 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

  2. Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.

    PubMed

    Banji, David; Banji, Otilia J F; Pratusha, N Gouri; Annamalai, A R

    2013-09-01

    The study investigated the role of Spirulina platensis in reversing sodium fluoride-induced thyroid, neurodevelopment and oxidative alterations in offspring of pregnant rats. The total antioxidant activity, phycocyanins, and β carotene content were quantified in Spirulina. Thirty female pregnant rats were allocated to six groups and treatment initiated orally from embryonic day (ED) 6 to postnatal day (PND) 15. Treatment groups included control, Spirulina alone, sodium fluoride (20 mg/kg) alone, and sodium fluoride along with Spirulina (250 and 500 mg/kg). Serum fluoride levels were determined on ED 20 and PND 11. Offspring were subjected to behavioural testing, estimation of thyroid levels, oxidative measurements in brain mitochondrial fraction and histological evaluation of the cerebellum. Fluoride-induced alterations in thyroid hormones, behaviour and increased oxidative stress. Spirulina augmented the displacement of fluoride, facilitated antioxidant formation, improved behaviour and protected Purkinje cells. Supplementing Spirulina during pregnancy could reduce the risk of fluoride toxicity in offspring. PMID:23578649

  3. 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

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

    PubMed Central

    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

  5. 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

  6. 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

  7. Moderate exercise with a dietary vitamin C and E combination protects against streptozotocin-induced oxidative damage to the blood and improves fetal outcomes in pregnant rats.

    PubMed

    Naziroğlu, Mustafa; Simşek, Mehmet; Kutlu, Mehmet

    2004-05-01

    A considerable amount of clinical and experimental evidence now exists suggesting that many biochemical pathways strictly associated with diabetes increase the production of reactive oxygen species (ROS). However, daily moderate exercise and vitamins C and E (VCE) supplementation can be beneficial to diabetes due to reducing blood glucose and free radical production. In the present study, we investigated the effect of VCE and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the blood of STZ-induced diabetic pregnant rats. Fifty female Wistar rats were used and were randomly divided into five groups. The first and second were used as the control and pregnant control groups, respectively. The third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Body weights in the five groups were recorded weekly. Plasma and red blood cell (RBC) samples were taken from all animals on day 20. Glutathione peroxidase (GSH-Px), catalase and reduced glutathione (GSH) levels in plasma and RBCs, glucose, vitamins A, E and beta-carotene in plasma, the number of fetuses, and body weight were lower in pregnant diabetic rats than in control animals, whereas there was a significant increase in platelet counts and plasma and RBC MDA levels. The decreased antioxidant enzymes did not improve through exercise only. However, the decreased vitamins, and increased MDA, glucose levels and white blood cell (WBC) counts were improved either by exercise or exercise plus VCE supplementation. There were no significant changes in the RBC counts and hemoglobin values in the five groups. In conclusion, these data demonstrate that there is an increase in MDA in the blood of diabetic pregnant animals, whereas there is a decrease in the number of fetuses, antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system due to reducing ROS. They may play a role in preventing diabetes-related diseases of pregnant subjects. PMID:15202787

  8. Effect of afobazole administered to pregnant rats during organogenesis on prenatal development of fetuses.

    PubMed

    Bugayova, L I; Denisova, T D; Morozova, Yu A; Sergeeva, S A; Kharlamov, I V

    2014-11-01

    Experiments on pregnant rats have demonstrated the absence of damaging effect of Afobazole administered during the antenatal period on organogenesis in fetuses. Afobazole in a dose of 5 mg/kg given to pregnant rats on gestation days 6-16 reduced pre- and post-implantation fetal mortality and improved fertility; 20-day-old embryos had no developmental abnormalities and did not differ from controls by craniocaudal size, body weight, and skeleton ossification. Afobazole in a dose of 100 mg/kg reduced pre- and post-implantation fetal mortality, but had no effect on fertility. No congenital malformations were found in the fetuses, but they were characterized by lower craniocaudal size, body weight, and number of ossification foci in the sternum and spine. PMID:25403398

  9. 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

  10. Suckling-induced prolactin release potentiates mifepristone-induced lactogenesis in pregnant rats.

    PubMed

    Deis, R P; Carrizo, D G; Jahn, G A

    1989-09-01

    Suckling, starting at 19:00 h on Day 18 of pregnancy, induced a significant increase in serum prolactin concentration at 20:00 h on Day 19 of pregnancy, but no increase in mammary gland casein or lactose content. Mifepristone (2 mg/kg) injection at 08:00 h on Day 19 of pregnancy induced significant increases in casein, but not in lactose, 24 h after administration. Mifepristone alone did not induce prolactin secretion, indicating that lactogenesis was induced by placental lactogen in the absence of progesterone action. When mifepristone was injected into suckling rats, serum prolactin concentrations were higher than in the untreated suckling rats. Casein in these rats increased significantly 12 h after mifepristone administration and lactose at 24 h after. If the suckling mifepristone-treated rats were given two injections of bromocriptine (1.5 mg/kg) at 12:00 h on Days 18 and 19 of pregnancy, serum prolactin concentrations were not increased by suckling, but casein and lactose concentrations in the mammary gland showed values similar to those obtained in the mifepristone-treated non-suckling rats. Mifepristone can therefore potentiate suckling-induced prolactin release in pregnant rats, demonstrating a direct central inhibitory action of progesterone on prolactin secretion. This suckling-induced prolactin secretion, unable to induce casein or lactose synthesis in the presence of progesterone, enhanced significantly synthesis of these milk components in the absence of progesterone action (rats treated with mifepristone). Fatty acid synthase, which is stimulated by the suckling stimulus in lactating rats, was not modified by mifepristone or suckling in pregnant rats. PMID:2621690

  11. Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats.

    PubMed

    Hines, T; Lindheimer, M D; Barron, W M

    1993-12-01

    Pressor responses to angiotensin II (ANG II) are markedly attenuated in reflex-intact pregnant animals, a phenomenon widely attributed to intrinsic changes in vascular reactivity. To test the hypothesis that gestational augmentation of neural reflex activity contributes importantly to this phenomenon, changes in mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were compared during constant infusion (25-400 ng.kg-1.min-1) of ANG II in conscious virgin and pregnant rats, using a model of total autonomic blockade (chlorisondamine chloride and methscopolamine bromide), with restoration of baseline hemodynamics by infusion of norepinephrine. Basal CO was higher and TPR lower in pregnant (CO 121.8 +/- 3.8 ml/min; TPR 0.78 +/- 0.04 mmHg.ml-1.min) compared with virgin (CO 95.9 +/- 3.9 ml/min; TPR 1.05 +/- 0.08 mmHg.ml-1.min) rats (P < 0.005). Pressor responses to ANG II were similar in both groups of reflex-blocked animals due to comparable changes in TPR and CO (not significant by repeated-measures analysis of variance). Other experiments demonstrated that changes in MAP after bolus administration of ANG II did not differ in areflexic virgin and gravid rats. Thus in the absence of autonomic control ANG II has similar effects on systemic resistance in pregnant and nonpregnant rats, suggesting that reflex neural mechanisms contribute significantly to gestational changes in pressor responsiveness. These data further suggest that pregnancy is not accompanied by a generalized decrease in vascular reactivity to all pressor agents. PMID:7904425

  12. 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

  13. Fulminant hepatic failure from hepatitis E in a non-pregnant female traveller.

    PubMed

    Chris, Robert B; Keystone, Jay S

    2016-04-01

    A non-pregnant Canadian woman returning from India presented with a 1-week history of jaundice and malaise. Subsequently, she developed fulminant hepatic failure caused by hepatitis E virus (HEV). HEV can cause fulminant hepatic failure, most commonly in pregnant women and those with chronic liver disease; however, all travellers are at risk. PMID:27069000

  14. 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

  15. 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

  16. 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.

  17. Temporal changes in insulin resistance and secretion in 24-h-fasted conscious pregnant rats.

    PubMed

    Rossi, G; Sherwin, R S; Penzias, A S; Lapaczewski, P; Jacob, R J; Shulman, G I; Diamond, M P

    1993-12-01

    To determine the temporal sequence of pregnancy-induced changes in insulin action and secretion, awake midpregnant (11-12 days) and late pregnant (19-20 days) rats underwent a two-step euglycemic hyperinsulinemic or a hyperglycemic clamp study after a 24-h fast. During euglycemia, insulin-stimulated increments in glucose uptake and clearance in midpregnant rats were reduced by 60-70% at the lower dose (insulin approximately 360 pM) and by 20-30% at the higher dose (insulin approximately 1,750 pM; P < 0.01 vs. virgin controls). Insulin action was also diminished in late pregnant rats. However, the magnitude of resistance did not increase. Insulin-mediated suppression of glucose production was only minimally impaired in midpregnancy. In contrast, glucose production was virtually unchanged in late pregnancy, even at the highest insulin dose. During hyperglycemia, insulin responses in late pregnancy were markedly increased 5-fold above controls and 2.5-fold above midpregnant rats (P < 0.05). We conclude that rat pregnancy is characterized by the early appearance of peripheral insulin resistance. As pregnancy progresses toward term, marked hepatic insulin resistance and insulin hypersecretion develop, whereas peripheral insulin resistance demonstrates negligible changes. These data imply that insulin hypersecretion during late pregnancy is most closely linked to hepatic insulin resistance, at least in 24-h-fasted animals. PMID:8279539

  18. Comparison of aortic calcium and contractility in male, female and lactating female rats.

    PubMed

    DeFelice, A F; Joiner, P D

    1975-07-01

    Catecholamine-induced vascular smooth muscle contration is enhanced in female animals and in presence of emale sex hormones in vitro. Androgens appear to depress these responses. Sex steroids may also alter calcium ion (Ca++) binding and metabolism. We compared contractility as well as quantity and relative lability of tissue calcium pools in male and female rat isolated aortic strips bathed in Ca++-free solution. We also studied aortic strips from 21-day postpartum lactating female rats to determine the effects of previous high circulating levels of female sex steroids (present during pregnancy) and prolactin (present during lactation). Rat aortic strips were found to contain loosely and more tightly held calcium stores. Strips from males were unresponsive in Ca++-free solution unless previously exposed to a Ca++-rich bathing medium. They accumulated more tissue calcium when bathed in Ca++-rich solution than did strips from females. This extra calcium appears to reside in the loosely-held fraction. Tissues from males first incubated in Ca++-rich solution to enhance the loosely held fraction respond more readily in Ca++-free solution to a high potassium (K+) concentration than to epinephrine. Strips from females respond about equally to high K+ or epinephrine whereas aorta from lactating female rats are much more responsive to epinephrine in Ca++-free solution and gain less calcium in Ca++-rich medium than those of the other rats. These data suggest that in the presence of high circulating levels of female sex hormones or other female factors (e.g., prolactin) enhanced binding or sequestration of potential activator ions occurs which increases the responsiveness of the tissue to catecholamines. Male sex hormones and/or factors promote the capacity of the rat aorta to gain a more loosely held calcium fraction which is readily used for contraction by K+ depolarization. PMID:1151750

  19. Suppression of erythrocyte production in zinc deficient pregnant rats

    SciTech Connect

    Morgan, P.N.; Wehr, C.M.; King, J.C. )

    1991-03-15

    Rat dams fed zinc (Zn) deficient diets during pregnancy accumulate excessive liver iron (Fe) concentrations. In this study, the authors investigated the effect of Zn deficiency on erythropoiesis. Sprague-Dawley rats were fed diets containing 50 {mu}g (ZnAd) or less than 0.5 {mu}g (Zndef) Zn/g diet from d0 to d19 of gestation; food intake and weight were recorded daily. Dams were killed by CO{sub 2} asphyxiation on d19 of pregnancy. Smears were made from dam femur bone marrow and analyzed for erythrocyte (RBC) number and maturity. Plasma, liver and bone were analyzed for Zn and Fe concentrations by AAS. In the ZnAd and Zndef dams, mean ({plus minus}sem) bone Zn was 140 {plus minus} 3 and 104 {plus minus} 2 {mu}g/g; plasma Zn was 112 {plus minus} 3 and 41 {plus minus} 4 {mu}g/dl; and liver Fe was 104 {plus minus} 10 and 185 {plus minus} 16 {mu}g/g, respectively. During gestation, mean weight gain of ZnAd was 91 {plus minus}4 g, and Zndef dams had no weight gain. Mean number of fetuses/dam of ZnAd were 12 {plus minus} 2 and Zndef were 7 {plus minus} 2. Fetal weight was 2.3 {plus minus} 0.1 g in ZnAd and 1.4 {plus minus} 0.1 g in Zndef. Zndef dams resorbed 44% of their implantation sites and 34% of their fetuses had gross teratology. Compared to ZnAd dams, the newly formed RBCs of Zndef dams show marked reduction, indicating suppression of bone marrow erythropoiesis. Thus, severely Zn deficient rat dams were unable to mobilize their excessively high liver Fe stores and could not maintain normal erythropoiesis.

  20. 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

  1. 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; Gómez, F; Segovia, S; Pérez-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

  2. Hypothyroidism prolongs corpus luteum function in the pregnant rat.

    PubMed

    Hapon, María Belén; Motta, Alicia B; Ezquer, Marcelo; Bonafede, Melisa; Jahn, Graciela A

    2007-01-01

    It has been shown that hypothyroidism in the rat produces a prolongation of pregnancy associated with a delay in the fall of circulating progesterone (P4) at term. The aim of the present work is to determine whether the delayed P4 decline in hypothyroid mother rats is due to a retarded induction of P4 degradation to 20alphaOH P4 or to a stimulation of its synthesis, and to investigate the possible mechanisms that may underlie the altered luteal function. We determined by RIA the circulating profile of the hormones (TSH, PRL, LH, P4, PGF2alpha, and PGE2) involved in luteal regulation at the end of pregnancy and, by semiquantitative RT-PCR, the expression of factors involved in P4 synthesis (CytP450scc, StAR, 3betaHSD, PRLR) and metabolism (20alphaHSD, PGF2alphaR, iNOS and COX2). Our results show that the delay in P4 decline and parturition is the resultant of retarded luteal regression, caused by a combination of decreases in luteolytic factors, mainly luteal PGF2alpha, iNOS mRNA expression and also circulating LH, and increased synthesis or action of luteotrophic factors, such as luteal and circulating PGE2 and circulating PRL. All these changes may be direct causes of the decreased 20alphaHSD mRNA and protein (measured by western blot analysis) expression, which in the presence of unchanged expression of the factors involved in P4 synthesis results in elevated luteal and circulating P4 that prolonged pregnancy and also may favor longer survival of the corpus luteum. PMID:17244746

  3. 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.

  4. 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

  5. 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

  6. Prenatal Exposure to Soy Isoflavones Altered the Immunological Parameters in Female Rats.

    PubMed

    Ebaid, Hala M; Elgawish, Rania Abdel Rahman; Abdelrazek, Heba M A; Gaffer, Ghada; Tag, Hend M

    2016-05-01

    Information on the effects of phytoestrogens on animals has increased recently; however, there were only few studies on prenatal exposure on cellular immune response. Pregnant rats were assigned to 3 groups (12 rats per group), the first was fed control diet, the second was fed low-dose (6.5 g/100 g of diet) soy isoflavones, while the third was fed high-dose (26 g/100 g of diet) soy isoflavones. The female offspring cell-mediated immune response was determined using phytohemagglutinin (PHA) injection, and intumesce index was calculated on postnatal day 50. After 24 hours of PHA injection, blood samples were collected for tumor necrosis factor α, interferon γ (IFN-γ), and interleukin (IL)-12 determination. Spleen, thymus, and PHA-injected footpads were fixed for histopathology. Intumesce index was significantly (P < 0.05) reduced in rats' offspring born from dams fed low- and high-dietary soy isoflavones than that in control groups. Thymic relative weights in offspring of rats fed high-dietary soy isoflavones showed a significant (P < 0.05) decrease compared to that in the control group. Female offspring where low and high-dietary soy isoflavones were fed to their dams showed a significant (P < 0.05) decrease in IFN-γ and IL-12 than that in control ones. Spleen of rats born from dams fed high dose of dietary soy isoflavones showed lymphocytic depletion in white pulp. Taking together, it is clear that dietary soy isoflavones at prenatal period had immunosuppressive effect on female offspring after PHA stimulation. This effect was mediated through reduced IFN-γ that interplayed in IL-12 production pathway thus reducing its level. PMID:26758869

  7. 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

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

    PubMed

    Zorzano, A; Lasunción, 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 14C-alanine, 14C-pyruvate, or 14C-glycerol. Concentrations of 0.2 mmols of 14C-glycerol or 14C-pyruvate, but not of 14C-alanine, enhanced 14C-glucose production in pregnant rats, whereas 1 mmol of any of the three 14C-substrates always enhanced 14C-glucose production in these rats. Both 1 mmol/L and 5 mmol/L 14C-alanine increased 14C-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. PMID:3959901

  9. 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.

  10. Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats.

    PubMed

    Hapon, María Belén; Varas, Silvia M; Jahn, Graciela A; Giménez, María S

    2005-06-01

    Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring development that may result from the effect on lactation of maternal metabolism dysfunction. We studied the effects of prolonged propylthiouracil (PTU)-induced hypoT (0.1% PTU in drinking water starting 8 days before mating until day 21 of pregnancy or for 30 days in virgin rats) on liver and mammary lipid metabolism and serum lipid concentrations. In virgins, hypoT reduced hepatic mRNAs associated with triglyceride (TG) and cholesterol synthesis (including fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase), and induced lobuloalveolar mammary development. Pregnancy increased hepatic mRNAs associated with TG and cholesterol synthesis and uptake (including LDL receptor) and with lipid oxidation, such as acyl CoA oxidase. HypoT decreased mRNAs and the activity of proteins associated with TG synthesis, and mRNAs associated with cholesterol uptake and lipid oxidation. Pregnancy increased mammary mRNAs related to lipid oxidation and decreased cholesterol synthesis, whereas hypoT decreased mRNAs and activities of proteins associated with TG synthesis and decreased epithelial mammary tissue. Virgin and pregnant hypoT rats had increased circulating VLDL + LDL cholesterol. HypoT decreased circulating TGs in pregnant rats. The observed effects of hypoT may result in decreased mammary lipid availability. This, along with the decreased epithelial mammary tissue during lactogenesis, may contribute to the future lactational deficit of hypoT mothers. PMID:15741655

  11. Influence of static magnetic field on cadmium toxicity: study of oxidative stress and DNA damage in pregnant rat tissues.

    PubMed

    Chater, Sihem; Douki, Thierry; Favier, Alain; Garrel, Cathrine; Sakly, Mohsen; Abdelmelek, Hafedh

    2008-01-01

    In our environment, we have numerous chances to be exposed to not only static magnetic fields (SMFs) but also many chemicals containing mutagens. Therefore, the aim of this study was to investigate the effects of co-exposure to SMF and cadmium (Cd) on the antioxidant enzymes activity and DNA damage in pregnant rat tissues. Pregnant rats were treated with cadmium (CdCl(2), 3.0 mg/Kg body weight) or exposed to SMF (128 mT/h/day) and treated with cadmium chlorides (3.0 mg/kg, body weight) for 13 consecutive days as from the 6th to 19th day of gestation. Cd treatment increased malondialdehyde (MDA) and 8-oxodGuo levels in kidney of pregnant rats. However, the activity of superoxide dismutase (SOD) and glutathione level were decreased in kidney. Interestingly, the combined effects of SMF and Cd have no effects on activities of antioxidant in both tissues compared to cadmium treated group. However, the association between SMF and Cd decreased plasma MDA concentration. The same treatment failed to alter 8-oxodGuo concentration. Sub-acute Cd treatment altered antioxidant enzymes and DNA in kidney of pregnant rats. The results suggest that a homeostatic defence mechanism was activated when SMF was associated to Cd in pregnant rats. PMID:19037788

  12. [The correlation of stress and neurosis vulnerability in the structure of nonspecific resistance to extreme factors in intact and pregnant rats].

    PubMed

    Chernositov, A V; Orlov, V I; Miroshnichenko, V G

    1994-01-01

    White male rats, intact and pregnant females were subjected for 3 days to deprivation of paradoxical sleep by the technique of Jouvet. The main resulting vectors of the extreme state outcome, i.e., lethality, susceptibility to stress, and neurotization, made it possible to establish corresponding levels of resistance. A relationship of each of the levels with the ability to form conditioned reflexes, initial functional interhemispheric asymmetry and behavioural status, expression of protective reactions and paradoxical sleep under conditions of an insoluble conflict situation was followed. High resistance of pregnant rats is considered to be associated with the formation of gestational ambilaterality of the brain of intact animals. Such an increase in resistance is selective as far as it concerns the organism of the pregnant and it does not ensure stability of the feto-maternal complex under extreme conditions. It was established that there was an inverse relationship between the expression of neurotic disorders of the higher nervous activity and vegeto-morphological features of acute stress. This gives reason to define more exactly the role of neurotic disorders in the pathogenesis of stress and mechanisms of resistance to extreme factors. PMID:7879434

  13. Effect of hypothyroidism on hormone profiles in virgin, pregnant and lactating rats, and on lactation.

    PubMed

    Hapon, M B; Simoncini, M; Via, G; Jahn, G A

    2003-09-01

    Thyroid dysfunctions can produce reproductive problems. Untreated maternal hypothyroidism has serious consequences on development of offspring, resulting in stunted growth and mental retardation. The effects of propylthiouracyl-induced hypothyroidism (0.1 g l(-1) in drinking water starting 8 days before mating, or given to virgin rats for 30 or 50 days) on the serum profiles of hormones related to reproduction and mammary function (prolactin, growth hormone (GH), progesterone, corticosterone, oestradiol, insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH), triiodothyronine and tetraiodothyronine), and on mammary function in virgin, pregnant and lactating rats, were investigated. Propylthiouracyl treatment severely decreased circulating triiodothyronine and tetraiodothyronine concentrations, and increased serum TSH concentrations. Virgin rats showed prolonged periods of vaginal dioestrus, increased circulating progesterone concentrations and afternoon peaks of prolactin concentration, which are indicative of prolactin-induced pseudopregnancy. Propylthiouracyl-treated virgin rats had mammary development comparable to that of midpregnancy, and half of these rats had increased mammary casein and lactose concentrations. Serum prolactin concentrations were decreased on the afternoon of day 5 of pregnancy, increased during late pregnancy (days 15-21) and were normal during lactation. Circulating GH concentrations decreased on days 15-21 of pregnancy, whereas progesterone concentrations increased during late pregnancy and early lactation. Circulating oestradiol (measured in late pregnancy and in virgin rats), IGF-I and corticosterone concentrations were decreased. Although assessment of mammary histology showed no differences in extent of development, casein content was increased in propylthiouracyl-treated rats on day 21 of pregnancy; litter growth was severely reduced and at day 20 of age the pups were hypothyroid, with decreased GH serum concentrations. An acute suckling experiment was performed on days 10-12 of lactation to determine whether some impairment in mammary function or the suckling reflex might account for these differences. After an 8 h separation of mothers from their litters and 30 min of suckling, circulating prolactin values were not affected by propylthiouracyl treatment, but serum oxytocin concentration and milk excretion were reduced. In conclusion, hypothyroidism induces various alterations in the hormone profiles of virgin and pregnant rats, and induces pseudopregnancies and mammary development in virgin rats. These alterations do not appear to have an overt impact on the outcome of pregnancy and on mammary function during lactation, with the exception of the milk ejection reflex, which may account at least partially for the reduced litter growth. PMID:12968945

  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. 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 ...

  16. 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…

  17. 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 ...

  18. 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.

  19. Neonatal handling and reproductive function in female rats.

    PubMed

    Gomes, C M; Raineki, C; Ramos de Paula, P; Severino, G S; Helena, C V V; Anselmo-Franci, J A; Franci, C R; Sanvitto, G L; Lucion, A B

    2005-02-01

    Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis. PMID:15684351

  20. MDMA administration to pregnant Sprague-Dawley rats results in its passage to the fetal compartment.

    PubMed

    Campbell, Nicholas G; Koprich, James B; Kanaan, Nicholas M; Lipton, Jack W

    2006-01-01

    Recent investigations have demonstrated that prenatal 3,4-methylenedeoxymethamphetamine (MDMA; ecstasy) exposure in rats results in significant and persistent changes in the developing brain. However, no published pharmacokinetic studies exist demonstrating that MDMA administered during pregnancy passes to the fetal compartment. This leaves open the question whether MDMA is directly acting on the fetal brain to produce the observed changes in previous studies, or whether such effects are an indirect result of MDMA administration to the pregnant dam. Therefore, pregnant rats were administered a single dose of MDMA (15 mg/kg, subcutaneous) at embryonic day 14 (E14) and the levels of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) were quantified in maternal plasma, amniotic fluid, and fetal brain over 8 h by HPLC. The time course of MDMA and MDA metabolism was reliable and reproducible in all tissues. There was a strong correlation between fetal amniotic fluid and fetal brain suggesting that amniotic fluid could be used to reliably estimate fetal brain levels without directly utilizing fetal brain tissue. These data also provide a framework for subsequent in vitro cell culture studies using biologically relevant MDMA doses. PMID:16905291

  1. 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.

  2. Toxoplasmosis screening and risk factors amongst pregnant females in Natal, northeastern Brazil.

    PubMed

    Barbosa, Isabelle Ribeiro; de Carvalho Xavier Holanda, Cecília Maria; de Andrade-Neto, Valter Ferreira

    2009-04-01

    Toxoplasmosis results in systemic disease, and if the mother is infected for the first time during gestation, the fetus may suffer substantial damage. Relatively little is known about the epidemiology of toxoplasmosis in pregnancy in most states of northeastern Brazil. Seroprevalence of toxoplasmosis among pregnant woman was studied in Natal, capital of Rio Grande do Norte State, in northeastern Brazil, from March to December 2007. The sera were tested for IgM and avidity of IgG antibodies to Toxoplasma by a microparticle enzyme immunoassay. The overall seroprevalence was high [126/190 (66.3%)]; prevalence increased with age indicating that in this setting most infections occur in adulthood (third decade of life). Only one pregnant woman was IgM positive and had high-avidity antibodies. The high percentage of pregnant women who are vulnerable to this parasite (33.1%) favors primary infection during pregnancy. Our studies show that direct contact with cats or dogs was highly associated with toxoplasmosis (odds ratio 2.72, P<0.001, 95% CI 1.46-5.02). The number of years in school (P<0.001), precarious socioeconomic status and limited knowledge about the disease (P

  3. Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats

    PubMed Central

    Bae, Soochan; Gilbert, Raymond D; Ducsay, Charles A; Zhang, Lubo

    2005-01-01

    The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia–reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg−1) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKCɛ and phospho-PKCɛ levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKCɛ gene expression in the male heart may play an important role. PMID:15677681

  4. The effect of exercise on carbohydrate preference in female rats.

    PubMed

    Keeley, R J; Zelinski, E L; Fehr, L; McDonald, R J

    2014-02-01

    Exercise has a myriad of health benefits, including positive effects against heart disease, diabetes, and dementia. Cognitive performance improves following chronic exercise, both in animal models and humans. Studies have examined the effect of exercise on feeding, demonstrating a preference towards increased food consumption. Further, sex differences exist such that females tend to prefer carbohydrates over other macronutrients following exercise. However, no clear effect of exercise on macronutrient or carbohydrate selection has been described in animal or human studies. This research project sought to determine the effect of voluntary exercise on carbohydrate selection in female rats. Preference for a complex (starch) versus a simple (dextrose) carbohydrate was assessed using a discriminative preference to context paradigm in non-exercising and voluntarily exercising female rats. In addition, fasting blood glucose and performance in the Morris water task was examined in order to verify the effects of exercise on performance in this task. Female rats given access to running wheels preferred a context previously associated with starch, whereas females with no running wheel access preferred a context previously associated with dextrose. No changes in blood glucose were observed. However, cognitive differences in the Morris water task were observed such that voluntary exercise allowed rats to find a new location of a hidden platform following 4 days of training to an old platform location. These results suggest that voluntary exercise may decrease preservative behaviors in a spatial navigation task through the facilitation of plasticity mechanisms. This study is the first of its kind to demonstrate the influence of exercise on taste preference for complex and simple carbohydrates with this context conditioning paradigm. PMID:24406468

  5. Endocannabinoid influence on partner preference in female rats.

    PubMed

    Memos, Nicoletta K; Vela, Rebekah; Tabone, Courtney; Guarraci, Fay A

    2014-09-01

    The present study investigated the role of the endocannabinoid system on sexual motivation in the female rat. In Experiment 1, gonadally intact female rats were first tested for partner preference after a vehicle injection. Approximately 2 weeks later, all rats were tested again after an injection of the endocannabinoid antagonist, SR141716 (SR; also known as Rimonabant; 1.0mg/kg). During the first 10 min of each partner preference test, subjects could spend time near either a male or female stimulus animal that was placed behind a wire mesh (No-Contact). During the second 10 min of each partner preference test, subjects had unrestricted access to both stimulus animals (Contact). When the female subjects were treated with SR, they made fewer visits to either stimulus animal during the no-contact phase of the partner preference test compared to when they were treated with vehicle. In Experiment 2, ovariectomized (OVX) subjects primed with estrogen were administered SR or vehicle and tested for partner preference (Experiment 2A). Approximately 2 weeks later, the subjects from the control group were tested again after an injection of SR (Experiment 2B). In contrast to Experiment 1, treatment with SR reduced the number of visits specifically to the male stimulus during the contact phase of the test in Experiment 2. Experiment 3 tested the effects of SR on general locomotion and found no effect of SR on line crossings in an open field. Finally, in Experiment 4, OVX estrogen- and progesterone-primed subjects were administered the endocannabinoid agonist anandamide (AEA: 1.0mg/kg) or vehicle and tested for partner preference. AEA-treated subjects made more visits to the male stimulus than vehicle-treated subjects during the contact phase of the test. The results of the present study suggest that the endocannabinoid system may contribute to sexual motivation in female rats by specifically altering approach behavior. PMID:25042777

  6. 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-o’clock 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-o’clock 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-o’clock position and MUCP at the 12-o’clock 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

  7. Lactogenic actions of different growth hormone preparations in pregnant and lactating rats.

    PubMed

    Carón, R W; Jahn, G A; Deis, R P

    1994-09-01

    We studied the capacity of different GH preparations, natural human (h)GH, recombinant hGH (rhGH), rat (r)GH, ovine (o)GH, bovine (b)GH and porcine (p)GH, and ovine prolactin (oPRL), to stimulate lactogenesis in ovario-hysterectomized pregnant rats or intact lactating rats treated with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in mammary casein and lactose and positive response to the oxytocin test, 28 h later. Lactogenesis was prevented by treatment with BC (1.5 mg/kg) immediately after surgery (OVX-HYS-BC). The hormones were given at doses of 0.25 or 0.5 mg/rat (except rhGH given only at 0.5 mg/rat) at 1200 and 2000 h on day 19. Casein was increased by both doses of oPRL and hGH, rhGH and 0.25 mg oGH, and lactose by both doses of oPRL, rhGH and 0.25 mg rGH. The other GH preparations had no effect. The oxytocin test demonstrated the presence of milk in the mammary tissues of the OVX-HYS rats and in the OVX-HYS-BC plus oPRL (0.25 and 0.5 mg) or rhGH-treated groups. Injection of BC to pregnant rats at 2000 h on day 20 and at 0800 h on day 21 decreased litter growth on the first 4 days postpartum. Two-thirds of the litters resumed growth after day 4, indicating the recuperation of milk production, while the rest never recuperated. Serum prolactin in BC-treated rats was reduced until day 4 postpartum. On day 6 the rats which had recuperated had normal values, while those which had still not recuperated had lower values. BC-treated rats were injected s.c. with 0.25 mg each of oPRL, hGH, rGH, oGH, bGH or pGH, or 0.25 or 0.5 mg rhGH/rat, immediately postpartum and 12, 24 and 36 h later. hGH and 0.5 mg rhGH induced levels of milk production similar to controls except on day 3. oPRL and rhGH (0.25 mg), induced a partial reversion of the effect of BC. rGH and oGH had a slight effect on days 1 and 2 and all the litters resumed growth on day 7. In contrast, pGH and bGH were inactive. The affinity of hGH for the prolactin receptor, measured as displacement of 125I-labelled oPRL binding to crude liver membranes, was comparable with that of oPRL. While rhGH was ten times less active than oPRL, rPRL was 100 times lower and all the other GH preparations had at least 10(4) times lower capacity to displace 125I-labelled oPRL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7964304

  8. 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.

  9. 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.

  10. Moderate Exercise Attenuates Lipopolysaccharide-Induced Inflammation and Associated Maternal and Fetal Morbidities in Pregnant Rats

    PubMed Central

    Macdonald-Goodfellow, Shannyn K.; Surita, Fernanda G.; Pinto e Silva, João L.; Tayade, Chandrakant; Othman, Maha; Ozolinš, Terence R. S.

    2016-01-01

    Fetal growth restriction (FGR) and coagulopathies are often associated with aberrant maternal inflammation. Moderate-intensity exercise during pregnancy has been shown to increase utero-placental blood flow and to enhance fetal nutrition as well as fetal and placental growth. Furthermore, exercise is known to reduce inflammation. To evaluate the effect of moderate-intensity exercise on inflammation associated with the development of maternal coagulopathies and FGR, Wistar rats were subjected to an exercise regime before and during pregnancy. To model inflammation-induced FGR, pregnant rats were administered daily intraperitoneal injections of E. coli lipopolysaccharide (LPS) on gestational days (GD) 13.5–16.5 and sacrificed at GD 17.5. Control rats were injected with saline. Maternal hemostasis was assessed by thromboelastography. Moderate-intensity exercise prevented LPS-mediated increases in white blood cell counts measured on GD 17.5 and improved maternal hemostasis profiles. Importantly, our data reveal that exercise prevented LPS-induced FGR. Moderate-intensity exercise initiated before and maintained during pregnancy may decrease the severity of maternal and perinatal complications associated with abnormal maternal inflammation. PMID:27124733

  11. 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; Vinícius Dias, Kümpel; Luiz, Yamauchi Junior; Fernando, Frei; Telma Gonçalves 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

  12. Safety evaluation of Phytovagex, a pessary formulation of Nigella sativa, on pregnant rats

    PubMed Central

    Salarinia, Reza; Rakhshandeh, Hassan; Oliaee, Davood; Gul Ghasemi, Sima; Ghorbani, Ahmad

    2016-01-01

    Objective: The possible toxicity of drugs in pregnancy should be tested before their use in pregnant patients. In the present study, we aimed to evaluate the safety of phytovagex, a pessary formulation of Nigella sativa (N. sativa), which is already in clinical use for vaginal fungal infection. Materials and Methods: The pregnant rats were treated intravaginal with physiological saline (vehicle) or phytovagex pessary in the first half of their pregnancy (days 1 to 10 of gestation). Duration of pregnancy and health parameters of the newborns were recorded after parturition. Also, cytotoxicity of N. sativa hydroalcoholic extract was tested against ovary Cho cells. Results: The phytovagex had no significant effect on the duration of pregnancy, number of newborns, weight of neonates, and percent of stillbirth. No deformity or general behavioral abnormality was observed in neonates monitored for 30 days after birth. N. sativa extract had no significant effect on the viability of ovary cells at the concentrations of 12.5-200 µg/mL. Conclusion: Results of this animal study showed that phytovagex has no overall effect on the duration of pregnancy and health parameters of the newborns. Also, its active agent, N. sativa, does not induce any cytotoxic effect on ovary cells.

  13. Considerations in Management of Rhegmatogenous Retinal Detachment in One Eyed Pregnant Females: A Report of Two Cases

    PubMed Central

    Ashish, M; Alok, S; Elesh, J; Shubhi, T

    2015-01-01

    The aim of this case report is to discuss issues related to management of one eyed pregnant female. A 26-year-old female (Patient A) and 28-year-old female (Patient B) both in second trimester and one eyed presented to our outpatient department with diminution of vision due to rhegmatogenous retinal detachment (RRD). Retina was attached in Patient A following scleral buckling surgery but Patient B required pars plana vitrectomy with silicon oil tamponade. Best corrected visual acuity in both patients did improve from 1/60 to 6/24 and 6/18, respectively at 6 months follow-up. Exudative RDs are known to occur in pregnancy as a complication of preeclampsia, but RRD in pregnancy although co-incidental poses certain challenge with regard to management of such cases especially if the patient is one-eyed. Things to consider for management include (1) type of anesthesia (2) surgical positioning (3) positioning after surgery (4) anti-glaucoma medication if required (5) corticosteroid treatment in pregnancy (6) to provide them ambulatory vision as early as possible. With proper management and monitoring it is possible to provide them with early ambulatory vision without offering any harm to her pregnancy and fetus. PMID:27057392

  14. 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

  15. 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

  16. Endocrine Disrupting Effects of Triclosan on the Placenta in Pregnant Rats

    PubMed Central

    Zhang, Zhaobin; Shi, Jiachen; Jiao, Zhihao; Shao, Bing

    2016-01-01

    Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5α-reductase 1 (SRD5A1) and steroid 5α-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ERα) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth. PMID:27149376

  17. 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.

  18. Endocrine Disrupting Effects of Triclosan on the Placenta in Pregnant Rats.

    PubMed

    Feng, Yixing; Zhang, Pin; Zhang, Zhaobin; Shi, Jiachen; Jiao, Zhihao; Shao, Bing

    2016-01-01

    Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5α-reductase 1 (SRD5A1) and steroid 5α-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ERα) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth. PMID:27149376

  19. 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

  20. In-flight dose estimates for aircraft crew and pregnant female crew members in military transport missions.

    PubMed

    Alves, J G; Mairos, J C

    2007-01-01

    Aircraft fighter pilots may experience risks other than the exposure to cosmic radiation due to the characteristics of a typical fighter flight. The combined risks for fighter pilots due to the G-forces, hypobaric hypoxia, cosmic radiation exposure, etc. have determined that pregnant female pilots should remain on ground. However, several military transport missions can be considered an ordinary civil aircraft flight and the question arises whether a pregnant female crew member could still be part of the aircraft crew. The cosmic radiation dose received was estimated for transport missions carried out on the Hercules C-130 type of aircraft by a single air squad in 1 month. The flights departed from Lisboa to areas such as: the Azores, several countries in central and southern Africa, the eastern coast of the USA and the Balkans, and an estimate of the cosmic radiation dose received on each flight was carried out. A monthly average cosmic radiation dose to the aircraft crew was determined and the dose values obtained were discussed in relation to the limits established by the European Union Council Directive 96/29/Euratom. The cosmic radiation dose estimates were performed using the EPCARD v3.2 and the CARI-6 computing codes. EPCARD v3.2 was kindly made available by GSF-National Research Centre for Environment and Health, Institute of Radiation Protection (Neuherberg, Germany). CARI-6 (version July 7, 2004) was downloaded from the web site of the Civil Aerospace Medical Institute, Federal Aviation Administration (USA). In this study an estimate of the cosmic radiation dose received by military aircraft crew on typical transport missions is made. PMID:17277329

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Brain microsomal metabolism of phencyclidine in male and female rats.

    PubMed

    Laurenzana, E M; Owens, S M

    1997-05-01

    These studies examined the microsomal brain metabolism of phencyclidine (PCP) in male and female Sprague-Dawley rats. Several monohydroxylated metabolites of PCP were detected including cis- and trans-1-(1-phenyl-4-hydroxycyclohexyl)piperidine (c-PPC and t-PPC) and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (PCHP). The in vitro formation of these metabolites required NADPH and was inhibited by carbon monoxide. c-PPC was formed in the male and female brain microsomes at rates of 7.1 +/- 1.3 and 5.7 +/- 1.1 fmol/min per mg, respectively, while t-PPC was formed at rates of 16.2 +/- 3.3 and 16.5 +/- 4.2 fmol/min per mg. PCHP had the highest formation rate at 50.7 +/- 8.9 and 48.2 +/- 8.8 fmol/min per mg, respectively. Although previous studies with rat liver microsomes find higher levels of PCP metabolism in male rats and the formation of an irreversibly bound metabolite in male rats, the present study of brain metabolism found no sex differences in brain metabolism. The formation of PCP metabolites in male rat livers is at least partially mediated by the male-specific isozyme CYP2C11, and possibly CYP2D1. Nevertheless, the formation of the major brain metabolite, PCHP, was not inhibited by an anti-CYP2C11 or an anti-CYP2D6 antibody. However, PCHP formation was inhibited by drug inhibitors of CYP2D1-mediated metabolism, suggesting the involvement of a CYP2D isoform. These data indicate brain metabolism of PCP is significant, but unlike the liver it is not sexually dimorphic. PMID:9187340

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. Prenatal stress produces sex-specific changes in depression-like behavior in rats: implications for increased vulnerability in females.

    PubMed

    Sickmann, H M; Arentzen, T S; Dyrby, T B; Plath, N; Kristensen, M P

    2015-10-01

    Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression-like behavior as well as circadian patterning of motor activity in both male and female offspring. For this purpose, we exposed pregnant Sprague-Dawley rats to multiple stressors during gestational days 13-21. Subsequently, we monitored locomotor and rearing/climbing activities in home-like cages for 24 h and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute stressor (elevated platform) before EPM testing. Dams exposed to the stressor battery had increased plasma corticosterone levels compared with controls. Male PS offspring displayed changes in locomotor and rearing/climbing activity relative to controls. Additionally, anxiety measures in the EPM were affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects of PS. These findings indicate that the PS rat model reflects multiple clinical depression characteristics, including elevated female vulnerability. PMID:26152908

  12. 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

  13. Bladder function in female rats: effects of aging and pregnancy.

    PubMed

    Wilfehrt, H M; Carson, C C; Marson, L

    In vivo anesthetized cystometrograms and in vitro bladder tissue strip responses were examined in three groups of female rats: young virgins (3 month), older virgins (8 month), and retired breeders (8-9 month). Significant age-related in vivo changes were observed including greater resting pressures, but smaller voided volumes, void durations and void-to-void intervals in older versus young virgin rats. There were significant age-related changes in the in vitro responses. Greater peak and steady state contractions to high K+-modified Krebs (80 mM) depolarization were observed in young animals compared to older animals. Plus, young virgins exhibited greater sensitivity but smaller maximal, normalized contractions to acetylcholine (ACh) than older virgins. Diminished responses to adenosine-5'-triphosphate (ATP) were detected in young versus older virgin rats. Pregnancy-related changes were compared between retired breeders and their age-matched controls, older virgin rats. In vivo voided volumes were greater in the retired breeders than in the older virgins. Smaller in vitro steady state contractions to high K+-modified Krebs depolarization and smaller normalized contractions to maximal concentrations of ACh were observed in the retired breeders than in the older virgins. Retired breeders exhibited diminished relaxation responses to norepinephrine compared to older virgins. ATP produced greater dose-dependent responses and greater maximal contractions in the retired breeders compared to the older virgins. In conclusion, age-related changes were present even prior to the onset of senescence, and multiple pregnancies altered bladder function. PMID:10627081

  14. Release of Zn from maternal tissues in pregnant rats deficient in Zn or Zn and Ca

    SciTech Connect

    Hurley, L.S.; Masters, D.G.; Lonnerdal, B.; Keen, C.L.

    1986-03-05

    Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of Zn deficiency. The hypothesis that Zn may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague Dawley females were injected with Zn-65; after equilibration, the two major pools of Zn, bone and muscle, had different specific activities (SA), muscle being much higher. Females were mated and fed diets adequate in Zn and Ca (C) or deficient in Zn (ZnD) or deficient in both Zn and Ca (ZnCaD). Calculations using weight loss in ZnD and ZnCaD rats, Zn content of maternal bone and muscle, and total fetal Zn at term indicated that in ZnCaD rats a relatively small amount of Zn from bone early in pregnancy was sufficient to prevent abnormal organogenesis, but most fetal Zn came from breakdown of maternal muscle in the last 3 days of pregnancy. Isotope data supported this conclusion. SA of Zn in ZnD fetuses was equal and high, indicating that most Zn came from the same maternal tissue. High muscle SA prior to mating, and increased SA in tibia and liver during pregnancy suggest that muscle provided Zn for other maternal tissues as well as fetuses. In contrast, SA in C fetuses was less than 30% of that of the D groups, consistent with the earlier hypothesis that most fetal Zn in C rats is accrued directly from the diet.

  15. 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.

  16. Vaginal and endocervical microorganisms in symptomatic and asymptomatic non-pregnant females: risk factors and rates of occurrence.

    PubMed

    Tibaldi, C; Cappello, N; Latino, M A; Masuelli, G; Marini, S; Benedetto, C

    2009-07-01

    Physiological or non-physiological factors may affect the vaginal flora. The occurrence of genital microorganisms in non-pregnant females of all ages was studied, as were the risk factors associated with each microorganism. A retrospective analysis of vaginal and endocervical cultures and wet smears from 27,172 non-pregnant women, between 1996 to 2005, was performed taking into consideration clinical and socio-demographic characteristics. No microorganisms were observed in 55.7% of the individuals studied and 44.3% had positive cultures. There was no microbiological aetiology in 49% of women with genital symptoms. Poor hygiene, chemical irritants, sexual behaviour, vaginal blood, birth control type, and/or the lack of an oestrogen effect may have caused the symptoms. The highest occurrence of Gram-negative bacteria (p<0.01), mainly Escherichia coli, was observed in prepubescent girls. The highest occurrence of Candida species (p<0.01) was in women of childbearing age, and of Gram-positive bacteria (p<0.01) in menopausal women. Adolescents, particularly asymptomatic girls, carried more frequently Ureaplasma urealyticum and Chlamydia trachomatis (p<0.01). Hormonal contraception and consistent condom use was protective against bacterial vaginosis and U. urealyticum colonization. Users of intrauterine devices had an increased risk of bacterial vaginosis or of contracting U. urealyticum, Mycoplasma hominis and Candida species. Genital complaints were an independent indicator of Candida species, Gram-negative and Gram-positive bacteria, Trichomonas vaginalis and bacterial vaginosis.Chlamydia trachomatis infections were often asymptomatic. It is concluded that the hormonal milieu and non-physiological factors are major determinants of the vaginal flora. If diagnosis of genital infections is based on symptoms alone and not on culture results, it may be erroneous. Sexual abuse should be investigated when a child presents with a sexually transmitted disease. PMID:19558525

  17. [Prenatal experience and postnatal development of the rat hippocampus: sleep deprivation of pregnant rats].

    PubMed

    Kudriashov, I E; Pigareva, M L; Kudriashova, I V

    2006-01-01

    The effects of sleep deprivation in pregnancy on the development of hippocampal function of the offspring have been investigated. For this purpose we compared electrophysiological characteristics in the hippocampal slices of 15-20-old-day rats of the control and two experimental groups. In the first experimental group the pups were taken from mother for weighting three times during the first postnatal week and then weekly. Another experimental group was brought up without handling. We found that CA1 population spikes developed to significantly less amplitude in experimental groups of rat pups. This phenomenon was observed at higher intensity of monosynaptic activation, although near-threshold stimuli didn't reveal any differences among groups. However, under paired-pulse stimulation (70 ms inter-pulse interval) small amplitudes in the hippocampal slices of experimental animals could facilitate up to control value, and second in pair responses didn't differ from corresponding control. Our data doesn't confirm the hypothesis about decreased connectivity in the hippocampus of experimental rats, but the efficacy of CA3-CA1 inputs seems to be lower. Besides excitatory transmission, the effectiveness of inhibition of paired-pulse facilitation at 15 ms inter-pulse interval was also significantly decreased. The observed effects of prenatal influences seem to develop under postnatal experience. We observed significant trend to more pronounced modifications upon age especially in the case of early handling and testing. PMID:16869276

  18. 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

  19. 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

  20. The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries

    PubMed Central

    Casais, Marilina; Delgado, Silvia M; Sosa, Zulema; Telleria, Carlos M; Rastrilla, Ana M

    2006-01-01

    Background Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1) the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2) the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3) the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary. Methods The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1) noradrenaline in the ganglion compartment; 2) LH in the ovarian compartment; and 3) noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline) was also measured in the ovarian compartment by HPLC. Results The most relevant result concerning the action of noradrenaline in the celiac ganglion was found on day 21 of pregnancy resulting in the inhibition of androstenedione release from the ovarian compartment. In addition on day 15 of pregnancy, LH placed in the ovarian compartment led to an inhibition of the release of androstenedione, and this inhibitory effect was further reinforced by the joint action of noradrenaline in the celiac ganglion and LH in the ovary. The levels of catecholamines in the ovarian compartment showed differences among the experiments; of significance, the joint treatment of noradrenaline in the celiac ganglion and LH in the ovary resulted in a remarkable increase in the ovarian levels of noradrenaline and adrenaline when compared to the effect achieved by either one of the compounds added alone. Conclusion Our results demonstrate that the noradrenergic stimulation of the celiac ganglion reinforces the LH-induced inhibition of androstenedione production by the ovary of late pregnant rats, and that this effect is associated with marked changes in the release of catecholamines in the ovary. PMID:17184551

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. Receptors and neurotransmitters involved in the dual modulation of prolactin release by the serotoninergic system in pregnant and lactating rats.

    PubMed

    Jahn, G A; Kalia, V; Hole, D; Wilson, C A; Deis, R P

    1999-07-01

    The receptors and neurotransmitter pathways that may participate in the inhibitory action of 5-hydroxytryptamine (5HT) on prolactin release during late pregnancy and lactation in rats were studied. Administration of the 5HT synthesis inhibitor, p-chlorophenylalanine, to late pregnant rats induced a significant increase in serum prolactin concentrations at 17:00 h on day 19 of pregnancy that was partially blocked by injections of the 5HT precursor, 5-hydroxytryptophan, or the 5HT agonists, 8-hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (S1a), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (S2) and N-(3-chlorophenyl)imidodicarbonimide diamide HCl (S3), but not by RU 24969 (S1b) or 1-meta-(chlorophenyl)-piperazine-2-HCl (S1a-2c). The 5HT neurotoxins, fenfluramine and p-chloroamphetamine, which selectively destroy fine axon serotoninergic fibres but not coarse ones, prevented the increase in circulating prolactin observed at 18:00 h on pro-oestrus and on day 21 of pregnancy, but did not modify serum prolactin concentrations at 17:00 h on day 19 of pregnancy. Administration of the adrenergic antagonists, metoprolol or prazosin, also prevented the stimulatory effects of p-chlorophenylalanine or ketanserin in pregnant rats on day 19 (17:00 h) or on days 10-12 (16:30 h) in lactating rats separated from their litters. Administration of p-chlorophenylalanine to pregnant rats on day 19 reduced dopamine concentrations in the arcuate nucleus and in the anterior hypothalamus and noradrenaline concentrations in the anterior hypothalamus and the suprachiasmatic nucleus. These results indicate that the inhibitory actions of 5HT on prolactin release in pregnant and lactating rats are mediated by S1a, S2a and S3 receptors and by the coarse axon serotoninergic fibres. In addition, the inhibitory actions of 5HT may modulate the action of a stimulatory adrenergic pathway, as well as the concentrations of noradrenaline and dopamine in different hypothalamic areas, which, in turn, particularly arcuate nucleus dopamine, regulate prolactin release. PMID:10615251

  10. 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...

  11. 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.

  12. 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...

  13. Daily exercise reduces fat, protein and body mass in male but not female rats.

    PubMed

    Cortright, R N; Chandler, M P; Lemon, P W; DiCarlo, S E

    1997-07-01

    This study was designed to compare the estimated energy balance, linear growth (body and bone lengths) and body composition (all components including body mass, total body water, fat, protein and ash) response to daily spontaneous running (DSR) in young male and female rats. We tested the hypothesis that due to gender differences in energy efficiency, DSR would reduce linear growth and body composition more in male rats. Fourteen male and sixteen female weanling Sprague-Dawley rats were randomly assigned to either a sedentary (SED) control (male 7, female 8) or DSR (male 7, female 8) group. The DSR rats were allowed to run spontaneously in running wheels while SED rats remained in standard rat cages for 9 weeks. Body mass, running distance and food intake were measured over the nine week period. Subsequently, chemical analysis was performed to measure carcass content of water, protein, fat and ash. Linear growth was assessed by measures of body and bone lengths. The estimated energy balance of the DSR rats was computed and compared between genders. Estimated energy balance was significantly more negative in females than males due to significantly greater DSR distance. Body and bone lengths were similar among the SED and DSR female and SED and DSR male rats. However, whole body mass, fat mass and protein mass were significantly lower only in DSR males. These results demonstrate that DSR reduced body mass, body fat and protein mass in male rats but not in female rats despite a more negative estimated energy balance in female rats. These findings suggest that females are better protected from an energy deficit due to DSR. Possible mechanisms include gender-specific hormonal responses. PMID:9226349

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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 ...

  19. 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, Virgínia Bodelão; 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

  20. Dopamine transmission increases in the nucleus accumbens of male rats during their first exposure to sexually receptive female rats.

    PubMed

    Wenkstern, D; Pfaus, J G; Fibiger, H C

    1993-07-30

    In vivo microdialysis was used to monitor extracellular concentrations of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the nucleus accumbens of sexually naive male rats during their first exposure to sexually receptive or nonreceptive females. DA, DOPAC, and HVA increased progressively and significantly in males that copulated to ejaculation with receptive females. In contrast, DA, DOPAC, and HVA did not increase significantly in males exposed to non-receptive females, despite several attempts by these males to mount the non-receptive females. These results indicate that DA is released unconditionally in the nucleus accumbens of male rats by exposure to sexually receptive female rats, and that copulation with intromission, but not mounting alone, leads to further increases in DA release. PMID:8402177

  1. 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.

  2. 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

  3. 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

  4. 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. Sprague–Dawley 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

  5. 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

  6. Latent inhibition is affected by phase of estrous cycle in female rats.

    PubMed

    Quinlan, Matthew G; Duncan, Andrew; Loiselle, Catherine; Graffe, Nicole; Brake, Wayne G

    2010-12-01

    Estrogen has been shown to have a strong modulatory influence on several types of cognition in both women and female rodents. Latent inhibition is a task in which pre-exposure to a neutral stimulus, such as a tone, later impedes the association of that stimulus with a particular consequence, such as a shock. Previous work from our lab demonstrates that high levels of estradiol (E2) administered to ovariectomized (OVX) female rats abolishes latent inhibition when compared to female rats with low levels of E2 or male rats. To determine if this E2-induced impairment also occurs with the natural variations of ovarian hormones during the estrous cycle, this behavior was investigated in cycling female rats. In addition, pre-pubertal male and female rats were also tested in this paradigm to determine if the previously described sex differences are activational or organizational in nature. In a latent inhibition paradigm using a tone and a shock, adult rats were conditioned during different points of the estrous cycle. Rats conditioned during proestrus, a period of high E2 levels, exhibited attenuated latent inhibition when compared to rats conditioned during estrus or metestrus, periods associated with low levels of E2. Moreover, this effect is not seen until puberty indicating it is dependent on the surge of hormones at puberty. This study confirms recent findings that high E2 interferes with latent inhibition and is the first to show this is based in the activational actions of hormones. PMID:20817338

  7. Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats

    PubMed Central

    Xu, Lina; Sun, Liyun; Lu, Liqin; Qin, Jianhua

    2014-01-01

    Polychlorinated biphenyls (PCBs) are widespread persistent residual environmental pollutants, which affect seriously the growth and reproductive alterations in humans and animals. Aroclor 1254 is a commercial mixture of PCBs. Quercetin is a flavonoid, which acts on estrogen receptors and causes the development of estrogen-related diseases. In this paper, the primary cultured endometrial cells in the pregnant rats were isolated and Aroclor 1254 was used to induce the injured endometrial cells model. The cells were treated with gradient quercetin, the viability of the endometrial cells, the expressions of CYP450, the contents of TNF-α, IL-6, estradiol (E2), and progesterone (P4) were measured. It showed that the viability of the cultured endometrial cells, the expression of CYP1A1 and CYP2B1, and the contents of TNF-α, E2, and IL-6 in the injured endometrial cells increased with the treatment of quercetin. It shows that quercetin has protective effect on the injured endometrial cells in the pregnant rats, this provide a basis on herbal medicine protection for animal reproductive diseases caused by environmental endocrine disruptors. PMID:24711995

  8. Decreased Seizure Threshold in an Eclampsia-Like Model Induced in Pregnant Rats with Lipopolysaccharide and Pentylenetetrazol Treatments

    PubMed Central

    Huang, Qian; Liu, Lei; Hu, Bihui; Di, Xiaodan; Brennecke, Shaun Patrick; Liu, Huishu

    2014-01-01

    Objective Eclampsia is a poorly understood but potentially fatal complication of pregnancy. Research to date on this disorder has been hampered by the lack of a suitable animal model. To correct this deficiency, this report describes the generation of a rat eclampsia-like model using pentylenetetrazol (PTZ) in a previously established rat preeclampsia model. Method Rats were administered lipopolysaccharide (1.0 µg/kg) by tail vein injection on gestational day 14 to establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal-pregnant, P) were injected intraperitoneally (i.p.) with PTZ (40 mg/kg) to induce seizures. In separate experiments, MgSO4 (270 mg/kg IP) was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures. Results PE conditions were verified in rats after LPS administration by significantly higher blood pressure (P<0.01) and urinary albumin excretion (P<0.05), elevated sFlt-1 (P<0.05) and decreased PlGF serum levels (P<0.05), and evidence of hepatic dysfunction compared to control groups. PTZ successfully induced seizure activity in all groups studied. Latency to seizure was significantly (P<0.01) less in the PE-PTZ group (73.2±6.6 sec.) than in PTZ-treated controls (107.0±7.4 sec.). Pretreatment with MgSO4 prolonged (P<0.05) latency to seizure, shortened seizure duration and decreased seizure rates. Significant increased (P<0.05) in the serum levels of the inflammatory cytokines TNF-α and IL-1β in PE and PE-PTZ groups, and decreased (P<0.05) in their levels following MgSO4 administration. Conclusion This PTZ-induced eclampsia-like rat model is comparable to the human condition of eclampsia and may serve as a useful research tool for future studies of this disease. The increased inflammatory cytokines in preeclampsia are coincident with a decreased threshold for PTZ-induced seizures, suggesting that an inflammatory mechanism may contribute to the susceptibility to seizure activity and inflammation might have an important role in eclampsia. PMID:24586695

  9. 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...

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

    PubMed

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

    2014-10-01

    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 Hebb-Williams 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

  11. 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

  12. 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

  13. 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.

  14. Transient Receptor Potential C4/5 Like Channel Is Involved in Stretch-Induced Spontaneous Uterine Contraction of Pregnant Rat

    PubMed Central

    Chung, Seungsoo; Kim, Young-Hwan; Joeng, Ji-Hyun

    2014-01-01

    Spontaneous myometrial contraction (SMC) in pregnant uterus is greatly related with gestational age and growing in frequency and amplitude toward the end of gestation to initiate labor. But, an accurate mechanism has not been elucidated. In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant myometrium and among them, TRPC4 are predominant throughout gestation, suggesting a possible role in regulation of SMC. Therefore, we investigated whether the TRP channel may be involved SMC evoked by mechanical stretch in pregnant myometrial strips of rat using isometric tension measurement and patch-clamp technique. In the present results, hypoosmotic cell swelling activated a potent outward rectifying current in G protein-dependent manner in rat pregnant myocyte. The current was significantly potentiated by 1µM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10µM 2-APB (TRPC4-7 inhibitor). In addition, in isometric tension experiment, SMC which was evoked by passive stretch was greatly potentiated by lanthanide (1µM) and suppressed by 2-APB (10µM), suggesting a possible involvement of TRPC4/5 channel in regulation of SMC in pregnant myometrium. These results provide a possible cellular mechanism for regulation of SMC during pregnancy and provide basic information for developing a new agent for treatment of premature labor. PMID:25598665

  15. 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...

  16. 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 ...

  17. 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 GTP’s antioxidant capacity. The current study further evaluates whether GTP can restore bone microstructure along with related mechanism in rats wit...

  18. 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

  19. 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

  20. Acetylcholinesterase and neuropathy target esterase activity in female and male rats exposed to pesticide terbufos.

    PubMed

    Kim, Jung-Ran; Kim, Hyo-Joon; Kwon, Oh-Seung

    2005-07-01

    An organophosphate pesticide terbufos (S-t-butylthiomethyl-O,O-diethyl phosphorodithioate; TBF) has been extensively used as an insecticide. A sexual dimorphism in TBF toxicity was not reported and remains unclear. The objective of the work was to investigate the influence of TBF on sexual dimorphism after oral administration of TBF to rats by using acetylcholinesterase (AChE) and neuropathy target esterase (NTE) as endpoints. TBF was orally administered to Sprague-Dawley rats, where female rats were received 0, 0.1, 0.4 and 0.8mg/kg TBF for 2 days and male rats 0, 0.1, 0.5 and 1.0mg/kg TBF for 3 days for dose-dependent study. Age-matched female and male rats also received equally 0.5mg/kg TBF for 2 days and sacrificed 0, 6, 12, 24 and 72h after the last dose for time-dependent study. In the dose-dependent study, mortality was 25% in 1.0mg/kg TBF group of male and 50% in 0.4 and 0.8mg/kg TBF groups of female rats, resulting in about two-fold higher in female than male. AChE was significantly decreased only in the frontal and entorhinal cortexes of female rats receiving 0.4 or 0.8mg/kg TBF. In the time-dependent study, the maximal inhibition in the brain regions or plasma was two- or three-fold higher in female, which occurred 6 or 12h after the last dose. However, effects of TBF on alteration of NTE activity were minor, compared to AChE, indicating that AChE is more sensitive marker than NTE in TBF toxicity. These results also indicate that female was more vulnerable to AChE inhibition than male rats after exposure to TBF. PMID:21783582

  1. 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.

  2. Gonadal Hormone Modulation of Mu, Kappa, and Delta Opioid Antinociception in Male and Female Rats

    PubMed Central

    Stoffel, Erin C.; Ulibarri, Catherine M.; Folk, John E.; Rice, Kenner C.

    2005-01-01

    Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50°C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. In females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat. Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. PMID:15820914

  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. 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

  5. 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

  6. 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

  7. 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

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

    PubMed Central

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

    2016-01-01

    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

  9. 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

  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. 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

  12. 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.

  13. 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

  14. Oral Metformin Treatment Prevents Enhanced Insulin Demand and Placental Dysfunction in the Pregnant Rat Fed a Fructose-Rich Diet

    PubMed Central

    Alzamendi, Ana; Del Zotto, Hector; Castrogiovanni, Daniel; Romero, Jose; Giovambattista, Andres; Spinedi, Eduardo

    2012-01-01

    The intake of a fructose-rich diet (FRD) in the normal female rat induces features similar to those observed in the human metabolic syndrome phenotype. We studied the impact of FRD administration to mothers on pregnancy outcome. On gestational day (Gd) zero rats were assigned to either group: ad libitum drinking tap water alone (normal diet, ND) or containing fructose (10% w/vol; FRD) through pregnancy; all rats were fed a Purina chow diet ad libitum ND and FRD rats were daily cotreated or not with metformin (60 mg/Kg/day oral; ND + MF and FRD + MF) and submitted to a high glucose load test on Gd 14. Additionally, placentas from different groups were studied on Gd 20. Data indicated that: (1) although FRD rats well tolerated glucose overload, their circulating levels of insulin were significantly higher than in ND rats; (2) the mesometrial triangle blood vessel area was significantly lower in placentas from FRD than ND dams; (3) the detrimental effects of FRD administration to mothers were ameliorated by metformin cotreatment. Our study suggests that excessive intake of fructose during pregnancy enhanced the risk for developing gestational diabetes and subsequent preeclampsia, and that metformin prevented the poor pregnancy outcome induced by FRD. PMID:22957268

  15. 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

  16. 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

  17. Orexin-1 receptor mediation of cocaine seeking in male and female rats.

    PubMed

    Zhou, Luyi; Ghee, Shannon M; Chan, Clifford; Lin, Li; Cameron, Michael D; Kenny, Paul J; See, Ronald E

    2012-03-01

    Previous studies have shown that female rats exhibit enhanced cocaine seeking during multiple phases of cocaine addiction compared with males. The orexin/hypocretin system recently has been implicated in drug addiction in male rats. Based on the known sex differences in cocaine addiction, in the current study we examined orexin-mediated cocaine seeking during self-administration, extinction, and reinstatement in age-matched male (initial weight 250-300 g) and female (initial weight 175-225 g) Sprague-Dawley rats by using the orexin-1 receptor (OX1R) antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea (SB-334867) (10-30 mg/kg). OX1R blockade had no effect on established cocaine self-administration, but attenuated cocaine seeking during extinction in both male and female rats. It is noteworthy that OX1R blockade potently attenuated cue-induced reinstatement in males but had no effect on females. SB-334867 also reduced cocaine seeking during pharmacological stress-induced (yohimbine, 2.5 mg/kg) and yohimbine + cue-induced reinstatement in both sexes. SB-334867 failed to affect reinstatement induced by cocaine (10 mg/kg) in either male or female rats, but selectively reduced cocaine + cue-induced reinstatement only in males. In separate experiments examining basal and cocaine-induced locomotion, SB-334867 attenuated locomotion in both male and female rats. Finally, assessment of plasma and brain levels of SB-334867 showed that estrus females had slightly higher plasma levels than diestrus females, but no overall sex differences or estrous cycle differences were observed in plasma or brain SB-334867 concentrations. These results show that OX1R signaling plays a role in mediating cocaine seeking, but differs between the sexes for cue-induced reinstatement. PMID:22186370

  18. Effects of perinatal, combined exposure to 1,4-dichlorobenzene and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene on rat female reproductive system.

    PubMed

    Makita, Yuji

    2008-04-01

    Prenatal or early postnatal exposure to some synthetic chemicals may affect the later reproductive system of the offspring. 1,4-Dichlorobenzene (DCB) is used as an air freshener and a moth repellent and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) is a persistent metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane that was used as a pesticide before. DCB concentrations of residential air and oral p,p'-DDE intake through marine products are demonstrated to be rather high in Japan. Such situations lead to high body burden of these pollutants in pregnant women. Consequently, foetuses and neonates will be exposed much more to DCB and p,p'-DDE via the mother. Therefore, the effects of the perinatal, combined exposure to DCB and p,p'-DDE on the female reproductive system have been investigated in mature rat female offspring of dams ingesting 25 p.p.m. DCB (approximately 2 mg/kg) and 125 p.p.m. p,p'-DDE (approximately 10 mg/kg) during the gestational and lactational period. Sexual maturation was fully developed in the rat female offspring perinatally exposed to DCB and/or p,p'-DDE through maternal exposure. The combined effect of DCB and p,p'-DDE was observed, and the ovarian weight was seen to decrease to approximately 80% of the control rat in matured female offspring following perinatal exposure to DCB and p,p'-DDE. This alteration might lead to reproductive dysfunction in matured female offspring. However, biological relevance of the alteration in the ovary remained uncertain in the present study. Further investigations concerning the reproductive function and mechanistic implication are required for elucidating the combined effects of perinatal exposure to DCB and p,p'-DDE on the later female reproductive system entirely. PMID:18341512

  19. 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...

  20. 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

  1. 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

  2. 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 μg/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 μg/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 μg/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

  3. 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

  4. 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

  5. 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

  6. Reproductive status and testosterone among females in cooperative mole-rat societies.

    PubMed

    Lutermann, Heike; Young, Andrew J; Bennett, Nigel C

    2013-06-15

    Sexual selection acts on traits that increase reproductive success. Variation in reproductive success is often higher among males than females. Consequently, sexual selection has been studied extensively in males while its possible role in females has only recently attracted considerable attention. In some cooperatively breeding species females compete intensely for reproductive opportunities and may thereby have evolved 'male-like' traits such as increased intra-sexual aggression and exaggerated secondary sexual traits. The expression of the latter tends to be testosterone-dependent in male vertebrates but whether this is also the case among females remains poorly understood. Here, we compare two cooperatively breeding mole-rat species (Natal, Cryptomys hottentotus natalensis, and Damaraland mole-rats, Fukomys damarensis) in which a single female monopolises reproduction through behavioural and physiological suppression, respectively, to evaluate the effect of female intra-sexual competition. Consistent with the hypothesis that intra-sexual competition has shaped patterns of testosterone (T) secretion among females in these species, we show that (i) female T levels in both species are significantly higher among breeding (BFs) (who may face the highest degree of intra-sexual competition) compared to non-breeding females (NBFs), (ii) that T levels in both species are significantly higher when access to unrelated males can be assumed to be greatest (i.e., wet season), and (iii) that the average female T levels are a full order of magnitude higher in the absence of a physiological mechanism of reproductive suppression. Together, our results suggest a role for intra-sexual competition in shaping patterns of T secretion among females of the social mole-rats and raise the possibility of a modulatory role for the mode of reproductive suppression on competition-related traits in females. PMID:23583770

  7. 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, 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

  8. 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

  9. 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

  10. 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

  11. The Pharmacokinetics of Methamphetamine Self-Administration in Male and Female Rats

    PubMed Central

    Milesi-Hallé, Alessandra; Hambuchen, Michael D.; McMillan, Donald E.; Owens, S. Michael

    2015-01-01

    Background Because methamphetamine (METH) pharmacokinetics after single iv doses show significant differences between male and female rats, we hypothesized that pharmacokinetic differences in METH disposition could be a contributing factor to the patterns of METH self-administration behaviors in rats. Methods For the studies, we used a passive (non-contingent) METH dosing schedule consisting of 27 METH iv bolus injections (0.048 mg/kg) over 2 hrs derived from a previous active (contingent) METH self-administration behavioral study in male rats. After METH dosing of male and female Sprague-Dawley rats (n=5/group), METH and amphetamine serum concentrations were determined by LC-MS/MS. Pharmacokinetic analysis, including predictive mathematical simulations of the data, was then conducted. Results Male and female rats achieved relatively stable METH serum concentrations within 20 min, which remained constant from 20–120 min. While not statistically different, METH clearance and volume of distribution values for females were 25% and 33% lower (respectively) than males. Linear regression analysis of predicted METH concentrations from pharmacokinetic simulations versus observed concentrations showed a substantially better correlation with male data than female data (r2 = 0.71 vs. 0.56; slope = 0.95 vs. 0.45, respectively). At 120 min, the time of predicted peak METH serum concentrations, female values were 42% higher than expected, while male values were within 3%. Conclusions Unlike METH male pharmacokinetic data, the female data was less predictable during multiple METH administrations and produced overall higher than expected METH concentrations. These findings demonstrate that METH pharmacokinetics could contribute to differences in METH self-administration behaviors in rats. PMID:25796510

  12. Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

    PubMed Central

    Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

    2008-01-01

    Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12−17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation. PMID:17445242

  13. Partner preference behavior of estrous female rats affected by castration of tethered male incentives.

    PubMed

    Broekman, M; de Bruin, M; Smeenk, J; Slob, A K; van der Schoot, P

    1988-09-01

    Estrous female rats were allowed to interact with either of two tethered intact male rats or to stay in an empty middle part of a three-compartment observation cage during a 60-min test. Sexual interactions occurred with both males (resulting in one to five ejaculations) but most time was spent in the empty compartment. After castration of one of the males, females spent more time with this male than with the intact male, although sexual interactions continued with both incentive animals. This "preference" for the castrated male persisted through the second hour of observation in a second experiment (total test time 115 min) although sexual interactions had virtually ceased during this period. Females' preference for castrated males seemed largely the consequence of aversion to genital stimulation received during intromissions by intact animals: (a) when intromissions were prevented through vaginal occlusion, intact males became by far the preferred partners for the whole 2-hr period of testing while sexual behavior continued to occur throughout the test; (b) when choice was allowed between a testosterone-treated ovariectomized female and an intact male, sexual interaction occurred with both tethered incentive rats but the female became the preferred animal. The results suggest that two opposite tendencies play a role in sexual motivation of estrous female rats: attraction resulting from the action of ovarian hormones on the central nervous system and rejection resulting from genital sensory stimulation through the male's genitalia. PMID:3169698

  14. 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

  15. /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)

  16. 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.

  17. 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

  18. 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

  19. Studies of embryotoxicity and the incidence of external malformations after continuous intravenous infusion of alpha-chaconine in pregnant rats.

    PubMed

    Hellenäs, K E; Cekan, E; Slanina, P; Bergman, K

    1992-05-01

    Embryotoxicity and effects on the incidence of external malformations of the major potato glycoalkaloid alpha-chaconine (alpha-cha) were studied in rats. Pregnant Sprague-Dawley rats (n = 17) were given a continuous intravenous infusion of alpha-cha via implanted osmotic minipumps (1.7 mg/kg/day), to maintain a stable blood concentration on days 6-13 of gestation. Control animals received physiological saline solution or were left untreated, respectively. Blood serum levels of alpha-cha were monitored at selected time intervals during the treatment using a specific HPLC method. The foetal body weights and the number of resorbed or dead foetuses per litter in the alpha-cha treated group were not significantly different from the control groups. No case of malformation was detected among 143 foetuses inspected in the treated group. The average maternal blood serum concentration of alpha-cha measured during the experiment was 340 ng/ml. This is more than 20 times the average peak serum level previously reported for human volunteers after intake of potatoes with a total glycoalkaloid content at the upper safe limit for acute adverse effects. The results support the view that potato glycoalkaloids, at levels normally found in potatoes, do not present a risk for teratogenicity in humans. PMID:1608927

  20. Antinociception and sedation following intracerebroventricular administration of Δ⁹-tetrahydrocannabinol in female vs. male rats.

    PubMed

    Wakley, Alexa A; Craft, Rebecca M

    2011-01-01

    Systemically administered cannabinoids produce greater antinociceptive and sedative effects in female compared to male rats. Sex differences in the brain endocannabinoid system have also been reported. The aim of this study was to determine whether sex differences in antinociceptive and motoric effects of a cannabinoid can be attributed to supraspinal mechanisms. Vehicle or Δ⁹-tetrahydrocannabinol (THC, 100 μg) was administered i.c.v., and behavioral effects were compared between gonadally intact male and female rats, and among females in different estrous stages (early proestrus, late proestrus, estrus and diestrus). Antinociception on the tail withdrawal and paw pressure tests after i.c.v. THC was slightly but not significantly greater in females (pooled across estrous stages) compared to males. THC suppressed locomotor activity similarly in all groups, with the exception that only males showed hyperlocomotion at 4 h post-injection. When females in the four estrous stages were compared, females in late proestrus showed significantly greater THC-induced antinociception than females in estrus (and males). These results suggest that supraspinal mechanisms may contribute to greater systemic THC effects in females compared to males, and to estrous stage-dependent differences in THC effects among females. PMID:20692296

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Factor analysis shows that female rat behaviour is characterized primarily by activity, male rats are driven by sex and anxiety.

    PubMed

    Fernandes, C; González, M I; Wilson, C A; File, S E

    1999-12-01

    This experiment explored sex differences in behaviour using factor analysis to describe the relationship between different behavioral variables. A principal component solution with an orthogonal rotation of the factor matrix was used, ensuring that the extracted factors are independent of one another, and thus reflect separate processes. In the elevated plus-maze test of anxiety, in male rats factor 1 accounted for 75% of the variance and reflected anxiety, factor 2 represented activity, and accounted for 24% of the variance. This contrasted with the finding in female rats in which factor 1 was activity, accounting for 57% of the variance, with the anxiety factor accounting for only 34% of the variance. When behaviour in both the plus-maze and holeboard were analysed, a similar sex difference was found with anxiety emerging as factor 1 in males and holeboard activity as factor 1 in females. Locomotor activity in the inner portion of the holeboard loaded on the anxiety factor for males, but on activity for females. When behaviours in the plus-maze and sexual orientation tests were analysed, anxiety emerged as factor 1 in males, sexual preferences factor 2, and activity factor 3. In females, activity was factor 1, sexual preference factor 2, anxiety factor 3, and social interest factor 4. These results suggest caution should be exercised in interpreting the results from female rats in tests validated on males because the primary controlling factor may be different. PMID:10593196

  6. Estrogen in prefrontal cortex blocks stress-induced cognitive impairments in female rats.

    PubMed

    Yuen, Eunice Y; Wei, Jing; Yan, Zhen

    2016-06-01

    Animal and human studies have found that males and females show distinct stress responses. Recent studies suggest the contribution of estrogen in the brain to this sexual dimorphism. Repeated stress has been found to impair cognitive behaviors via suppressing glutamatergic transmission and glutamate receptor surface expression in pyramidal neurons of prefrontal cortex (PFC) in male rats. On the contrary, female rats exposed to the same stress paradigms show normal synaptic function and PFC-mediated cognition. The level of aromatase, the enzyme for the biosynthesis of estrogen, is significantly higher in the PFC of females than males. The stress-induced glutamatergic deficits and memory impairment are unmasked by blocking estrogen receptors or aromatase in females, suggesting a protective role of estrogen against the detrimental effects of repeated stress. PMID:26321384

  7. 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

  8. Extensive juvenile "babysitting" facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase-2 expression in female laboratory rats.

    PubMed

    Harding, Kaitlyn M; Lonstein, Joseph S

    2016-05-01

    Pregnancy and parturition can dramatically affect female neurobiology and behavior. This is especially true for laboratory-reared rodents, in part, because such rearing prevents a host of developmental experiences that females might undergo in nature, including juvenile alloparenting. We examined the effect of chronic exposure to pups during post-weaning juvenile life (days 22-36) on adult maternal responsiveness, anxiety-related behaviors, and dorsal raphe tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) levels in nulliparous rats. Adult females with juvenile alloparental experience showed significantly faster sensitized maternal responsiveness, less anxiety, and more dorsal raphe TPH2. Juvenile alloparenting did not affect females' later social novelty and preference behaviors toward adults, suggesting their increased interest in pups did not extend to all social partners. In a second experiment, suckling a pregnant dam (achieved by postpartum estrus reinsemination), interacting with her after standard laboratory weaning age, and a 3-day exposure to younger siblings also reduced juvenile females' later anxiety but did not affect maternal responsiveness or TPH2. Thus, extensive juvenile "babysitting" can have long-term effects reminiscent of pregnancy and parturition on maternal responsiveness and anxiety, and these effects may be driven by upregulated serotonin. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 492-508, 2016. PMID:26806471

  9. 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

  10. Evaluation of sex difference in tissue repair following acute carbon tetrachloride toxicity in male and female Sprague-Dawley rats.

    PubMed

    Moghaddam, A P; Eggers, J S; Calabrese, E J

    1998-09-15

    Cellular regeneration and tissue repair greatly influence the outcome of acute carbon tetrachloride (CCl4) hepatotoxicity. This study examined the temporal kinetics of cellular regeneration and tissue repair processes in male and female Sprague Dawley (SD) rats following an acute CCl4 exposure (0.8 ml/kg, i.p.). In female rats, hepatic damage peaked at 24 h following the treatment and was approximately 2.5-fold (AST 2.7-fold, ALT 2.3 fold) greater than the damage observed in male rats. The hepatic damage in male rats appeared to peak by 3 h post-exposure and did not significantly change through the 36-h time-point. The activity of cytochrome P 4502E1 was 20% greater in male rats and did not correlate with the magnitude of hepatic damage. Morphometric analysis of cell cycle indices revealed that cellular regeneration was significantly greater in female rats as compared to male rats at 48 h and corresponded proportionally to the extent of liver damage. This study demonstrated that female SD rats respond more severely to acute CCl4 hepatotoxicity than male SD rats and the extent of tissue repair and cellular regeneration was greater in female rats. Furthermore, our results suggest that tissue repair is unlikely to result in accounting for the different responses exhibited by male and female SD rats to CCl4 hepatotoxicity. PMID:9865477

  11. Dual regulation of luteal progesterone production by androstenedione during spontaneous and RU486-induced luteolysis in pregnant rats.

    PubMed

    Tellería, C M; Stocco, C O; Stati, A O; Rastrilla, A M; Carrizo, D G; Aguado, L I; Deis, R P

    1995-12-01

    The effect of androstenedione on luteal progesterone production was studied during luteolysis preceding parturition as well as that induced by the antiprogestin RU486 in late pregnant rats. Luteal cells from animals on days 19, 20 or 21 of pregnancy and incubated with 10 microM androstenedione increased progesterone production by 99, 136, and 277%, respectively. The animals receiving androstenedione (10 mg/rat s.c.) on day 19 of pregnancy showed an increase in serum progesterone levels, a decline in luteal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity and an increase in corpus luteum weight without modifying 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity on day 21 of pregnancy. Androstenedione and testosterone but not dihydrotestosterone were able to prevent the decrease in serum progesterone concentration and corpus luteum weight observed 58 h after treatment with RU486 (2 mg/kg) on day 18 of pregnancy. However, the three androgens studied inhibited the luteal 3 beta-HSD activity but 20 alpha-HSD activity was not affected, when compared with animals receiving RU486 alone. The co-administration of androstenedione with the aromatase inhibitor 4-hydroxyandrostenedione or with the specific antioestrogen ICI 164,384 did not modify the effects induced by androstenedione in RU486-treated rats, indicating that the action of androstenedione on progesterone production and secretion at the time of luteolysis seems to occur through an androgenic mechanism and is not mediated by previous conversion of the androgens to oestrogens. In all experiments the high luteal 20 alpha-HSD activity, that characterizes a luteolytic process, was not modified by androgens. Androstenedione administered to adrenalectomized rats was also able to prevent the decrease in serum progesterone concentration observed in spontaneous or RU486-induced luteolysis. The administration of androstenedione to RU486-treated rats induced a decrease in luteal progesterone content concomitant with an increase in serum progesterone levels. These studies demonstrate that androgens during luteolysis, are able to stimulate luteal progesterone secretion, prevent the loss in corpora lutea weight and enhance the decrease in 3 beta-HSD activity, without affecting the increase in 20 alpha-HSD activity. PMID:8541235

  12. Somatosensory determinants of lordosis in female rats: behavioral definition of the estrogen effect.

    PubMed

    Pfaff, D; Montgomery, M; Lewis, C

    1977-02-01

    By coating the ventral surface of male rats with a dye, regions of contact between male and female during male mounting were recorded precisely on the female's hair and skin. The male rat touches the female's flanks, rump, tailbase, perineum, and perivaginal surfaces during the female's initiation and maintenance of lordosis. Film analyses showed that the male's paws and pelvic thrusting stimulate the female's skin with dominant frequencies between 10 and 20 per second. Somatosensory stimuli were applied by the experimenter to the female skin locations contacted by the male. Deflection of hair on the flanks or perineum alone did not cause lordosis. Light stimulation simultaneously on flanks and perineum caused lordosis only in some females given high estrogen dosages supplemented by progesterone. When flank stimuli were followed by pressure on the rump, tailbase, and perineum, lordosis was triggered reliably in hormone-treated females. Here the estrogen-dependence of the reflex was shown, and progesterone synergized with the estrogen effect. Among lordosis components, rump and head elevations in response to pressure stimuli on the rump, tailbase, and perineum appear to be hormone-sensitive. These results help to define the minimal cutaneous sensory requirement for lordosis. In turn, the estrogen effect on lordosis may be defined behaviorally as increased responsiveness to pressure on rump, tailbase, and perineal skin, after flank stimulation. These results illustrate how estrogen, progesterone, and somatosensory stimuli interact in causing lordosis, increases in the strength of one factor compensating for decreases in another. PMID:838911

  13. 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

  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. 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...

  16. 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

  17. Production of fat-1 transgenic rats using a post-natal female germline stem cell line.

    PubMed

    Zhou, Li; Wang, Lei; Kang, Jing X; Xie, Wenhai; Li, Xiaoyong; Wu, Changqing; Xu, Bo; Wu, Ji

    2014-03-01

    Germline stem cell lines possess the abilities of self-renewal and differentiation, and have been established from both mouse and human ovaries. Here, we established a new female germline stem cell (FGSC) line from post-natal rats by immunomagnetic sorting for Fragilis, which showed a normal karyotype, high telomerase activity, and a consistent gene expression pattern of primordial germ cells after 1 year of culture. Using an in vitro differentiation system, the FGSC line could differentiate into oocytes. After liposome-based transfection with green fluorescent protein (GFP) or fat-1 vectors, the FGSCs were transplanted into the ovaries of infertile rats. The transplanted FGSCs underwent oogenesis, and the rats produced offspring carrying the GFP or fat-1 transgene after mating with wild-type male rats. The efficiency of gene transfer was 27.86-28.00%, and 2 months was needed to produce transgenic rats. These findings have implications in biomedical research and potential applications in biotechnology. PMID:24258451

  18. Fluctuations in selenium status during the female rat estrous cycle

    SciTech Connect

    Cha, C.; Smith, A.M.; Kimura, R.E. Ohio State Univ., Columbus )

    1991-03-11

    A suggested relationship between selenium (Se) status and sex hormones is based on sex-linked differences in Se status of the liver and dramatic changes in Se status during pregnancy. The effect of estrous cycle hormone fluctuation on Se status was studied in the chronically-catheterized rat model. Se status, measured as plasma and RBC Se and glutathione peroxidase activity (GPx), was assessed at each stage of the 4-day estrous cycle. Stages, determined by cytological exam of vaginal smears, were estrus (E), metestrus (ME), diestrus (DE), and proestrus (PE). Five rats fed a 0.1 ppm Se diet, were catheterized at the abdominal aorta, allowing serial blood draws under nonstressful conditions. At least three blood samples per rat were collected daily for two consecutive cycles. Plasma Se during PE was significantly greater than that at E, ME, or DE. Peak plasma Se occurred at 1,000 hr PE. Peak estrogen and progesterone levels have been reported to occur later in PE. Peak plasma occurred during ME and early PE. A significant decrease in plasma GPx during late PE corresponds with reported peaks in estrogen and progesterone. There were no significant differences in RBC Se or GPx during the estrous cycle. The results of this study suggest that changes in plasma Se and GPx during the estrous cycle may precede similar fluctuations in estrogen and progesterone.

  19. Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems

    PubMed Central

    Lukkes, Jodi L.; Engelman, Glenn H.; Zelin, Naomi S.; Hale, Matthew W.; Lowry, Christopher A.

    2012-01-01

    Our previous studies have shown that post-weaning social isolation of male rats leads to sensitization of serotonergic systems and increases in anxiety-like behavior in adulthood. Although studies in humans suggest that females have an increased sensitivity to stress and risk for the development of neuropsychiatric illnesses, most studies involving laboratory rats have focused on males while females have been insufficiently studied. The objective of this study was to investigate the effects of post-weaning social isolation on subsequent responses of an anxiety-related dorsal raphe nucleus (DR)-basolateral amygdala system to pharmacological challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142; a partial inverse agonist at the benzodiazepine allosteric site on the γ-aminobutyric acid (GABA)A receptor). Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-reared for an additional 2 weeks. We then used dual immunohistochemical staining for c-Fos and tryptophan hydroxylase in the DR or single immunohistochemical staining for c-Fos in the basolateral amygdala. Isolation-reared rats, but not group-reared rats, injected with FG-7142 had increased c-Fos expression within the basolateral amygdala and in serotonergic neurons in the dorsal, ventrolateral, caudal and interfascicular parts of the DR relative to appropriate vehicle-injected control groups. These data suggest that post-weaning social isolation of female rats sensitizes a DR-basolateral amygdala system to stress-related stimuli, which may lead to an increased sensitivity to stress- and anxiety-related responses in adulthood. PMID:22297173

  20. Exercise improves learning and memory impairments in sleep deprived female rats.

    PubMed

    Saadati, Hakimeh; Esmaeili-Mahani, Saeed; Esmaeilpour, Khadije; Nazeri, Masoud; Mazhari, Shahrzad; Sheibani, Vahid

    2015-01-01

    Inadequate sleep is a common problem in modern societies. It has been previously shown that female rats are more vulnerable to the deleterious effects of sleep deprivation on cognitive functions. Physical exercise has been suggested to attenuate the cognitive impairments induced by sleep deprivation in male rats. The objective of the current study was to investigate the effects of physical exercise on cognitive functions of female rats following paradoxical sleep deprivation. Intact and ovariectomized (OVX) female Wistar rats were used in the present study. The exercise protocol was 4 weeks of treadmill running. The multiple platform method was applied for the induction of 72h paradoxical sleep deprivation and the cognitive function was evaluated using Morris water maze (MWM). Plasma corticosterone level was evaluated in separate groups of study. ANOVA and repeated measures were used to analyze the data and P<0.05 was considered statistically significant. Throughout the investigation, significant learning impairment was observed in sleep-deprived OVX rats compared to the intact and the other OVX groups. Short term memory impairment was observed in both sleep-deprived OVX and intact groups. Physical exercise alleviated the PSD-induced learning and memory impairments in both intact and OVX groups. Corticosterone levels were not statistically significant among the different groups. The results of our study confirmed the negative effects of PSD on cognitive functions in female rats and regular physical exercise seems to protect rats from these effects. Further studies are suggested to be carried out in order to evaluate the possible underlying mechanisms, and also to evaluate the possible interactions between sex hormones and PSD-induced cognitive impairments. PMID:25447468

  1. Anxiety-like behavior in weanling and young adult male and female malnourished rats.

    PubMed

    Rocinholi, Luciene F; Landeira-Fernandez, J

    2011-01-10

    The present study determined whether protein-calorie malnutrition alters anxiety-like behavior in weanling and young adult, male and female malnourished rats. On the day of birth, litters of Wistar rats were divided into Control (C) and Malnutrition (M) groups. In the C group, litters were fed by dams receiving ad libitum lab chow, whereas in the M group, litters were fed by dams receiving 40% of the total amount of the diet offered to dams in the C group. After weaning (PND21) until PND50, animals received the same food as theirs mothers (i.e., ad libitum access in the C group and 40% of the C group food in the M group). On PND21 and PND50, independent C (male [CM] and female [CF]) and M (male [MM] and female [MF]) groups were exposed to the elevated T-maze. The time taken to withdraw four paws from this arm was recorded (baseline latency [BL]). The same measurement was repeated twice at 30s intervals (avoidance trial 1 [AT1] and avoidance 2 [AT2]). The cutoff time in each trial was 300s. ANOVA indicated a four-way age×diet×sex×trials interaction. Post hoc comparisons revealed that PND50 rats had a lower BL and AT1 latency compared with PND21 rats. Training increased both AT1 and AT2 latencies compared with BL in both the CM and CF groups. Weanling malnourished rats exhibited reduced anxiety-like behavior and young adult male rats presented less anxiety-like behavior than young adult female rats in this experimental model. PMID:20888355

  2. Role of Oestrogen α 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; Ågmo, A

    2015-11-01

    The present study investigated the role of oestrogen receptor (ER)α 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 ERα to reduce the number of ERα 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 8 days. 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 ERα 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 ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. PMID:26314929

  3. Early consumption of blueberry diet protects against sex steroid deficiency-induced bone loss in adult female rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We studied the effects of blueberry consumption in early development on bone loss in ovariectomized (OVX) female rats later in life. Weanling female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder from PND 21 to PND34 (short-term group), or PND21 to PND81 (chro...

  4. Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats.

    PubMed

    Morel, G R; Andersen, T; Pardo, J; Zuccolilli, G O; Cambiaggi, V L; Hereñú, C B; Goya, R G

    2015-09-10

    The hippocampus, a medial temporal lobe structure necessary for the formation of spatial memory, is particularly affected by both normal and pathologic aging. In previous studies, we observed a significant age-related increase in dopaminergic neuron loss in the hypothalamus and the substantia nigra of female rats, which becomes more conspicuous at extreme ages. Here, we extend our studies by assessing spatial memory in 4-6 month-old (young), 26-month-old (old) and 29-32-month-old (senile) Sprague-Dawley female rats as well as the age-related histopathological changes in their dorsal hippocampus. Age changes in spatial memory performance were assessed with a modified version of the Barnes maze test. We employed two probe trials (PTs), one and five days after training, respectively, in order to evaluate learning ability as well as short-term and longer-term spatial memory retention. A set of relevant hippocampal cell markers was also quantitated in the animals by means of an unbiased stereological approach. The results revealed that old rats perform better than senile rats in acquisition trials and young rats perform better than both aging groups. However, during short-term PT both aging groups showed a preserved spatial memory while in longer-term PT, spatial memory showed deterioration in both aged groups. Morphological analysis showed a marked decrease (94-97%) in doublecortin neuron number in the dentate gyrus in both aged groups and a reduction in glial fibrillary acidic protein-positive cell number in the stratum radiatum of aging rats. Astroglial process length and branching complexity decreased in aged rats. We conclude that while target-seeking activity and learning ability decrease in aged females, spatial memory only declines in the longer-term tests. The reduction in neuroblast number and astroglial arborescence complexity in the dorsal hippocampus are likely to play a role in the cognitive deficits of aging rats. PMID:26141841

  5. Prenatal testosterone exposure permanently masculinizes anogenital distance, nipple development, and reproductive tract morphology in female Sprague-Dawley rats.

    PubMed

    Hotchkiss, Andrew K; Lambright, Christy S; Ostby, Joseph S; Parks-Saldutti, Louise; Vandenbergh, John G; Gray, Leon E

    2007-04-01

    In mammals, abnormal increases in fetal androgens disrupt normal development of the female phenotype. Due to the recent concern regarding environmental androgen-active chemicals, there is a need to identify sources of fetal androgen variation and sensitive developmental markers for androgenic activity in female rats. Anogenital distances (AGD), nipple retention, reproductive tract, and external genitalia are morphological parameters organized by prenatal androgens and are predictive of altered masculinized/defeminized phenotype in adult female mice and rats. The objectives of this study were to (1) characterize the natural prenatal androgen environment of rats including the magnitude of the intrauterine position (IUP) effect, (2) characterize the permanent effects of prenatal androgen exposure on female rats, and (3) determine the ability of AGD and areolas to predict these permanent androgenic alterations in female rats. Untreated male fetal rats had higher tissue testosterone (T) concentrations than females in the amniotic fluid, reproductive tract, gonad, and fetal body. The intrauterine position (IUP) of male and female fetuses did not affect T concentrations or AGD in male or female rats at gestational day (GD) 22. Female offspring exposed to 0, 1.5, and 2.5 mg/kg/day testosterone propionate (TP) on GDs 14-18 displayed increased AGD at postnatal day (PND) 2 and decreased nipples at PND 13 and as adults. TP-induced changes in neonatal AGD and infant areola number were reliable indicators of permanently altered adult phenotype in female rats. Further, females in the two high-dose groups displayed increased incidences of external genital malformations and the presence of prostatic tissue, not normally found in female rats. PMID:17218470

  6. 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.

  7. Effects of maternal exposure to aflatoxin B1 during pregnancy on fertility output of dams and developmental, behavioral and reproductive consequences in female offspring using a rat model.

    PubMed

    Supriya, Ch; Akhila, B; Pratap Reddy, K; Girish, B P; Sreenivasula Reddy, P

    2016-03-01

    A suboptimal in utero environment can have detrimental effects on the pregnancy and long-term adverse "programing" effects on the offspring. Aflatoxin B1 is one of the potent reproductive toxicants and currently detected in both milk and tissues. This article focuses on the effects of prenatal exposure to graded doses of aflatoxin B1 on the pregnancy outcomes of dams and postnatal developments of the female offspring, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats were injected intramuscularly with vehicle or aflatoxin B1 (10, 20, 50 or 100 μg/kg body weight/day) on days 12-19 of gestation. At parturition, newborns were observed for clinical signs of toxicity and survival. The female offspring were examined through a battery of tests in order to evaluate their developmental, behavioral and reproductive end points. All animals were born alive. The litter size of the aflatoxin B1 treated rats was comparable to the controls. However, the birth weight of the pups in the experimental group was significantly lower when compared to controls. Significant and persistent lags in cliff avoidance, negative geotaxis, surface rightening activity and ascending wire mesh, with a delay in elapsed time for vaginal opening were detected in the female progeny exposed to aflatoxin B1 during embryonic development. The locomotor activity and exploratory behavior in experimental females were significantly decreased than that of controls. Embryonic exposure to aflatoxin B1 also resulted in prolonged stress response, irregular estrus and suppressed fertility output in the progeny at their adulthood. These results indicate that in utero exposure to aflatoxin B1 severely compromised postnatal development of neonatal rats and caused irregular estrus that was accompanied by suppressed fertility output. PMID:26956420

  8. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

    PubMed

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2016-02-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PMID:26523890

  9. 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

  10. 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-OH¬vit-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...

  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. 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

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

    PubMed Central

    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.

    2013-01-01

    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 CA1/3 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

  15. 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...

  16. 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

  17. 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...

  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. 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...

  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. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. The toxicokinetic profile of curdione in pregnant SD rats and its transference in a placental barrier system detected by LC-MS/MS.

    PubMed

    Meng, Xiang; Zhang, Ting; Li, Ying; Pan, Qi; Jiang, Juan; Luo, Yongwei; Chong, Liming; Yang, Yang; Xu, Sichong; Zhou, Li; Sun, Zuyue

    2015-03-01

    The objective of this study was to determine the toxicokinetic profile of curdione in pregnant SD rats as well as the transference of curdione into the fetus through the placental barrier system using LC-MS/MS. Thirteen pregnant SD rats were treated with 7, 21 and 63 mg/kg curdione once daily from gestational day 6 (GD₆) to GD₁₅. Blood samples were collected at different time points on GD₆ and GD₁₅. Maternal plasma, placental plasma, placenta tissue, amniotic fluid and fetal tissue were collected for concentration analysis after all the animals were sacrificed following one repeated dose on GD₁₉. The results indicated that Cmax, AUC(₀₋t) and AUC(₀₋∞) increased in a dose-dependent manner both on GD₆ and GD₁₅. At 7 mg/kg group, the total serum clearance value on GD₁₅ was reduced to approximately 16.4% of that on GD₆, and the volume of distribution was also significantly decreased (p<0.05). Curdione could be detected in the maternal plasma, placental plasma, placenta tissue, amniotic fluid and fetal tissue, and its concentration in the fetal tissue reached saturation at 21 mg/kg. In conclusion, curdione presents with the risk of accumulation in pregnant SD rats and may affect the fetus via transference through the placental barrier system. PMID:25527910

  7. 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

  8. 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.

  9. 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

  10. Treatment with Iodine in Pregnant Rats with Marginal Iodine Deficiency Improves Cell Migration in the Developing Brain of the Progeny.

    PubMed

    Zhang, Le; Zhai, Xiaodan; Liu, Yuhui; Li, Jing; Shan, Zhongyan; Teng, Weiping

    2016-05-01

    Marginal iodine deficiency is a common health problem in pregnant women. Epidemiological and animal studies had shown that marginally maternal iodine deficiency could cause the mild changes of maternal thyroid function, eventually lead to a negative effect on neurodevelopment. But the underlying mechanisms responsible for the neurological impairment remain unclear. The aim of this study is to explore whether marginally maternal iodine deficiency could produce subtle changes in cell migration and cognitive function of offspring, and the optimal time of giving intervention to minimize the adverse effects. In the present study, we established a marginal iodine deficiency model, and iodine supplement was performed on pre-pregnancy (PP), G13 (gestation day 13), and postnatal day 0 (P0). Our data showed that there were changes in the cytoarchitecture and the percentage of bromodeoxyuridine (BrdU)-labeled cells in the cerebral cortex in marginal iodine deficiency rats. The Reelin expression was significantly lower, but Tenascin-C was higher in the cerebral cortex of marginal iodine deficiency group on P7 than the normal group, respectively. When iodine supplement, especially before G13 could reverse the abnormal expression of the two proteins involved in cell migration, which was consistent with the results of Morris Water Maze test. The three intervention groups had shorter escape latencies than the marginal iodine deficiency rats. The earlier that iodine is supplied, the better behavior performance would reach. Our findings suggested that iodine supplement in early stage of pregnancy could improve the cell migration of cerebral cortex and neurodevelopment of offspring. PMID:25963726

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

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

    PubMed

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

    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

  17. Protective effect of dienogest on chemotherapy-induced reduced fertility in female rats.

    PubMed

    Tsuyoshi, Hideaki; Orisaka, Makoto; Fukuda, Shin; Hattori, Katsushige; Tsang, Benjamin K; Yoshida, Yoshio

    2015-01-01

    Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy. PMID:25449767

  18. 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

  19. 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

  20. In utero and lactational exposure to blueberry via maternal diet promotes mammary epithelial differentiation in prepubescent female rats.

    PubMed

    Wu, Xianli; Rahal, Omar; Kang, Jie; Till, S Renee; Prior, Ronald L; Simmen, Rosalia C M

    2009-11-01

    Early developmental events influence the fine tuning of later susceptibility to adult diseases. Diet is a determinant of breast cancer risk, and our previous studies showed that diet-mediated changes in transcriptional programs promote early mammary gland differentiation. Although consumption of fruits is considered to elicit multiple health benefits, little is known on whether associated bioactive components modify the early differentiation program in developing mammary glands. Here, we evaluated the hypothesis that early exposure (in utero and lactational) to blueberry through maternal diet enhances mammary epithelial differentiation in female offspring. Pregnant Sprague-Dawley rats beginning at gestation day 4 were fed American Institute of Nutrition-based diets containing casein and whole blueberry powders added to casein at 2.5%, 5.0%, and 10% weight/weight. Female pups at weaning were evaluated for growth and mammary tissue parameters. Blueberry at 5% dose increased body and adipose fat weights, relative to the other diets. Mammary branch density and terminal end bud size were highest for the 5% blueberry group, whereas terminal end bud numbers were not affected by all diets. Mammary ductal epithelial cells of the 5% blueberry group had lower nuclear phosphorylated histone 3 and higher nuclear tumor suppressor phosphatase and tensin homolog deleted in chromosome 10 (PTEN) levels than the casein group. Although sera of both diet groups had similar antioxidant capacity, 5% blueberry sera elicited higher nuclear PTEN accumulation in human MCF-10A mammary epithelial cells. Our studies identify developing mammary glands as early targets of blueberry-associated bioactive components, possibly through systemic effects on epithelial PTEN signaling. PMID:19932869

  1. Intravenous self-administration of mephedrone, methylone and MDMA in female rats.

    PubMed

    Creehan, Kevin M; Vandewater, Sophia A; Taffe, Michael A

    2015-05-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation. PMID:25600245

  2. Intravenous self-administration of mephedrone, methylone and MDMA in female rats

    PubMed Central

    Creehan, Kevin M.; Vandewater, Sophia A.; Taffe, Michael A.

    2015-01-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants (“bath salts”) mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation. PMID:25600245

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

    PubMed

    Gualberto, Erivan Clementino; Theodoro, Letícia Helena; Longo, Mariellén; Novaes, Vivian Cristina Noronha; Nagata, Maria José 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 30 days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7 days, 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 30 days 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

  4. Antifertility effects of Pouzolzia mixta in female Wistar rats.

    PubMed

    Sewani-Rusike, Constance Rufaro

    2013-01-01

    The continued use of plants by women to prevent pregnancy suggests there are plants out there with potential use as contraceptives. In Zimbabwe, Pouzolzia mixta is used as a "morning after" contraceptive, thus it may possess postcoital antifertility activity. To test contraceptive activity, animals (n=8/group) were orally pretreated with aqueous (AqPM) or ethanolic (EtPM) extract of P. mixta at 300mg/kg b.wt for 7 days followed by mating with continued treatment for 10 days post-conception. To test for postcoital activity, treatment was initiated on day-1 of pregnancy and continued for 10 days. Laparotomy was performed and implantations counted. For estrogenic activity, immature ovariectomised rats were treated for 7 days after which vaginal opening and uterine weights were determined. In vitro oxytocic effects were performed using uterine tissue in an organ bath with De Jalon's solution. Acetylcholine (Ach) was the positive control. Results showed modest contraceptive activity with EtPM more effective in inhibiting fertility compared to AqPM (37.5% vs 25%) with a similar trend for antiimplantation effects (31% vs 19%). There was potent postcoital antifertility effects with AqPM more effective in inhibiting implantation (94.6% vs 86%) and fertility (87.5% vs 75%) compared to EtPM. Immature rat bioassay for estrogenic activity demonstrated pronounced estrogenic activity by both extracts. Oxytocic effects at 400ng/ml were more pronounced for the AqPM (92% of 100ng/ml Ach) than EtPM (25% of 100ng/ml Ach). Findings demonstrate the antifertility effects of aqueous and ethanolic extracts of P. mixta. The antifertility effects may be attributed to antiimplantation, estrogenic and oxytocic effects of the plant extracts. PMID:24146484

  5. Luteolytic action of RU486: modulation of luteal 3 beta-hydroxysteroid dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase activities in late pregnant rats.

    PubMed

    Tellería, C M; Stocco, C O; Deis, R P

    1995-06-01

    The effect of the synthetic antiprogestin RU486 on luteal function in late pregnant rats was studied by evaluating the activities of the enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). RU486 (2 mg/kg) administered to rats on day 18 of pregnancy at 10.00 h induced preterm delivery 26.4 +/- 0.35 h (n = 8) after treatment. Luteal 3 beta-HSD activity increased 24 and 34 h after RU486 injection, but a significant and progressive decrease started at 48 h with the maximal reduction 72 h after RU486 treatment, when compared with controls. Serum progesterone concentration decreased at the time of 3 beta-HSD activity reduction. Interestingly, 20 alpha-HSD activity started to increase 58 h after RU486 injection. The administration of the cyclooxygenase inhibitor, diclofenac (1.3 mg/kg), on days 17-19 of pregnancy to RU486-treated rats, delayed abortion and the duration of delivery, and prevented the decrease in 3 beta-HSD and the increase in 20 alpha-HSD activities observed 58 h after antiprogesterone treatment. RU486 administered intrabursally (1 microgram per ovary) on day 20 (14.00-15.00 h) increased 3 beta-HSD and decreased 20 alpha-HSD luteal activities at 18.00 h on day 21 of pregnancy, without modifying serum progesterone concentration, when compared with normal pregnant rats. In conclusion, the luteolytic process after preterm delivery induced by RU486 administration in late pregnant rats is characterized by a decrease in luteal 3 beta-HSD activity and circulating progesterone, which may trigger the increase in luteal 20 alpha-HSD activity. Prostaglandins seems to be involved in the increase of 20 alpha-HSD activity and therefore, in the demise of corpora lutea. PMID:7779760

  6. 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.

  7. 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

  8. 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

  9. High-fat diets promote insulin resistance through cytokine gene expression in growing female rats.

    PubMed

    Flanagan, Anne M; Brown, Jackie L; Santiago, Consuelo A; Aad, Pauline Y; Spicer, Leon J; Spicer, Maria T

    2008-08-01

    To determine if tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). IL-6 gene expression is influenced by amount and source of dietary fat, 30 weanling female rats were randomly assigned to a moderate-fat soybean oil (MFS; 22% of total energy fed as fat), high-fat (HF) soybean oil (HFS; 39% of total energy fed as fat), or HF tallow (HFT; 39% of total energy fed as fat) diet treatments. Oral glucose tolerance tests (OGTT) were conducted serially over 10 weeks of treatment. HFT and HFS rats gained more weight and had greater body fat than the MFS rats fed similar amounts of energy. Both groups of HF-fed rats had greater (P<.05) insulin resistance (homeostasis model assessment) than MFS-fed rats. TNF-alpha mRNA abundance quantified by real-time reverse transcriptase-polymerase chain reaction was greater (P<.05) in liver and lower (P<.05) in adipose tissue in HFT compared to HFS and MFS rats. There were positive correlations (P<.05) between hepatic TNF-alpha mRNA and insulin resistance, and negative correlations between insulin sensitivity and hepatic TNF-alpha mRNA and hepatic IL-6 mRNA. During Week 3 and Week 6 OGTTs, hyperinsulinemic responses were observed in the HFT group, after which, on Week 9, insulin secretion was diminished in response to the OGTT, suggesting impaired pancreatic insulin secretion. HFS rats exhibited insulin resistance on Week 9 OGTT. In summary, an HFT diet fed to growing female rats caused insulin resistance associated with increased hepatic TNF-alpha mRNA leading to pancreatic insufficiency. Early-onset insulin resistance related to the inflammatory process in obesity is influenced by the amount and type of fat in the diet. PMID:17904344

  10. 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

  11. 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

  12. Histomorphometry of the tibia and mandible of healthy female Wistar rats at different stages of growth.

    PubMed

    Nenda, María M; Lewicki, Marianela; Mandalunis, Patricia M

    2016-05-20

    Female Wistar rats are frequently used in experimental models to study hormone and bone pathologies and treatments. Most experimental studies involving histomorphometric evaluation assessed long bones, and few reports also studied mandibular bone. The aim of this work was to clarify and distinguish the age-related histomorphometric changes that occur in the tibia (subchondral bone) and in the mandible (interradicular bone), and thus obtain reference histomorphometric data of healthy female Wistar rats at different growth stages. Three groups of 8 healthy female Wistar rats were euthanized at 6 (GI), 10 (GII), and 14 (GIII) weeks. The tibiae and mandible were resected and histologically processed to obtain H&E stained sections of the tibia and the lower first molar to analyze the following histomorphometric parameters: Bone volume, trabecular width, trabecular number (Th.N)(1/mm), growth cartilage width, hypertrophic cartilage width and number of osteoclasts per area in the tibiae, and bone volume and number of osteoclasts per area N.Oc/mm(2) in the interradicular bone of the first lower molar. A significant decrease in subchondral bone volume as a result of a decrease in trabecular number and growth cartilage width was observed in 14-week-old rats. Conversely, interradicular bone volume was found to increase with age. The results highlight the importance of analyzing both types of bone to better understand the response of two different trabecular bones, contributing in turn to decision making regarding treatment strategies and disease management. PMID:26568145

  13. Histomorphometry of the tibia and mandible of healthy female Wistar rats at different stages of growth

    PubMed Central

    Nenda, María M.; Lewicki, Marianela; Mandalunis, Patricia M.

    2015-01-01

    Female Wistar rats are frequently used in experimental models to study hormone and bone pathologies and treatments. Most experimental studies involving histomorphometric evaluation assessed long bones, and few reports also studied mandibular bone. The aim of this work was to clarify and distinguish the age-related histomorphometric changes that occur in the tibia (subchondral bone) and in the mandible (interradicular bone), and thus obtain reference histomorphometric data of healthy female Wistar rats at different growth stages. Three groups of 8 healthy female Wistar rats were euthanized at 6 (GI), 10 (GII), and 14 (GIII) weeks. The tibiae and mandible were resected and histologically processed to obtain H&E stained sections of the tibia and the lower first molar to analyze the following histomorphometric parameters: Bone volume, trabecular width, trabecular number (Th.N)(1/mm), growth cartilage width, hypertrophic cartilage width and number of osteoclasts per area in the tibiae, and bone volume and number of osteoclasts per area N.Oc/mm2 in the interradicular bone of the first lower molar. A significant decrease in subchondral bone volume as a result of a decrease in trabecular number and growth cartilage width was observed in 14-week-old rats. Conversely, interradicular bone volume was found to increase with age. The results highlight the importance of analyzing both types of bone to better understand the response of two different trabecular bones, contributing in turn to decision making regarding treatment strategies and disease management. PMID:26568145

  14. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

    PubMed

    Lumbroso, Delphine; Joseph, Vincent

    2009-08-01

    We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude. PMID:19494172

  15. 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.

  16. 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.

  17. 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

  18. Prolactin regulates kisspeptin neurons in the arcuate nucleus to suppress LH secretion in female rats.

    PubMed

    Araujo-Lopes, Roberta; Crampton, Jessica R; Aquino, Nayara S S; Miranda, Roberta M; Kokay, Ilona C; Reis, Adelina M; Franci, Celso R; Grattan, David R; Szawka, Raphael E

    2014-03-01

    Prolactin (PRL) is known to suppress LH secretion. Kisspeptin neurons regulate LH secretion and express PRL receptors. We investigated whether PRL acts on kisspeptin neurons to suppress LH secretion in lactating (Lac) and virgin rats. Lac rats displayed high PRL secretion and reduced plasma LH and kisspeptin immunoreactivity in the arcuate nucleus (ARC). Bromocriptine-induced PRL blockade significantly increased ARC kisspeptin and plasma LH levels in Lac rats but did not restore them to the levels of non-Lac rats. Bromocriptine effects were prevented by the coadministration of ovine PRL (oPRL). Virgin ovariectomized (OVX) rats treated with either systemic or intracerebroventricular oPRL displayed reduction of kisspeptin expression in the ARC and plasma LH levels, and these effects were comparable with those of estradiol treatment in OVX rats. Conversely, estradiol-treated OVX rats displayed increased kisspeptin immunoreactivity in the anteroventral periventricular nucleus, whereas oPRL had no effect in this brain area. The expression of phosphorylated signal transducer and activator of transcription 5 was used to determine whether kisspeptin neurons in the ARC were responsive to PRL. Accordingly, intracerebroventricular oPRL induced expression of phosphorylated signal transducer and activator of transcription 5 in the great majority of ARC kisspeptin neurons in virgin and Lac rats. We provide here evidence that PRL acts on ARC neurons to inhibit kisspeptin expression in female rats. During lactation, PRL contributes to the inhibition of ARC kisspeptin. In OVX rats, high PRL levels suppress kisspeptin expression and reduce LH release. These findings suggest a pathway through which hyperprolactinemia may inhibit LH secretion and thereby cause infertility. PMID:24456164

  19. 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.

  20. Urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury in female rats

    PubMed Central

    Furuta, Akira; Suzuki, Yasuyuki; Asano, Koji; de Groat, William C.; Egawa, Shin; Yoshimura, Naoki

    2011-01-01

    Introduction and hypothesis To investigate the urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury. Methods In naive, acute pudendal nerve transection (PNT) and 4 weeks after PNT (PNT-4w) female rats, leak point pressures (LPPs) during bladder compression were measured before and after the application of hexamethonium (C6), propranolol and Nωnitro-L-arginine methyl ester (L-NAME), or terazosin and atropine. Responses to carbachol and phenylephrine of proximal and middle urethral muscle strips from naive and PNT-4w rats were also examined. Results LPPs were significantly decreased in PNT rats but not in PNT-4w rats. LPPs in PNT rats were significantly increased by C6 or L-NAME while LPPs in PNT-4w rats were significantly decreased by C6, or terazosin and atropine. Excitatory responses to carbachol and phenylephrine in the proximal urethral muscle were significantly larger in PNT-4w rats. Conclusions These results suggest that α1-adrenoceptor and muscarinic receptor-mediated contractility is upregulated in the proximal urethra 4 weeks after PNT. PMID:21445696

  1. Streptozotocin-induced diabetes blocks the positive feedback release of luteinizing hormone in the female rat.

    PubMed

    Kienast, S G; Fadden, C; Steger, R W

    1993-01-01

    The effects of streptozotocin-induced (STZ) diabetes on the release of gonadotropins was studied in female rats. In the first experiment, rats were ovariectomized and 2 days later were injected with STZ. Three weeks later rats were treated with estrogen and progesterone and blood samples were taken via intraatrial cannulae for luteinizing hormone (LH) assay. Afternoon surges of LH were seen in 4/5 control but 0/8 STZ rats. Pituitary responses to LH-releasing hormone in vitro did not differ. In the 2nd experiment, ovariectomized estrogen-primed rats were killed prior to and during a progesterone-induced LH surge. As in Experiment 1, STZ-treatment inhibited the LH surge but did not effect the afternoon rise in median eminence norepinephrine turnover which has previously been shown to be important in stimulating LH release. Turnover of norepinephrine in the anterior hypothalamus was depressed in the diabetic rats both prior to and during the expected time of the LH surge. Dopamine turnover was depressed in all three brain regions studied. It can be concluded that the positive feedback control of LH release is severely attenuated in diabetic rats but the mechanism explaining the loss is not clear. Diabetes-induced alterations in hypothalamic catecholamine metabolism may be involved but further work is needed to more carefully define these relationships. PMID:8221130

  2. 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

  3. Lycopene intake facilitates the increase of bone mineral density in growing female rats.

    PubMed

    Iimura, Yuki; Agata, Umon; Takeda, Satoko; Kobayashi, Yuki; Yoshida, Shigeki; Ezawa, Ikuko; Omi, Naomi

    2014-01-01

    Intake of the antioxidant lycopene has been reported to decrease oxidative stress and have beneficial effects on bone health. However, few in vivo studies have addressed these beneficial effects in growing female rodents or young women. The aim of this study was to investigate the effect of lycopene intake on bone metabolism through circulating oxidative stress in growing female rats. Six-week-old Sprague-Dawley female rats were randomly divided into 3 groups according to the lycopene content in their diet: 0, 50, and 100 ppm. The bone mineral density (BMD) of the lumbar spine and the tibial proximal metaphysis increased with lycopene content in a dose-dependent manner; the BMD in 100 ppm group was significantly higher than in the 0 ppm group. The urine deoxypyridinoline concentrations were significantly lower in the 50 and 100 ppm groups than in the 0 ppm group, and the serum bone-type alkaline phosphatase activity was significantly higher in 100 ppm group than in the 0 ppm group. No difference in systemic oxidative stress level was observed; however, the oxidative stress level inversely correlated with the tibial BMD. Our findings suggested that lycopene intake facilitates bone formation and inhibits bone resorption, leading to an increase of BMD in growing female rats. PMID:24975219

  4. Neural mechanisms of female sexual behavior in the rat; comparison with male ejaculatory control.

    PubMed

    Veening, J G; Coolen, L M; Gerrits, P O

    2014-06-01

    The sequential organization of sexual behavior of the female rat is described, eventually leading to the lordotic posture, shown during mating. A complex set of signals: olfactory, cutaneous sensory as well as genitosensory, is guiding the female to this specific posture, eventually. Genitosensory signals converge in the lumbosacral levels of the spinal cord, from where they are dispersed to a series of supraspinal brain areas, in the brainstem, thalamus, hypothalamus and limbic system. The similarity with the neural activation patterns observed in the male rat is remarkable. In a number of brain areas, however: the midbrain periaqueductal gray, the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) and the medial preoptic-lateral septum regions, specific male-female differences have been observed. Especially the VMHvl is an intriguing area, as it has been shown that the same neurons may be involved in 'opposite behavior' like aggression and the induction of lordosis. The motor mechanisms controlling the lordosis posture in the rat as well as in some other mammals are discussed, as well as some aspects of the reward mechanisms contributing to female sex. We conclude that we have collected a great amount of neurophysiological knowledge over the last 20 years, but that the unresolved questions are still numerous. In this field, there is still much to explore. PMID:24291647

  5. Neuroprotective effects of testosterone on dendritic morphology following partial motoneuron depletion: Efficacy in female rats

    PubMed Central

    Wilson, Randall E.; Coons, Kellie D.; Sengelaub, Dale R.

    2009-01-01

    Motoneuron loss is a significant medical problem, capable of causing severe movement disorders and even death. We have previously demonstrated that partial depletion of motoneurons induces dendritic atrophy in remaining motoneurons, with a concomitant reduction in motor activation. Treatment of male rats with testosterone attenuates the regressive changes following partial motoneuron depletion. To test whether testosterone has similar effects in females, we examined potential neuroprotective effects in motoneurons innervating muscles of the quadriceps of female rats. Motoneurons were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were given implants containing testosterone or left untreated. Four weeks later, surviving motoneurons were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. Compared to normal females, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons, and this atrophy was greatly attenuated by testosterone treatment. These findings suggest that testosterone has neuroprotective effects on morphology in both males and females, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system. PMID:19735695

  6. Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

    PubMed Central

    Zlebnik, Natalie E.; Saykao, Amy T.; Carroll, Marilyn E.

    2014-01-01

    BACKGROUND Individually, both treatment with progesterone and concurrent access to an exercise wheel reduce cocaine self-administration under long-access conditions and suppress cocaine-primed reinstatement in female rats. In the present study, wheel running and progesterone (alone and combined) were assessed for their effects on reinstatement of cocaine-seeking primed by yohimbine, cocaine, and cocaine-paired cues. METHODS Male and female rats were implanted with an intravenous catheter and allowed to self-administer cocaine (0.4 mg/kg/inf, iv) during 6-h sessions for 10 days. Subsequently, the groups of male and female rats were each divided into 2 groups that were given concurrent access to either a locked or unlocked running wheel under extinction conditions for 14 days. Next, all 4 groups were tested in a within-subjects design for reinstatement of cocaine-seeking precipitated by separate administration of cocaine-paired stimuli, yohimbine, or cocaine; or the combination of yohimbine + cocaine-paired stimuli or cocaine + cocaine-paired stimuli. These priming conditions were tested in the presence of concurrent wheel access (W), pretreatment with progesterone (P), or both (W+P). RESULTS In agreement with previous results, females responded more for cocaine than males during maintenance. Additionally, concurrent wheel running attenuated extinction responding and cocaine-primed reinstatement in females but not males. Across all priming conditions, W+P reduced reinstatement compared to control conditions, and for cocaine-primed reinstatement in male rats, the combined W+P treatment was more effective than W or P alone. CONCLUSION Under certain conditions, combined behavioral (exercise) and pharmacological (progesterone) interventions were more successful at reducing cocaine-seeking behavior than either intervention alone. PMID:24595506

  7. 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

  8. Nature of changes in adrenocortical function in chronic hyperleptinemic female rats.

    PubMed

    Perelló, Mario; Moreno, Griselda; Camihort, Gisela; Luna, Georgina; Cónsole, Gloria; Gaillard, Rolf C; Spinedi, Eduardo

    2004-07-01

    Neonatal treatment of rats with monosodium L-glutamate, which destroys hypothalamic arcuate nucleus neuronal bodies, induces several metabolic abnormalities; as a result, rats develop a phenotype of pseudoobesity. This study was designed to explore, in the monosodium L-glutamate-treated female rat, the influence of chronic hyperleptinemia on adrenal cortex functionality. For this purpose, we evaluated in control and hypothalamic-damaged rats: (a) in vivo and in vitro adrenocortical function, (b) adrenal leptin receptor immunodistribution and mRNA expression, and (c) whether the inhibitory effect of leptin on adrenal function remains. Our results indicate that, compared to normal counterparts, pseudoobese animals displayed (1) hyperadiposity, despite being hypophagic and of lower body weight, (2) in vivo and in vitro enhanced adrenocortical response to ACTH stimulation, (3) an in vitro adrenal fasciculata-reticularis cell hyper-sensitivity to ACTH stimulus, (4) hyperplasia of their adrenal zona fasciculata cells, and (5) adrenal fasciculata-reticularis cell refractoriness to the inhibitory effect of leptin on ACTH-stimulated glucocorticoid production due, at least in part, to decreased adrenal leptin receptor expression. These data further support that increased hypothalamo-pituitary-adrenal axis function, in the adult neurotoxin-lesioned female rat, is mainly dependent on the development of both hyperplasia of adrenal zona fasciculata and adrenal gland refractoriness to leptin inhibitory effect. Our study supports that adrenal leptin resistance could be responsible, at least in part, for enhanced glucocorticoid circulating levels in this phenotype of obesity. PMID:15347844

  9. 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

  10. Estradiol alters the chemosensitive cardiac afferent reflex in female rats by augmenting sympathoinhibition and attenuating sympathoexcitation.

    PubMed

    Pinkham, Maximilian I; Barrett, Carolyn J

    2015-06-01

    The chemosensitive cardiac vagal and sympathetic afferent reflexes are implicated in driving pathophysiological changes in sympathetic nerve activity (SNA) in cardiovascular disease states. This study investigated the impact of sex and ovarian hormones on the chemosensitive cardiac afferent reflex. Experiments were performed in anaesthetized, sinoaortic baroreceptor denervated male, female and ovariectomized female (OVX) Wistar rats with either intact cardiac innervation or bilateral vagotomy. To investigate the chemosensitive cardiac afferent reflexes renal SNA, heart rate (HR) and arterial pressure (AP) were recorded before and following application of capsaicin onto the epicardial surface of the left ventricle. Compared to males, ovary-intact females displayed similar cardiac afferent reflex mediated changes in renal SNA albeit with a reduced maximum sympathetic reflex driven increase in renal SNA. In females, ovariectomy significantly attenuated the cardiac vagal afferent reflex mediated inhibition of renal SNA (renal SNA decreased 2 ± 17% in OVX versus -50 ± 4% in ovary-intact females, P < 0.05) and augmented cardiac sympathetic afferent reflex mediated sympathoexcitation (renal SNA increased 91 ± 11% in OVX vs 62 ± 9% in ovary-intact females, P < 0.05) so that overall increases in reflex driven sympathoexcitation were significantly enhanced. Chronic estradiol replacement, but not progesterone replacement, begun at time of ovariectomy restored cardiac afferent reflex responses to be similar as ovary-intact females. Vagal denervation eliminated all group differences. The current findings show ovariectomy in female rats, mimicking menopause in women, results in greater chemosensitive cardiac afferent reflex driven sympathoexcitation and does so, at least partly, via the loss of estradiols actions on the cardiac vagal afferent reflex pathway. PMID:25810130

  11. 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

  12. High salt diet increases the pressor response to stress in female, but not male ETB-receptor-deficient rats

    PubMed Central

    Speed, Joshua S; D'Angelo, Gerard; Wach, Paul A; Sullivan, Jennifer C; Pollock, Jennifer S; Pollock, David M

    2015-01-01

    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

  13. 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

  14. 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

  15. 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

  16. Bradykinin B2 receptor-dependent enhancement of enalapril-evoked hypotension in ethanol-fed female rats

    PubMed Central

    El-Mas, Mahmoud M.; Abdel-Rahman, Abdel A.

    2010-01-01

    Our previous studies showed that chronic ethanol feeding attenuates centrally (clonidine)- and potentiates peripherally (hydralazine)-evoked hypotension in female rats. In this study, we investigated whether chronic ethanol (8 weeks, 5% w/v) alters hemodynamic responses elicited by angiotensin converting enzyme (ACE) inhibition (enalapril) in telemetered female rats. Given the intimate interaction between ACE and bradykinin, studies were extended to investigate the role of bradykinin receptor (B2R) in ethanol-enalapril interaction. Compared with pair-fed controls, ethanol-fed female rats exhibited: (i) higher renal expressions of ACE and B2R proteins and angiotensin II levels, and (ii) lower blood pressure (BP). Pharmacological inhibition of ACE and B2R support functional role for the higher levels of these two proteins in ethanol-fed rats because enalapril (10 mg/kg i.p) caused significantly greater hypotensive response in ethanol-fed rats than in control rats. Further, blockade of B2R with bradyzide (2 mg/kg i.p.) abrogated the enhanced hypotensive effect of enalapril in ethanol-fed rats but had no effect on enalapril-evoked hypotension in control rats. Finally, enalapril enhancement of spontaneous baroreflex sensitivity (BRS) in control was absent in ethanol-fed rats. These findings demonstrate that chronic ethanol produces B2R-dependent enhancement of the hypotensive response elicited by enalapril and abrogates enalapril-evoked enhancement of spontaneous baroreflex response in female rats. PMID:20966761

  17. Metagenomic Analysis of Antibiotic-Induced Changes in Gut Microbiota in a Pregnant Rat Model

    PubMed Central

    Khan, Imran; Azhar, Esam I.; Abbas, Aymn T.; Kumosani, Taha; Barbour, Elie K.; Raoult, Didier; Yasir, Muhammad

    2016-01-01

    Food and Drug Administration (FDA, USA)-approved category B antibiotics are commonly prescribed to treat infections during pregnancy. The aim of this study was to investigate antibiotic-induced changes in gut microbiota (GM) that occur during pregnancy. The 16S rRNA amplicon deep-sequencing method was used to analyze the effect of category B antibiotics (azithromycin, amoxicillin and cefaclor) on GM during pregnancy using a rat model. The GM composition was substantially modulated by pregnancy and antibiotics administration. Firmicutes, Bacteroidetes, Proteobacteria, Chlamydiae, Actinobacteria, and Cyanobacteria were the dominant phyla. Antibiotic treatment during pregnancy increased the relative abundance of Proteobacteria and reduced Firmicutes. The genera Shigella, Streptococcus, Candidatus Arthromitus, and Helicobacter were significantly (p < 0.05) more abundant during pregnancy. Antibiotics significantly (p < 0.05) reduced the relative abundance of Lactobacillus but increased that of Enterobacter. There was a significant (p < 0.05) decrease in Lactobacillus sp., Lactobacillus gallinarum and Lactobacillus crispatus during pregnancy. Antibiotic treatment reduced bacterial diversity; the lowest number of operational taxonomic units (OTUs) were detected in the cefaclor-treated groups. Antibiotics significantly (p < 0.05) promoted weight gain during pregnancy, and increased relative abundance of Shigella sonnei, Enterococcus hormaechei, and Acinetobacter sp. GM perturbations were accompanied by increases in Proteobacteria abundance and weight gain in pregnancy following antibiotic treatment. PMID:27199748

  18. Metagenomic Analysis of Antibiotic-Induced Changes in Gut Microbiota in a Pregnant Rat Model.

    PubMed

    Khan, Imran; Azhar, Esam I; Abbas, Aymn T; Kumosani, Taha; Barbour, Elie K; Raoult, Didier; Yasir, Muhammad

    2016-01-01

    Food and Drug Administration (FDA, USA)-approved category B antibiotics are commonly prescribed to treat infections during pregnancy. The aim of this study was to investigate antibiotic-induced changes in gut microbiota (GM) that occur during pregnancy. The 16S rRNA amplicon deep-sequencing method was used to analyze the effect of category B antibiotics (azithromycin, amoxicillin and cefaclor) on GM during pregnancy using a rat model. The GM composition was substantially modulated by pregnancy and antibiotics administration. Firmicutes, Bacteroidetes, Proteobacteria, Chlamydiae, Actinobacteria, and Cyanobacteria were the dominant phyla. Antibiotic treatment during pregnancy increased the relative abundance of Proteobacteria and reduced Firmicutes. The genera Shigella, Streptococcus, Candidatus Arthromitus, and Helicobacter were significantly (p < 0.05) more abundant during pregnancy. Antibiotics significantly (p < 0.05) reduced the relative abundance of Lactobacillus but increased that of Enterobacter. There was a significant (p < 0.05) decrease in Lactobacillus sp., Lactobacillus gallinarum and Lactobacillus crispatus during pregnancy. Antibiotic treatment reduced bacterial diversity; the lowest number of operational taxonomic units (OTUs) were detected in the cefaclor-treated groups. Antibiotics significantly (p < 0.05) promoted weight gain during pregnancy, and increased relative abundance of Shigella sonnei, Enterococcus hormaechei, and Acinetobacter sp. GM perturbations were accompanied by increases in Proteobacteria abundance and weight gain in pregnancy following antibiotic treatment. PMID:27199748

  19. Characterization of maternal transfer of decabromodiphenyl ether (BDE-209) administered to pregnant Sprague-Dawley rats.

    PubMed

    Cai, Yunmei; Zhang, Wenbing; Hu, Junjie; Sheng, Guoying; Chen, Dunjin; Fu, Jiamo

    2011-01-01

    To evaluate maternal transfer of decabromodiphenyl ether (BDE-209), Sprague-Dawley rats were given daily oral doses of 5 μmol/kgb.w. BDE-209 in peanut oil from gestation day (GD) 7 to postpartum day (PD) 4. BDE-209 was increased temporally in maternal blood, placenta, fetuses and neonates. Furthermore, more BDE-209 was found in neonate whole-body samples obtained during lactational period (PD 4) than in that of fetal whole-body samples during pregnancy GD 15 and 21. Overall an increase was observed over time for nona-BDE levels in maternal blood and placenta, but these congeners were decreased in fetuses or neonates. Slight changes were observed for octa-BDEs in both maternal blood and placenta while a significant decrease was observed in the fetuses or neonates for BDE-196 and 198/203. These results demonstrated that BDE-209 and its metabolites can transport to the placenta and milk, and eventually enter the fetuses and/or the neonates. PMID:20851178

  20. Metabolic response to starvation in late pregnant rats. II. Fetal response.

    PubMed

    Nowacka, M; Górski, 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

  1. 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.

  2. Pharmacological modulation of the endocannabinoid signalling alters binge-type eating behaviour in female rats

    PubMed Central

    Scherma, M; Fattore, L; Satta, V; Businco, F; Pigliacampo, B; Goldberg, SR; Dessi, C; Fratta, W; Fadda, P

    2013-01-01

    Background and Purpose Binge eating disorder (BED) is characterized by excessive food intake during short periods of time. Recent evidence suggests that alterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. In this study, we investigated whether pharmacological manipulation of endocannabinoid transmission may be effective in modulating the aberrant eating behaviour present in a validated rat model of BED. Experimental Approach Binge-type eating was induced in female rats by providing limited access to an optional source of dietary fat (margarine). Rats were divided into three groups, all with ad libitum access to chow and water: control (C), with no access to margarine; low restriction (LR), with 2 h margarine access 7 days a week; high restriction (HR), with 2 h margarine access 3 days a week. Key Results Compared with the LR group, the HR group consumed more margarine and this was accompanied by an increase in body weight. The cannabinoid CB1/CB2 receptor agonist Δ9-tetrahydrocannabinol significantly increased margarine intake selectively in LR rats, while the fatty acid amide hydrolase inhibitor URB597 showed no effect. The CB1 receptor inverse agonist/antagonist rimonabant dose-dependently reduced margarine intake in HR rats. Notably, in HR rats, chronic treatment with a low dose of rimonabant induced a selective long-lasting reduction in margarine intake that did not develop tolerance, and a significant and persistent reduction in body weight. Conclusions and Implications Chronic pharmacological blockade of CB1 receptors reduces binge eating behaviour in female rats and may prove effective in treating BED, with an associated significant reduction in body weight. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-4 & http://dx.doi.org/10.1111/bph.2012.167.issue-8 PMID:23072421

  3. 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

  4. Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium.

    PubMed

    Hanley, Jacqui-Ann; Weeks, Andrew; Wray, Susan

    2015-10-15

    Lactate is increased in myometrial capillary blood from women in slow or non-progressive labour (dystocia), suggesting that it is detrimental to uterine contractions. There are, however, no studies of the effect of lactate on the myometrium. We therefore investigated its effects and mechanism of action on myometrial strips from term pregnant rats. The effects on spontaneous and oxytocin-induced contractility in response to sodium lactate and other weak acids (1-20 mM) were studied. In some experiments, simultaneous force and intracellular Ca(2+) or pH (pH(i)) were measured with Indo-1 or Carboxy-SNARF, respectively. Statistical differences were tested using non-parametric tests. Lactate significantly decreased spontaneous contractility with an EC50 of 3.9 mM. Propionate, butyrate and pyruvate also reduced contractions with similar potency. The effects of lactate were reduced in the presence of oxytocin but remained significant. Lactate decreased pH(i) and nulling the decrease in pH(i) abolished its effects. We also show that lactate inhibited Ca(2+) transients, with these changes mirroring those produced on force. If Ca(2+) entry was enhanced by depolarization (high KCl) or applying the Ca(2+) channel agonist, Bay K 4644, the effects of lactate were abolished. Taken together, these data show that lactate in the physiological range potently decreases myometrial contractility as a result of its inhibition of Ca(2+) transients, which can be attributed to the induced acidification. The present study suggests that the accumulation of extracellular lactate will reduce myometrial contractions and could therefore contribute to labour dystocia. PMID:26223765

  5. 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

  6. Beneficial effects of vitamin C treatment on pregnant rats exposed to formaldehyde: Reversal of immunosuppression in the offspring.

    PubMed

    Ibrahim, Beatriz Silva; Barioni, Éric Diego; Heluany, Cíntia; Braga, Tárcio Teodoro; Drewes, Carine Cristiane; Costa, Silvia Goes; Câmara, Niels Olsen Saraiva; Farsky, Sandra Helena Poliselli; Lino-Dos-Santos-Franco, Adriana

    2016-06-01

    Inhalation of formaldehyde (FA) during the pregnancy induces oxidative stress in the uterus, and here we hypothesized that this mechanism may be responsible for the impaired immune response detected in the offspring. In order to investigate the protective effects of Vitamin C on the oxidative stress induced by FA in the uterine microenvironment, pregnant Wistar rats were treated with vitamin C (150mg/kg, gavage) or vehicle (distilled water, gavage) 1h before FA exposure (0.92mg/m(3), 1h/day, 5days/week), for 21days, and the 30days old offspring were submitted to LPS injection (Salmonella abortus equi, 5mg/kg, i.p.). The enhanced gene expression of iNOS, COX-1 and COX-2 and decreased gene expression of SOD-2 in the uterus of FA exposed mothers was rescued by Vit C treatment. Moreover, vitamin C rescued the impaired immune response elicited by LPS in the offspring from FA exposed mothers, by increasing the number of blood and bone marrow leukocytes, and augmenting gene expression of IL-6 and reducing mRNA levels of IL-10 and IFN in the lungs. Vitamin C treatment did not rescue the impaired TLR4-NF-kB pathway in the lung of the offspring, suggesting that FA-induced uterine oxidative stress affects other inflammatory pathways activated by LPS in the offspring. Together, data obtained here confirm our hypothesis that FA-induced oxidative stress in the uterine microenvironment modifies the programming mechanisms of the immune defenses of offspring, leading to an impaired host defense. PMID:27020608

  7. 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.

  8. Participation of intraluteal progesterone and prostaglandin F2 alpha in LH-induced luteolysis in pregnant rat.

    PubMed

    Stocco, C O; Deis, R P

    1998-02-01

    We examined the participation of the intraluteal levels of progesterone (P4) and prostaglandin F2 alpha (PGF2 alpha) in the induction of luteolysis by LH and its relationship with the induction of the 20 alpha-hydroxysteroid dehydrogenase activity (20 alpha-HSD). Subcutaneous administration of four doses of 10 microgram ovine LH (oLH) at 0800, 0900, 1000 and 1100 h on day 19 of pregnancy induced a decrease in the activity of the enzyme 3 beta-HSD 24 and 48 h after treatment and an increase in luteal 20 alpha-HSD activity 48 h after oLH treatment when compared with control rats. Intraluteal and serum P4 levels were lower than control values 24 and 48 h after oLH treatment, with a significant increase in luteal PGF2 alpha content and a decrease in corpus luteum (CL) weight 48 h after oLH treatment. Intrabursal ovarian (i.b.) treatment with an inhibitor of PG's biosynthesis (diclofenac) (70 microgram/ovary) or P4 (3 microgram/ovary) on day 20 of pregnancy, prevented the increase in 20 alpha-HSD activity observed 48 h after oLH treatment, without any effect on 3 beta-HSD activity. The i.b. administration of P4 prevented the increase in intraluteal PGF2 alpha content induced by oLH treatment and the increases in 20 alpha-HSD activity and intraluteal PGF2 alpha content observed in control animals on day 21 of pregnancy. The inhibition of PG biosynthesis also prevents the decrease in intraluteal and serum P4 level induced by oLH. These results provide good evidence of the important participation of intraluteal P4 and PGF2 alpha on the oLH-induced luteolysis in pregnant rats. We also found the P4 produced by the CL is involved, in part, in the regulation of luteal PG synthesis. Thus, the early decline in 3 beta-HSD activity and the consequent fall in intraluteal P4 content, may trigger the synthesis of PGs and thereafter the increase in luteal 20 alpha-HSD activity to establish luteolysis. PMID:9518870

  9. 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

  10. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    PubMed Central

    Castro, C.L.; Aguiar-Nemer, A.S.; Castro-Faria-Neto, H.C.; Barros, F.R.; Rocha, E.M.S.; Silva-Fonseca, V.A.

    2013-01-01

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression. PMID:24345912

  11. Maternal treatment of spontaneously hypertensive rats with pentaerythritol tetranitrate reduces blood pressure in female offspring.

    PubMed

    Wu, Zhixiong; Siuda, Daniel; Xia, Ning; Reifenberg, Gisela; Daiber, Andreas; Münzel, Thomas; Förstermann, Ulrich; Li, Huige

    2015-01-01

    Pentaerythritol tetranitrate is devoid of nitrate tolerance and shows no reproductive or developmental toxicity in animal studies. Recently, pentaerythritol tetranitrate has been demonstrated to reduce the risk of intrauterine growth restriction and the risk of preterm birth in women with abnormal placental perfusion. This study was conducted to test the perinatal programming effect of pentaerythritol tetranitrate in spontaneously hypertensive rats, a rat model of genetic hypertension. Parental spontaneously hypertensive rats were treated with pentaerythritol tetranitrate (50 mg/kg per day) during pregnancy and lactation periods; the offspring received standard chow without pentaerythritol tetranitrate after weaning. Maternal treatment with pentaerythritol tetranitrate had no effect on blood pressure in male offspring. In the female offspring, however, a persistent reduction in blood pressure was observed at 6 and 8 months. This long-lasting effect was accompanied by an upregulation of endothelial nitric oxide synthase, mitochondrial superoxide dismutase, glutathione peroxidase 1, and heme oxygenase 1 in the aorta of 8-month-old female offspring, which was likely to result from epigenetic changes (enhanced histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation) and transcriptional activation (enhanced binding of DNA-directed RNA polymerase II to the transcription start site of the genes). In organ chamber experiments, the endothelium-dependent, nitric oxide-mediated vasodilation to acetylcholine was enhanced in aorta from female offspring of the pentaerythritol tetranitrate-treated parental spontaneously hypertensive rats. In conclusion, maternal pentaerythritol tetranitrate treatment leads to epigenetic modifications, gene expression changes, an improvement of endothelial function and a persistent blood pressure reduction in the female offspring. PMID:25385760

  12. 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

  13. 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

  14. Topographies and isoforms of the progesterone receptor in female human, rat and mouse bladder.

    PubMed

    Gevaert, Thomas; Rietjens, Roma; Voets, Thomas; Everaerts, Wouter; De Ridder, Dirk

    2016-05-01

    Steroid hormones such as progesterone are known to influence bladder function. Progesterone effects are mediated by the progesterone receptor (PR) but no detailed studies of PR in bladder exist. We have investigated the presence, topography and subtypes of PR in mouse, rat and human bladder. Fresh tissue samples were obtained from cystectomies in female humans, rats and mice (n = 7 per group). Tissue samples were processed for immunohistochemistry (IHC), immunofluorescence (IF) and western blot (WB) and, for each species, a panel of specific PR antibody clones was used. Interpretation of IHC/IF was carried out by light/fluorescent microscopy and of WB via standard WB software. IHC/IF in female human bladder showed PR on the interstitial cells in the lamina propria and between detrusor smooth muscle cells, whereas in female rat and mouse bladder, PR was only found on the urothelium. WB in human bladder showed a 78-kD and a 60-kDa band, respectively, corresponding to a modified PR isoform A and PR isoform C. WB in rat and mice bladder showed a 60 kDa band and a 37 kDa band, respectively corresponding with PR isoform C and an unknown isoform. This is the first detailed investigation of the precise location and presence of several isoforms of PR in bladder, together with a comparison of these data between human, rat and mouse. Our study has revealed complex PR families in bladders from the various species studied and demonstrates obvious inter-species differences in PR topography and isoforms. PMID:26650465

  15. 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

  16. 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

  17. 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

  18. 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...

  19. 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

  20. Effect of acute stress on sexual behavior in female rats: participation of the central angiotensinergic system.

    PubMed

    Cecconello, Ana Lúcia; Raineki, Charlis; Sebben, Vanise; Lucion, Aldo Bolten; Sanvitto, Gilberto Luiz

    2010-03-01

    Stress might influence the reproductive behavior in females, and central angiotensin II (Ang II) is a peptide that plays a role in stress response and in the modulation of sexual behavior. The medial amygdala (MeA), an important structure that regulates this behavior, is strongly involved in stress response. The aim of the present study was to evaluate the effect of acute restraint stress on the night of proestrus on sexual receptivity in female rats and the participation of Ang II and MeA in this effect. Adult female Wistar rats with regular estrous cycles were utilized. The acute stress protocol utilized was the restraint stress for 15 min on the night of proestrus. The participation of Ang II was evaluated by injecting Ang II and Ang II receptor antagonists (losartan and PD12319) into the MeA. The lordosis quotient was recorded. The stress or the microinjection of Ang II into the MeA significantly reduced sexual behavior. The blockade of AT(1) or AT(2) receptors in the MeA prevented the effect of stress and the effect of Ang II microinjection into this nucleus on sexual receptivity. We concluded that acute restraint stress on the night of proestrus reduces sexual behavior in rats, and this effect is mediated by both AT(1) and AT(2) receptors in the MeA. PMID:19879304

  1. 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-β 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-β under conditions of excess tissue Ang II and circulating aldosterone. PMID:24847333

  2. Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats.

    PubMed

    Rodrigues, Samya Mere L; Ximenes, Carolina F; de Batista, Priscila R; Simões, Fabiana V; Coser, Pedro Henrique P; Sena, Gabriela C; Podratz, Priscila L; de Souza, Leticia N G; Vassallo, Dalton V; Graceli, Jones B; Stefanon, Ivanita

    2014-03-21

    Organotin compounds such as tributyltin (TBT) are used as antifouling paints by shipping companies. TBT inhibits the aromatase responsible for the transformation of testosterone into estrogen. Our hypothesis is that TBT modulates the vascular reactivity of female rats. Female Wistar rats were treated daily (Control; CONT) or TBT (100 ng/kg) for 15 days. Rings from thoracic aortas were incubated with phenylephrine (PHE, 10(-10)-10(-4) M) in the presence and absence of endothelium, and in the presence of N(G)-Nitro-L-Arginine Methyl Ester (L-NAME), tetraethylammonium (TEA) and apocynin. TBT decreased plasma levels of estrogen and the vascular response to PHE. In the TBT group, the vascular reactivity was increased in the absence of endothelium, L-NAME and TEA. The decrease in PHE reactivity during incubation with apocynin was more evident in the TBT group. The sensitivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was reduced in the TBT group. TBT increased collagen, reduced α1-smooth muscle actin. Female rats treated with TBT for 15 days showed morphology alteration of the aorta and decreased their vascular reactivity, probably due to mechanisms dependent on nitric oxide (NO) bioavailability, K(+) channels and an increase in oxidative stress. PMID:24468273

  3. 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

  4. Pomegranate Flower Extract does not Prevent Cisplatin-Induced Nephrotoxicity in Female Rats

    PubMed Central

    Jilanchi, Sima; Nematbakhsh, Mehdi; Mazaheri, Safoora; Talebi, Ardeshir; Zolfaghari, Behzad; Pezeshki, Zahra; Eshraghi-Jazi, Fatemeh; Moeini, Maryam

    2014-01-01

    Background: Nephrotoxicity is the major side-effect of cisplatin (CDDP), and it is reported to be gender-related. We evaluated the effects of pomegranate flower extract (PFE) as an antioxidant on CDDP-induced nephrotoxicity in female rats. Methods: Twenty-three adult female rats in four groups treated as following. Groups 1 and 2 received PFE at doses of 25 and 50 (mg/kg/day), respectively, for 9 days, and from day 3 on, they also received cisplatin (CDDP) (2.5 mg/kg) daily. Group 3 was treated as group 1 expects saline instead of PFE, and group 4 received PFE (25 mg/kg/day) alone. Results: Cisplatin alone increased the serum levels of blood urea nitrogen, creatinine, and nitrite; and kidney tissue damage score and kidney weight. However, PFE not only did not ameliorate the induced nephrotoxicity, but also aggravated renal tissue damage. Conclusions: Pomegranate extract as an antioxidant did not ameliorate CDDP-induced nephrotoxicity in female rats. PMID:25709800

  5. 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

  6. 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.

  7. Accumulation of organotins in seafood leads to reproductive tract abnormalities in female rats.

    PubMed

    Podratz, Priscila L; Merlo, Eduardo; Sena, Gabriela C; Morozesk, Mariana; Bonomo, Marina M; Matsumoto, Silvia T; da Costa, Mércia B; Zamprogno, Gabriela C; Brandão, Poliane A A; Carneiro, Maria T W D; Miguel, Emilio de C; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2015-11-01

    Organotins (OTs) are environmental contaminants used as biocides in antifouling paints that have been shown to be endocrine disrupters. However, studies evaluating the effects of OTs accumulated in seafood (LNI) on reproductive health are particularly sparse. This study demonstrates that LNI leads to impairment in the reproductive tract of female rats, as the estrous cycle development, as well as for ovary and uterus morphology. Rats were treated with LNI, and their reproductive morphophysiology was assessed. Morphophysiological abnormalities, such as irregular estrous cycles, abnormal ovarian follicular development and ovarian collagen deposition, were observed in LNI rats. An increase in luminal epithelia and ERα expression was observed in the LNI uteri. Together, these data provide in vivo evidence that LNI are toxic for reproductive morphophysiology, which may be associated with risks to reproductive function. PMID:26050607

  8. 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

  9. [Morphological characteristics of spermatogenesis in the offspring of female rats with chronic alcohol intoxication].

    PubMed

    Sizonenko, M L; Briukhin, G V; La'skov, D S

    2013-01-01

    Using general histological and morphometric methods, the peculiarities of spermatogenic epithelium were studied in the offspring of female rats with chronic alcohol intoxication, which was created before the onset of pregnancy by substitution of the drinking water by 15% solution of ethyl alcohol for the period of 3 months. Total number of animals was equal to 62 rat pups which were studied at postnatal days 15, 30 and 45, including 32 rats of the intact group (10 litters) and 30 pups of the experimental group (8 litters). It was found that in the offspring of female rats with chronic alcohol intoxication, the inhibition of the processes of spermatogenesis took place, as reflected by the reduction in the area of the convoluted seminiferous tubules (CST), decrease in the number of spermatogenic cells of the seminiferous layer, increase in the proportion of CST with desquamated epithelium and giant spermatogenic cells, as well as by the reduction of spermatogenic index, which reflects the average number of layers of spermatogenic cells in each CST. PMID:23805617

  10. 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

  11. EFFECTS OF NICOTINE ON DEPRESSIVE-LIKE BEHAVIOR AND HIPPOCAMPAL VOLUME OF FEMALE WKY RATS

    PubMed Central

    Tizabi, Yousef; Hauser, Sheketha R.; Tyler, Khandra Y.; Getachew, Bruk; Madani, Reza; Sharma, Yukti; Manaye, Kebreten F.

    2009-01-01

    The observed high incidence of smoking amongst depressed individuals has led to the hypothesis of ‘self medication” with nicotine in some of these patients. The inbred Wistar-Kyoto (WKY) rats exhibit depressive-like characteristics as evidenced by exaggerated immobility in the forced swim test (FST). One aim of this study was to investigate whether nicotine may have an antidepressant-like effect in these animals. Moreover, because of human postmortem studies indicating a reduction of the hippocampus volume in depressed patients, it was of interest to determine whether such an anatomical anomaly may also be manifested in WKY rats and whether it would be affected by chronic nicotine treatment. Adult female WKY and their control Wistar rats were administered nicotine consecutively (0.2 mg/kg, ip, once or twice daily for 14 days) and their activity in an open field, as well as their immobility in FST were assessed either 15 min or 18 hr after the last injection. Another set of animals was treated twice daily with 0.2 mg/kg nicotine for 14 days and sacrificed on day 15 for stereological evaluation of the hippocampal volume. When tested 15 min after the last injection, once or twice daily nicotine exacerbated the immobility in the FST in WKY rats only. When tested 18 hr after the last injection, only twice daily nicotine treatment resulted in less immobility in the FST in WKY rats. Open field locomotor activity was not affected by any nicotine regimen. WKY rats had significantly less hippocampal volume (approximately 20%) than Wistar rats which was not altered by nicotine. These findings further validate the use of WKY rats as an animal model of human depression and signify the importance of inherent genetic differences in final behavioral outcome of nicotine. PMID:19800382

  12. Ovarian-steroid modulation of locus coeruleus activity in female rats: involvement in luteinising hormone regulation.

    PubMed

    Szawka, R E; Rodovalho, G V; Monteiro, P M; Carrer, H F; Anselmo-Franci, J A

    2009-07-01

    The noradrenergic nucleus locus coeruleus (LC) has been reported to regulate luteinising hormone (LH) secretion in female rats. Both oestrogen and progestin receptors have been demonstrated in LC neurones, suggesting that these cells are possibly responsive to variations in circulating levels of ovarian steroids. We therefore evaluated changes in the activity of LC neurones during the oestrous cycle and after ovarian-steroid treatment in ovariectomised (OVX) rats, as determined by immunoreactivity to Fos-related antigens (FRA), which comprises all of the known members of the Fos family. Effects of ovarian steroids on the firing rate of LC neurones were also determined in a slice preparation. The number of FRA/tyrosine hydroxylase (TH)-immunoreactive (ir) neurones in the LC increased from 14.00-16.00 h on pro-oestrus, coinciding with the onset of the LH surge and rise in plasma progesterone. FRA immunoreactivity was unaltered during dioestrus. Oestradiol-treated OVX rats (OVX+E) displayed marked reduction in FRA/TH-ir neurones in LC compared to oil-treated OVX rats. Accordingly, oestradiol superfusion significantly reduced the spontaneous firing rate of LC neurones in slices from OVX rats. Compared to OVX+E, oestradiol-treated rats injected with progesterone at 08.00 h (OVX+EP) exhibited higher number of FRA/TH-ir neurones in the LC at 10.00 h and 16.00 h, and great amplification of the LH surge. Bath application of progesterone significantly increased the spontaneous firing rate of OVX+E LC neurones. Our data suggest that ovarian steroids may physiologically modulate the activity of LC neurones in females, with possible implications for LH secretion. Moreover, oestradiol and progesterone appear to exert opposite and complementary effects (i.e. whereas oestradiol inhibits, progesterone, after oestradiol priming, stimulates LC activity). PMID:19490365

  13. 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

  14. 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

  15. In vivo exposure of female rats to toxicants may affect oocyte quality.

    PubMed

    Berger, Trish; Horner, Catherine M

    2003-01-01

    A potential endpoint for female reproductive toxicants is fertilizability of the oocytes. This endpoint has not been adequately examined for mammalian females. The objective of these studies was to evaluate fertilizability of rat oocytes following in vivo exposure to known male reproductive toxicants that exert effects via pathways that do not include endocrine disruption and to 4-vinylcyclohexene diepoxide, known to interfere with early follicular development. Oocytes were obtained from females following exposure and quality assessed by in vitro fertilization rate. One study evaluated fertilizability following 2 weeks exposure of females to inhaled tetrachloroethylene (2h/day, 5 days/week). The remaining studies evaluated fertilizability immediately following 2 weeks exposure via drinking water to tetrachloroethylene, trichloroethylene, the fuel oxidants methyl tertiary butyl ether (MTBE), ethyl tertiary butyl ether (ETBE), tertiary amyl methyl ether (TAME), and a metabolite of the first two ethers 2-methyl-1,2-propanediol (2M2P), and to 4-vinylcyclohexene diepoxide. The percentage of oocytes fertilized was reduced following inhalation exposure to tetrachloroethylene, or consumption of trichloroethylene or TAME. Fertilizability was not altered by exposures to the other reproductive toxicants or to the other fuel oxidants. Consistent with the reduced oocyte fertilizability following exposure to trichloroethylene, oocytes from exposed females had a reduced ability to bind sperm plasma membrane proteins. Female reproductive capability assessed by the endpoint, oocyte fertilizability, was reduced by exposure to trichloroethylene and inhaled tetrachloroethylene. PMID:12759095

  16. 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

  17. 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

  18. 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

  19. Anhedonia in postpartum rats.

    PubMed

    Navarre, Brittany M; Laggart, Jillian D; Craft, Rebecca M

    2010-01-12

    Postpartum depression (PPD) is a debilitating illness, yet little is known about its causes. The purpose of this study was to examine a major symptom of depression during the postpartum period, anhedonia, by comparing sucrose preference in female rats that had undergone actual pregnancy or hormone-simulated pregnancy (HSP) to their respective controls. Whereas HSP rats showed significantly less preference than vehicle control rats for 1% sucrose solution during the first three weeks of the "postpartum" period, previously pregnant females showed only slightly depressed sucrose preference for the first 1-2 days postpartum, compared to non-pregnant controls. Habituation to 1% sucrose during the pregnancy period, which increased preference upon later testing in previously pregnant rats tested on postpartum day 2, did not significantly increase preference in HSP rats, suggesting that depressed preference in the latter group was not due to neophobia. Pre-treatment with desipramine did not prevent suppressed sucrose preference in HSP rats, and preference was even further suppressed following chronic sertraline treatment. These results suggest that estradiol withdrawal following HSP may cause anhedonia during the early "postpartum" period. In contrast, females that have undergone actual pregnancy are less likely to show this effect, suggesting that postpartum hormonal changes other than the dramatic decline in estradiol may buffer its negative mood effects. PMID:19850056

  20. Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr) and normal (Sprague-Dawley) female rats.

    PubMed

    Valdez, Susana R; Penissi, Alicia B; Deis, Ricardo P; Jahn, Graciela A

    2007-04-01

    Lactation deficiency may have important consequences on infant health, particularly in populations of low socioeconomic status. The OFA hr/hr (OFA) strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation and is a good model of lactation failure. We examined the reproductive performance and hormonal profiles in OFA and SD strains to determine the cause(s) of the lactation failure of the OFA strain. We measured hormonal (PRL, GH, gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant, and lactating rats and in response to suckling. Dopaminergic metabolism was assessed by determination of mediobasal hypothalamic dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine hydroxylase expression by immunocytochemistry and western blot. OFA rats have normal fertility but 50% of the litters die of malnutrition on early lactation; only 6% of the mothers show normal lactation. The OFA rats showed lower circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and impaired milk ejection with decreased PRL and oxytocin response to suckling. Before parturition, PRL release and lactogenesis were normal, but dopaminergic metabolism was altered, suggesting activation of the dopaminergic system in OFA but not in SD rats. The number of arcuate and periventricular neurons expressing tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was higher in OFA rats at the end of pregnancy and early lactation. These results suggest that the OFA rats have impaired PRL release linked with an augmented dopaminergic tone which could be partially responsible for the lactational failure. PMID:17504926

  1. Prediction of seizure incidence probability in PTZ model of kindling through spatial learning ability in male and female rats.

    PubMed

    Haeri, Narges-Al-Sadat; Palizvan, Mohammad Reza; Sadegh, Mehdi; Aghaei, Zohre; Rafiei, Mohammad

    2016-07-01

    Epilepsy is a common neurological disease characterized by periodic seizures. Cognitive deficits and impairments in learning and memory are also associated with epilepsy. Neuronal changes and synaptic modifications in kindling model of epilepsy are similar to those occur during the learning procedure and memory formation. Herein we investigated whether seizure susceptibility in pentylenetetrazol (PTZ) model of kindling is predictable based on the learning ability in the Morris water maze (MWM) task in male and female rats. Allocentric learning was tested using MWM in present of light while egocentric learning was evaluated by MWM in dark room. The results indicated no significant differences in allocentric learning abilities between male and female rats. However, male rats were able to memorize the location of the platform more effectively compared to females in egocentric test. In addition, a statistically significant negative correlation between learning abilities (working memory) and seizure susceptibility in male rats was found while this correlation was positive in female rats. On the other hand, although there was no significant correlation between retrieval (reference memory) of spatial memories and seizure parameters in male rats, female rats showed a significant negative correlation. These findings may provide some evidences for prediction of seizure susceptibility according to learning ability and memory retention. PMID:27098273

  2. 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.

  3. The effects of unilateral truncal vagotomy on gastric carcinogenesis in hypergastrinemic Japanese female cotton rats.

    PubMed

    Fossmark, Reidar; Sørdal, Øystein F; Bakkelund, Karin E; Nordrum, Ivar Skjåk; Waldum, Helge

    2013-06-10

    The stomach is innervated by the vagal nerve. Several studies have demonstrated that the vagal nerve has a trophic effect on the rat oxyntic mucosa and that the trophic effect of hypergastrinemia is dependent on intact vagal innervation. The effect of vagal denervation on gastric carcinogenesis has been examined in Mastomys natalensis and hypergastrinemic transgenic INS-GAS mice, with no effect of unilateral vagotomy in Mastomys but an anti-carcinogenic effect in INS-GAS mice. A proportion of female Japanese cotton rats develop spontaneous hypergastrinemia and ECL cell derived gastric carcinomas. In the current study we have examined the effects of unilateral anterior subdiaphragmatic vagotomy on gastric carcinogenesis. Female Japanese cotton rats were operated with unilateral anterior vagotomy or sham-operation at age 2 months and were terminated at age 10 months. Ten of fifteen animals operated by anterior vagotomy and 11 of 16 sham-operated developed hypergastrinemia. Vagotomy did not affect intragastric pH or serum gastrin. When comparing the anterior and posterior sides of the stomachs, vagotomy did not affect the occurrence of dysplasia or carcinoma development in the oxyntic mucosa. However, vagotomy resulted in lower stomach weight and reduced oxyntic mucosal thickness on the anterior side. Vagotomy also resulted in a reduction in volume density of chromogranin A positive cells in the oxyntic mucosa. In conclusion, vagotomy reduced the trophic effects of hypergastrinemia on the ECL cell and oxyntic mucosa, but did not prevent gastric carcinogenesis in female Japanese cotton rats. The effects of vagotomy on gastric carcinogenesis in animal models are conflicting and further studies in patients should be done to clarify the clinically significant effects of vagotomy. PMID:23499800

  4. Effects of Salsalate Therapy on Recovery From Vascular Injury in Female Zucker Fatty Rats

    PubMed Central

    Murthy, Subramanyam N.; Desouza, Cyrus V.; Bost, Neal W.; Hilaire, Rose-Claire St.; Casey, David B.; Badejo, Adeleke M.; Dhaliwal, Jasdeep S.; McGee, Jennifer; McNamara, Dennis B.; Kadowitz, Philip J.; Fonseca, Vivian A.

    2010-01-01

    OBJECTIVE Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury. RESEARCH DESIGN AND METHODS Salsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied. RESULTS Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) κB subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats. CONCLUSIONS The present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NFκB, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures. PMID:20876710

  5. Delta opioid receptors: reflexive, defensive and vocal affective responses in female rats.

    PubMed

    Haney, M; Miczek, K A

    1995-09-01

    Ultrasonic vocalizations may be an expression of the affective pain response in laboratory animals. The present experiment compares the effects of morphine to the delta agonist, DPDPE (D-Pen2,D-Pen5 enkephalin) on a range of reflexive, behavioral and affective responses during an aggressive interaction. In experiment 1, naive female Long-Evans rats received morphine (0, 1, 3, 6, 10 micrograms ICV), or DPDPE (0, 30, 60, 100 micrograms ICV). In experiment 2, female rats were treated with naltrindole (1.0 mg/kg IP) 20 min before DPDPE (0, 60, 100 micrograms ICV). The following endpoints were measured: (1) latency to tail flick in response to heat stimuli; (2) high (33-65 kHz) and low (20-32 kHz) frequency ultrasonic and audible vocalizations; (3) defensive behavior; and (4) motoric activity. Following a brief exposure to attack, rats were threatened by the aggressor but protected from further attack by a large, wire mesh cage, thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made during the attack and then during a portion of the protected encounter (2 min). Morphine suppressed pain reactions varying in complexity from a spinal reflex, to an organized escape reaction, to an affective vocal response. The delta agonist, DPDPE, attenuated high frequency ultrasonic calling and tail flick responding. Defensive behaviors were also modulated by DPDPE at doses that had no effect on walking or rearing, indicating behavioral specificity. By contrast, doses of morphine that decreased defensive upright and escape also decreased motor activity. In female rats, morphine and DPDPE share a common profile of effects on a range of functional end-points, but DPDPE appears to modulate more selectively the reactions related to aversiveness without exerting sedative effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8545526

  6. 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.

  7. 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

  8. Unit: Males and Females, Inspection Pack, National Trial Print.

    ERIC Educational Resources Information Center

    Australian Science Education Project, Toorak, Victoria.

    This is a National Trial Print of an Australian Science Education Project unit entitled Males and Females. Materials provided consist of a teacher's edition of the written materials, a student record book, and seven large black and white photographs showing various stages in the dissection of a pregnant rat. This unit has been written to help…

  9. Ketogenic diet decreases circulating concentrations of neuroactive steroids of female rats.

    PubMed

    Rhodes, Madeline E; Talluri, Jayanth; Harney, Jacob P; Frye, Cheryl A

    2005-09-01

    Ketogenic diet (KD) is used to manage intractable epilepsy; however, the mechanisms underlying its therapeutic effects are not known. Steroid hormones, such as progesterone and testosterone, are derived from cholesterol, and are readily 5alpha-reduced to dihydroprogesterone and dihydrotestosterone, which are subsequently converted to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) and 3alpha-androstanediol, neuroactive steroids that can influence seizures. The present study examined the effects of the KD on circulating concentrations of these neuroactive steroids, and their precursors, in intact female rats. Thirty-six, 22-day-old female Sprague-Dawley rats (weaned at 21 days) were fasted for 8 hours prior to placement on one of three dietary regimens for 6 weeks: ad libitum chow, calorie-restricted chow, or KD. After 6 weeks of the diet, when six rats in each dietary condition were in diestrus and six were in behavioral estrus, all rats were administered pentylenetetrazole (PTZ, 70 mg/kg, i.p.). The latency and incidence of seizures were recorded by an observer who was uninformed of the estrous cycle and dietary treatment conditions of the rats. Immediately after each test, trunk blood was obtained for later measurement of pregnane (progesterone, dihydroprogesterone, 3alpha,5alpha-THP) and androstane (testosterone, dihydrotestosterone, 3alpha-androstanediol) neuroactive steroid concentrations in plasma by radioimmunoassay. KD tended to lengthen the latency to, and significantly reduced the number of, PTZ-induced barrel roll seizures. KD also significantly reduced plasma levels of the pregnane (dihydroprogesterone, 3alpha,5alpha-THP) and androstane (dihydrotestosterone, 3alpha-androstanediol) 5alpha-reduced metabolites. These data suggest that levels of pregnane and androstane neuroactive steroids, or their precursors, may underlie some of the antiseizure effects of KD. PMID:16054440

  10. 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

  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. Place Aversion by Morphine in Offspring Born of Female Morphine Administered Wistar Rats

    PubMed Central

    Karami, Manizheh; Zarrindast, Mohammad Reza

    2011-01-01

    This research was designed to study sexual differences in place conditioning induced by morphine in offspring born of female Wistar rats mated with drug-naïve males. Mothers were exposed to morphine during the 14th-16th days of gestational. Control dams were simply saline-injected. Female and male virgin offspring born of morphine-treated or saline-treated mothers were separately housed until become fully matured. A 3-day schedule of an unbiased conditioning procedure was used to the induce conditioning to morphine (2.5-7.5 mg/Kg, SC) in the offspring. According to the results, female offspring born of saline-administered mothers were morphine place-conditioned at lower doses of opioid (2.5 mg/Kg) in comparison to the males. An increase in locomotor activity in the females at 7.5 mg/Kg of opioid was also revealed. In contrast, administration of morphine (2.5-7.5 mg/Kg, SC), induced a significant aversion in either sexes of offspring born of morphine-exposed mothers. Moreover, female offspring of this category acquired more pronounced aversion at higher doses of morphine than males. In addition, a significant morphine-dose effect (7.5 mg/Kg, SC) on locomotor activity of these females’ offspring was observed. This study may highlight sex differences in conditioning effects induced by morphine between offspring derived of morphine-treated mothers and those of saline-treated. PMID:24250391

  13. 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

  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. Abdominal muscle activity during voiding in female rats with normal or irritated bladder.

    PubMed

    Cruz, Yolanda; Downie, John W

    2006-05-01

    The aims of the present study were to determine in female rats whether abdominal muscle discharges during normal voiding and to describe the effect of bladder irritation on this visceromotor activity. The sensory pathway of this reflex was also determined. Electromyograms (EMGs) indicated that in awake rats, the abdominal muscle was consistently activated during spontaneous voiding and during voiding induced by saline infusion. Similarly, in anesthetized animals, the muscle discharged during urine expulsion. The abdominal EMG activity was not abolished by hypogastric (Hgnx) or sensory pudendal neurectomy (SPdnx). SPdnx dramatically decreased the intercontraction interval and voided volume. Acetic acid infusion reduced the intercontraction interval and increased bladder contraction duration. It also reduced the pressure threshold for evoking the abdominal EMG response and increased the EMG duration and amplitude. Although SPdnx and Hgnx modified some urodynamic parameters, they did not reverse the acetic acid effect on EMG activity. Thus the afferents activating the visceromotor reflex during normal voiding and the increased reflex in response to acetic acid are probably both carried by the pelvic nerve. Abdominal muscle activity induced by bladder distension has been considered to be a pain marker. However, we conclude that in female rats, the abdominal muscle is reflexively activated during physiological urine expulsion. On the other hand, bladder irritation is marked by an exaggeration of this abdominal visceromotor reflex. PMID:16373437

  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. 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

  18. GABA release in the medial preoptic area of cyclic female rats.

    PubMed

    Mitsushima, D; Shwe, T-T-W; Funabashi, T; Shinohara, K; Kimura, F

    2002-01-01

    GABA is a potent regulator of gonadotropin-releasing hormone neurons in the hypothalamus. To determine the profile of GABA release in the medial preoptic area where the gonadotropin surge generator resides, an in vivo microdialysis study was performed in cyclic female rats. The microdialysis samples were collected and sequential blood samples (150 microl each) were also obtained, at 1-h intervals. During estrus and diestrus 1, GABA release in the medial preoptic area was relatively low. A small increase in the GABA release began in the afternoon of diestrus 1 and attained its peak in the morning of diestrus 2, but declined in the afternoon of that day. The GABA release markedly increased from late in the night of diestrus 2 through the morning of proestrus, when it attained its peak, and thereafter it declined sharply until the critical period of proestrus. A distinct preovulatory luteinizing hormone surge was observed in the afternoon of proestrus in all proestrous rats. From these results we suggest that the preovulatory elevation of the GABA release from the night through to the morning of proestrus, followed by a sharp decline, is closely associated with the onset of the preovulatory luteinizing hormone surge in cyclic female rats. The present study is the first to report the 4-day profile of GABA release in the medial preoptic area during the estrous cycle. PMID:12123689

  19. Gentamicin Induced Nephrotoxicity: The Role of Sex Hormones in Gonadectomized Male and Female Rats

    PubMed Central

    Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Moslemi, Fatemeh

    2016-01-01

    Background. Gentamicin (GM) induced nephrotoxicity may be sex hormones related. The effects of sex hormones on GM induced nephrotoxicity in gonadectomized rats were investigated. Methods. Ovariectomized rats received 0.25, 0.5, or 1 mg/kg/week of estradiol (ES) alone or accompanied with 10 mg/kg/week of progesterone (Pro) for two weeks followed by GM (100 mg/kg/day) for 9 days. Castrated rats were also treated with 10, 50, or 100 mg/kg/week of testosterone (TS) for two weeks and then received GM. In addition, a single castrated group received 0.25 mg/kg/week of ES plus GM. Results. GM increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and kidney tissue damage score (KTDS) (P < 0.05). TS had no effect on the serum levels of BUN and Cr and KTDS, while low dose of ES intensified these parameters in male (P < 0.05). ES (0.5 mg/kg) without Pro ameliorated KTDS in female (P < 0.05) while ES (1 mg/kg) with or without Pro exacerbated the BUN values and Cr values, KTDS, and body weight loss (P < 0.05). Conclusion. ES (0.5 mg/kg) without Pro ameliorated kidney damage induced by GM in female while neither TS nor ES had beneficial effect on nephrotoxicity induced by GM in male, although ES aggravated it. PMID:27213082

  20. 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.

  1. The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats.

    PubMed

    Lehmann, J; Pryce, C R; Bettschen, D; Feldon, J

    1999-12-01

    A single 24-h maternal separation (MS) in the rat during the stress hyporesponsive period alters adult behavior and neuroendocrine stress response. The age of the animal at MS might be a crucial factor for effects in adulthood. We report here on adult behavioral effects of MS performed on postnatal day 4 (MS4), 9 (MS9), or 18 (MS18) in male and female Wistar rats. Unrelated subjects were used to avoid confounding litter effects. Subjects were tested on paradigms of unconditioned fear/anxiety, i.e., open field and elevated plus-maze, and on paradigms involving learning in an aversive situation, i.e., conditioned freezing, active avoidance, and water maze. In line with our predictions we obtained (a) sex differences that were consistent with enhanced fear/anxiety in males relative to females, (b) evidence that MS4 yielded deficits in active avoidance learning and conditioned freezing (trend level), whereas MS9 yielded enhanced active avoidance and water maze learning, (c) evidence (at trend level) that these effects of MS are greater in males than in females. There was no evidence for an effect of MS on paradigms of unconditioned fear/anxiety. We conclude that MS, irrespective of the age at separation, does not provide a robust environmental model of modified behavior in aversive situations. PMID:10593193

  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 estrogen antagonists and agonists on the ACTH response to restraint stress in female rats.

    PubMed

    Young, E A; Altemus, M; Parkison, V; Shastry, S

    2001-12-01

    Previous studies have found that female rats are less sensitive than males to hypothalamic-pituitary-adrenal axis feedback inhibition by exogenous glucocorticoid administration. To determine whether estrogen contributes to this sex difference, we examined the effects of the estrogen antagonists tamoxifen and C1628 on the ACTH and corticosterone responses to restraint stress. CI628 increased both the ACTH and corticosterone response to restraint stress, and tamoxifen increased the ACTH response to restraint. Using overiectomized female rats, we also examined the effects of seven days of estradiol and/or progesterone replacement. Low dose estradiol decreased the ACTH but not the corticosterone response to restraint stress while progesterone had no effect on ACTH or corticosterone responses. The combination of estradiol and progesterone also decreased the ACTH response to stress, and the magnitude of the effect did not differ from that found with estradiol treatment alone. These data suggest that in the physiological range estradiol is an important inhibitory factor in the hypothalamic-pituitary-adrenal stress response of females. PMID:11750181

  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. 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

  6. Pulmonary sensitivity to ozone exposure in sedentary versus chronically trained, female rats.

    PubMed

    Gordon, Christopher J; Phillips, Pamela M; Beasley, Tracey E; Ledbetter, A; Aydin, Cenk; Snow, Samantha J; Kodavanti, Urmila P; Johnstone, Andrew F

    2016-06-01

    Epidemiological data suggest that a sedentary lifestyle may contribute to increased susceptibility for some environmental toxicants. We developed an animal model of active versus sedentary life style by providing female Sprague-Dawley rats with continuous access to running wheels. Sedentary rats were housed in standard cages without wheels. After training for 12 wks, rats were exposed to 0, 0.25, 0.5 or 1.0 ppm ozone [O3 for 5 h/d, 1 d/wk, for 6 wk (N = 10 per group)]. Body composition (%fat, lean and fluid) was monitored noninvasively over the course of the study. Ventilatory parameters [tidal volume, minute ventilation, frequency and enhanced pause (Penh)] were assessed using whole-body plethysmography prior to O3 and 24 h after the 5th O3 exposure. Trained rats lost ∼2% body fat after 12 wk of access to running wheels. Peak wheel activity was reduced by 40% after exposure to 1.0 ppm O3. After the 5th O3 exposure, body weight and %fat were reduced in sedentary but not trained rats. Penh was significantly elevated in sedentary but not trained rats the day after exposure to 1.0 ppm O3. However, lung lavage cell counts and biomarkers of pulmonary inflammation measured 1 day after the final exposure were inconsistently affected by training. Wheel running led to marked physiological responses along with some indication of improved pulmonary recovery from O3 exposure. However, wheel running with O3 exposure may also be a detriment for some pulmonary endpoints. Overall, a sedentary lifestyle may increase susceptibility to O3, but additional studies are needed. PMID:27160658

  7. 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

  8. 17β-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 17β-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

  9. Micro-computed tomography evaluation and pathological analyses of female rats with collagen-induced arthritis

    PubMed Central

    Kim, Young Hee

    2015-01-01

    Imaging techniques have been introduced to assess the efficacy and toxicity of developing pharmaceuticals. The purpose of this study was to perform a comprehensive characterization of collagen-induced arthritis (CIA) in rats using micro-computed tomography (micro-CT) and to compare the results with data from conventional pathological examination. Arthritis was induced by collagen in 24 female Wistar rats. Micro-CT and pathological analyses were performed to assess arthritis progression. Micro-CT analysis showed marked joint destruction occurring in a time-dependent manner following collagen administration. Bone volume was significantly decreased in the tibia at weeks 3 and 4 compared to week 0 (p < 0.05 and p < 0.01, respectively). Additionally, percent bone volume was significantly reduced in the tibia at week 4 compared to week 0 (p < 0.05). In contrast, bone surface/bone volume and trabecular separation were significantly increased in the tibia of the animals at week 4 compared to week 0 (p < 0.05). Severe joint destruction with extensive inflammation, erosion of cartilage and bone, and infiltration of inflammatory cells were observed in the knee joints of the collagen-treated rats. Taken together, micro-CT made it possible to quantify CIA lesions and should be performed with pathological examination in rats. PMID:25643800

  10. Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats.

    PubMed

    Singh, N D; Sharma, A K; Patil, R D; Rahman, S; Leishangthem, G D; Kumar, M

    2014-02-01

    Citrinin is the one of the well-known mycotoxins, which is possibly spread all over the world. The graded doses of citrinin (1, 3 and 5 ppm CIT in feed) in female Wistar rats 10 weeks prior to mating, during mating and during organogenesis resulted in resorptions and post implantation losses, decreased fetal body weights and crown-rump lengths in fetuses of all groups. Various developmental anomalies recorded in fetuses of treated rats included gross (wrist drop, curled tail, stretched forelimb, subcutaneous haematoma), skeletal (incomplete ossification of skull bones, incomplete fusion of vertebral bodies, complete and partial agenesis of sternaebrae, metacarpals, metatarsals and phalanges, fused ribs and swing out ribs) and visceral (internal and external hydrocephalus, cerebellar hypoplasia, microphthalmia, roundening of heart, contracted kidneys, dilated renal pelvis and cryptorchid testes). The results suggest that CIT has adverse effects on fetal development which may be due to the longer bioavailability of citrinin in the animals. PMID:24597149

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

    PubMed

    Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; 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

  16. 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

  17. Androgens increase spine synapse density in the CA1 hippocampal subfield of ovariectomized female rats.

    PubMed

    Leranth, Csaba; Hajszan, Tibor; MacLusky, Neil J

    2004-01-14

    The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in ovariectomized (OVX) adult female rats. Treatment of OVX rats with testosterone propionate (TP; 500 microg/d, s.c., 2 d) significantly increased spine synapse density (from 0.661 +/- 0.016 spine synapse/microm3 in OVX rats to 1.081 +/- 0.018 spine synapse/microm3 after TP treatment). A smaller, but still statistically significant, increase in synapse density (0.955 +/- 0.029 spine synapse/microm3) was observed in OVX animals after treatment with the nonaromatizable androgen dihydrotestosterone (DHT; 500 microg/d, s.c., 2 d). Administration of 1 mg of letrozole, a powerful nonsteroidal aromatase inhibitor, 1 hr before the steroid injections almost completely blocked the synaptic response to testosterone, resulting in a mean synapse density (0.723 +/- 0.003 spine synapse/microm3) only slightly higher than in OVX control rats. By contrast, the response to DHT was unaffected by letrozole pretreatment. These data suggest that androgen secretion during the female reproductive cycle may contribute to cyclical changes in hippocampal synaptic density. They also indicate that androgen treatment may be as effective as estrogen replacement in reversing the decline in hippocampal CA1 spine synapses that follows loss of ovarian function. Induction of hippocampal synapse formation by androgen is not mediated entirely via intracerebral estrogen biosynthesis, however, because aromatase-independent mechanisms also significantly affect CA1 spine synapse density. PMID:14724248

  18. Sexual activity increases dopamine transmission in the nucleus accumbens and striatum of female rats.

    PubMed

    Pfaus, J G; Damsma, G; Wenkstern, D; Fibiger, H C

    1995-09-25

    In vivo microdialysis was used to monitor extracellular concentrations of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and dorsal striatum of sexually active female rats during tests of locomotor activity, exposure to a novel chamber, exposure to sex odors, the presentation of a sexually active male rat, and copulation. DA increased slightly but significantly in the nucleus accumbens when a sexually active male was placed behind a wire-mesh screen, and further during copulation. DA also increased significantly in the dorsal striatum during copulation; however, the magnitude of this effect was significantly lower than that observed in the nucleus accumbens. The metabolites DOPAC and HVA generally followed DA with a delay, and increased significantly during copulation in both regions. In contrast, forced locomotion on a rotating drum, exposure to a novel testing chamber, and exposure to sex odors did not increase DA significantly in either region, although forced locomotion increased DOPAC significantly in both regions, and HVA significantly in the nucleus accumbens. The magnitude of DA release in the nucleus accumbens was significantly greater during copulation than running, whereas no significant difference was detected for striatal DA release between these two behavioral conditions. These results indicate that novelty or locomotor activity alone do not account for the increase in DA observed in the nucleus accumbens of female rats during copulation, and suggest that DA transmission in the nucleus accumbens is associated with anticipatory and consummatory aspects of sexual activity, as it is in male rats. In the dorsal striatum, however, DA release during copulation may reflect an increase in locomotor activity associated with active pacing of the male. PMID:8653411

  19. Dietary (n-6 : n-3) fatty acids alter plasma and tissue fatty acid composition in pregnant Sprague Dawley rats.

    PubMed

    Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

    2012-01-01

    The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

  20. Estrogens Suppress Spinal Endomorphin 2 Release in Female Rats in Phase with the Estrous Cycle

    PubMed Central

    Kumar, Arjun; Storman, Emiliya M.; Liu, Nai-Jiang; Gintzler, Alan R.

    2015-01-01

    Background/Aims Male and female rats differ in their ability to utilize spinal endomorphin 2 (EM2; the predominant mu-opioid receptor ligand in spinal cord) and in the mechanisms that underlie spinal EM2 analgesic responsiveness. We investigated the relevance of spinal estrogen receptors (ERs) to the in vivo regulation of spinal EM2 release. Methods ER antagonists were administered directly to the lumbosacral spinal cord of male and female rats, intrathecal perfusate was collected, and resulting changes in EM2 release were quantified using a plate-based radioimmunoassay. Results Intrathecal application of an antagonist of either estrogen receptor-α (ERα) or the ER GPR30 failed to alter spinal EM2 release. Strikingly, however, the concomitant blockade of ERα and GPR30 enhanced spinal EM2 release. This effect was sexually dimorphic, being absent in males. Furthermore, the magnitude of the enhancement of spinal EM2 release in females was dependent upon estrous cycle stage, suggesting a relationship with circulating levels of 17β-estradiol. The rapid onset of enhanced EM2 release following intrathecal application of ERα/GPR30 antagonists (within 30–40 min) suggests mediation via ERs in the plasma membrane, not the nucleus. Notably, both ovarian and spinally synthesized estrogens are essential for membrane ER regulation of spinal EM2 release. Conclusion These findings underscore the importance of estrogens for the regulation of spinal EM2 activity and, by extension, endogenous spinal EM2 antinoci-ception in females. Components of the spinal estrogenic mechanism(s) that suppress EM2 release could represent novel drug targets for improving utilization of endogenous spinal EM2, and thereby pain management in women. PMID:25925013

  1. 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

  2. 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

  3. 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

  4. 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

  5. Abnormally rapid reversal learning and reduced response to antipsychotic drugs following ovariectomy in female rats.

    PubMed

    Arad, Michal; Weiner, Ina

    2012-02-01

    Epidemiological and clinical life cycle studies indicate that favorable illness course and better response to antipsychotic drugs (APDs) in women with schizophrenia are positively correlated with estrogen levels. Accordingly, the estrogen hypothesis of schizophrenia proposes a neuroprotective role of estrogen in women vulnerable to schizophrenia. Previously we demonstrated in the rat that low levels of estrogen induced by ovariectomy led to disruption of latent inhibition (LI) reflecting impairment of selective attention, a core deficit of schizophrenia. LI disruption was reversed by 17β-estradiol and the atypical APD clozapine, whereas the typical APD haloperidol was ineffective unless co-administered with 17β-estradiol. Here we aimed to extend these findings by testing ovariectomized rats in another selective attention task, discrimination reversal. Ovariectomy led to a loss of selective attention as manifested in abnormally rapid reversal. The latter was normalized by high dose of 17β-estradiol (150 μg/kg) and clozapine (2.5mg/kg), but not by haloperidol (0.1mg/kg) or lower doses of 17β-estradiol (10 and 50 μg/kg). However, co-administration of haloperidol with 17β-estradiol (50 μg/kg) was effective. In sham rats low 17β-estradiol (10 μg/kg) produced rapid reversal, while high 17β-estradiol (150 μg/kg), haloperidol alone, or haloperidol-17β-estradiol combination reduced reversal speed. Clozapine did not affect reversal speed in sham rats. These results strengthen our previous results in suggesting that schizophrenia-like attentional abnormalities as well as reduced response to APDs in female rats are associated with low level of gonadal hormones. In addition, they support the possibility that estrogen may have an antipsychotic-like action in animal models. PMID:21723667

  6. 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....

  7. 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

  8. QRFP in Female Rats: Effects on High Fat Food Intake and Hypothalamic Ge