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[Model study of afobazole distribution in pregnant and lactating female rats and infant rat pups].  


Afobazole and M-11, its major metabolite were detected in placental and embryonic rat tissues after single peroral administration to pregnant female rats at a dose of 100 mg/kg. The anxiolytic drug and its metabolite are also detected in rat milk and body of the breast-fed infant rat pups after 4 days of daily administration (200 mg/kg, per os) to lactating female rats. PMID:20919552

Shreder, O V; Kolyvanov, G B; Litvin, A A; Bastrygin, D V; Shreder, E D; Solomina, A S; Viglinskaia, A O; Zabrodina, V V; Zherdev, V P; Durnev, A D; Seredenin, S B



Effect of obesity on the acute inflammatory response in pregnant and cycling female rats.  


Nonpregnant female rats have a lower inflammatory response to lipopolysaccharide (LPS) than males and, at late stages of gestation, the fever response to this immunogen is almost completely suppressed. We have shown in males that obesity exacerbates sickness responses to pathogenic stimuli. In the present study, we investigated whether obesity would have a similar effect in females and reverse some of the suppressive effects of pregnancy on the innate immune response. Lean and diet-induced obese adult Wistar rats were randomly separated into either cycling or mated groups. On day 18 of pregnancy or in the metestrous/dioestrous phase in cycling rats, a single injection of LPS (100 ?g/kg) was administered and rats were sacrificed 8h or 24 h later. In pregnant females, LPS induced a higher increase in body temperature in obese rats only at the 24-h time point and lower hypothalamic interleukin (IL)-1? expression and higher circulating levels of IL-1 receptor antagonist (ra) than their cycling counterparts. Conversely, there was no suppression of inflammatory signals in the white adipose tissue of pregnant rats. At 24 h post LPS, the cell surface marker CD11c and IL-6 mRNA expression were increased in white adipose tissue from obese rats regardless of reproductive state, whereas IL-1ra was highest in the LPS-treated obese pregnant group. In cycling females, LPS induced a higher fever response in obese rats accompanied by higher circulating levels of IL-6 and IL-1ra, as well as an increase in circulating leptin only in the obese cycling group. In the hypothalamus, obese rats showed significantly higher expression of nuclear factor-IL-6 in at the 8-h time point. Collectively, these results show that diet-induced obesity in females is associated with a similar pattern of response to that previously observed in males. On the other hand, obesity had limited effects in pregnant rats, with the exception of white adipose tissue. PMID:23331909

Pohl, J; Luheshi, G N; Woodside, B



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


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

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



[Bioinsecticides risk influence estimation on intestinal microbiocenosis of the pregnant females and posterity in experiment].  


It is carried out research by a method of paired correlations of the bioinsecticides influence on intestinal microbiota of the pregnant females rats and them 1, 2 monthly posterities in conditions of preparations repeated inhalation influence during all pregnancy at various concentrations. PMID:22568023

Orlenkovich, L N




Microsoft Academic Search

A SERIES of experiments were undertaken, which had for their object the testing of the effects of injections of various species' lens antisera into pregnant mice and rats. Guyer and Smith found that by injecting anti-rabbit lens serum into pregnant female rabbits some of the progeny born under such treatment had defective eyes, and that this defect became hereditary. Further,



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

PubMed Central

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

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



Selenium-vitamin E combination and melatonin modulates diabetes-induced blood oxidative damage and fetal outcomes in pregnant rats.  


Oxidative stress is considered to be the main cause of diabetic complications. In the current study, we investigated the effect of selenium-vitamin E combination and melatonin on lipid peroxidation (LPO) and scavenging enzyme activity in the blood of streptozocin (STZ)-induced diabetic pregnant rats. Forty female Wistar rats were randomly divided into five groups. The first and second groups were used as the non-pregnant control and pregnant control groups, respectively. The third group was the pregnant diabetic group. Vitamin E plus selenium and melatonin were administered to the diabetic pregnant rats consisting fourth and fifth groups, respectively. Diabetes was induced on day 0 of the study by STZ. Blood samples were taken from all animals on the 20th day of pregnancy. LPO level was higher in diabetic pregnant rats than in control, although superoxide dismutase, catalase, and glutathione peroxidase activities were lower in diabetic pregnant animals than in control. LPO levels were lower both in the two treatment groups than in the diabetic pregnant rats, whereas selenium-vitamin E combination and melatonin caused a significant increase in the activities of these antioxidant enzymes (p<0.01). In conclusion, vitamin E plus selenium seems to be a more potent antioxidant compared to melatonin in diabetic pregnant rats. Melatonin did not significantly affect the elevated glucose concentration of diabetic pregnant treated with melatonin group. Vitamin E plus selenium may play a role in preventing diabetes-related diseases of pregnant subjects. PMID:21240568

Guney, Mehmet; Erdemoglu, Evrim; Mungan, Tamer



Uteroplacental insufficiency programmes vascular dysfunction in non-pregnant rats: compensatory adaptations in pregnancy.  


Intrauterine growth restriction is a risk factor for cardiovascular disease in adulthood. We have previously shown that intrauterine growth restriction caused by uteroplacental insufficiency programmes uterine vascular dysfunction and increased arterial stiffness in adult female rat offspring. The aim of this study was to investigate vascular adaptations in growth restricted female offspring when they in turn become pregnant. Uteroplacental insufficiency was induced in WKY rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of pregnancy. F0 pregnant females delivered naturally at term. F1 Control and Restricted offspring were mated at 4 months of age and studied on day 20 of pregnancy. Age-matched non-pregnant F1 Control and Restricted females were also studied. Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of all four groups. Collagen and elastin fibres were quantified using polarized light microscopy and qRT-PCR. F1 Restricted females were born 10–15% lighter than Controls (P <0.05). Non-pregnant Restricted females had increased uterine and renal artery stiffness compared with Controls (P <0.05), but this difference was abolished at day 20 of pregnancy. Vascular smooth muscle and endothelial function were preserved in all arteries of non-pregnant and pregnant Restricted rats. Collagen and elastin content were unaltered in uterine arteries of Restricted females. Growth restricted females develop compensatory vascular changes during late pregnancy, such that region-specific vascular deficits observed in the non-pregnant state did not persist in late pregnancy. PMID:22586217

Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Dragomir, Nicoleta M; Parry, Laura J; Wlodek, Mary E



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


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 ?mol/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 ?mol/L for bupivacaine, 157 ?mol/L for ropivacaine, > 1000 ?mol/L for lidocaine, and 26.3 ?mol/L for tetracaine. In non-pregnant myometrium, the IC(50) was 26.9 ?mol/L for bupivacaine, 40 ?mol/L for ropivacaine, 384 ?mol/L for lidocaine, and 7.4 ?mol/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

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



Luteal activity of pregnant rats with hypo-and hyperthyroidism  

PubMed Central

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



Megaloblastic hematopoiesis in a 20 year old pregnant female  

PubMed Central

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

Trivette, Evan T.; Hoedebecke, Kyle; Berry-Caban, Cristobal S.; Jacobs, Brandy R.



Pathogenesis of digitoxin-induced duodenal ulcers in pregnant rats. Roles of gastric acid and duodenal alkaline secretion.  


Late-stage pregnant rats (day 17) had higher rates of gastric acid secretion (45-55 mu eq/15 min) as compared to nonpregnant and middle-stage pregnant (day 10) rats (20-25 mu eq/15 min). In contrast, basal rates of duodenal alkaline secretion were significantly lower (2-3 mu eq/15 min) in pregnant rats (day 10 and 17) than those in nonpregnant rats (approximately 5 mu eq/15 min), although the duodenal mucosa responded to acid with a significant rise in HCO3- output in these three groups of rats. In pregnant rats (day 17), a single injection of digitoxin, a Na+ K+-ATPase inhibitor (10 mg/kg, subcutaneously), had no effect on basal acid and alkaline secretions, but significantly blocked the acid-induced HCO3- secretion for more than 18 hr from 6 hr after administration. This drug, when given once daily for four days (10 mg/kg, subcutaneously), produced well-defined ulcers in the proximal duodenum with few lesions in the stomach of female rats, and the severity and incidence were significantly higher in late-stage pregnant rats than in the other two groups of rats. Following repeated administration of digitoxin (10 mg/kg) to late-stage pregnant rats (days 17-20), acid secretion significantly declined after two days of treatment, while the acid-induced HCO3- secretion was significantly attenuated after one day of treatment and remained inhibited during the whole period. These results suggest that an impairment of the mechanisms related to acid-induced HCO3- secretion may be associated with the induction of duodenal ulcers caused by digitoxin in female rats, and the high incidence of these ulcers in late-stage pregnant rats may be due to acid hypersecretion. PMID:3378483

Furukawa, O; Takeuchi, K; Nishiwaki, H; Okabe, S



Effect of streptozotocin diabetes on polysomal aggregation and protein synthesis rate in the liver of pregnant rats and their offspring.  


To study the effect of diabetes on hepatic protein synthesis and polysomal aggregation in pregnant rats, female rats were treated with streptozotocin prior to conception. Some animals were mated, and studied at day 20 of pregnancy, whereas, others were studied in parallel under non pregnant conditions. The protein synthesis rate measured with an "in vitro" cell-free system was higher in pregnant than in virgin control rats. It decreased with diabetes in both groups, although values remained higher in diabetic pregnant rats than in the virgin animals. The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they showed a higher protein synthesis rate than either their respective mothers or virgin rats. Liver RNA concentration was higher in control and diabetic, pregnant rats than in virgin rats, and the effect of diabetes decreasing this parameter was only significant for pregnant rats. Liver RNA concentration in fetuses was lower than in their mothers, and did not differ between control and diabetic animals. The decreased protein synthesis found in diabetic animals was accompanied by disaggregation of heavy polysomes into lighter species, indicating an impairment in peptide-chain initiation. PMID:7544168

Martin, M E; Garcia, A M; Blanco, L; Herrera, E; Salinas, M



Attenuated glomerular arginine transport prevents hyperfiltration and induces HIF-1? in the pregnant uremic rat.  


Pregnancy worsens renal function in females with chronic renal failure (CRF) through an unknown mechanism. Reduced nitric oxide (NO) generation induces renal injury. Arginine transport by cationic amino acid transporter-1 (CAT-1), which governs endothelial NO generation, is reduced in both renal failure and pregnancy. We hypothesize that attenuated maternal glomerular arginine transport promotes renal damage in CRF pregnant rats. In uremic rats, pregnancy induced a significant decrease in glomerular arginine transport and cGMP generation (a measure of NO production) compared with CRF or pregnancy alone and these effects were prevented by l-arginine. While CAT-1 abundance was unchanged in all experimental groups, protein kinase C (PKC)-?, phosphorylated PKC-? (CAT-1 inhibitor), and phosphorylated CAT-1 were significantly augmented in CRF, pregnant, and pregnant CRF animals; phenomena that were prevented by coadministrating l-arginine. ?-Tocopherol (PKC inhibitor) significantly increased arginine transport in both pregnant and CRF pregnant rats, effects that were attenuated by ex vivo incubation of glomeruli with PMA (a PKC stimulant). Renal histology revealed no differences between all experimental groups. Inulin and p-aminohippurate clearances failed to augment and renal cortical expression of hypoxia inducible factor-1? (HIF-1?) significantly increased in CRF pregnant rat, findings that were prevented by arginine. These studies suggest that in CRF rats, pregnancy induces a profound decrease in glomerular arginine transport, through posttranslational regulation of CAT-1 by PKC-?, resulting in attenuated NO generation. These events provoke renal damage manifested by upregulation of renal HIF-1? and loss of the ability to increase glomerular filtration rate during gestation. PMID:22552935

Schwartz, Idit F; Grupper, Ayelet; Soetendorp, Hila; Hillel, Oren; Laron, Ido; Chernichovski, Tamara; Ingbir, Merav; Shtabski, Allexander; Weinstein, Talia; Chernin, Gil; Shashar, Moshe; Hershkoviz, Rami; Schwartz, Doron



Perinatal androgenic exposure and reproductive health effects female rat offspring.  


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

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



Distribution of ochratoxin A in the pregnant rat  

E-print Network

DISTRIBUTION OF OCHRATOXIN A IN THE PREGNANT RAT A Thesis By ilICHAEI BRENT BALL INGER Submitted to the Graduate College c- Texas AAN University in partia1 fuifi11ment of the requirements for tho degree of HASTER OF SCIENCE August 1983... Najor Subject: Laboratory Anima1 Pedi ', ne DISTRIBUTION OF OCHRATOXIN A IN THE PREGNANT RAT A Thesis by MICHAEL BRENT BALLINGER Approved as to style and content by: G. N. , Joiner (Co-Chairman of Committee) n s (Co-Chairman of Committee) . N...

Ballinger, Michael Brent



Clinical and morphological studies in streptozotocin diabetic pregnant rats.  


Diabetes was induced in pregnant rats by administration of streptozotocin and the changes of the feto-placental unit were investigated. Dead fetuses were found in 12% of the untreated diabetic animals. In comparison to the controls, the fetal weights were significantly smaller and placental weights greater in diabetic animals. The changes were clearly characterized by the ratio fetal placental weight. Edema and cystic degeneration were characteristic of insulin treated diabetic placentas while fibrosis and ischemia were observed mainly in untreated animals. Insulin treatment resulted in hemorrhages and necrosis in the placenta of normal pregnant rats; the change is ascribed to hypoglycaemia. PMID:135471

Szalay, J; Gaál, M



Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats1 Efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensas  

Microsoft Academic Search

Purpose: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR). Methods: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1). Pregnancy was confirmed by sperm-positive vaginal smear (Day 0). Wistar-EPM- 1 rats served as counterpart control (C-1). SHR rats

Sousa Ayres de Moura; Nelson Sass; Sérgio Botelho Guimarães; Paulo Roberto; Leitão de Vasconcelos; Luis Kulay Jr



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...


Chronic effects of azidothymidine and acyclovir on pregnant rats  

Microsoft Academic Search

1.1. The antiviral effect of azidothymidine (AZT) can be potentiated by acyclovir (ACV), and this drug association has been used in the management of HIV-infected patients. In the present study we examined the effects of such an association on rat pregnancy.2.2. AZT (60 mg\\/kg b.w.) and ACV (60 mg\\/kg b.w.) were given to groups of pregnant rats once a day

João A. V. Mamede; Manuel De J. Simões; Neil F. Novo; Yara Juliano; Ricardo M. Oliveira-Filho; Luiz Kulay



Sildenafil Citrate and Fetal Outcome in Pregnant Rats  

Microsoft Academic Search

Objective: To determine the effects of sildenafil citrate on fetal growth in maternal rats exposed to hypoxia. Methods: Timed pregnant rats were randomized to either hypoxia or control on gestational days (GD) 18–20, and received either sildenafil (45 mg\\/kg) orally every 12 h on GD 18–21 or an equal volume of sterile water. Fetal pups were retrieved by laparotomy on

Jerrie S. Refuerzo; Robert J. Sokol; Jacob V. Aranda; Mordechai Hallak; John W. Hotra; Michael Kruger; Yoram Sorokin



[Consequences for posterity of two generations of an irradiation pregnant from females rats Wistar in small doses during a bookmark of reproduction system of fetuses development of posterity of the second generation and it reproduction function].  


With the purpose of study of consequences for development and reproduction functions of posterity of the second generation from females rats Wistar of a total unitary gamma-irradiation in dozes 0.25; 0.5 and 1 Gy (capacity of a doze 0.03 sGy/s) on 10th day of pregnancy (the period of the onset of fetuses reproduction system development) is investigated more than 630 females, 1400 with the age of 19th days, and about 3200 young rats. The revealed deviations(rejections) in development of posterity of two generations parents, antenatal irradiated in not sterilizing dozes, in he period of a beginning of formation of reproduction system, them a variety at different dozes of radiating influence, shown as at posterity of the irradiated mothers, and fathers, testify about instability genoms in a line of generations requiring the account and acceptance of necessary measures for preservation normal genofund. PMID:17020103

Palyga, G F; Chibisova, O F



Zinc deficiency and dietary folate metabolism in pregnant rats.  


Five groups of pregnant Wistar rats (zinc-deficient diet without folate supplementation; folinic acid, folate monoglutamate, folate polyglutamate-supplemented groups receiving zinc-deficient diet; pair-fed groups as controls) were fed from day one of fertilization with a semisynthetic zinc-deficient diet containing 0.2 mg/kg of Zn in the diet for the 4 deficient groups and 100 mg/kg for the pair-fed group. After 20 days, the zinc status (plasma, liver, femoral bone) was significantly decreased in the zinc-deficient groups. The liver and plasma folate levels were lower in the zinc-deficient groups compared to the pair-fed group. Moreover, the folinic acid and the polyglutamate folate supplementations (100 mg/kg diet) did not normalize the folate status of the animals. Only the supplementation with folate monoglutamate led to correct folate levels in the pregnant rats. Nevertheless, no form of folate supplementation prevented fetal growth retardation in any of the zinc-deficient groups. These results indicate that zinc deficiency in pregnant rats decreases folate bioavailability of folinic acid, folate polyglutamates and, to a lesser extent, that of folate monoglutamate. However, no form of folate supplementation (i.e., folate monoglutamate) prevents fetal growth defect and the incidence of malformation in zinc-deficient rats. PMID:8400843

Favier, M; Faure, P; Roussel, A M; Coudray, C; Blache, D; Favier, A



Effect of the chemical form of supranutritional selenium on selenium load and selenoprotein activities in virgin, pregnant, and lactating rats1  

Microsoft Academic Search

Virgin, pregnant, and lactating rats were used to assess the influence of selenomethionine and selenocystine, fed at four to seven times the daily Se requirement (supranutritional), on Se load and sele- noprotein activities. Female Sprague Dawley rats (n = 48; age = 13 wk), reared on a low-Se torula yeast diet, were assigned to one of three reproductive states (n

J. B. Taylor; J. W. Finley; J. S. Caton


[Transgenerational consequences of acute antenatal stress in pregnant rats].  


The aim of the present study was to investigate the effects of acute hypobaric hypoxia in early organogenesis on three following generations including pregnant females (FO) and two generations of their posterity (F1 and F2). Animals of all generations mentioned above demonstrated marked changes in motor and exploratory activity as well as in anxiety level while the litter of F1 and F2 generations showed also changes in learning ability. Besides, acute hypobaric hypoxia interfered in maternal behavior of females of the FO and F1 generations. The revealed changes kept till pubertal period. Possible mechanisms of gestational stress influence are discussed. PMID:22645942

Graf, A V; Dunaeva, T Iu; Maklakova, A S; Maslova, M V; Sokolova, N A; Trofimova, L K



Influence of treatment with quercetin on lipid parameters and oxidative stress of pregnant diabetic rats.  


Among the numerous coadjuvant therapies that could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in clinical trials. We investigated the effect of quercetin on biochemical parameters in streptozotocin-induced (60 mg/kg body mass, by intraperitoneal injection) diabetic rats. A total of 32 female Wistar rats were distributed among 4 groups as follows: control (G1); control treated with quercetin (G2); diabetic (G3); and diabetic treated with quercetin (G4). Quercetin administered to pregnant diabetic rats controlled dyslipidemia and improved lipid profiles in diabetes mellitus, regulated oxidative stress by reducing the generation of lipid hydroperoxides, and increased the activity of the antioxidant enzyme glutathione peroxidase. PMID:23458202

Pereira Braga, Camila; Momentti, Ana Carolina; Barbosa Peixoto, Fernando; de Fátima Ferreira Baptista, Rafaela; dos Santos, Felipe André; Fava, Fábio Henrique; Fernandes, Ana Angélica Henrique



Smooth muscle pharmacology in the isolated virgin and pregnant rat uterus and cervix.  


Uterine smooth muscle function is established, but comparatively little is known about cervical smooth muscle pharmacology. We performed a proof-of-principle experiment that smooth muscle was expressed in the cervix in both virgin and pregnant rats, using the uterus as a comparator. We tested whether all tissues were pharmacologically responsive to contractile and relaxant agonists. Immunohistochemistry revealed the expression of smooth muscle ?-actin in all tissues. The isolated tissue bath was used to measure isometric contractility of uterine strips and whole cervices from virgin and pregnant (day 11 ± 2) female Sprague-Dawley rats. We tested classic activators of uterine smooth muscle contraction and relaxation in both uterus and cervix. All tissues contracted to the depolarizing agent potassium chloride, prostaglandin F2?, muscarinic cholinergic agonist carbachol [2-[(aminocarbonxyl)oxy]-N,N,N-trimethylethanaminium chloride], and 5-hydroxytryptamine. Unlike other tissues, the pregnant cervix did not contract to oxytocin, but the oxytocin receptor was present. Both cervix and uterus (virgin and pregnant) had concentration-dependent, near-complete relaxation to the adrenergic agonist norepinephrine and adenylate cyclase activator forskolin [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10-10b-trihydroxy-3,4a,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f] chroment-5-yl acetate]. The ?-adrenergic receptor agonist isoproterenol was less potent in pregnant cervix versus virgin by ?10-fold. All tissues, particularly the cervix, responded poorly to the nitric-oxide donor sodium nitroprusside, relaxing ?20% maximally. These findings support the importance of smooth muscle in the cervix, the use of the isolated cervix in pharmacological studies, and a similarity between smooth muscle pharmacology of the nonpregnant uterus and cervix. This work highlights the unappreciated smooth muscle function of the cervix versus uterus and cervical changes in pharmacology during pregnancy. PMID:22366660

Darios, Emma S; Seitz, Bridget; Watts, Stephanie W



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...


Effect of diabetes on protein synthesis rate and eukaryotic initiation factor activities in the liver of virgin and pregnant rats.  


To study the effect of prolonged diabetes on protein synthesis and on the activities of initiation factors eIF-2 and eIF-2B in the liver, female rats were treated with streptozotocin. Some animals were mated and studied on day 20 of pregnancy, whereas others were kept virgin and studied in parallel. The protein synthesis rate was measured with an "in vitro' cellfree system, and was lower in diabetic pregnant and virgin animals than in pregnant and virgin controls (30-60%). The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they always showed a higher protein synthesis rate than their mothers or virgin rats. Protein synthesis rate, RNA concentration, and initiation factor 2 activity were higher in pregnant than in virgin rats. Both activity and level of eIF-2 factor changed in parallel to the protein synthesis rate, although no differences could be detected between control and diabetic animals. The eIF-2B activity in tissue extracts from diabetic virgin rats and fetuses was lower than in extracts from their controls, whereas no differences could be detected between pregnant and virgin control rats nor between pregnant control and pregnant diabetic animals. The percentage of the phosphorylated form of eIF-2 factor, eIF-2(alpha P), was slightly lower in virgin than in pregnant rats but was unaffected by the diabetic condition, while in diabetic fetuses this parameter was lower than in their corresponding controls. The cyclic adenosine monophosphate dependent protein kinase level was lower in diabetic rats than in controls, whereas no changes in the activity of casein kinase II were found. The isoelectric forms of the beta subunit of eIF-2 factor, eIF-2 beta, were different in the diabetic and the control animals, indicating that insulin deficiency modifies the phosphorylation of specific substrates. Since no differences were detected in RNA or eIF-2 content between control and diabetic rats, translation may, at least partly, be inhibited in the liver by an impairment of peptide chain initiation caused by the decreased eIF-2B activity which nevertheless is independent of eIF-2 alpha phosphorylation. PMID:8777248

Garcia, A M; Martin, M E; Blanco, L; Martin-Hidalgo, A; Fando, J L; Herrera, E; Salinas, M




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...


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


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

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



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


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

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



Placentophagia in Weanling Female Laboratory Rats  

PubMed Central

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

Harding, Kaitlyn M.; Lonstein, Joseph S.



Hypergravity induced prolactin surge in female rats  

NASA Technical Reports Server (NTRS)

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.

Megory, E.; Oyama, J.



The effects of spaceflight on mammary metabolism in pregnant rats  

NASA Technical Reports Server (NTRS)

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.

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



Prenatal Exposure to Nicotine in Pregnant Rat Increased Inflammatory Marker in Newborn Rat  

PubMed Central

This study aimed to investigate any inflammatory effect of nicotine on rat embryo by exposing their mothers to different dosages of nicotine during pregnancy. During this experimental study, 32 pregnant healthy Wistar rats were divided into 4 equal groups, including a control and 3 nicotine exposure groups. Injections were performed subcutaneously starting at the first day of pregnancy until parturition. As the dosages of nicotine were increased, the weight gain by pregnant rats and the mean weight of their newborns were significantly reduced. Mean ± SD of hs-CRP was significantly higher among groups exposed to various dosages of nicotine (2, 4, and 6?mg/kg) compared to the control group (P < 0.0001) and its increasing rate was also dose dependent. Mean ± SD serum level of IL-6 and TNF-? among all groups exposed to nicotine, except for 2?mg/kg nicotine injected group, was increased significantly (P < 0.0001). Mean ± SD of serum level of TGF-? and nitrite oxide among exposure groups showed significant differences compared to the control group only at the dosage of 6?mg/kg (P < 0.0001). The current study showed that exposing pregnant rats to nicotine causes a dose dependent increase in the rate of all the studied inflammatory serum markers among their newborns. PMID:25242867

Mohsenzadeh, Yosouf; Rahmani, Asghar; Cheraghi, Javad; Pyrani, Maryam



Oxidative damage in pregnant diabetic rats and their embryos.  


Free radical mechanisms may be involved in the teratogenesis of diabetes. The contribution of oxidative stress in diabetic complications was investigated from the standpoint of oxidative damage to DNA, lipids, and proteins in the livers and embryos of pregnant diabetic rats. Diabetes was induced prior to pregnancy by the administration of streptozotocin (45 mg/kg). Two groups of diabetic rats were studied, one without any supplementation (D) and another treated during pregnancy with vitamin E (150 mg/d by gavage) (D + E). A control group was also included (C). The percentage of malformations in D rats were 44%, higher than the values observed in C (7%) and D + E (12%) animals. D Group rats showed a higher concentration of thiobarbituric acid reactive substances in the mother's liver, however, treatment with vitamin E decreased this by 58%. The levels of protein carbonyls in the liver of C, D, and D + E groups were similar. The "total levels" of the DNA adducts measured, both in liver and embryos C groups were similar to the D groups. Treatment of D groups with vitamin E reduced the levels by 17% in the liver and by 25% in the embryos. In terms of the "total levels" of DNA adducts, the embryos in diabetic pregnancy appear to be under less oxidative stress when compared with the livers of their mothers. Graziewicz et al. (Free Radical Biology & Medicine, 28:75-83, 1999) suggested "that Fapyadenine is a toxic lesion that moderately arrests DNA synthesis depending on the neighboring nucleotide sequence and interactions with the active site of DNA polymerase." Thus the increased levels of Fapyadenine in the diabetic livers and embryos may similarly arrest DNA polymerase, and in the case of this occurring in the embryos, contribute to the congenital malformations. It is now critical to probe the molecular mechanisms of the oxidative stress-associated development of diabetic congenital malformations. PMID:11121718

Viana, M; Aruoma, O I; Herrera, E; Bonet, B



Cadmium toxicity in the thyroid gland of pregnant rats  

SciTech Connect

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.

Yoshizuka, M.; Mori, N.; Hamasaki, K.; Tanaka, I.; Yokoyama, M.; Hara, K.; Doi, Y.; Umezu, Y.; Araki, H.; Sakamoto, Y. (Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan))



An evaluation of the teratogenic potential of protracted exposure of pregnant rats to 2450?MHz microwave radiation. II. postnatal psychophysiologic analysis  

Microsoft Academic Search

The objective of this study was to determine whether protracted prenatal exposure of rats to 2450?MHz microwave radiation at a power density level of 20 mW\\/cm would significantly alter postnatal growth and psychophysiologic development. Of 75 pregnant rats, 12 were exposed to microwave radiation, 4 sham?irradiated, and 59 served as environmental control animals. Forty?five females were allowed to deliver their

Ronald P. Jensh; Wolfgang H. Vogel; Robert L. Brent



Disposition of styrene-acrylonitrile (SAN) trimer in female rats: single dose intravenous and gavage studies.  


Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [3H]SAN Trimer following a single intravenous administration (26 mg/kg) to nonpregnant rats; a single gavage administration (nominal doses of 25 mg/kg, 75 mg/kg, or 200 mg/kg in corn oil) to nonpregnant rats; and a single gavage administration (nominal dose of 200 mg/kg in corn oil) to pregnant and lactating rats. SAN Trimer was rapidly eliminated from blood (T1/2 approximately 1h) following a single intravenous dose and following single oral doses (T1/2 approximately 3-4h). SAN Trimer was also rapidly excreted in the urine and feces following single oral doses, while total radioactivity was cleared more slowly. In pregnant rats, the concentrations of both radioactivity and SAN Trimer 2h after dosing were highest in the blood, followed by the placenta, with the lowest levels in the fetus. In lactating rats, the concentrations of both radioactivity and SAN Trimer were higher in milk than in maternal blood. Total radioactivity and SAN Trimer blood concentrations in nonpregnant, pregnant, and lactating rats were both higher in lactating rats compared to nonpregnant and pregnant rats. PMID:18384980

Gargas, Michael L; Collins, Brad; Fennell, Timothy R; Gaudette, Norman F; Sweeney, Lisa M



The effect of Bromelia pinguin extract on the pregnant rat uterus.  


A non proteinaceous extract of Bromelia pinguin fruit was examined for activity on the rat uterus in vivo and in vitro. The in vivo experiments involved pregnant rats given the extract intraperitoneally. These rats did not abort nor were any foetal deformities observed. The extract inhibited spontaneous activity of the pregnant rat uterus in vitro. These results do not support the claimed folklore use of the plant as an abortifacient. The extract of Bromelia pinguin fruit may have some utero-active compound which inhibits uterine motility. PMID:10639838

Matadial, L; West, M E; Gossell-Williams, M; The, T L



Protein malnourishment: a predisposing factor in acrylamide toxicity in pregnant rats.  


Exposure to acrylamide (3-10 mg/kg body weight) was found to be lethal for protein-deficient pregnant rats as evidenced by their increased mortality. It had no such effect on the normal protein diet fed pregnant and nonpregnant rats and the protein-malnourished nonpregnant rats. Protein deficiency during pregnancy caused a significant decrease in the activity of brain monoamine oxidase and acetylcholinesterase and striatal [3H]spiperone binding, known to label dopamine receptors; had no significant effect on the binding of 3H-QNB (quinuclidinyl benzilate) to cerebellar and [3H]diazepam to frontocortical membranes, known to label muscarinic and benzodiazepine receptors, respectively; and had no significant effect on brain glutathione (GSH) levels in comparison with pregnant rats fed normal protein diet. Exposure to acrylamide (2 mg/kg body weight) in protein-malnourished pregnant rats caused a marked decrease in the activity of monoamine oxidase and acetylcholinesterase and also in the binding of [3H]spiperone, [3H]QNB, and [3H]diazepam to striatal, cerebellar, and frontocortical membranes, respectively. Kinetic studies revealed that decreased binding of these ligands in the specific brain regions were due to decreased receptor sites (Bmax). A reduction in the brain glutathione content was also observed in these animals in comparison with those fed a low-protein diet during pregnancy. Pregnant rats fed a normal-protein diet on acrylamide exposure, however, showed no such biochemical changes in comparison with the pregnant rats fed normal protein diet. Also, no effect on any of the parameters studied was observed in the adult nonpregnant rats fed a low-protein diet (for 18 d) and those exposed to the monomer (d 6-17) fed either a normal- or low-protein diet in comparison with respective controls. The results indicate that pregnancy under conditions of malnutrition modifies the susceptibility of pregnant rats toward acrylamide. PMID:1324327

Khanna, V K; Husain, R; Seth, P K



Alphafetoprotein and atretic follicles in the ovary of the pregnant rat.  


Previous experiments have been conducted concerning the role of alphafetoprotein in genital system blockade in several cases: during adult rat N2-fluorenylacetamide hepatocarcinogenesis, after alphafetoprotein injections into normal adult female rats, during fetal life, and during postnatal and prepuberal development. In these conditions, alphafetoprotein is present at high plasma levels, and the normal cyclic ovarian function is stopped or nonexistent. The degenerating oocytes observed in the ovaries are often AFP-positive by histo-immunolocalization. Pregnancy corresponds to a physiological state in which alphafetoprotein levels are high while the gonadal activity is not characterized by ovulatory cycles. In order to assess our hypothesis, alpha-fetoprotein was studied in the ovary of pregnant rats from day 18 to 21 of gestation by an immunofluorescent technique, and alpha-fetoprotein was assayed in plasma samples. The results of this work show that, during pregnancy, follicular maturation is blocked at the antral stage, and the follicles contain degenerating oocytes that are AFP-positive in immunofluorescence. In conclusion, we suggest that the alpha-fetoprotein produced by the fetal liver and the yolk sac is disseminated in the amniotic fluid and passes through the placenta, and then reaches the ovarian follicles and the oocytes. The possible role of alphafetoprotein in follicular atresia is discussed. PMID:2428090

Seralini, G E; Lafaurie, M; Krebs, B; Stora, C



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

NASA Astrophysics Data System (ADS)

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.

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



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

PubMed Central

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

Rezazad, Maryam; Farokhi, Farah



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

PubMed Central

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. Images Figure 3 Figure 4 Figure 1 Figure 2 PMID:65916

Stamler, F. W.



Short and long effects of Citrullus colocynthis L. on reproductive system and fertility in female Spague-Dawley rats.  


Aim of this study is to investigate the toxic effects of Citrullus colocynthis L. (400 mg/kg/body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and Citrullus colocynthis L. were intraperitoneally injected to experimental animals in dose of 400 mg/kg/body wight. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using students t and Chi-square tests. The effect of Citrullus colocynthis L. exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Citrullus colocynthis L. for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Citrullus colocynthis L. were observed. Exposure to Citrullus colocynthis L. for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed a decrease in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Citrullus colocynthis L. causes adverse effects on the reproductive system and fertility. PMID:19070085

Qazan, Walid Sh; Almasad, Motasem M; Daradka, Haytham



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


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

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



Coronary Flow Reserve in Pregnant Rats with Increased Left Ventricular Afterload  

PubMed Central

Background Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats. Methods Afterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ?10 days or by subjecting them to transverse aortic constriction (TAC) for ?14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline. Results CFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p?=?0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p?=?0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p?=?0.03) were significantly lower in pregnant rats compared to non-pregnant. Conclusions CFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC. PMID:25007056

Songstad, Nils Thomas; Serrano, Maria C.; Sitras, Vasilis; Johansen, Davis; Ytrehus, Kirsti; Acharya, Ganesh



Female rats learn trace memories better than male rats and consequently retain a greater proportion  

E-print Network

Female rats learn trace memories better than male rats and consequently retain a greater proportion the survival of neurons generated in the adult hippocam- pus. Male and female adult rats were injected with one if they required many trials to do so. Because females emitted more learned responses than males did, they retained

Shors, Tracey J.


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

PubMed Central

K-sensitive microelectrodes were used to measure K+ within the extracellular space (Ko) of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used. Double-barreled electrodes allowed monitoring of electrical activity 15 microns from the site of Ko measurement. From double-barreled electrode experiments, the bioelectrical burst started first, and then Ko began to rise 0.6 ± 0.1 seconds later. This delay indicates that K+ leaves the cells in response to local electrical activity rather than vice versa. Four control experiments were performed to assess the influence of electrical artifacts caused by tissue motion on Ko values. When observed, artifacts were negative and transient, and hence would result in an underestimation of Ko rises. Artifacts were minimized when tissue motion was minimized by fixing the tissue at both ends. At 37°C, 7 single barreled experiments and 45 contractions were analyzed. Resting Ko was within 1 mM of bath K+ (5 mM) at the beginning and end of the experiments. Ko rose during the contraction, fell after the completion of the contraction, and normalized before the next contraction began. Peak Ko values observed during force production were 18.8 ± 5.9 mM, a value high enough to modulate tissue-level electrical activity. Ko required 15.7 ± 2.8 seconds to normalize halfway (t50). Six experiments expressing 38 contractions were performed at 24°C. The contraction period was longer at 24°C. Values for peak Ko (26.2 ± 9.9 mM) and t50 (29.8±16.2 sec) were both larger than at 37°C (p<0.0003 for both). The direct relationships between peak Ko, t50 and the contraction period, suggest elevations in Ko may modulate contraction frequency. The myometrial interstitial space appears to be functionally important, and Ko metabolism may participate in cell-cell interactions. PMID:23724127

Young, Roger C.; Goloman, Gabriela



Disposition of Orally Administered 2,2Bis(4-hydroxyphenyl)propane (Bisphenol A) in Pregnant Rats and the Placental Transfer to Fetuses  

Microsoft Academic Search

We studied the disposition of bisphenol A (BPA) in pregnant female F344\\/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g\\/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36µg\\/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the

Osamu Takahashi; Shinshi Oishi



Oxytocin regulates the expression of aquaporin 5 in the late-pregnant rat uterus.  


Aquaporins (AQPs) are integral membrane channels responsible for the transport of water across a cell membrane. Based on reports that AQPs are present and accumulate in the female reproductive tract late in pregnancy, our aim was to study the expression of AQP isoforms (AQP1, 2, 3, 5, 8, and 9) at the end of pregnancy in rat in order to determine if they play a role in parturition. Reverse-transcriptase PCR revealed that specific Aqp mRNAs were detectable in the myometrium of non-pregnant and late-pregnancy (Days 18, 20, 21, and 22 of pregnancy) rat uteri. The expression of Aqp5 mRNA and protein were most pronounced on Days 18-21, and were dramatically decreased on Day 22 of pregnancy. In contrast, a significant increase was found in the level of Aqp5 transcript in whole-blood samples on the last day of pregnancy. The effect of oxytocin on myometrial Aqp5 expression in an organ bath was also investigated. The level of Aqp5 mRNA significantly decreased 5 min after oxytocin (10(-8) M) administration, similarly to its profile on the day of delivery; this effect was sensitive to the oxytocin antagonist atosiban. The vasopressin analog desmopressin (3.7 × 10(-8) M), on the other hand, did not alter the expression of Aqp5, but did increased the amount of Aqp2 mRNA, an effect that was atosiban-resistant. These results lead us to propose that oxytocin selectively influences the expression of Aqp5 at the end of pregnancy, and may participate in events that lead to parturition in the rat. The sudden increase of AQP5 in the blood on the last day of pregnancy may serve as a marker that indicates the initiation of delivery. PMID:24644013

Ducza, Eszter; Seres, Adrienn B; Hajagos-Tóth, Judit; Falkay, George; Gáspár, Róbert



Placental ischemia impairs middle cerebral artery myogenic responses in the pregnant rat.  


One potential mechanism contributing to the increased risk for encephalopathies in women with preeclampsia is altered cerebral vascular autoregulation resulting from impaired myogenic tone. Whether placental ischemia, a commonly proposed initiator of preeclampsia, alters cerebral vascular function is unknown. This study tested the hypothesis that placental ischemia in pregnant rats (caused by reduced uterine perfusion pressure [RUPP]) leads to impaired myogenic responses in middle cerebral arteries. Mean arterial pressure was increased by RUPP (135±3 mm Hg) compared with normal pregnant rats (103±2 mm Hg) and nonpregnant controls (116±1 mm Hg). Middle cerebral arteries from rats euthanized on gestation day 19 were assessed in a pressure arteriograph under active (+Ca(2+)) and passive (0 Ca(2+)) conditions, whereas luminal pressure was varied between 25 and 150 mm Hg. The slope of the relationship between tone and pressure in the middle cerebral artery was 0.08±0.01 in control rats and was similar in normal pregnant rats (0.05±0.01). In the RUPP model of placental ischemia, this relationship was markedly reduced (slope=0.01±0.00; P<0.05). Endothelial dependent and independent dilation was not different between groups, nor was there evidence of vascular remodeling assessed by the wall:lumen ratio and calculated wall stress. The impaired myogenic response was associated with brain edema measured by percentage of water content (RUPP P<0.05 versus control and normal pregnant rats). This study demonstrates that placental ischemia in pregnant rats leads to impaired myogenic tone in the middle cerebral arteries and that the RUPP model is a potentially important tool to examine mechanisms leading to encephalopathy during preeclamptic pregnancies. PMID:22068864

Ryan, Michael J; Gilbert, Emily L; Glover, Porter H; George, Eric M; Masterson, C Warren; McLemore, Gerald R; LaMarca, Babbette; Granger, Joey P; Drummond, Heather A



A developmental toxicity study of tretinoin administered topically and orally to pregnant Wistar rats  

Microsoft Academic Search

Background: Although it is well established that oral tretinoin produces embryofetal developmental toxicity in various laboratory animals, the toxic potential of topical tretinoin has not been clearly established. Objective: This study of tretinoin administration to pregnant Wistar rats was conducted to determine whether topical tretinoin is associated with adverse effects on reproductive function or embryofetal growth and development and to

Robert E. Seegmiller; William H. Ford; Melvin W. Carter; Joseph J. Mitala; William J. Powers



Role of Endothelin in Mediating Tumor Necrosis Factor-Induced Hypertension in Pregnant Rats  

Microsoft Academic Search

Hypertension during preeclampsia is associated with an increase in plasma levels of tumor necrosis factor (TNF)-, a cytokine known to contribute to endothelial dysfunction. Recently, our laboratory reported that a 2-fold increase in plasma TNF- produces hypertension in pregnant rats. Endothelin is also elevated in preeclampsia and endothelin synthesis is enhanced by TNF-. The purpose of this study was to

B. Babbette; D. LaMarca; Kathy Cockrell; Elizabeth Sullivan; William Bennett; Joey P. Granger




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...



EPA Science Inventory

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


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

NASA Astrophysics Data System (ADS)

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.

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



Distribution of free amino acids in streptozotocin-induced diabetic pregnant rats, their placentae and fetuses.  


Amino acid levels in the non-pregnant streptozotocin (STZ)-induced diabetic rat have been shown to be abnormal. Our preliminary studies showed that placental transport, fetal serum levels and tissue uptake of the non-metabolizable amino acid alpha-amino isobutyric acid (AIB) were decreased in STZ-diabetic pregnant rats. In the present experiments, amino acid concentrations were measured in maternal (MS) and fetal (FS) sera and placentae (PL) by high performance liquid chromatography (HPLC) after triple extraction in 80% ethanol. Control (C), STZ-diabetic (D) and insulin-treated diabetic (DI) animals were studied at 22 days gestation. Pregnant diabetic rats had low serum levels of Gln, Lys, and Ser and insulin treatment corrected Gln and Ser but not Lys levels. Branched-chain amino acids did not show the large elevation characteristic of the non-pregnant diabetic rat. Placental levels of Tau, Gln, HPr, Thr and Lys were depressed in the diabetic animals and insulin treatment only partially improved these amino acid profiles. Placental amino acid levels did not always reflect maternal serum levels. Serum levels of most amino acids were lower in the fetus of the diabetic rat than in the fetus of the control rat. The notable exception was Ala which was higher in the fetuses of the diabetic animals. Insulin treatment of the mother did not correct many of the fetal amino acid levels even though maternal and fetal serum glucose levels at the time of autopsy were normal. The ability to maintain normal serum levels of many amino acids is impaired in the fetus of the diabetic rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2182503

Copeland, A D; Hendrich, C E; Porterfield, S P



Thermal physiology of pregnant and lactating female and male long-eared bats, Nyctophilus geoffroyi and N. gouldi  

Microsoft Academic Search

During roosting in summer, reproductive female bats appear to use torpor less frequently and at higher body temperatures (T\\u000a b) than male bats, ostensibly to maximise offspring growth. To test whether field observations result from differences in thermal\\u000a physiology or behavioural thermoregulation during roosting, we measured the thermoregulatory response and energetics of captive\\u000a pregnant and lactating female and male long-eared

Christopher Turbill; Fritz Geiser



Streptozotocin-induced diabetic pregnant rats exhibit signs and symptoms mimicking preeclampsia.  


The number of patients with hypertension, obesity, diabetes, and hyperlipidemia is increasing. This tendency is observed in pregnant women, in whom many obstetrical and perinatal complications occur. The prevention of these abnormalities is important in reducing perinatal mortality and the risk of coronary disease. We established a pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or citrate buffer was injected into the tail vein. After STZ administration, plasma glucose was increased within 48 hours and sustained at a high level until day 20 of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ-treated versus control rats. The systolic blood pressure, urinary protein, and hematocrit were increased significantly in STZ-treated rats. Total cholesterol and triglycerides were also elevated in STZ-treated rats, but plasma leptin levels were decreased. The STZ-induced diabetic pregnant rat model exhibited preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine growth restriction. This model closely mimics the features of human pregnancy complicated by diabetes and is useful for the basic study of the pathophysiology of pregnancy with diabetes. PMID:10909994

Ishihara, G; Hiramatsu, Y; Masuyama, H; Kudo, T



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


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 ? 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

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



Localization of glycogen in the placenta and fetal and maternal livers of cadmium-exposed diabetic pregnant rats.  


This study was designed to investigate the effects of Cd exposure on the glycogen localization in the placenta and in fetal and maternal livers in streptozotocin (STZ)-induced-diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200-220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on d 13 of pregnancy by a single intraperitoneal injection of STZ in the STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on d 13 of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on d 15 and d 20 of pregnancy. Blood samples were taken for determination of the serum glucose and insulin levels. Fetal and maternal livers of sacrificed rats in all groups were harvested on d 15 and d 20 of pregnancy, whereas placentas were harvested only on d 20 of pregnancy for histochemical examination. Although both Cd and STZ caused hyperglycemia and decreased insulin secretion, Cd-alone treatment increased the glycogen content only in the placental labyrinth, whereas STZ-alone treatment increased the glycogen content only in the maternal part of the placenta. Increased glycogen localization was observed in both the placental labyrinth and the maternal part of placenta when Cd and STZ were given together. Fetal and maternal livers of control and other treatment groups were not different regarding the glycogen content on d 15 or d 20 of pregnancy. It was concluded that Cd exposure during pregnancy might produce a glycogen localization in the placenta of diabetic rats. However, the function and the mechanisms of increased glycogen contents in the placenta of Cd-exposed pregnant diabetic rats remain unclear and further studies are needed. PMID:14716101

Yoruk, Mecit; Kanter, Mehmet; Meral, Ismail; Agaoglu, Zahid



Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat.  


This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous. PMID:14532904

Natif, Noam; Sclarovsky-Benjaminov, Fabiana; Van Dijk, David Jonathan; Sulkes, Jacklin; Gafter, Uzi; Boner, Geoffrey; Erman, Arie



Altered ovarian sterol carrier protein expression in the pregnant streptozotocin-treated diabetic rat.  


Reproductive dysfunction in the diabetic female rat is associated with impaired folliculogenesis, reduced corpus luteum progesterone output, and spontaneous abortion. The underlying mechanism for reduced steroid production remains unresolved. In this study we examined whether or not diabetes alters levels of P450 side-chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), or the cholesterol transport proteins, steroidogenic acute regulatory (StAR) protein and sterol carrier protein-2 (SCP2), leading to lower progesterone levels and pregnancy loss. Rats (Day 3 pregnant) received an injection of streptozotocin (STZ, 60 mg/kg; i.v.) to induce a diabetic state; P450scc, 3 beta-HSD, and SCP2 were examined by Western and Northern blot analysis in ovarian tissue 12 days after injection of STZ (diabetic rats, n = 12) or vehicle (nondiabetic rats, n = 12). Serum progesterone, triglyceride, and beta-hydroxybutyrate (beta-HBA) levels were also examined. Results indicate that diabetic rats that aborted (diabetic-fetus [Ft], n = 6) had significantly lower progesterone levels (7.04 +/- 2.6 ng/ml; p < 0.004) than nondiabetic animals (108.6 +/- 5.15 ng/ml) and diabetic +Ft animals (74.3 +/- 8.9 ng/ml, n = 6). Western blot analysis of ovarian P450scc and 3 beta-HSD in the nondiabetic rats and the diabetic rats with fetuses indicated no significant difference. In contrast, ovaries from diabetic animals without fetuses had significantly lower SCP2 levels (p < 0.017) compared to controls. Concomitant with the reduction in SCP2, a 58-kDa SCP2-immunoreactive protein, referred to as sterol carrier protein-X (SCPx), increased significantly (p < 0.001). The C-terminal sequence of SCPx is identical to SCP2, while its N-terminal region is homologous with 3-oxoacyl coenzyme A thiolase, an enzyme involved in fatty acid metabolism. Increased SCPx expression coincided with increased serum triglyceride and beta-HBA levels, suggesting that the enhanced SCPx level may coincide with an ovarian shift to fatty acid metabolism. When SCPx steady-state mRNA levels were measured using an SCPx-specific riboprobe (280-bp protected fragment) in a ribonuclease protection assay, ovarian SCPx mRNA levels in the diabetic animals were increased 4.2-fold compared to control SCPx mRNA levels. Ovarian StAR mRNA levels were increased slightly in the diabetic animals, and ovarian P450scc and 3 beta-HSD mRNA levels were increased 3-fold in the diabetic animals that aborted relative to the nondiabetic animals and the +Ft diabetic animals. Results of this study confirm that SCPx mRNA levels are elevated following diabetes onset and that StAR, P450scc, and 3 beta-HSD mRNA levels do not correspond with the reduced steroid hormone profile associated with diabetes. These results are concordant with the possibility that reduced steroid levels in the diabetic animals reflect a loss of SCP2-mediated cholesterol transport capacity as SCPx/3-oxoacyl coenzyme A thiolase expression is enhanced. PMID:8793056

McLean, M P; Warden, K J; Sandhoff, T W; Irby, R B; Hales, D B



The disposition of a human relaxin (hRlx-2) in pregnant and nonpregnant rats.  


The pharmacokinetics and tissue distribution of a human relaxin were investigated after intravenous (iv) bolus administration to pregnant or nonpregnant rats. Human gene-2 relaxin (hRlx-2) serum concentrations after iv bolus administration were described as the sum of three exponentials. The pharmacokinetics were comparable in pregnant and nonpregnant rats. The serum clearance (CL) was 7.4-10.2 ml/min/kg at doses of 46-93 micrograms/kg and was linear in this range. The half-lives were 1.1-2.0, 15.1-16.4, and 53.7-67.9 min, respectively. The volume of the central compartment (Vc) was 48-79 ml/kg and the volume of distribution at steady state (Vss) was 271-336 ml/kg. Increasing the dose to 463 micrograms/kg increased the dose-corrected area under the serum concentration-time curve and significantly decreased CL and Vss. The distribution of radioactivity in the tissues of pregnant rats was followed after iv bolus dosing with hRlx-2 internally labeled with 35S-cysteine. Comparison of the extent of organ uptake of radiolabel after 35S-hRlx-2 or 35S-cysteine administration suggested that the kidneys were the principal site of uptake; the liver was of secondary importance. In perfusion experiments utilizing livers isolated from pregnant or nonpregnant rats, 36-52% of the dose of hRlx-2 was cleared from the perfusate in 2 hr. These studies showed that the pharmacokinetics of hRlx-2 in rats appeared to be unaffected by pregnancy and suggested that the kidneys and liver both play a role in the elimination of hRlx-2. PMID:1614978

Cossum, P A; Dwyer, K A; Roth, M; Chen, S A; Moffat, B; Vandlen, R; Ferraiolo, B L



Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring.  


The increased incidence of congenital malformations in diabetic pregnancy may be associated with an excess of free oxygen radicals in the embryo. We have previously blocked the dysmorphogenesis of rat embryos exposed to high glucose and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant capacity of the conceptus. In the present study, we attempted to diminish the teratogenic process in vivo in a rat model of diabetic pregnancy. Thus, pregnant diabetic and normal rats were fed either a standard diet or a diet enriched with 1% of the antioxidant butylated hydroxytoluene (BHT). The fetuses of the diabetic rats were smaller than the fetuses of the normal rats (body weight 2.70 g vs. 3.68 g) when the mothers were fed a standard diet. The BHT diet increased the fetal weight in the offspring of diabetic rats (3.17 g), with no change in fetuses of the normal rats (3.65 g). The placentas of diabetic rats were heavier than the placentas of normal rats; this difference was not present in the BHT-fed rats. The BHT treatment had no effect on the rate of resorptions, which was increased in the diabetic rats compared with the normal rats. In contrast, the increased rate of congenital malformations in the offspring of diabetic rats (19%), compared with that in the normal rats (0%), was markedly decreased by the BHT diet (2.3%). No malformations were found in the normal rats treated with BHT. These data support the notion that an excess of free oxygen radicals in the embryo contributes to the teratogenic process of diabetic pregnancy and, thus, suggest an area for future preventive therapeutic treatment. PMID:8866552

Eriksson, U J; Simán, C M




E-print Network

rats showed anovulatory sterility when adult, in contrast to control animals which had received the TP significantly. The results indicate, that estrogens are involved in the postnatal development and priming on gonadotropic hormone release already in very young immature female rats as well as an inhibitory action

Paris-Sud XI, Université de


Effects of acetamiprid on immune system in female wistar rats  

Microsoft Academic Search

A subacute toxicity study of acetamiprid was undertaken in 72 female wistar rats in four groups (18 each). Three different\\u000a concentrations of acetamiprid (25, 100 and 200 mg\\/kg of body weight) were administered orally to rats. Untreated rat served\\u000a as control. The antibody titre of sheep red blood cells (SRBC) in all the treated groups and decrease in cell mediated

Samiran Mondal; R. C. Ghosh; M. S. Mate; D. B. Karmakar



Lipaemia and liver composition in pregnant rats consuming olive oil and olive oil used for frying  

Microsoft Academic Search

Summary The effect of the consumption of unused olive oil (polar content, 2 %; oleic acid, 78.9 mg\\/100 mg oil, and linoleic acid 7 mg\\/100 mg oil) and olive oil used discontinuously for frying potatoes 15 times (polar content, 9 %; oleic acid, 75.8 mg\\/100 mg oil and linoleic acid 6.2 mg\\/100 mg oil) was studied in pregnant rats with

S. López-Varela; F. J. Sánchez-Muniz



Changes in antioxidant status and biochemical parameters after orally cadmium administration in females rats.  


The research was conducted to investigate the toxic effects of cadmium chloride (CdCl2), administered during gestation period on female Wistar rats. Pregnant rats received CdCl2 (20 mg/l, orally) from Day 6 to Day 19 of pregnancy. Results showed that Cd treatment induced a decrease in body weight gain. The relative liver weight increased significantly, with a marked decrease of glycogen and total lipids content. The administration of Cd induced hepatotoxicity as indicated by elevations in plasma alanine aminotransferase (ALT), aspartate aminotransferase and lactate dehydrogenase (LDH) activities (p < 0.05). Treatment with CdCl2 caused a significant (p < 0.05) increase in glucose. A significant increase was observed in the level of MDA and 8-oxodGuo tissues in the cadmium-exposed group compared to the control group (p < 0.05). Results showed that cadmium given to dams led to an oxidative stress and DNA damage in tissues of pregnant rats. PMID:19378926

Chater, S; Douki, T; Favier, A; Sakly, M; Abdelmelek, H



Effects of [123I]ADAM, a serotonin transporter radiopharmaceutical, on pregnant Sprague-Dawley rats.  


Serotonin transport abnormalities are implicated in neuropsychiatric disorders. [(123)I]ADAM ([(123)I]-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) is a novel radiotracer that targets serotonin transporters. We assessed the toxicity of [(123)I]ADAM (18.5 MBq) administered in early- and late-phases (8 and 14 day postfertilization, respectively) of pregnancy. The mortality, clinical status, and gross necropsy were measured in pregnant rats, and the fertility index was measured in rat offspring (weight, clinical observations). We found no dosing-related clinical signs. In conclusion, [(123)I]ADAM was not toxic in an animal pregnancy model. PMID:22960183

Chang, K W; Lin, M C; Lee, S Y; Chen, H Y; Chen, C C; Fu, Y K



Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.  


In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5?-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. PMID:24829217

Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin



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

SciTech Connect

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.

Shi, C. Y.; Xu, X. George; Stabin, Michael G. [Department of Radiation Oncology, University of Texas Health Science Center, San Antonio, Texas 78229 (United States); Nuclear Engineering and Engineering Physics Program, Rensselaer Polytechnic Institute, Room 1-11, NES Building, Tibbits Avenue, Troy, New York 12180 (United States); Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232-2675 (United States)



Activity-Based Anorexia In Female Rats  

Microsoft Academic Search

Activity-based anorexia (ABA) in an animal model of anorexia nervosa, in which rats are allowed free access to running wheels but only 2 h food access per day. Rats exposed to this paradigm display symptoms similar to those seen in anorexic women. These include decreased food intake, increased activity, rapid body weight loss, and estrous cycle disruptions. Despite that anorexia

Deann Dixon



Disruption of Reproductive Aging in Female and Male Rats by Gestational Exposure to Estrogenic Endocrine Disruptors  

PubMed Central

Polychlorinated biphenyls (PCBs) are industrial contaminants and known endocrine-disrupting chemicals. Previous work has shown that gestational exposure to PCBs cause changes in reproductive neuroendocrine processes. Here we extended work farther down the life spectrum and tested the hypothesis that early life exposure to Aroclor 1221 (A1221), a mixture of primarily estrogenic PCBs, results in sexually dimorphic aging-associated alterations to reproductive parameters in rats, and gene expression changes in hypothalamic nuclei that regulate reproductive function. Pregnant Sprague Dawley rats were injected on gestational days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1 mg/kg), or estradiol benzoate (50 ?g/kg). Developmental parameters, estrous cyclicity (females), and timing of reproductive senescence were monitored in the offspring through 9 months of age. Expression of 48 genes was measured in 3 hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV), arcuate nucleus (ARC), and median eminence (females only) by real-time RT-PCR. Serum LH, testosterone, and estradiol were assayed in the same animals. In males, A1221 had no effects; however, prenatal estradiol benzoate increased serum estradiol, gene expression in the AVPV (1 gene), and ARC (2 genes) compared with controls. In females, estrous cycles were longer in the A1221-exposed females throughout the life cycle. Gene expression was not affected in the AVPV, but significant changes were caused by A1221 in the ARC and median eminence as a function of cycling status. Bionetwork analysis demonstrated fundamental differences in physiology and gene expression between cycling and acyclic females independent of treatment. Thus, gestational exposure to biologically relevant levels of estrogenic endocrine-disrupting chemicals has sexually dimorphic effects, with an altered transition to reproductive aging in female rats but relatively little effect in males. PMID:23592748

Walker, Deena M.; Kermath, Bailey A.; Woller, Michael J.



Increased oxidative stress in the placenta tissue and cell culture of tumour-bearing pregnant rats.  


Placental dysfunction leads to foetal damage, which jeopardises the exchange between the maternal and foetal systems. We evaluated the effects of tumour growth on the activity of antioxidant enzymes and oxidative stress in placental tissue and cell culture from tumour-bearing pregnant rats compared to non-tumour-bearing pregnant rats that were ascitic fluid injected. Ascitic fluid is obtained from Walker tumour-bearing rats and contains a cytokine called Walker factor (WF), which is a molecule similar to proteolysis-inducing factor (PIF), and induces changes in protein metabolism and oxidative stress. Pregnant Wistar rats were distributed into control (C), tumour-bearing (W) and ascitic fluid injected (A) groups and were sacrificed on days 16, 19 and 21 of pregnancy to analyse the profile of enzyme activities (glutathione-S-transferase (GST), catalase (CAT), alkaline phosphatase (AP)) and malondialdehyde (MDA) content in placental tissue. Meanwhile, placenta samples from all groups were obtained on day 21, placed in primary culture and treated with WF for 72 h. The presence of tumour or ascitic fluid reduced the protein content of the placental tissue. On day 16 there was a significant reduction in AP activity in W rats, and on day 19, CAT activity and MDA content significantly increased. These results indicate that the presence of cancer decreased antioxidant enzyme capacity in the placenta, increasing the amount of oxidation in these cells, which may contribute to irreversible placental damage and compromisefoetal development. WF treatment induces similar changes in placental cells in primary culture, resulting in less cell viability and increased oxidative stress. These results indicate that WF, provided by the tumour or inoculation of ascitic fluid, has negative effects on placental homeostasis, which impairs foetal health. PMID:21903263

Toledo, M T; Ventrucci, G; Gomes-Marcondes, M C C



Sodium and water reabsorption in the proximal and distal nephron in conscious pregnant rats and third trimester women.  

PubMed Central

1. Sodium and water reabsorption were determined in virgin controls and rats at 9 and 20 days of pregnancy during a water diuresis induced and maintained by infusion of 2.5% dextrose and in normally hydrated women during the third trimester and again 2-3 months after delivery. 2. Reabsorption from the proximal tubules and distal nephron segments was assessed using the clearance of lithium as a marker of the sodium and water delivery from the proximal tubules to the loops of Henle. 3. Glomerular filtration rate and whole-kidney reabsorption of sodium and water were significantly increased at both stages of pregnancy in rats and late in pregnancy in women when compared to the respective non-pregnant control. Fractional reabsorption was unaltered in pregnant rats but increased in pregnant women. 4. Proximal tubule sodium and water reabsorption were increased in pregnant rats and women; fractional reabsorption was unaltered. 5. Absolute reabsorption of sodium and water in distal nephron segments were increased during pregnancy in both rats and women. Although increases in fractional reabsorption were detected in pregnant women, this was not the case at either stage of gestation in rats. PMID:3411501

Atherton, J C; Bielinska, A; Davison, J M; Haddon, I; Kay, C; Samuels, R



Sonomorphology of the reproductive tract in male and pregnant and non-pregnant female Rothschild's giraffes (Giraffa camelopardalis rotschildi).  


The application of real-time-B-mode ultrasonography to wild and zoo animal medicine has been shown to improve the understanding of reproductive physiology in many species. Ultrasound technology is especially helpful for monitoring urogenital health, which in turn has advantages for giraffe breeding and welfare in captivity. This study aimed to ultrasonographically describe the genital organs of reproductively healthy male and female giraffes. Through the use of a restrainer, repeated rectal ultrasound examinations were performed over a 2 year period in 2.6 Rothschild's giraffes. Changes in ovarian activity were monitored throughout four different reproductive stages in the females and included immature, mature-cycling, pregnancy, post-partum-period. In the immature giraffes the ovaries showed multiple follicles of which larger ones luteinized to form pseudo-corpora lutea. By comparison, in the mature giraffes the dominant follicle reached an ovulatory diameter of 18.5+/-0.89 mm. After ovulation, a single corpus luteum rapidly formed and reached a maximum diameter of 33.0+/-2.4mm on average. Pregnancy was detected for the first time by the embryonic vesicle, visualized around 28 days post copulation. Follicular development remained ongoing during early pregnancy. In the males, as in other ruminants, the bulbourethral glands and the seminal vesicles were prominent, whereas the prostate gland was indistinct. Knowledge about the reproductive tract morphology and physiology is necessary for diagnosing medical disorders and abnormalities in giraffes. The aim of this study was to help consolidate the current knowledge on basic reproductive parameters for this species. PMID:19297015

Lueders, Imke; Niemuller, Cheryl; Pootoolal, Jason; Rich, Peter; Gray, Charlie; Streich, Wolf Jürgen; Hildebrandt, Thomas Bernd



Identification of Site of Morphine Action in Pregnant Wistar Rat Placenta Tissue: A C14-Morphine Study  

PubMed Central

Objective: In previous studies it has been emphasized that the site of morphine action may be either in the embryo or the placenta. In the present study, we attempt to identify the site of morphine action on the fetal section of Wistar rat placenta by using C14-morphine. Materials and Methods: In this study (experimental), female Wistar rats (weights: 170-200 g) were mated with male rats and their coupling times recorded. Experimental groups received daily doses of 0.05 mg/ml of C14-morphine in their drinking water. On the 9th and14th embryonic days, the pregnant rats were anesthetized and the placenta and uterus surgically removed. Placentas were fixed in 10% formalin for two weeks, then processed, sectioned in 5 µm and 25 µm thicknesses, and fixed on glass slides for further evaluation. The 25 µm sections were delivered to black and white film for three days. Films were processed and evaluated with a digital inverse microscope for possible radiological impression. The 5 µm sections were processed for hematoxylin and eosin (H&E) staining, and evaluated by light microscope and MOTIC software. Results: Our results indicated that the site of action of C14-morphine was possibly located on the blood plexus of the fetal portion of the placenta. In addition, oral morphine consumption was shown to inhibit fetal and maternal placental development in the experimental groups. Conclusion: We conclude that morphine’s effectiveness on the reduction of embryo growth and development may be via its effects on the blood plexus of the fetal section of the placenta. PMID:23508019

Kazemi, Masoomeh; Sahraei, Hedayat; Dehghani, Leila



Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets  

Microsoft Academic Search

A comparison of the dose-dependent blood burden of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague–Dawley rats and marmosets were treated orally with 30 or 500 mg DEHP\\/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14–19 (rats) and 96–124 (marmosets). In

Winfried Kessler; Wanwiwa Numtip; Konstanze Grote; György A. Csanády; Ibrahim Chahoud; Johannes G. Filser




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 ...



EPA Science Inventory

Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, was significantly induced in female rat liver following oral administration of the pesticide, mirex. fter dual oral exposure (120 mg/kg; 21 and 4 hrs prior to sacrifice) induction of ODC activity in r...


Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats  

ERIC Educational Resources Information Center

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…

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



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

NASA Technical Reports Server (NTRS)

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.

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)



Teratogenicity and metabolism of water-soluble forms of vitamin A in the pregnant rat  

SciTech Connect

Retinoyl {beta}-glucuronide, unlike retinoic acid, has been shown to be non-teratogenic when administered orally, even in large doses, to pregnant rats. The degree to which water-solubility is associated with low teratogenicity is not known. Other water-soluble forms of vitamin A have now been synthesized in our laboratory and are being evaluated for teratogenicity. New water-soluble forms of vitamin A were administered orally to pregnant Sprague-Dawley rats in a single dose of 0.35 mmole/kg bw on day 8 of gestation. On day 19, the dams were sacrificed and the litters were examined. Control animals received either vehicle only or an equivalent dose of all-trans retinoic acid. Maternal and fetal tissues were taken and analyzed by HPLC for vitamin A metabolites. In another experiment, a large single oral dose of the radiolabelled water-soluble compound was administered on day 10. At either 30 minutes or 1 hour after the dose, dams were sacrificed and the embryos analyzed both for radioactivity and for specific metabolites. In contrast to retinoyl {beta}-glucuronide, retinoyl {beta}-glucose is highly teratogenic under identical conditions. Thus, water-solubility does not seem to be the determining factor in the teratogenicity of retinoic acid conjugates.

Gunning, D.B.; Barua, A.B.; Olson, J.A. (Iowa State Univ., Ames (United States))



Uterine distension differentially affects remodelling and distensibility of the uterine vasculature in non-pregnant rats.  


During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non-pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type. PMID:22781934

Osol, George; Barron, Carolyn; Mandalà, Maurizio



Endocannabinoid influence on partner preference in female rats.  


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

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



Reproductive toxicity associated with acrylamide treatment in male and female rats  

SciTech Connect

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.

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



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

Microsoft Academic Search

Based on the human and animal studies, Astrup et al. (1972) implied fetal hypoxia induced by carbon monoxide (CO) in the cigarette smoke to be responsible for the event mentioned above. Tachi and Aoyama (1983) demonstrated that pregnant rats which had inhaled either cigarette smoke or CO at the similar CO concentration, had smaller conceptuses than those in the control

Norihide Tachi; Mitsuko Aoyama



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

NASA Technical Reports Server (NTRS)

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.

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



Dietary protein, fat, and minerals in nephrocalcinosis in female rats.  


Young female rats fed semipurified diets containing casein or a soy protein isolate had extensive nephrocalcinosis at the junction between the outer and inner stripe of the outer medullary zone after 5 wk on the diets, whereas rats fed a diet containing a lactalbumin concentrate did not. Although the percentages of actual protein and of total ash were similar in all three diets, the concentrations of individual minerals were not, owing to methods used in isolating the proteins. Comparison of the individual mineral contents of these diets with those in other laboratories as compiled from the literature suggested that factors other than minerals, including protein, are also implicated. Dietary fat appeared to be another such factor in a series of experiments in which saturated medium-chain triglycerides and corn oil were included in diets containing soy protein isolate. Although these diets had identical mineral compositions, the rats fed medium-chain triglycerides had less severe lesions. PMID:1246208

Kaunitz, H; Johnson, R E



Chlorpyrifos induced toxicity in reproductive organs of female Wistar rats.  


Chlorpyrifos (CPF) is an organophosphate (OP) insecticide extensively used in agricultural and domestic settings. Healthy adult female albino rats were divided into three groups of six rats in each. Two groups were dosed orally with CPF in vegetable oil (0.1 and 2.5 mg/kg/day) and third group was given vegetable oil for 8 weeks. Non-significant changes were observed for body weight and feed intake. A disruption in estrous cyclicity was observed with a prolonged metestrous. Erythrocyte osmotic fragility and lipid peroxidation levels increased significantly. Mammary gland whole mounts revealed a significant (P<0.05-0.0001) increase in the ductal thickness, number of branches, alveolar and terminal end bud number and terminal end bud diameter. A significant increase in ovarian surface epithelium height, follicular diameter and follicular atresia was observed in treated rats (P<0.05-0.0001). A similar significant increase in the uterine surface epithelium height, endometrial gland epithelium height and myometrium thickness in higher dose group was recorded (P<0.05-0.0001). Luminal epithelium height and endometrial gland diameter was increased significantly in both the treated groups (P<0.05-0.0001). The results indicate that sub-chronic exposure of CPF causes oxidative stress and negative effects on the reproductive organs of female rats, which may be a pointer towards beginning of cancer incidence. PMID:24140463

Nishi, Kumari; Hundal, Swarndeep Singh



Effect of a Single Dose of Cadmium on Pregnant Wistar Rats and their Offspring.  


Cadmium (Cd) is a well-known toxicant targeting many organs, among them placenta. This heavy metal also has embryonary and foetal toxicity. This study was undertaken to analyse the effect of a single Cd dose administered at 4, 7, 10 or 15 days of gestation on the offspring of pregnant rats sacrificed at 20 days of gestation. Cadmium chloride was administered subcutaneously at 10 mg/kg body weight to Wistar pregnant dams; control animals received a proportionate volume of sterile normal saline by the same route. Maternal uteri, livers, kidneys and lungs, and foetuses were examined at necropsy. Samples of maternal organs and whole foetuses were collected for histopathologic examination, determination of Cd levels and staining by the Alizarin red S technique. Results revealed a clear embryotoxic and a teratogenic effect of this heavy metal, the former as a significant increase in the number of resorptions, and the latter as significant decrease of the gestational sac weight, and the size and weight of foetuses of Cd-treated dams as well as induced malformations in skull bones, vertebrae and thoracic, and pelvian limbs. The deleterious effects found were similar to those previously reported for other animal models suggesting a high conservation of the pathogenic mechanisms of Cd. Additionally, many of the addressed aspects showed a slight dependence on the time of administration of the toxic that might be due to the accumulation of the metal in different organs, as we were able to demonstrate by the analysis of its concentration. PMID:25322905

Díaz, M Del C; González, Nv; Gómez, S; Quiroga, Ma; Najle, R; Barbeito, Cg



Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase  

PubMed Central

Although thyroid hormones are critically important for the coordination of morphogenic processes in the fetus and neonate, premature exposure of the embryo to levels of the hormones present in the adult is detrimental and can result in growth retardation, malformations, and even death. We report here that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3?,5-triiodothyronine by 5-deiodination. Both D3 mRNA and activity were present at the implantation site as early as gestational day 9 (E9), when expression was localized using in situ hybridization to uterine mesometrial and antimesometrial decidual tissue. At later stages of gestation, uterine D3 activity remained very high, and the levels exceeded those observed in the placenta and in fetal tissues. After days E12 and E13, as decidual tissues regressed, D3 expression became localized to the epithelial cells lining the recanalized uterine lumen that surrounds the fetal cavity. These findings strongly suggest that the pregnant uterus, in addition to the placenta, plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones. J. Clin. Invest. 103:979–987 (1999). PMID:10194470

Galton, Valerie Anne; Martinez, Elena; Hernandez, Arturo; St. Germain, Emily A.; Bates, Joanne M.; St. Germain, Donald L.



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

SciTech Connect

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.

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



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

NASA Technical Reports Server (NTRS)

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.

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



Quality of obstetric and midwifery care for pregnant women who have undergone female genital mutilation.  


Despite the availability of professional guidelines for the pregnancy management of women affected by female genital mutilation (FGM), this study demonstrated major deficits in identification, management and safeguarding. PMID:23815196

Zenner, N; Liao, L-M; Richens, Y; Creighton, S M



"Pregnant and Operating": Evaluation of a Germany-wide Survey Among Female Gynaecologists and Surgeons  

PubMed Central

The current law on the protection of expectant and nursing mothers largely rules out surgical activities during pregnancy for female doctors who perform surgical roles in hospitals. The proportion of female junior staff in gynaecology amounts to 80?%, and, for many of these women, surgical further training is not possible following official notification of an existing pregnancy. In a Germany-wide survey of female gynaecologists and surgeons using a questionnaire, it was determined to what extent female doctors worked in surgery during pregnancy, whether it led to complications in the pregnancy, when the employer was notified about the pregnancy, and what desire for change there is with regard to the law on the protection of expectant and nursing mothers. The data from 164 female doctors, of which 136 are gynaecologists and 28 surgeons, was evaluated. On average, the pregnancy was announced during the 14th week of pregnancy (WOP), and the doctor was not allowed to perform surgical activities in the 21st WOP. Female doctors in higher professional roles tended to announce the pregnancy later and ended their surgical activities later. There was no link between the time of ceasing surgical activities and an increased occurrence of complaints or complications during the pregnancy. In total, only 53?% of respondents had an appraisal during pregnancy and 75?% wanted a change in the law on the protection of expectant and nursing mothers. PMID:25278630

Knieper, C.; Ramsauer, B.; Hancke, K.; Woeckel, A.; Ismail, L.; Buhren, A.; Toth, B.



Maternal and fetal toxicity of methylmercuric chloride administered to pregnant Fischer 344 rats.  


Various doses of methylmercuric chloride (MMC) were administered orally to pregnant Fischer 344 rats on d 7 of gestation. On d 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed. Maternal body weights were decreased for 2 d and 6 d in rats given 10 and 20 mg/kg MMC, and were continuously decreased for those given 30 mg/kg MMC. Maternal weight gain of each group was decreased to 86.2%, 78.9%, and 61.9% of control group on d 20 of gestation. The reduction of litter weight was greatly enhanced with increasing MMC doses, presumably due to postimplantation loss, which was already increased at high treatment levels. The LD50 of MMC for fetuses was determined to be 16.5 mg/kg. Mercury content in maternal organs was highest in kidney, followed by blood, spleen, liver, and brain, while in fetal organs it was highest in liver. Fetal liver and brain contained more mercury than maternal liver and brain. However, fetal kidney retained less mercury than maternal kidney. Fetal ossification center was not completely formed in sternebrae, particularly in fifth and second bones, pelvic bones, and pectoral phalanges of fetuses in rats treated with 30 mg/kg MMC. The ossified lengths of skeletal bone stained with alizarin red S were developed least in fifth sternebrae, metacarpals in the pectoral girdle, and ischium in the pelvic girdle, and were severely retarded in development as position of the ribs goes from the sixth bone (center) to the first and 13th bone (each edge). These results indicate that MMC is embryotoxic in Fischer 344 rats. PMID:7643429

Lee, J H; Han, D H



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

NASA Technical Reports Server (NTRS)

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.

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



Female-specific hypertension loci on rat chromosome 13  

PubMed Central

A 3.7 Mb region of rat chromosome 13 (45.2–49.0 Mb) affects blood pressure (BP) in females only, indicating the presence of gender-specific BP loci in close proximity to the Renin locus. In the present study, we used a series of Dahl salt-sensitive/Mcwi (SS)-13 Brown Norway (BN) congenic rat strains to further resolve BP loci within this region. We identified 3 BP loci affecting female rats only, of which the 2 smaller loci (line9BP3 and line9BP4) were functionally characterized by sequence and expression analysis. Compared with SS, the presence of a 591 Kb region of BN chromosome 13 (line9BP3) significantly lowered BP by 21 mmHg on an 8% NaCl diet (153±7 vs 174±5 mmHg, P<0.001). Unexpectedly, the addition of 23 Kb of BN chromosome 13 (line9BP4) completely erased the female-specific BP protection on 8% NaCl diet, suggesting that BN hypertensive allele(s) reside in this region. The congenic interval of the protective line 9F strain contains 3 genes (Optc, Prelp, and Fmod) and the hypertensive line 9E contains 1 additional gene (Btg2). Sequence analysis of the 2 BP loci revealed a total of 282 intergenic variants, with no coding variants. Analysis of gene expression by RT-qPCR revealed strain- and gender-specific differences in Prelp, Fmod, and Btg2 expression, implicating these as novel candidate genes for female-specific hypertension. PMID:23817491

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



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

NASA Astrophysics Data System (ADS)

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.

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



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

PubMed Central

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

Takahashi, O; Oishi, S



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

SciTech Connect

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.

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



Role of Reactive Oxygen Species in Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats  

PubMed Central

BACKGROUND Although recent studies indicate preeclampsia (PE) is associated with increased oxidative stress, the role of reactive oxygen species in the hypertension associated with PE remains unclear. We sought to test the hypothesis that placental ischemia increases oxidative stress which in turn, contributes to hypertension. METHODS Reduction in uterine perfusion pressure (RUPP) was induced by placing silver clips on the abdominal aorta and the ovarian arteries on day 14 of pregnancy. On day 20 of pregnancy, mean arterial pressure (MAP) was measured and oxidative stress was assessed in renal and placental tissues whereas systemic administration of tempol, a superoxide dismutase (SOD) mimetic, was used to evaluate the contribution of reactive oxygen species on RUPP-induced hypertension. RESULTS MAP (120 ± 2 mm Hg vs.106 ± 3 mm Hg), placental levels of 8-isoprostane (1.9 ± 0.4 ng/g tissue vs. 0.8 ± 0.1 ng/g tissue), and malondialdehyde (MDA) (6.9 ± 0.6 ?mol/g tissue vs. 3.9 ± 0.4 ?mol/g tissue) were increased, whereas renal cortical SOD activity was decreased in RUPP rats (1.2 ± 0.1 units/mg protein vs. 1.6 ± 0.1 units/ mg protein) at day 20 of gestation (20 dG) compared to controls. Chronic treatment with tempol attenuated the hypertension (RUPP + tempol 112 ± 2 mm Hg vs. RUPP, 120 ± 2 mm Hg) associated with RUPP, whereas tempol had no effect on MAP (NP, 106 ± 3 vs. NP + tempol, 108 ± 2) in control rats. CONCLUSION The results of this study indicate that placental ischemia decreases innate antioxidant activity resulting in elevated oxidative stress which appears to play a role in mediating hypertension associated with chronic RUPP in pregnant rats. PMID:18670418

Sedeek, Mona; Gilbert, Jeffrey S.; LaMarca, Babbette B.; Sholook, Myssara; Chandler, Derrick L.; Wang, Yuping; Granger, Joey P.



Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats.  


We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R = 0.5908, P = 0.0024; R = 0.4877, P = 0.0134, respectively) and the number of malformations per fetus (R = 0.6103, P = 0.0015; R = 0.4875, P = 0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R = 0.3887, P = 0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R = 0.3999, P = 0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes. PMID:22821472

Saito, Felipe Hiroshi; Damasceno, Débora Cristina; Dallaqua, Bruna; Linhares, Iara Moreno; Rudge, Marilza Vieira Cunha; De Mattos Paranhos Calderon, Iracema; Witkin, Steven S



Behavioral Effects of Enrichment and Nicotine in Female Sprague Dawley Rats.  

National Technical Information Service (NTIS)

Three experiments examined effects of environmental enrichment and nicotine on body weight, food consumption, and activity in 52 female Sprague Dawley rats. Rats were housed in physically, socially, or super (social and physical) enriched or non-enriched ...

C. A. Rose



Food restriction in pregnant rat-like hamsters ( Cricetulus triton) affects endocrine, immune function and odor attractiveness of male offspring  

Microsoft Academic Search

We studied the effect of intrauterine food restriction (FR) on the immune function, endocrine status and attractiveness of scents of male rat-like hamsters, Cricetulus triton. Work was conducted on field-caught parents from the North China plain and their laboratory-born progeny. Restricted pregnant dams were fed 70% of the mean daily intake of hamsters with free access to food. FR caused

Hong Liang; Jianjun Zhang; Zhibin Zhang



Pancreatic islet transplantation in diabetic pregnant rats prevents acquired malformation of the ventromedial hypothalamic nucleus in their offspring.  


Exposure to a diabetic intrauterine environment leads to diabetogenic disturbances throughout later life in rats. This is accompanied by a fetally acquired dysplasia of the ventromedial hypothalamic nucleus (VMN) which is decisively involved in the regulation of metabolism. We investigated whether malformation of the VMN is preventable by normalization of gestational hyperglycaemia. Correction of hyperglycaemia in pregnant streptozotocin-diabetic rats was achieved by pancreatic islet transplantation. The number of neurons in the VMN was significantly reduced in adult offspring of non-treated, sham-transplanted mother rats (P<0.05), but did not differ between offspring of islet-transplanted mother rats and offspring of control mothers. In conclusion, prevention of VMN malformation in offspring of islet-transplanted diabetic mothers might be co-responsible for normalization of their glucose homeostasis during life. PMID:11166944

Harder, T; Aerts, L; Franke, K; Van Bree, R; Van Assche, F A; Plagemann, A



The ontogeny of exploratory behavior in male and female adolescent rats ( Rattus norvegicus )  

Microsoft Academic Search

During adolescence, rats gain independence from their mothers and disperse from the natal burrow, with males typically dispersing further than females. We predicted that, if dispersal patterns are associated with responsiveness to novelty, exploratory behavior in novel environments would increase across adolescence, and males would explore more than females. Alternatively, females might explore more than males, if females are more

Debra A. Lynn; Gillian R. Brown



Comparison of the “Nursing” and Other Parental Behaviors of Nulliparous and Lactating Female Rats  

Microsoft Academic Search

Virgin female rats display maternal behaviors after continuous exposure to pups (sensitization) that are in some respects similar to those of postpartum females. We herein provide a detailed comparison of the “nursing” and other parental behaviors of maternally sensitized virgin females and postpartum lactating dams. Ovariectomized and intact virgin females were exposed to pups until displaying maternal behavior. On the

Joseph S. Lonstein; Christine K. Wagner; Geert J. De Vries



Effects of cadmium exposure on morphological aspects of pancreas, weights of fetus and placenta in streptozotocin-induced diabetic pregnant rats.  


This study was designed to evaluate the effects of Cd exposure on morphological aspects of beta-cell and weights of fetus and placenta in streptozotocin (STZ)-induced diabetic pregnant rats. Ninety-nine virgin female Wistar rats (200-220 g) were mated with 33 males for at least 12 h. From the onset of pregnancy, the rats were divided into four experimental groups (control, Cd treated, STZ treated, and Cd+STZ treated). The Cd-treated group was injected subcutaneously daily with CdCl2 dissolved in isotonic NaCl, starting at the onset of pregnancy throughout the experiment. Diabetes was induced on the 13th d of pregnancy by a single intraperitoneal injection of STZ in STZ-treated group. In addition to the daily injection of Cd, a single intraperitoneal injection of STZ was also given on the 13th d of pregnancy in the Cd+STZ-treated group. The rats received the last injection 24 h before being sacrificed and 10 randomly selected rats in each group were sacrificed on the 15th and 20th d of pregnancy. Blood samples were taken for the determination of the serum glucose and insulin levels. Maternal pancreases, fetuses, and placentas of sacrificed rats in all groups were harvested (fetal pancreas was also harvested only on the 20th d of pregnancy) for morphological and immunohistochemical examinations. Cd exposure alone caused a degeneration, necrosis, and weak degranulation, but Cd exposure with STZ caused a severe degeneration, necrosis, and degranulation in the beta-cells of the pancreatic islets. No morphological or immunohistochemical differences were found in beta-cells of fetal pancreatic islets of control or other treatment groups. Cd exposure alone also decreased the fetal and placental weights. The administration of STZ alone, on the other hand, increased the placental weight. Cd, STZ, and Cd+STZ administration increased the glucose and decreased the insulin level. The increase in glucose and decrease in insulin levels were higher when Cd and STZ were given together. All of these changes were more severe on the 20th d than those on the 15th d of the pregnancy. It is concluded that Cd exposure during pregnancy may reduce the birth and placental weights and produce necrosis, degeneration, and degranulation in beta-cells of pancreatic islets, causing an increase in the serum glucose level. These changes might be severe in diabetic pregnant mothers. PMID:12835501

Kanter, Mehmet; Yoruk, Mecit; Koc, Ahmet; Meral, Ismail; Karaca, Turan



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

PubMed Central

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

Chinnathambi, Vijayakumar; Yallampalli, Chandrasekhar; Sathishkumar, Kunju



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

NASA Technical Reports Server (NTRS)

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.

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



Selective regulation of hepatic lipid metabolism by the AMP-activated protein kinase pathway in late-pregnant rats.  


The liver plays an essential role in maternal metabolic adaptation during late pregnancy. With regard to lipid metabolism, increased secretion of very low-density lipoprotein (VLDL) is characteristic of late pregnancy. Despite this well-described metabolic plasticity, the molecular changes underlying the hepatic adaptation to pregnancy remain unclear. As AMPK is a key intracellular energy sensor, we investigated whether this protein assumes a causal role in the hepatic adaptation to pregnancy. Pregnant Wistar rats were treated with vehicle or AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) for 5 days starting at gestational day 14. At the end of treatment, the rats were subjected to an intraperitoneal pyruvate tolerance test and in situ liver perfusion with pyruvate. The livers were processed for Western blot analysis, quantitative PCR, thin-layer chromatography, enzymatic activity, and glycogen content measurements. Blood biochemical profiles were also assessed. We found that AMPK and ACC phosphorylation were reduced in the livers of pregnant rats in parallel with a reduced level of hepatic gluconeogenesis of pyruvate. This effect was accompanied by both a reduction in the levels of hepatic triglycerides (TG) and an increase in circulating levels of TG. Treatment with AICAR restored hepatic levels of TG to those observed in nonpregnant rats. Additionally, AMPK activation reduced the upregulation of genes related to VLDL synthesis and secretion observed in the livers of pregnant rats. We conclude that the increased secretion of hepatic TG in late pregnancy is concurrent with a transcriptional profile that favors VLDL production. This transcriptional profile results from the reduction in hepatic AMPK activity. PMID:25163923

Rodrigues, Sandra C; Pantaleão, Lucas C; Nogueira, Tatiane C; Gomes, Patrícia R; Albuquerque, Gabriela G; Nachbar, Renato T; Torres-Leal, Francisco L; Caperuto, Luciana C; Lellis-Santos, Camilo; Anhê, Gabriel F; Bordin, Silvana



Immunization of Wistar female rats with 255-Gy-irradiated Toxoplasma gondii: Preventing parasite load and maternofoetal transmission.  


Toxoplasmosis, caused by an obligate intracellular protozoan parasite, Toxoplasma gondii, is an worldwide parasitic disease, with significant importance for animal production and considerable impact to the public health. This study was aimed to evaluate the dynamic of the distribution of T.gondii in tissues of female Wistar rats and their puppies tissues, 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 follow: 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 the rats were sacrificed and the tissues were researched for the DNA of T. gondii by polymerase chain reaction (PCR) and the 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 most organs analyzed, although not prevent the establishment of infection with the parasite. And also, the immunization showed a favorable effect on the birth rate and litter size. PMID:25169764

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



The Effects of Alcohol and Age on Astrocytes In Female Rats Following an Inflammatory Stimulus  

E-print Network

THE EFFECTS OF ALCOHOL AND AGE ON ASTROCYTES IN FEMALE RATS FOLLOWING AN INFLAMMATORY STIMULUS A Senior Scholars Thesis by ASHLEY NICOLE SIMPSON Submitted to the Office of Undergraduate Research Texas A...&M University In partial fulfillment of the requirements for the designation as UNDERGRADUATE RESEARCH SCHOLAR April 2006 Major: Biology THE EFFECTS OF ALCOHOL AND AGE ON ASTROCYTES IN FEMALE RATS FOLLOWING...

Simpson, Ashley



Isolated small uterine arteries from non-pregnant and term pregnant rats exhibit regulatory responses to elevations in extravascular pressure.  


An adequate blood supply is essential for the maintenance of uterine function and fetal health during parturition. However, labouring uterine contractions will impart compressive forces on small uterine arteries (SUA). We demonstrate that isolated, pressurised rat SUA arteries, pre-constricted with arginine vasopressin or high potassium solution, exhibit regulatory responses to elevations in extravascular pressure (EVP) which maintain internal diameter constant at EVPs of 0-40 mm Hg. This response is endothelium independent and is not modulated by pregnancy. No regulation was observed in calcium free solution. SUA myogenic responses to elevated EVP likely represents a mechanism for limiting reductions in uterine blood flow during uterine contraction. PMID:23195572

Withers, S; Taggart, M; Austin, C



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


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

Ko?ci?ski, Krzysztof



[The role of prolactin on sexual maturation of female rat].  


The role of prolactin (PRL) in sexual maturation of immature female rats was examined in drug induced hyper-or hypoprolactinemic models. 1. In order to examine the role of PRL before the third week after birth, at which the serum PRL level of female rats is known to be low under physiological conditions, hyperprolactinemia was induced by daily subcutaneous injections of sulpiride from day 10 to day 20. Ovarian and uterine weights, serum hormone levels and in vitro estradiol (E2) release from removed ovary were evaluated on day 15 and day 20. The inhibition of uterine growth on both days a low serum E2 concentration on day 20 and inhibition of in vitro ovarian E2 release were demonstrated as the result of sulpiride treatment. 2. In order to examine the role of PRL after the fourth week, when the serum PRL level is known to become high, hyper- or hypoprolactinemia was induced from day 22 by per os administration of sulpiride or bromocriptine. Timing of the onset of puberty weights of the ovary, uterus and adrenal gland and serum hormone levels at the onset of puberty were evaluated. In the sulpiride treated group the timing of the onset of puberty was not affected and lower adrenal gland weight and a low serum FSH concentration were observed. In the bromocriptine treated group the timing of the onset of puberty was delayed and greater adrenal gland weight was observed. Serum hormone levels were not affected. These results suggest that (i) prolactin could have an inhibitory effect on sexual maturation before the 3rd week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8371016

Tozawa, H



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

Microsoft Academic Search

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

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


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

Microsoft Academic Search

Ethionine causes a decrease in the amount of rough endoplasmic reticulum in rat liver, the effect being greater in female than in male rats. Rough endoplasmic reticulum isolated from rat liver 24 hr after ethionine injection and stripped of its ribosomes partially lost itsin vitro ribosome binding capacity. However, no differences were detected between the binding affinities of ribosomes, isolated

H. H. Czosnek; A. Ascarelli; N. Groot; M. Hergenhahn; A. A. Hochberg



Prenatal Testosterone Exposure Leads to Hypertension That Is Gonadal Hormone-Dependent in Adult Rat Male and Female Offspring1  

PubMed Central

ABSTRACT Prenatal testosterone exposure impacts postnatal reproductive and endocrine function, leading to alterations in sex steroid levels. Because gonadal steroids are key regulators of cardiovascular function, it is possible that alteration in sex steroid hormones may contribute to development of hypertension in prenatally testosterone-exposed adults. The objectives of this study were to evaluate whether prenatal testosterone exposure leads to development of hypertension in adult males and females and to assess the influence of gonadal hormones on arterial pressure in these animals. Offspring of pregnant rats treated with testosterone propionate or its vehicle (controls) were examined. Subsets of male and female offspring were gonadectomized at 7 wk of age, and some offspring from age 7 to 24 wk received hormone replacement, while others did not. Testosterone exposure during prenatal life significantly increased arterial pressure in both male and female adult offspring; however, the effect was greater in males. Prenatal androgen-exposed males and females had more circulating testosterone during adult life, with no change in estradiol levels. Gonadectomy prevented hyperandrogenism and also reversed hypertension in these rats. Testosterone replacement in orchiectomized males restored hypertension, while estradiol replacement in ovariectomized females was without effect. Steroidal changes were associated with defective expression of gonadal steroidogenic genes, with Star, Sf1, and Hsd17b1 upregulation in testes. In ovaries, Star and Cyp11a1 genes were upregulated, while Cyp19 was downregulated. This study showed that prenatal testosterone exposure led to development of gonad-dependent hypertension during adult life. Defective steroidogenesis may contribute in part to the observed steroidal changes. PMID:22302690

Chinnathambi, Vijayakumar; Balakrishnan, Meena; Yallampalli, Chandrasekhar; Sathishkumar, Kunju



Effects of 2Acetylaminofluorene on Liver Cell Proliferation after Partial Hepatectomy of Female Rats1  

Microsoft Academic Search

SUMMARY The effect of the hepatocarcinogen 2-acetylaminofluorene (AAF) on liver regeneration in female Sprague-Dawley rats was studied. While livers of normal female rats were highly resistant to this carcinogen, partial hepatectomy of female animals maintained on diet containing 0.04% AAF disclosed a marked hepatotoxicity which resulted in abnormal, nodular regeneration. The incorporation of thymidine-3H into DNA and the mitotic index

Carlton D. Jackson; Charles C. Irving


Effects of changing the ionic environment on passive and active membrane properties of pregnant rat uterus.  


1. In pregnant rat myometrium electrotonic potentials, produced by externally applied current, were recorded intracellularly.2. The space constant, lambda, was 1.8 mm, the time constant, tau(m), 120 msec. The values obtained on the 7th day and on the 20th day of pregnancy were the same.3. The magnitude of the electrotonic potential and the time constant of the membrane were increased in the absence of potassium from the external solution and decreased by excess potassium.4. The magnitude of the electrotonic potential and the time constant of the membrane were increased by the replacement of chloride with C(6)H(5)SO(3) (-) or SO(4) (2-), and decreased with NO(3) (-) or I(-) replacement.5. When the sodium chloride was replaced with sucrose (16.7 mM sodium remaining in the buffers) the spontaneous spikes deteriorated and activity stopped within 30 min. However, for periods up to 4 hr, a spike of larger amplitude and faster rate of rise than in normal solution could be evoked when a depolarizing current was applied.6. When the external calcium concentration was raised (5 and 10 mM) the amplitude and the rate of rise of the evoked spike were increased. They were decreased by reducing calcium. In zero calcium spontaneous activity stopped within 15 min.7. The effects of calcium deficiency were much less marked and slower in onset when, simultaneously, the sodium concentration was reduced to 16.7 mM.8. When calcium was replaced with strontium (2.5 mM), the membrane was depolarized and the duration of the spontaneous and evoked action potential was prolonged, mainly due to a slowed rate of repolarization. When the concentration of strontium was raised to 7.5 or 12.5 mM the membrane was hyperpolarized, the duration of the action potential became short and the amplitude of the spike was increased.9. Addition of barium or the replacement of calcium with barium caused depolarization and oscillatory membrane activity. However, a spike could be evoked by applying conditioning hyperpolarization.10. Manganese abolished the spontaneous and evoked spike. Tetrodotoxin had no effect.11. The results show that rat uterus has cable-like properties. The action potential may be due to calcium entry, while sodium, by influencing the membrane potential in competition with calcium, may be involved in the spontaneous spike generation and the spread of excitation. PMID:5103422

Abe, Y



Decreased uterine blood flow in the diabetic pregnant rat does not modify the augmented glucose transfer to the fetus.  


To determine whether changes in uterine blood flow affect placental glucose transfer in the diabetic pregnant rat, on the 7th day of gestation rats were intravenously treated with either streptozotocin (45 mg/kg) (diabetics) or buffer (controls). On the 20th day of gestation, fetal body weight and uterine blood flow appeared reduced whereas fetal/maternal plasma glucose was enhanced and lactate ratios were unchanged in diabetics versus controls. After 20 min of (U-14C)-D-glucose infusion through the maternal left uterine artery, plasma values of fetuses from left and right uterine horns were higher for 14C-glucose and lower for 14C-lactate in diabetics versus controls, and placental glucose transfer was greatly augmented in diabetics whether or not uterine blood flow was included in its calculation. Whereas a linear correlation existed between placental glucose transfer and maternal plasma glucose concentration, transferred glucose conversion into lactate remained stable even when the maternal glucose level was high. It was concluded that enhanced placental glucose transfer in the pregnant diabetic rat is not modified by reduced uterine blood flow. The limited capacity of the fetus to handle the great incoming flux of glucose through the placenta of a severely diabetic mother produces permanent hyperglycemia which may impair fetal growth. PMID:4063414

Palacín, M; Lasunción, M A; Martín, A; Herrera, E



[Psychophysiological development of two generations of female rats chronically exposed to gamma-irradiation during pregnancy in the total dose of 1 Gy and its modification by melanin].  


The purpose of the work was to study the embryotoxic action of chronic gamma-irradiation of pregnant female rats (F0) during the first 10 days of pregnancy in the total dose of 1 Gy (mean dose rate of 5.31 mGy/hour) on psychophysiological development of posterity of the first (F1) and the second (F2) generations and its modification by natural pigment melanin (peroral 10 mg/kg once per day during the irradiation). 54 pregnant female Wistar rats were the objects of research were their 180 descendants of the first generation and about 400 descendants of the second generation of maternal and of paternal lines. Psychophysiological development and its correction by melanin estimated on ability to learning with the test of training a conditioned avoidance reflex in the shuttle box. Precise negative action of gamma-irradiation in the aforesaid dose on psychophysiological development of posterity of the first generation is established. At rats of the second generation the inferiority is shown mainly at descendants of maternal line. Application of melanin of natural origin in most cases diminished negative consequences of the irradiation. PMID:17571726

Pavlova, L N; Zhavoronkov, L P; Palyga, G F; Kolganova, O I; Glushakova, V S; Chibisova, O F; Ivanov, V L



Adverse effects of 4-tert-octylphenol on the production of oxytocin and hCG in pregnant rats  

PubMed Central

Endocrine-disrupting chemicals (EDCs) are exogenous substances that alter the structure or function of the endocrine system. 4-Tert-octylphenol (OP) is one of the most representative EDCs and has estrogenic effects. In this study, we examined the effects of ethinyl estradiol (EE) and OP on the pituitary gland, placenta, and uterus of pregnant rats. Expression levels of human chorionic gonadotropin (hCG), oxytocin (OT), and contraction-associated proteins (CAPs) were determined, and uterine contractile activity was measured by uterine contraction assay. EE and OP both increased mRNA expression of OT and hCG in the pituitary gland but not the placenta. Since OT and hCG control uterine contraction, we next examined CAP expression in the uterus. Expression of 15-hydroxyprostaglandin-dehydrogenase (PGDH) was upregulated by OP, whereas expression of other CAPs was unaffected. To clarify the effect of OP on uterine contraction in pregnant rats, uterine contraction assay was performed. The 17?-Estradiol (E2) did not affect contraction of primary uterine cells harvested from pregnant rats in a 3D collagen gel model. However, OP showed different effects from E2 by significantly reducing contraction activity. In summary, we demonstrated that OP interferes with regulation of OT and hCG in the pituitary gland as well as PGDH in the uterus, thereby reducing uterine contraction activity. This result differs from the action of endogenous E2. Collectively, these findings suggest that exposure to EDCs such as OP during pregnancycan reduce uterine contractile ability, which may result in contraction-associated adverse effects such as metratonia, bradytocia, and uterine leiomyomata. PMID:25324873

Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Lee, Jae-Eon; Hong, So-Hye; An, Sung-Min; Kim, Seung-Chul; Hwang, Dae-Youn



The effects of adrenalectomy and corticosterone replacement on induction of maternal behavior in the virgin female rat  

E-print Network

to the rapid onset of maternal behavior shown at parturition by the new mother rat, virgin female and male rats in the virgin female rat Stephanie L. Rees a , Sonia Panesar a , Meir Steiner b , Alison S. Fleming a evidence to show that corticosterone enhances mother rats' memory for pups during the postpartum period

Sokolowski, Marla


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

Microsoft Academic Search

PurposeHomeless 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

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



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

NASA Technical Reports Server (NTRS)

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.

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)



l-Arginine supplementation abolishes the blood pressure and endothelin response to chronic increases in plasma sFlt-1 in pregnant rats  

PubMed Central

While soluble fms-like tyrosine kinase-1 (sFlt-1) and endothelin-1 (ET-1) have been implicated in the pathogenesis of preeclampsia (PE), the mechanisms whereby increased sFlt-1 leads to enhanced ET-1 production and hypertension remain unclear. It is well documented that nitric oxide (NO) production is reduced in PE; however, whether a reduction in NO synthesis plays a role in increasing ET-1 and blood pressure in response to chronic increases in plasma sFlt-1 remains unclear. The purpose of this study was to determine the role of reduced NO synthesis in the increase in blood pressure and ET-1 in response to sFlt-1 in pregnant rats. sFlt-1 was infused into normal pregnant (NP) Sprague-Dawley rats (3.7 ?g·kg?1·day?1 for 6 days beginning on day 13 of gestation) treated with the NO synthase inhibitor NG-nitro-l-arginine methyl ester (100 mg/l for 4 days) or supplemented with 2% l-Arg (in drinking water for 6 days beginning on day 15 of gestation). Infusion of sFlt-1 into NP rats significantly elevated mean arterial pressure compared with control NP rats: 116 ± 2 vs. 103 ± 1 mmHg (P < 0.05). NO synthase inhibition had no effect on the blood pressure response in sFlt-1 hypertensive pregnant rats (121 ± 3 vs. 116 ± 2 mmHg), while it significantly increased mean arterial pressure in NP rats (128 ± 4 mmHg, P < 0.05). In addition, NO production was reduced ?70% in isolated glomeruli from sFlt-1 hypertensive pregnant rats compared with NP rats (P < 0.05). Furthermore, prepro-ET-1 in the renal cortex was increased ?3.5-fold in sFlt-1 hypertensive pregnant rats compared with NP rats. Supplementation with l-Arg decreased the sFlt-1 hypertension (109 ± 3 mmHg, P < 0.05) but had no effect on the blood pressure response in NP rats (109 ± 3 mmHg) and abolished the enhanced sFlt-1-induced renal cortical prepro-ET expression. In conclusion, a reduction in NO synthesis may play an important role in the enhanced ET-1 production in response to sFlt-1 hypertension in pregnant rats. PMID:22071155

Murphy, Sydney R.; LaMarca, Babbette; Cockrell, Kathy; Arany, Marietta



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


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

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



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

PubMed Central

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-?, 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-?, 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

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



Extracts from rabbit skin inflamed by the vaccinia virus attenuate bupivacaine-induced spinal neurotoxicity in pregnant rats?  

PubMed Central

Extracts from rabbit skin inflamed by the vaccinia virus can relieve pain and promote repair of nerve injury. The present study intraperitoneally injected extracts from rabbit skin inflamed by the vaccinia virus for 3 and 4 days prior to and following intrathecal injection of bupivacaine into pregnant rats. The pain threshold test after bupivacaine injection showed that the maximum possible effect of tail-flick latency peaked 1 day after intrathecal injection of bupivacaine in the extract-pretreatment group, and gradually decreased, while the maximum possible effect in the bupivacaine group continued to increase after intrathecal injection of bupivacaine. Histological observation showed that after 4 days of intrathecal injection of bupivacaine, the number of shrunken, vacuolated, apoptotic and caspase-9-positive cells in the dorsal root ganglion in the extract-pretreatment group was significantly reduced compared with the bupivacaine group. These findings indicate that extracts from rabbit skin inflamed by the vaccinia virus can attenuate neurotoxicity induced by intrathecal injection of bupivacaine in pregnant rats, possibly by inhibiting caspase-9 protein expression and suppressing nerve cell apoptosis.

Cui, Rui; Xu, Shiyuan; Wang, Liang; Lei, Hongyi; Cai, Qingxiang; Zhang, Hongfei; Wang, Dongmei




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...


Nicotine-Induced Antinociception in Male and Female Sprague-Dawley Rats.  

National Technical Information Service (NTIS)

Nicotine is a key pharmacologically-active ingredient in tobacco that has cognitive and behavioral effects, including antinociception. The present research examined effects of nicotine as an antinociceptive agent in male and female Sprague-Dawley rats. Ni...

N. Apatov



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


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

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



Estrogen modulates central and peripheral responses to cold in female rats  

Microsoft Academic Search

The aim of this study was to determine whether estrogen modulates central and peripheral responses to cold in female rats.\\u000a In ovariectomized female rats with and without administered estrogen [E2 (+) and E2 (?), respectively], the counts of cFos-immunoreactive cells in the medial preoptic nucleus (MPO) and dorsomedial hypothalamic\\u000a nucleus (DMH) in the hypothalamus were greater in the E2 (+)

Yuki Uchida; Masumi Kano; Saki Yasuhara; Akiko Kobayashi; Ken Tokizawa; Kei Nagashima



Heightened Cocaine and Food Self-Administration in Female Rats with Neonatal Isolation Experience  

Microsoft Academic Search

Previously, we demonstrated that the early life stress of neonatal isolation facilitates acquisition of cocaine and food self-administration in adult female rats. We now test whether it enhances responding for these reinforcers after operant performance is established. Adult female rats were derived from litters that were either subjected to neonatal isolation (1 h\\/day isolation; postnatal days 2–9) or were nonhandled

Therese A Kosten; Xiang Yang Zhang; Priscilla Kehoe



Sudden Darkness Induces a High Activity-Low Anxiety State in Male and Female Rats  

Microsoft Academic Search

NASELLO, A. G., C. MACHADO, J. F. BASTOS AND L. F. FELICIO.Sudden darkness induces a high activity-low anxiety state in male and female rats.PHYSIOL BEHAV 63(3) 451–454, 1998.—The effects of sudden darkness on spontaneous motor activity in an open field and performance in an elevated plus-maze (EPM) were assessed in adult male and female rats. In the open field test,

Antonia G Nasello; Cybelle Machado; Jaime F Bastos; Luciano F Felicio



Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in male and female rats  

PubMed Central

Significant sex differences have been demonstrated in clinical and preclinical studies of cocaine addiction, with some of the most consistent differences noted in regards to the role of stress and craving. The current study examined stress-induced reinstatement of cocaine seeking in male and female rats in an animal model of relapse using corticotropin-releasing factor (CRF) administration. Both male and female rats demonstrated increased cocaine seeking in response to CRF. CRF-induced reinstatement was highly variable across both male and female rats, and further analysis revealed a subpopulation that was particularly sensitive to CRF (high responders). Female high responders displayed significantly increased responding to CRF compared to males. Individual differences in stress responsivity could thus contribute to the likelihood of relapse, with females showing greater heterogeneity to stress-induced relapse. PMID:21889522

Buffalari, Deanne M.; Baldwin, Chelsey K.; Feltenstein, Matthew W.; See, Ronald E.



Glomerular capillary network of cortical nephrons is reduced in male but not in female aging rats.  


The gender differences in the age-related changes of glomerular structures were determined in 10- and 30-month-old rats. In adult animals, glomerular volume, urinary space, capillary lumen area and mesangial domains of deep and superficial nephrons were larger in males than in females. Glomerular hypertrophy was evidenced with age in both males and females. This hypertrophy was greater in female (+70%) than in male (+20%) rats. Age-related hypertrophy concerned equally the urinary space and the glomerular tuft. The mesangial domain, however, increased more markedly than glomerular volume (+400%). As a result, the ratio of mesangial domain to glomerular section area was more than doubled between 10 and 30 months. In females, the age-related renal hypertrophy was associated with a constant total capillary lumen area in cortical nephrons. In contrast, the total capillary lumen area of male rats was reduced by 20% in superficial glomeruli and by 36% in deep glomeruli between 10 and 30 months. These morphological changes are in good agreement with the maintained glomerular filtration rate reported in old female rats and the decrease in renal blood flow and filtration rate reported in male rats. They suggest that the aging process does not similarly affect the vascular system of the kidney of male and female rats, although their mean blood pressure was comparable. PMID:8910256

Francois, V; Heudes, D; Bariety, J; Bruneval, P; Corman, B



Female-induced sexual arousal in male mice and rats: behavioral and testosterone response.  


Exposure of a male mouse to a female mouse separated from it by a holed partition induced specific behavior and an increase in blood testosterone in the male. The male made more approaches to the partition and spent more time at it. The time spent by the male mouse over the first 10 min at the partition, behind which an estrus female was placed, was increased sixfold compared to the time spent by a male mouse exposed to the vacant neighboring compartment; and 1.5-fold compared to that spent by a male mouse exposed to a nonreceptive female or a male. Increased blood testosterone level was detected at 20 min of exposure to a receptive female in winter and at 40 min in summer. No variation in blood testosterone levels in the male mouse exposed to a nonreceptive female or a male was observed. Similar response to a receptive female placed in the neighboring compartment was shown in a male rat. The time spent by the male rat at the partition was 12 times higher when there was an estrus female behind it than in control. Blood testosterone in the male rat increased in response to a female rat and did not change in response to a male rat indicating female-induced motivation. It was concluded that the partition time might serve as a quantitative measure of sexual motivation in the males and that the model of female-induced sexual arousal used was suitable for studying both motivational and hormonal components of sexual arousal in male mice and rats. PMID:15555495

Amstislavskaya, Tamara G; Popova, Nina K



Effects of early rearing conditions on cognitive performance in prepubescent male and female rats  

Microsoft Academic Search

The interactions between a mother and her offspring during early postnatal life impact cognitive development in altricial species. The current study examined the influence of postnatal rearing conditions on subsequent cognitive functioning in male and female Long-Evans rats prior to puberty. Maternal conditions were manipulated by repeated separations of rat pups from their dams on postnatal days 2 though 14.

Kathryn A. Frankola; Arianna L. Flora; Amanda K. Torres; Elin M. Grissom; Stacy Overstreet; Gary P. Dohanich



Effect of Molybdenum Supplementation on Hepatic Trace Elements and Enzymes of Female Rats1  

Microsoft Academic Search

The effects of molybdenum (Ato) supple mentation in the drinkingwater at the levels of 0.1, 0.5. 1.0, 2.0, 5.0 and 10.0 mg\\/l on the hepatic trace element concentrations and enzyme activities of female Sprague- Dawley rats were studied. The mean hepatic Mo concen trationincreased significantlyin the rats supplemented with 0.1 mg Mo\\/Ias compared to the nonsupplemented rats, but a furthersignificant



Multigenerational Exposure to Dietary Nonylphenol has No Severe Effects on Spatial Learning in Female Rats  

Microsoft Academic Search

Nonylphenol is a common intermediate in the production of many consumer compounds and reportedly acts as an estrogen mimic. Because estrogen affects the spatial learning and memory in rats, the effects of nonylphenol exposure on the performance of female rats in the Morris water maze were investigated. Here, Sprague–Dawley rats (F0) consumed soy-free diets containing 0, 25, 200 or 750ppm

Katherine M Flynn; Retha R Newbold; Sherry A Ferguson



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

Microsoft Academic Search

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

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



The role of odors and ultrasonic vocalizations in female rat (Rattus norvegicus) partner choice.  


Intrasexual competition for access to a female mate is believed to be unusual in wild male rats, which suggests that female choosiness could be more important. It has been shown that females spend more time with one male than with others when tested in a multiple partner paradigm. The male of first entry is visited most. The role of ultrasonic vocalizations (USVs) and male odors in the female rat's initial choice to approach one male instead of another are studied in these experiments. In Experiment 1, female rats were allowed to choose between 3 different intact males, whereas in Experiment 2, females could choose between a devocalized male and 2 intact males. Both experiments started with a 15-min period with inaccessible males followed by a 15-min period with accessible males in which the female could copulate with the males of her choice. The results showed that female rats spent more time with the male of first entry over the males visited subsequently. No differences were found in USV subtype patterns emitted by the different males or the time spent sniffing the different males in the period preceding the choice. In addition, the results of Experiment 2 showed that females visited the silent males as much as the vocalizing males. Thus, the present experiments did not offer any evidence suggesting that USVs or individual differences in male odors play any role in female mate choice. Other factors that were not investigated in this study might be involved in female rat mate selection, but it should also be considered that mate selection could be random. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:25133463

Snoeren, Eelke M S; Agmo, Anders



Pharmacokinetics of letrozole in male and female rats: influence of complexation with hydroxybutenyl-beta cyclodextrin.  


Cyclodextrins (CDs) are one of the most successful solutions to the problem of poor drug solubility. In this study, we examined the in-vitro effects of three CDs on the solubility of letrozole, a breast cancer drug that is practically insoluble in water. The most promising, hydroxybutenyl-beta-cyclodextrin (HBenbetaCD), was used for in-vivo studies in male and female Sprague-Dawley rats. Letrozole is a drug with dramatic gender-based differences in pharmacokinetics. For example, the terminal half-life (t(1/2)) of letrozole following intravenous administration in male rats was 11.5 +/- 1.8 h (n = 3), while in female rats it was 42.3 +/- 2.9 h (n = 3). HBenbetaCD increased the solubility and enhanced the dissolution rate of letrozole. Complexation of letrozole with HBenbetaCD improved oral absorption in male rats and maximized absorption in female rats. Regardless of gender, the presence of HBenbetaCD in the formulation increased the in-vivo rate of absorption. When administered in a capsule formulation with letrozole, HBenbetaCD resulted in a higher C(max) (61% in male rats, 42% in female), shorter T(max) values (8.4 to 6.3 h in male, 16.4 h to 5.4 h in female) and increased absolute oral bioavailability (46 +/- 2 vs 38 +/- 3 in male, 101 +/- 3 vs 95 +/- 2 in female). Thus, solubility limits both rate and extent of letrozole absorption in male rats, but limits only the rate of absorption in female rats. PMID:17637172

Wempe, Michael F; Buchanan, Charles M; Buchanan, Norma L; Edgar, Kevin J; Hanley, Gregory A; Ramsey, Michael G; Skotty, Jennifer S; Rice, Peter J



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

SciTech Connect

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.

Lewis, C.G.; Fields, M.; Beal, T. (Dept. of Agriculture, Beltsville, MD (USA))



Cues used by male and female hooded rats for locating a brightness change  

Microsoft Academic Search

Entries of and time spent in a novel Y-maze arm that had changed from white (during acquisition trials) to black (during retention trials) were investigated in male and female Long-Evans hooded rats after the apparatus had been horizontally rotated through 180° or left undisturbed. Maze rotation reduced responsiveness to this arm in males but not in females. When each arm

Robert N. Hughes; Michelle E. Maginnity



Responses of sexually experienced and naive male rats to cues from receptive vs. nonreceptive females  

Microsoft Academic Search

In order to learn more about their reaction to the female sex attractant, 61 male Norway rats were given two-choice preference\\u000a tests in which they reacted to cues from receptive vs. non-receptive females. In the first experiment, 16 heterosexually experienced\\u000a males showed a reliable preference (p < .01) for receptive over nonreceptive anesthetized females, as did 15 naive males (p

Michael R. Landauer; Robert E. Wiese; W. J. Carr



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

PubMed Central

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

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



Steroid regulation of gonadotropins in genetically hypoprolactinemic females (IPL nude rats).  


IPL nude females present an absence of lactation with hypoprolactinemia. While males present a slight but significant decrease in serum testosterone and gonadotropins, females show normal values of estradiol, progesterone, LH and FSH during all estrus cycle stages. In this work, we observed that the postovariectomy rise of LH and FSH was significantly lower in the IPL nude females. We studied also the effect of acute (1 injection of 25 micrograms/rat E2Bz) or long-term (E2Bz capsule for 8 days) estradiol benzoate (E2Bz) treatment, with or without progesterone injection (5 mg/rat) in ovariectomized (OVX) IPL and normal females. The sensitivity of gonadotropins to E2 negative feedback is decreased in the IPL nude rats, result in agreement with previous reports and which could be linked to both hypoprolactinemia and decreased beta-endorphin observed in the IPL nude rat. The responsiveness of LH to LHRH was also tested in OVX and OVX + E2Bz or OVX + E2B + P treated. In OVX females responsiveness of LH to LHRH was similar in IPL nude to that of normal females. However, LH responsiveness in acute and long-term steroid-treated OVX IPL nude was significantly depressed. Since the mechanism whereby PRL interacts with steroids to modify gonadotropin secretion is still unexplained, IPL nude rat could be a good model to study it. PMID:3084874

Cohen, H; Sabbagh, I; Guillaumot, P; Bertrand, J



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


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

Siegal, Nora; Dow-Edwards, Diana



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

PubMed Central

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

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




PubMed Central

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 [14C]-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, NMR and FT-IR 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 [14C]-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. PMID:18692083

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



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


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

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




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...


Physiologically based pharmacokinetic modeling of the pregnant rat: A multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid. (Reannouncement with new availability information). Interim report, April 1986-December 1988  

SciTech Connect

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 + 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0-045 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from Pregnancy, Physiologically Based Pharmacokinetic Modeling, Toxicology, Trichloroethylene, Trichloroacetic Acid.

Fisher, J.W.; Whittaker, T.A.; Taylor, D.H.; Clewell, H.J.; Andersen, M.E.



Characterization of the vasculature supplying the genital tissues in female rats  

PubMed Central

Introduction The internal pudendal arteries are the key resistance vessels controlling the peripheral circulatory component of sexual responses in both male and females. Previous studies in the male rat demonstrated that this vessel has markedly heightened susceptibility to vascular damage compared to other vessels in the body. Evidence suggests that the female may also be susceptible to vascular pathologies contributing to sexual dysfunction. Aim To characterize the anatomical, morphological and functional properties of the pudendal artery in female rats. Methods The pelvic arteries in young Sprague-Dawley female rats were dissected to generate a composite representation of the vascular gross anatomy. Morphometry was performed on perfusion-fixed pudendal arteries whereas others were mounted in a wire myograph to assess responses to vasoactive drugs. These measures were contrasted with a previous study examining male rats. Main Outcomes Measured Gross anatomy, lumen diameter, wall thickness, cross sectional area and contractile responses in the internal pudendal artery. Results The gross anatomy of the pudendal artery in female rats appears to parallel that found in male rats; acting as the primary feeder vessel of the clitoral, labial and vaginal tissue. Compared to the male rat, the female pudendal artery has a smaller lumen diameter (169±5.7 vs 303±13.8um), wall thickness (14±0.7 vs 47±2.2um) and cross-sectional area (8±0.4 vs 52±3.4×103 ?m2). These structural differences also translate into a decreased contractile capacity of the pudendal arteries from female rats vs. males (8.1±2.7 vs 20±1.4mN). Conclusions Although the gross anatomical features of the vasculature tree supplying the genital tissue in male and female rats appears to have similarities, the tissue specific properties of the vessel itself has a very different structure-function balance. We hypothesize this discordance likely reflects the very different sex-specific roles of this vessel in regulating blood flow during arousal. PMID:22023507

Hannan, Johanna L.; Cheung, Geoffrey L.; Blaser, Mark C.; Pang, Judith J.; Pang, Stephen C.; Webb, R. Clinton; Adams, Michael A.



Early onset of reproductive function in female rats treated with a high-fat diet.  


Puberty onset in mammals is tightly coupled to the animal's nutritional and metabolic state. In the present study, we evaluated the effects of a high-fat diet on leptin and adiponectin levels, leptin mRNA expression and puberty onset in female rats. On day 21, female rats were divided into 2 groups, normal food (NF) and high-fat food (HF). The HF group showed a significantly earlier (P<0.001) date of vaginal opening and lower body weight (P<0.001) than the NF group. The rats fed the HF food had a significantly heavier uterus (P<0.05) than those fed the NF food, whereas the serum leptin and adiponectin levels and leptin mRNA expression were not significantly different between the NF and HF groups. We speculate that the fat-induced nutritional imbalance in young females may lead to neuroendocrine dysfunction during adolescence. PMID:23154420

Fungfuang, Wirasak; Nakao, Nobuhiko; Nakada, Tomoaki; Yokosuka, Makoto; Saito, Toru R



Incentive salience of cocaine across the postpartum period of the female rat  

PubMed Central

Rationale–Objectives Our prior conditioned place preference (CPP) work demonstrates that late (day16) postpartum female rats consistently prefer cocaine- over pup-associated chambers, whereas far fewer early postpartum (day8) females prefer the cocaine-associated chamber. The present study examines early and late postpartum females’ preference for a cocaine-associated chamber when contrasted with a chamber associated with saline (rather than pups). Materials and methods Postpartum females were tested for conditioned preference for chambers associated with cocaine (10 mg/kg subcutaneous (SC) or 0.5, 5, 10, or 20 mg/kg intraperitoneal (IP) injections) versus saline; preferences of virgin female and male rats for select cocaine stimuli (10mg/kg SC or IP) were also tested. Locomotion was recorded during CPP conditioning and testing. Results Early and late postpartum females expressed strikingly similar preference for the cocaine-associated chamber across all administration routes and doses. IP cocaine produced an orderly, inverted U-shaped dose-preference curve, with preference peaking at the 5 mg/kg dose (83% of females). While many postpartum females preferred 10mg/kg cocaine administered either SC or IP, both virgin females and males expressed strong aversion to SC cocaine and, while virgin females strongly preferred IP cocaine, males remained relatively indifferent. Across 10mg/kg IP cocaine-conditioning sessions, locomotor sensitization occurred exclusively in cocaine- but not saline-preferring postpartum females. Locomotor rate was lower in preferred versus nonpreferred chambers at CPP test. Conclusions Early and late postpartum females may be equally and uniquely susceptible to sampling and/or abuse of modestly salient doses of cocaine (10mg/kg SC; 5mg/kg IP) compared to virgin females and/or males. PMID:18470696

Seip, Katharine M.; Pereira, Mariana; Wansaw, Michael P.; Reiss, Jenny I.; Dziopa, Eugenia I.; Morrell, Joan I.



Angiotensin type 2 receptor stimulation increases renal function in female, but not male, spontaneously hypertensive rats.  


Accumulating evidence suggests that the protective pathways of the renin-angiotensin system are enhanced in women, including the angiotensin type 2 receptor (AT2R), which mediates vasodilatory and natriuretic effects. To provide insight into the sex-specific ability of pharmacological AT2R stimulation to modulate renal function in hypertension, we examined the influence of the AT2R agonist, compound 21 (100-300 ng/kg per minute), on renal function in 18- to 19-week-old anesthetized male and female spontaneously hypertensive rats. AT2R stimulation significantly increased renal blood flow in female hypertensive rats (PTreatment<0.001), without influencing arterial pressure. For example, at 300 ng/kg per minute of compound 21, renal blood flow increased by 14.3±1.8% from baseline. Furthermore, at 300 ng/kg per minute of compound 21, a significant increase in urinary sodium excretion was observed in female hypertensive rats (+180±59% from baseline; P<0.05 versus vehicle-treated rats). This was seen in the absence of any major change in glomerular filtration rate, indicating that the natriuretic effects of AT2R stimulation were likely the result of altered renal tubular function. Conversely, we did not observe any significant effect of AT2R stimulation on renal hemodynamic or excretory function in male hypertensive rats. Finally, gene expression studies confirmed greater renal AT2R expression in female than in male hypertensive rats. Taken together, acute AT2R stimulation enhanced renal vasodilatation and sodium excretion without concomitant alterations in glomerular filtration rate in female hypertensive rats. Chronic studies of AT2R agonist therapy on renal function and arterial pressure in hypertensive states are now required to establish the suitability of AT2R as a therapeutic target for cardiovascular disease, particularly in women. PMID:24842923

Hilliard, Lucinda M; Chow, Charis L E; Mirabito, Katrina M; Steckelings, U Muscha; Unger, Thomas; Widdop, Robert E; Denton, Kate M



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

NASA Astrophysics Data System (ADS)

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.

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


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


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

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



Effects of nicotine on bone mass and strength in aged female rats  

Microsoft Academic Search

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg\\/kg\\/day) or high dose

M. P. Akhter; U. T. Iwaniec; G. R. Haynatzki; Y. K. Fung; D. M. Cullen; R. R. Recker



Acute stress impairs spatial memory in male but not female rats: influence of estrous cycle  

Microsoft Academic Search

We investigated how sex and estrous cycle influenced spatial recognition memory in the Y-maze after exposure to acute restraint stress. In Experiment 1, intact male and female rats were restrained for 1 h and then 2 h after the start of restraint, rats were trained on the Y-maze. After a 4 h delay, hippocampal-dependent spatial recognition memory was assessed. Acute

Cheryl D Conrad; Jamie L Jackson; Lindsay Wieczorek; Sarah E Baran; James S Harman; Ryan L Wright; Donna L Korol



Lateralization of Brain Trauma in Female Wistar Rats Determines the Immune and Neurological Status of Offspring  

Microsoft Academic Search

Unilateral trauma to the sensorimotor cortex in ambidextrous maternal female rats decreased the resistance of their offspring, as indicated by a reduction in the functional activity of natural killer cells. Offspring rats showed T-cell immunodeficiency regardless of the lateralization of the trauma in their mothers; this was more severe after right-sided trauma (both mature and immature T-lymphocytes were affected). The

T. V. Avaliani; R. P. Ogurtsov; V. P. Puzyreva; O. R. Seryakova



Effect of Estradiol and Progesterone Treatment on Carbohydrate Metabolizing Enzymes in Tissues of Aging Female Rats  

Microsoft Academic Search

The aim of this study was to determine the effect of administration of estradiol (E2), progesterone (P4), and combination of estradiol and progesterone (EP) in aging female rats. The changes in the activities of hexokinase (HK), glucose-6-phosphatase (G6P?tase) and glucose-6-phosphate dehydrogenase (G6PDH) enzymes, and in protein levels in tissues of rats namely brain (cerebral hemisphere), heart, liver, kidney and uterus

K. Moorthy; Umesh C. S. Yadav; M. R. Siddiqui; D. Sharma; S. F. Basir; N. Z. Baquer



The effects of atrazine on the sexual maturation of female rats.  


The mammalian hazard assessment of the herbicide atrazine (ATR) has focused on the induction of mammary tumors and accelerated reproductive aging of adult rats, and the relationship of these effects to the inhibition of leutinizing hormone (LH) release from the pituitary, an effect itself caused by inhibition of GnRH signaling by the adult rat hypothalamus. In earlier studies, Laws et al. (Toxicol. Sci., 58, 366-376, 2000) demonstrated a delay in female rat sexual maturation induced by ATR, effects that could equally have been caused by inhibition of hypothalamic GnRH release. The present studies were designed to compare the doses that interfere with GnRH signaling seen in previous studies in adult Sprague-Dawley (SD) rats (LH surge suppression) with doses that impair GnRH signaling in peripubertal rats, as indicated by delayed sexual maturation. The studies evaluated the effects of ATR treatment on the timing of uterine growth and vaginal opening (VO) in peripubertal female Wistar (Alderley Park, AP) and SD rats. Doses of 10, 30, and 100 mg/kg ATR were administered daily from postnatal day (pnd) 21 to up to pnd 46. Determinations of uterine weight were made at pnd 30, 33, 43 (AP), and 46 (SD) and the timing of VO was also assessed in the last two of these experiments. The centrally acting GnRH antagonist Antarelix (ANT) was used as a positive control agent as it has previously been shown to prevent uterine growth and to delay VO in peripubertal AP rats. Uterine growth and VO were completely prevented in AP rats exposed to ANT. Uterine growth was delayed at pnd 30 and 33 in AP rats exposed to 100 mg/kg ATR, but this growth inhibition had been overcome by pnd 43. VO was significantly delayed in AP rats for the 100 mg/kg ATR dose. By pnd 46, VO was significantly delayed in SD rats exposed to both 30 and 100 mg/kg ATR, but uterine weights were unaffected by that time (as for AP rats). It is concluded that the no-effect level for the effects of ATR on sexually immature rats (10 mg/kg in SD; 30 mg/kg AP) is approximately the same as reported previously by Laws et al. in peripubertal Wistar rats (25 mg/kg). However, the no-effect level in peripubertal female SD rats is nearly an order of magnitude greater than the no-observed effect level observed in female SD rats fed ATR for 6 months (1.8 mg/kg) where LH suppression was used as an indicator of effect on the pituitary/hypothalamic axis (USEPA, Atrazine-DACT Fourth Report of the Hazard Identification and Review Committee, April 5, 2002). These results support the conclusion that the pituitary/hypothalamic axis in peripubertal female SD rats is less sensitive than that in adult female SD rats. PMID:12202059

Ashby, J; Tinwell, H; Stevens, J; Pastoor, T; Breckenridge, C B



Long lasting alteration in REM sleep of female rats submitted to long maternal separation.  


Early adverse experiences represent risk factors for the development of anxiety and mood disorders. Maternal separation can induce biobehavioral alterations in male rodents similar to those seen in depressed humans, such as hyperresponsiveness to stress and sleep disturbances. Nonetheless, no study has yet explored the effects of early life events on the relationship between stress and sleep in female rats. Whole litters of Wistar rats were submitted to brief- or long maternal separations (15 [BMS] or 180 min/day [LMS], from postnatal days 2-14) or kept undisturbed with their mothers (CTL). When adults, female rats were sleep-recorded for 22 h before (baseline) and after a 1 h exposure to cold stress (post-stress). Additional subsets of animals were sacrificed before, 1 or 3 h after the stressor for plasma corticosterone determination. No differences in baseline sleep were observed among the groups. Female rats submitted to LMS exhibited a significant increase of REM sleep on the night following a 1 h exposure to cold stress, whereas the sleep of BMS rats was barely altered by stress. All groups exhibited similar basal and stress-induced corticosterone levels. The present results are compared to a previous study performed in male rats, and corroborate that manipulations applied during infancy modify the expression of stress-induced sleep rebound. PMID:17997461

Tiba, Paula Ayako; Tufik, Sergio; Suchecki, Deborah



Restoration of the LH surge and ovulation by insulin in alloxan-diabetic immature rats treated with pregnant mare's serum gonadotrophin.  


Immature alloxan-diabetic rats injected with pregnant mare's serum gonadotropin (PMSG) do not ovulate and the LH surge is absent. In the present studies we have examined the effects of several insulin treatments on the LH surge and ovulation in alloxan-diabetic rats. Rats were male diabetic by injection of alloxan on day 24 of age. Only those rats with fasting blood glucose concentrations exceeding 180 mg/100 ml on day 237 were considered diabetic. PMSG was injected on day 30. Rats received insulin either by injection (2, 3, 4 or 6 IU/100 g/day); Ultralente B.I.D.) or by subcutaneous implants (Alzet osmotic minipumps; 1.8 or 2.4 IU/day). None of the diabetic rats without insulin treatment ovulated. Some of the animals in each insulin treatment group ovulated, however, the percentage of animals ovulating was highly variable from experiment to experiment when the insulin was given by injection. When insulin was administered by osmotic minipump, the results were more consistent, with at least 60% of the rats ovulating in each experiment. LH surges were found on the afternoon of presumed pro-oestrus (day 32) in diabetic insulin-treated rats which ovulated. In confirmation of previous results, rats without insulin treatment did not have LH surges. Although the site of insulin action has not been determined, these data indicate that the LH surge mechanism in the immature PMSG-treated rat is insulin-dependent. PMID:7051719

Kirchick, H J; Keyes, P L; Frye, B E



Effect of Ovariectomy on Blood Pressure and Venous Tone in Female Spontaneously Hypertensive Rats  

Microsoft Academic Search

BackgroundVenous capacitance plays an important role in circulatory homeostasis. A number of reports have suggested an effect of estrogen on venous function. This study tested the hypothesis that ovariectomy would increase venous tone in the female spontaneously hypertensive rat (SHR) via autonomic mechanisms.MethodsFive-week-old female SHR were subjected to sham operation (Sham) or ovariectomy (OVX). At 10 weeks of age, the

Douglas S. Martin; Rebecca Redetzke; Erin Vogel; Connie Mark; Kathleen M. Eyster



Perinatal and chronic hypothyroidism impair behavioural development in male and female rats  

Microsoft Academic Search

Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the present study, behavioural effects of perinatal and chronic hypothyroidism were assessed during development in both male and female offspring

N. van Wijk; E. Rijntjes; Heijning van de B. J



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

PubMed Central

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

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



Selective retrieving by maternal and nonmaternal female rats.  


An earler study reported that nonpregnant females do not selectively retrieve a pup over a small plastic toy, while lactating mothers retrieve the pup more often than the toy. The present study was undertaken to see whether nonpregnant females made maternal by exposure to pups would act more like nonmaternal females than lactating mothers. The behavior toward a pup and a toy was studied in 1 group of nonmaternal virgins, 2 groups of maternal virgins, and 1 group of lactating mothers, during 7 daily 5-min. tests. Measures of the frequency and duration of retrieving-related behavior and analysis of behavioral sequences in relation to the pup and toy showed that pup-induced maternal virgins more closely resemble the lactating mothers than nonmaternal virgins. PMID:1167224

Rosenblatt, J S



[Mammary tumors in female rats with combined exposure to nitrosoethylurea and sex hormones].  


Transplacental treatment with sinestrol and testosterone-propionate reduces the incidence of spontaneous benign mammary tumors in rats. Treatment of immature female rats with nitrosoethylurea is followed by an earlier development of mammary fibroadenomas. A combined treatment with testosterone-propionate and nitrosoethylurea increases the incidence of mammary fibroadenoma and decreases its mean latent period. Fibroadenoma induction is accelerated by treating adult rats with nitrosoethylurea alone, while combined treatment induces primary mammary tumors at an earlier stage. The morphology of tumors induced by different schemes of combined treatment remains identical. PMID:7324402

Ird, E A; Smirnova, I O



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


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

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



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

PubMed Central

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

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



Effects of obesity on bone mass and quality in ovariectomized female Zucker rats.  


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 (Lepr(fa/fa)) Zucker rats and their heterozygous lean controls (Lepr(fa/+)) 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

Feresin, Rafaela G; Johnson, Sarah A; Elam, Marcus L; Jo, Edward; Arjmandi, Bahram H; Hakkak, Reza



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


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

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



Effect of Age on the Accumulation of (131I)Triiodothyronine in Male and Female Rat Brains and Other Tissues.  

National Technical Information Service (NTIS)

Accumulation of (131I)triiodothyronine(T3) by the brain and other tissues in young male and female adult (3 months old) rats was compared with that occurring in old (17 and 24 months) male and female rats. Brain tissues (cerebellum, cerebral white matter,...

D. H. Ford, R. K. Rhines



Effects of gonadal hormones and persistent pain on non-spatial working memory in male and female rats  

Microsoft Academic Search

There are indications of a modulatory role carried out by gonadal hormones and pain in cognitive functions. We have examined this issue in male and female rats by assessing the impact of gonadectomy and persistent pain on the object recognition test. Intact and gonadectomized male and female rats were exposed to an open field (15 min) in which three objects

Ilaria Ceccarelli; Andrea Scaramuzzino; Anna Maria Aloisi




Microsoft Academic Search

Introduction: Bladder histology and measures of maximal bladder pressure and maximal bladder volume during urinary loss in female rats submitted to bladder reconstruction with a myoperitoneal flap of rectus abdominis muscle were studied. Materials and Methods: Fifty female adult Wistar rats were studied, separated in 5 groups: Group 1 (immediate): submitted to laparotomy, cystostomy, and cystometry; Group 2 (sham): submit-



Effects of crude root extract of Polygonum hydropiper on estrous cycle and induction of reversible sterility in female albino rat  

Microsoft Academic Search

Summary Polygonum hydropiper is a wild plant found in Assam, a North-Eastern province of India. Tradition prevails among the folk women of Assam to use the root of this herb for fertility control. In the present investigation crude methanolic extract of root of this plant was tested for anti-fertility property in female albino rat. Adult cycling female rats were administered

Hazarika A; Sarma HN


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

NASA Technical Reports Server (NTRS)

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.

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



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


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

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



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


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

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



Effects of environmental conditions on food consumption in female and male rats  

Microsoft Academic Search

The present experiment examined food and water consumption under different housing conditions in 20 female and 20 male Wistar rats. Food and water consumption were measured for 6 h a day following an 18-h same-sex crowded or individual housing period for each of 6 days. All subjects were individually housed during the 6-h measurement period and had access to food

Kelly J. Brown; Neil E. Grunberg



The effects of iridium on the renal function of female Wistar rats  

Microsoft Academic Search

Despite the widespread use of iridium (Ir) in catalytic converters for improved capacity for reducing carbon monoxide (CO), hydrocarbon (HC) and nitrogen oxide (NOx) emissions, there is a lack of studies that have assessed possible toxicological hazards of exposure to Ir. The present investigation indicates that female Wistar rats exposed to Ir in the drinking water for 90 days displayed

Ivo Iavicoli; Luca Fontana; Alessandro Marinaccio; Alessandro Alimonti; Anna Pino; Antonio Bergamaschi; Edward J. Calabrese



Effects of Altered Food Intake during Pubertal Development in Male and Female Wistar Rats  

Microsoft Academic Search

The U.S. Environmental Protection Agency 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 nonspecific reduction in body weight (BWT) during the expo- sure period may

Susan C. Laws; Tammy E. Stoker; Janet M. Ferrell; Michelle G. Hotchkiss; Ralph L. Cooper



Effect of Estrogen on the Formation of Struvite Calculi in Female Rats  

Microsoft Academic Search

The administration of 1 mg estradiol every other week for 12 weeks to female rats resulted in a high incidence (about 50%) of bladder stones. Most calculi were struvite, suggesting the predisposition to urinary tract infection. Enterobacteria, staphylococcus and streptococcus were identified as infecting organisms. Metaplasia of the transitional bladder epithelium by estrogen to a stratified or pseudostratified columnar epithelium

Kazutaka Matsushita




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...


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

ERIC Educational Resources Information Center

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…

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



Chorda tympani nerve transection alters linoleic acid taste discrimination by male and female rats  

E-print Network

Chorda tympani nerve transection alters linoleic acid taste discrimination by male and female rats in revised form 17 May 2006; accepted 8 June 2006 Abstract Taste is intimately associated with food choice, yet little is known about the role of taste in preferences for dietary fat, a major component of many

Hull, Elaine



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...


A possible physiological role of taurine in the adult female rat liver  

E-print Network

intraperitoneally into the lactating female rat, is secreted in the milk and then transferred to the pups (Sturman were immediately removed, weighed, homogenized in cold distilled water (w/v = 1 g/3 ml), and the homogenate was treated as described in the above method. Expression of results. - Dietary taurine

Paris-Sud XI, Université de


Paradoxical effects of chronic corticosterone on forced swim behaviours in aged male and female rats  

Microsoft Academic Search

The effects of chronically administered corticosterone on forced swim test and open field test behaviours were explored in aged male and female rats. Though corticosterone has typically been associated with depressive behaviours, recent data have suggested a putative antidepressive effect of corticosterone. The current study used the forced swim test as a model of antidepressant efficacy in order to explore

Lori A. Brotto; Boris B. Gorzalka; Alasdair M. Barr



Prenatal morphine exposure differentially alters learning and memory in male and female rats  

Microsoft Academic Search

The present study tested the hypothesis that exposure to morphine on prenatal days 11–18 impairs performance on tasks requiring learning and memory in adult male and female rats. In Experiment 1, a symmetrical maze was used to measure learning. In Experiment 2, an eight-arm radial maze was used to assess working spatial memory. The results of Experiment 1 demonstrated that

Romana Šlamberová; Cheryl J Schindler; Marie Pometlová; Claudia Urkuti; Jennifer A Purow-Sokol; Ilona Vathy



Estradiol suppresses recovery of REM sleep following sleep deprivation in ovariectomized female rats  

Microsoft Academic Search

Sleep complaints such as insufficient sleep and insomnia are twice as prevalent in women. Symptoms of sleep disruption are often coincident with changes in the gonadal hormone profile across a women's lifespan. Data from a number of different species, including humans, non-human primates and rodents strongly implicate a role for gonadal hormones in the modulation of sleep. In female rats,

Michael D. Schwartz; Jessica A. Mong



Acute Oral Toxicity of DMSO (Dimethyl Sulfoxide) Process Stream Samples in Male and Female Rats.  

National Technical Information Service (NTIS)

The acute toxicities of a single oral dose of the DMSO process stream samples, DMSO Evaporator Sludge, DMSO Recycle Solvent, and Virgin DMSO, were determined in male and female albino Sprague-Dawley rats. The DMSO Evaporator Sludge and Virgin DMSO solutio...

C. W. White, J. Rodriguez, G. E. Marrs



Acute Oral Toxicity (LD50) of 4-Nitrophenyl Monochloromethyl (Phenyl) Phosphinate (TA009) in Female Rats.  

National Technical Information Service (NTIS)

The acute oral toxicity of 4-nitrophenyl monochloromethyl (phenyl) phosphinate was determined in female, albino, Sprague-Dawley rats by using the single dose oral gavage method. LD1, LD50, and LD95 with the 95% confidence limits were calculated by probit ...

C. W. White, J. Rodriguez, T. P. Kellner



Monosodium Glutamate Disruption of Behavioral and Endocrine Function in the Female Rat  

Microsoft Academic Search

Experiments weie conducted to determine the effects of neonatal administration of L-monosodium glutamate (MSG) on behavioral and endocrine function in the female rat. Administration of MSG (4 mg\\/kg body weight) at days 1, 3, 5, 7 and 9 in neonates results in a delay of vaginal opening (VO) and the absence of ovulation at the time of VO. However, some

Jorge F. Rodriguez-Sierra; R. Sridaran; Charles A. Blake



Changes in progressive ratio responding for intravenous cocaine throughout the reproductive process in female rats  

Microsoft Academic Search

Operant responding on a progressive ratio (PR) schedule for intravenous co- caine as well as sucrose reinforcement was examined in female rats throughout the reproductive process. Self-administration sessions began before mating, and continued throughout preg- nancy and until lactational Day 8; following parturition, litters were present with dams during operant sessions. Physiological changes associated with the reproductive process dramatically altered

Gerald S. Hecht; Norman E. Spear; Linda P. Spear




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...


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...


Coexpression of ER with ER and Progestin Receptor Proteins in the Female Rat Forebrain: Effects of  

E-print Network

Coexpression of ER with ER and Progestin Receptor Proteins in the Female Rat Forebrain: EffectsPont Pharmaceuticals Co. (E.A.A.), Wilmington, Delaware 19880 Estrogen and progestin receptors (ER, PgR) play of the recently cloned, ER , overlaps with both ER and PgR. To determine whether ER is found within ER - or Pg

Blaustein, Jeffrey D.



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...


Estrogenic chemicals at puberty change ER? in the hypothalamus of male and female rats  

Microsoft Academic Search

The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty. Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors (ER-?) in the arcuate nucleus (ARC), ventromedial nucleus (VMH) and medial preoptic area (MPA) of the

Ilaria Ceccarelli; Daniele Della Seta; Paolo Fiorenzani; Francesca Farabollini; Anna Maria Aloisi



Aging impairs heart rate reflexes earlier in female than in male sprague-dawley rats  

Microsoft Academic Search

We compared heart rate reflexes in conscious male or female Sprague-Dawley rats at ages of 4, 14, or 24 months to determine whether, with advancing age, baroreflex sensitivity diminishes uniformly in both sexes. Phenylephrine or sodium nitroprusside was infused intravenously to elevate or lower systemic arterial pressure and thereby elicit reflex changes in heart rate. Ensuing blood pressure responses to

Ruben D. Buñag; Lawrence W. Davidow



The effects of bisphenol A on sex hormone levels of F0 female rats and F1 male rats during weaning period  

Microsoft Academic Search

The effects of bisphenol A (BPA) were examined on sex hormones of F1 generation male rats during weaning period. Female rats were exposed to BPA from day 0 after pregnancy to the weaning period at doses of 50, 100, or 200 mg kg. The sex hormone levels of F1 generation male rats were determined. This study shows that F0 generation

Bo Lü; Ping Zhan



The effect of alcohol on the bone growth spurt of rats at a time equivalent to adolescent females  

E-print Network

The objective of this study is to determine the effect of long-term alcohol consumption on the growth spurt in adolescent rats. Female Sprague-Dawley rats were fed one of three diets (alcohol, pair-fed or chow) for 3 months. The rats were sacrificed...

Chaffin, Catherine Lee



Adolescent MDMA exposure diminishes the physiological and neurotoxic consequences of an MDMA binge in female rats.  


Intermittent MDMA pretreatment blocked the reductions in serotonin transporter (SERT) binding induced by an MDMA binge in a prior study in adolescent male rats. The objective of this investigation was to determine if the physiological, behavioral, and neurochemical responses to MDMA are sexually dimorphic. Female Sprague-Dawley rats received MDMA (10?mg/kg?×?2) or Saline on every fifth day from postnatal day (PD) 35-60 and an MDMA binge (5?mg/kg?×?4) on PD 67. The MDMA binge induced a pronounced temperature dysregulation in MDMA-naïve, but not MDMA-pretreated, groups. Similarly, MDMA-pretreated animals were resistant to the binge-induced SERT reductions, especially in the hippocampus. Motor activity at PD 68 was not reduced by the binge, unlike the responses found in males. These results show that female rats differ from males in their responses to an MDMA binge but are similar with respect to preconditioning from prior MDMA exposure. PMID:24752593

Piper, Brian J; Henderson, Christina S; Meyer, Jerrold S



The Effects of Ovariectomy on Binge Eating Proneness in Adult Female Rats  

PubMed Central

Ovarian hormones are associated with binge eating in women, however findings are limited by the lack of experimental control inherent in human studies. Animal research that manipulates ovarian hormone status and examines individual differences in extreme binge eating proneness are needed to model clinical phenotypes in humans and to confirm causal effects. The purpose of this study was to examine the effects of adult ovariectomy on overall binge eating risk and extreme binge eating phenotypes using the binge eating resistant (BER)/ binge eating prone (BEP) rat model. We predicted that palatable food consumption would significantly increase after ovariectomy in all rats because ovarian hormones generally suppress food intake. If differences in responsiveness to ovarian hormones underlie BER/BEP phenotypes, then differences in binge eating between BER and BEP rats would be eliminated or diminished after ovariectomy. Changes in palatable food (PF) intake were compared in BER and BEP rats before and after ovariectomy in two samples of adult females. Findings were highly similar in the two samples. PF intake increased significantly following ovariectomy in all rats. However, BEP rats consistently consumed larger amounts of PF than BER rats, both before and after ovariectomy. The consistency of findings across two samples of rats provides strong support for activational effects of ovarian hormones on binge eating. However, the immunity of extreme binge eating phenotypes to ovarian hormone ablation suggests that other, earlier mechanisms (e.g., organizational hormone effects or hormone-independent effects) determine the expression of binge eating phenotypes. PMID:21376721

Klump, Kelly L.; Suisman, Jessica L.; Culbert, Kristen M.; Kashy, Deborah A.; Keel, Pamela K.; Sisk, Cheryl L.



Binge Eating Proneness Emerges during Puberty in Female Rats: A Longitudinal Study  

PubMed Central

Puberty is a critical risk period for binge eating and eating disorders characterized by binge eating. Previous research focused almost entirely on psychosocial risk factors during puberty to the relative exclusion of biological influences. The current study addressed this gap by examining the emergence of binge eating during puberty in a rat model. We predicted that there would be minimal differences in binge eating proneness during pre-early puberty, but significant differences would emerge during puberty. Two independent samples of female Sprague-Dawley rats (n = 30 and n = 36) were followed longitudinally across pre-early puberty, mid-late puberty, and adulthood. Binge eating proneness was defined using the binge eating resistant (BER)/binge eating prone (BEP) model of binge eating that identifies BER and BEP rats in adulthood. Across two samples of rats, binge eating proneness emerged during puberty. Mixed linear models showed little difference in palatable food intake between BER and BEP rats during pre-early puberty, but significant group differences emerged during mid-late puberty and adulthood. Group differences could not be accounted for by changes in non-palatable food intake or body weight. Similar to patterns in humans, individual differences in binge eating emerge during puberty in female rats. Findings provide strong confirming evidence for the importance of biological risk factors in developmental trajectories of binge eating risk across adolescence. PMID:21574664

Klump, Kelly L.; Suisman, Jessica L.; Culbert, Kristen M.; Kashy, Deborah A.; Sisk, Cheryl L.



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


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

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



Kinetics of selected di-n-butyl phthalate metabolites and fetal testosterone following repeated and single administration in pregnant rats.  


Human exposure to phthalic acid diesters occurs through a variety of pathways as a result of their widespread use in consumer products and plastics. Repeated doses of di-n-butyl phthalate (DBP) from gestation day (GD) 12 to 19 disrupt testosterone synthesis and male sexual development in the fetal rat. Currently little is known about the disposition of DBP metabolites, such as monobutyl phthalate (MBP) and its glucuronide conjugate (MBP-G), during gestation after repeated exposure to DBP. In order to gain a better understanding of the effect of repeated dosing on maternal and fetal metabolism and distribution, pregnant Sprague-Dawley rats were given a single dose of 500 mg/kg DBP on GD 19 or daily doses of 50, 100, and 500 mg/(kg day) from GD 12 to 19 via corn oil gavage. Dose-response evaluation revealed a non-linear increase in maternal and fetal plasma concentrations of MBP. Maternal and fetal MBP levels were slightly lower in animals after 8 days of dosing at 500 mg/(kg day). Fetal plasma MBP levels closely followed maternal plasma, while the appearance and elimination of MBP-G in fetal plasma were significantly delayed. MBP-G accumulated over time in the amniotic fluid. Inhibition of testosterone was rapid in fetal testes when exposed to DBP (500 mg/(kg day)) on GD 19. Within 24h, the level of inhibition in the fetus was similar between animals exposed to a single or multiple daily doses of 500 mg/(kg day). Examination of testosterone time-course data indicates a rapid recovery to normal levels within 24h post-dosing at DBP doses of 50 and 100 mg/(kg day), with a rebound to higher than normal concentrations at later time-points. MBP kinetics in fetal testes allows direct comparison of active metabolite concentrations and testosterone response in the fetal testes. PMID:19010379

Clewell, Rebecca A; Kremer, John J; Williams, Carla C; Campbell, Jerry L; Sochaski, Mark A; Andersen, Melvin E; Borghoff, Susan J



Effects of larval tapeworm (Taenia taeniaeformis) infection on reproductive functions in male and female host rats.  


This report examined the effects of larval tapeworm infection on the reproductive functions in both male and female host rats. Female rats were matched by age, then randomly assigned to control and treatment groups (infected with larval tapeworms). Estrous cycles were determined by vaginal smear with 95% of the control group exhibiting 4-day normal cyclicity and only 55% of the treated group exhibiting normal cycles. Female fertility was then evaluated for the normally cycling rats based on the percentage of successful matings on the evening of proestrus, number of implantation sites on Day 8 of pregnancy, and number of pups born at term. The normally cycling rats exhibited 96% successful mating, 12.95 +/- 1.80 implantation sites, and 11.20 +/- 1.80 pups born. Five months after larval tapeworm infection, the fertility parameters were decreased to 79%, 9.10 +/- 1.20, and 7.50 +/- 1.50, respectively. The control females were then used in a study of male fertility after larval tapeworm infection employing the same parameters used to test female fertility. At the onset of the study, control groups exhibited 95% successful mating, 12.50 +/- 1.50 implantation sites, and 11.60 +/- 1.60 pups born at full term. After the 5-month infection period, the parameters were substantially reduced to 29%, 6.20 +/- 0.80 implantation sites, and 5.10 +/- 0.80 pups, respectively. Average testosterone concentrations in serum and testis from control male rats were 8.80 +/- 0.95 ng/ml and 3.88 +/- 0.25 ng/mg protein, respectively. After the 5-month infection period, these levels were reduced to 2.47 +/- 0.31 ng/ml and 1.28 +/- 0.12 ng/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2311716

Lin, Y C; Rikihisa, Y; Kono, H; Gu, Y



Vascular damage in obese female rats with hypoestrogenism.  


Increase in body weight and adiposity has deleterious consequences on health. The aim of this study was to compare morphological and metabolic changes in the arterial vessels of Wistar rats with conditions of obesity, hypoestrogenism, and hypoestrogenism plus obesity. Ovariectomized rats (hypoestrogenic condition) received 30 % sugar in drinking water plus standard diet during 10 weeks. The hypoestrogenic-obese (HE-OB) group presented increase in weight, blood pressure, hypertriglyceridemia, and hyperglycemia compared with other groups. The morphological study in aortic vessels from HE showed damage in endothelial smooth muscle tissue compared with the other groups. Adipose cells volume in HE-OB (59.33?±?2.38 ?(3)?×?10(5)) and obese (OB) (54.95?±?1.36 ?(3)?×?10(5)) groups were significantly larger than control group (36.38?±?0.98 ?(3)?×?10(5)). In the HE group adipocyte hyperplasia was observed, while in OB group adipocyte hypertrophy and hyperplasia was shown. The vascular reactivity in HE-OB and OB groups presented decrease in the relaxation to acetylcholine compared with control conditions (p?

Lima-Mendoza, Luis Angel; Colado-Velázquez, Juventino; Mailloux-Salinas, Patrick; Espinosa-Juárez, Josué V; Gómez-Viquez, Norma L; Molina-Muñoz, Tzindilu; Huang, Fengyang; Bravo, Guadalupe



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

SciTech Connect

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.

Tachi, N.; Aoyama, M.



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


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

Cason, Angie M; Aston-Jones, Gary



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

NASA Technical Reports Server (NTRS)

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.

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



Increased synthesis of tumor necrosis factor-alpha in uterine explants from pregnant diabetic rats and in primary cultures of uterine cells in high glucose.  


The production of tumor necrosis factor-alpha (TNF-alpha) was investigated in uterine explants from normal, diabetic, or insulin-treated diabetic pregnant rats. Explants from diabetic rats released more soluble TNF-alpha than did those in the other groups. The extent of this secretion was correlated with blood glucose concentration at the time of explantation. The concentration of cell membrane-associated TNF-alpha in the explants was not altered by diabetes. Daily insulin administration failed to normalize uterine TNF-alpha secretion despite correction of glycemia in the diabetic rats. Explants from normal pregnant rats cultured in vitro with increasing concentrations of D-glucose showed a dose-dependent increase in TNF-alpha secretion. The production of TNF-alpha in high glucose was also tested in primary cultures of uterine cells isolated from either immature or adult rats. TNF-alpha secretion was increased in high D-glucose but not in iso-osmolar concentrations of L-glucose, D-raffinose, D-galactose, or mannitol. Cell membrane-associated TNF-alpha was not influenced by high D-glucose. Semiquantitative reverse transcription-amplification of RNA extracted from primary cultures of uterine cells showed that the steady-state level of TNF-alpha transcripts was increased by high D-glucose but not by high L-glucose. The results are consistent with the hypothesis that hyperglycemia is instrumental in the overexpression of TNF-alpha in the diabetic uterus. Because TNF-alpha has a demonstrated negative impact on embryonic growth, enhanced TNF-alpha synthesis in the pregnant uterus may contribute to the embryopathy associated with maternal diabetes. PMID:9200658

Pampfer, S; Vanderheyden, I; De Hertogh, R



Effects of in utero exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on developmental landmarks, steroid hormone levels, and female estrous cyclicity in rats.  


Previous studies have revealed that one of the major metabolites of PCBs detected in human blood, 4-OH-2,3,3',4',5-pentaCB (4-OH-CB107), accumulated in fetal liver, brain, and plasma and reduced maternal and fetal thyroid hormone levels after prenatal exposure to pregnant rats from gestational days (GD) 10-16. In the present study, the effects of 4-OH-CB-107 on developmental landmarks, steroid hormone levels, and estrous cyclicity of rat offspring after in utero exposure to 4-OH-CB107 was investigated. Pregnant rats were exposed to 0, 0.5, and 5.0 mg 4-OH-CB107 per kg bw from GD 10 to GD 16. Another group of rats was exposed to Aroclor 1254 (25 mg/kg bw) to study the differences between effects caused by parent PCB congeners and the 4-OH-CB107 alone. A significant, dose-dependent prolongation of the estrous cycle was observed in 75% and 82% of female offspring exposed to 0.5 and 5.0 mg 4-OH-PCB107, respectively, compared to 64% of Aroclor 1254 (25 mg/kg) exposed offspring. The diestrous stage of the estrous cycle was prolonged, resembling a state of pseudopregnancy, which might reflect early signs of reproductive senescence. Plasma estradiol concentrations in female rat offspring were significantly increased (50%) in the proestrous stage after exposure to 5 mg 4-OH-CB107 per kg bw. No effects on estradiol levels were observed in Aroclor 1254 treated animals. These results indicate that in utero exposure to 4-OH-CB107 leads to endocrine-disrupting effects, especially in female offspring. The possible impact on neurobehavior following exposure to 4-OH-CB107 will be reported elsewhere. PMID:15310862

Meerts, Ilonka A T M; Hoving, Saske; van den Berg, Johannes H J; Weijers, Bert M; Swarts, Hans J; van der Beek, Eline M; Bergman, Ake; Koeman, Jan H; Brouwer, Abraham



In utero phthalate effects in the female rat: A model for MRKH syndrome?  

PubMed Central

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 phenomenon that is better studied in male offspring than females. The current study reports female reproductive tract malformations in the Sprague–Dawley rat similar to those characteristic of MRKH syndrome, following in utero exposure to a mixture of 5 PEs. We determined that females are ~2-fold less sensitive to the effects of the 5-PE mixture than males for reproductive tract malformations. We were not fully successful in defining the critical exposure period for females; however, incidence of malformations was 88% following dosing from GD8 to 19 versus 22% and 0% for GD8–13 and GD14–19, respectively. Overall, this study provides valuable information regarding female vulnerability to in utero phthalate exposure and further characterizes a potential model for the human MRKH syndrome. PMID:23542816

Hannas, Bethany R.; Howdeshell, Kembra L.; Furr, Johnathan; Gray, L. Earl



Fos expression induced by cocaine-conditioned cues in male and female rats.  


Previous studies have shown that female rats exhibit different patterns of drug seeking during multiple phases of cocaine addiction when compared with males. However, the underlying mechanisms for these sex differences remain largely unknown. Here, we used a cocaine self-administration/reinstatement model to examine neuronal activation, as determined by Fos expression, following cue-induced reinstatement of cocaine seeking in male and female rats. Fos expression revealed both similarities between sexes in some brain regions, as well as selective sexually dimorphic patterns. As compared to no cue control subjects, conditioned cues induced higher Fos expression in the Cg1 region of the anterior cingulate cortex, but lower expression in the nucleus accumbens in both males and females. Females exhibited higher Fos expression than males in multiple brain regions, including the agranular insular cortex, dorsal medial caudate-putamen, nucleus accumbens shell, ventral tegmental area, dorsal subiculum, and ventral CA1 and CA3 regions of the hippocampus. Notably, only Fos expression in the prelimbic cortex, nucleus accumbens shell, basolateral amygdala, and ventral subiculum correlated positively with lever responding in response to conditioned cues across males and females. These findings indicate that while sexually dimorphic Fos activation does occur, the relationship between cue-induced cocaine seeking and neuronal activation may be similar for males and females in key brain regions of the relapse circuit. PMID:23832598

Zhou, Luyi; Pruitt, Carla; Shin, Christina B; Garcia, Arturo D; Zavala, Arturo R; See, Ronald E



Gonadectomy Reverses The Sexually Diergic Patterns Of Circadian and Stress-Induced Hypothalamic-Pituitary-Adrenal Axis Activity In Male and Female Rats  

Microsoft Academic Search

Enhanced corticosterone release by female compared to male rats under basal and stress conditions is well documented. The demonstration that gonadectomy enhances stress-induced corticosterone secretion in male rats, but reduces such levels in female rats, suggests a causal association between gonadal steroids and corticosterone release. The present study examined the corticosterone profile of sham gonadectomized and gonadectomized female and male

J. V. Seale; S. A. Wood; H. C. Atkinson; E. Bate; S. L. Lightman; C. D. Ingram; D. S. Jessop; M. S. Harbuz



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


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

Lumbroso, Delphine; Joseph, Vincent



Chronic scream sound exposure alters memory and monoamine levels in female rat brain.  


Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. PMID:24952268

Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen



Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by Trypanosoma evansi.  


The goal of this study was to evaluate reproductive hormones in sera samples of female rats experimentally infected by Trypanosoma evansi during different phases of the estrous cycle. For that, 64 animals were divided into two groups: 24 rats for the control group (uninfected), and 40 animals were infected by T. evansi. These groups were divided into subgroups according to the time of infection (days 5 and 15 post-infection; PI) and the phase of the estrous cycle (proestrus, estrus, metestrus and diestrus). Serum was collected at days 5 and 15 PI and the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone and estradiol were assessed by enzyme immunoassay technique. The concentration of nitrite/nitrate (NOx), advanced oxidation protein products (AOPP), and thiobarbituric acid reactive substances (TBARS) were measured in ovaries and uteruses in these same periods. Infected females showed significant decrease (P<0.05) of LH, FSH, estradiol and progesterone in different periods and phases of the estrous cycle when compared to uninfected rats. In addition, it was observed an increase in the concentration of NOx, AOPP, and TBARS in the ovaries, which is indicative of cell damage. Therefore, our experimental study showed that T. evansi infection in female rats may cause changes in LH, FSH, estradiol, and progesterone levels regardless of the time of infection or phase of the estrous cycle. PMID:23816642

Faccio, Luciana; Da Silva, Aleksandro S; Tonin, Alexandre A; França, Raqueli T; Gressler, Lucas T; Copetti, Maíra M; Oliveira, Camila B; Sangoi, Manuela B; Moresco, Rafael N; Bottari, Nathieli B; Duarte, Marta M M F; Monteiro, Silvia G



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


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

Belviranl?, Muaz; Okudan, Nilsel; Atal?k, K?smet Esra Nurullaho?lu; Öz, Mehmet



Differential impact of cocaine on meal patterns in female and male rats.  


Female rats, relative to males, exhibit greater behavioral activation to cocaine and other psychostimulants, but the effect of sex and the estrous cycle in modulating the hypophagic action of cocaine has not been evaluated. Meal patterns were recorded in automated food hoppers during the first 3 h of the dark phase in adult female and male rats after administration of ascending cocaine doses (0, 7.5, and 15 mg/kg cocaine, i.p.) on successive trials. Cocaine produced a greater suppression of feeding as well as a reduction in meal number over a 3 h test period in female rats during estrus, relative to that noted during diestrus. In contrast, during the 180 min test period, male rats showed minimal hypophagic responses to 7.5 or 15 mg/kg cocaine. These results extend the range of behavioral perturbations induced by cocaine that are modulated by sex and by the estrous cycle and are consistent with the notion that estradiol may modulate the neurochemical actions of cocaine. PMID:18207198

Wellman, Paul J; Ho, Dao H; Nation, Jack R



Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: Role of endothelin-1  

PubMed Central

Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and endothelin ?1 (ET-1) are suggested to be important links between placental ischemia and hypertension during preeclampsia. Activation of the angiotensin II type 1 receptor (AT1R) increases endothelial cell production of ET-1; however, the importance of ET-1 in response to AT1-AA mediated AT1 R activation during preeclampsia is unknown. Furthermore, the role of AT1-AA mediated increases in blood pressure during pregnancy remains unclear. The objective of this study was to test the hypothesis that AT1-AA, increased to levels observed in preeclamptic women and placental ischemic rats, increases mean arterial pressure (MAP) by activation of the ET-1 system. Chronic infusion of purified rat AT1-AA into normal pregnant (NP) rats for 7 days increased AT1-AA from 0.68 ± 0.5 to 10.88 ± 1.1 chronotropic units (P<0.001). The increased AT1-AA increased MAP from 99 ± 1 to 119 ± 2 mmHg (P<0.001). The hypertension was associated with significant increases in renal cortices (11-fold) and placental (4-fold) ET-1. To determine whether ET-1 mediates AT1-AA-induced hypertension, pregnant rats infused with AT1-AA and NP rats were treated with an ETA receptor antagonist. MAP was 100 ± 1 mmHg in AT1-AA + ETA antagonist treated rats versus 98 ± 2 mmHg in ETA antagonist treated rats. Collectively, these data support the hypothesis that one potential pathway whereby AT1-AAs increase blood pressure during pregnancy is by an ET-1 dependent mechanism. PMID:19704104

LaMarca, Babbette; Parrish, Marc; Ray, Lillian Fournier; Murphy, Sydney R.; Roberts, Lyndsay; Glover, Porter; Wallukat, Gerd; Wenzel, Katrin; Cockrell, Kathy; Martin, James N.; Ryan, Michael J; Dechend, Ralf



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


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

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



Development of behavioral and hormonal disorders in prenatally stressed female rats on the model of posttraumatic stress disorder.  


The dynamics of changes in behavioral and hormonal manifestations of a pathological state in mature female rats born by mothers exposed to daily restraint stress on days 15-19 of pregnancy were studied in the experimental model of posttraumatic stress disorder (stress-restress paradigm). Experiments demonstrated increased anxiety in control and prenatally stressed female rats after combined stress followed by restress. This parameter remained enhanced until day 10 after restress in control rats and day 30 in prenatally stressed animals. The severity of depression increased on days 1 and 10 after restress in prenatally stressed female rats. Basal activity of the pituitary-adrenocortical axis increased only in prenatally stressed female rats under these conditions. This parameter increased 1 day after restress and decreased after day 30. It was concluded that prenatal stress could increase the predisposition to post-stress mental pathologies in experimental animals, which are manifested in increased severity and duration of behavioral and hormonal impairments. PMID:25065308

Pivina, S G; Akulova, V K; Rakitskaya, V V; Ordyan, N E



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

PubMed Central

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

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



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


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

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



Perinatal iron deficiency affects locomotor behavior and water maze performance in adult male and female rats.  


Iron deficiency during early growth and development adversely affects multiple facets of cognition and behavior in adult rats. The purpose of this study was to assess the nature of the learning and locomotor behavioral deficits observed in male and female rats in the absence of depressed brain iron levels at the time of testing. Adult female Wistar rats were fed either an iron-enriched diet (>225 mg/kg Fe) or an iron-restricted diet (3 mg/kg Fe) for 2 wk prior to and throughout gestation, and a nonpurified diet (270 mg/kg Fe) thereafter. Open-field (OF) and Morris water maze (MWM) testing began when the offspring reached early adulthood (12 wk). At birth, perinatal iron-deficient (PID) offspring had reduced (P < 0.001) hematocrits (-33%), liver iron stores (-83%), and brain iron concentrations (-38%) compared with controls. Although there were no differences in iron status in adults, the PID males and females exhibited reduced OF exploratory behavior, albeit only PID males had an aversion to the center of the apparatus (2.5 vs. 6.9% in controls, P < 0.001). Additionally, PID males required greater path lengths to reach the hidden platform in the MWM, had reduced spatial bias for the target quadrant, and had a tendency for greater thigmotactic behavior in the probe trials (16.5 vs. 13.0% in controls; P = 0.06). PID females had slower swim speeds in all testing phases (-6.2%; P < 0.001). These results suggest that PID has detrimental programming effects in both male and female rats, although the behaviors suggest different mechanisms may be involved in each sex. PMID:18424604

Bourque, Stephane L; Iqbal, Umar; Reynolds, James N; Adams, Michael A; Nakatsu, Kanji



mTORC1/2 and rapamycin in female Han:SPRD rats with polycystic kidney disease.  


Rapamycin slows disease progression in the male Han:SPRD (Cy/+) rat with polycystic kidney disease (PKD). The aim of this study was to determine the effect of rapamycin on PKD and the relative contributions of the proproliferative mammalian target of rapamycin complexes 1 and 2 (mTORC1 and mTORC2) in female Cy/+ rats. Female Cy/+ rats were treated with rapamycin from 4 to 12 wk of age. In vehicle-treated Cy/+ rats, kidney volume increased by 40% and cyst volume density (CVD) was 19%. Phosphorylated S6 (p-S6) ribosomal protein, a marker of mTORC1 activity, was increased in Cy/+ rats compared with normal littermate controls (+/+) and decreased by rapamycin. Despite activation of mTORC1 in female Cy/+ rats, rapamycin had no effect on kidney size, CVD, number of PCNA-positive cystic tubular cells, caspase-3 activity, or the number of terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive apoptotic cells. To determine a reason for the lack of effect of rapamycin, we studied the mTORC2 signaling pathway. On immunoblot of kidney, phosphorylated (Ser473) Akt (p-Akt), a marker of mTORC2 activity, was increased in female Cy/+ rats treated with rapamycin. Phosphorylated (Ser657) PKC?, a substrate of mTORC2, was unaffected by rapamycin in females. In contrast, in male rats, where rapamycin significantly decreases PKD, p-Akt (Ser473) was decreased by rapamcyin. PKC? (Ser657) was increased in male Cy/+ rats but was unaffected by rapamycin. In summary, in female Cy/+ rats, rapamycin had no effect on PKD and proproliferative p-Akt (Ser473) activity was increased by rapamycin. There were differential effects of rapamycin on mTORC2 signaling in female vs. male Cy/+ rats. PMID:20943770

Belibi, Franck; Ravichandran, Kameswaran; Zafar, Iram; He, Zhibin; Edelstein, Charles L



Proteomic analysis of amniotic fluid of pregnant rats with spina bifida aperta.  


Congenital spina bifida aperta is a common congenital malformation in children and has an incidence of 1‰ to 5‰ in China. However, we currently lack specific biomarkers for screening or prenatal diagnosis and there is no method to entirely cure or prevent such defects. In this study, we used two-dimensional gel electrophoresis (2-DE)/mass spectrometry (MS) to characterize differentially expressed proteins in amniotic-fluid samples (AFSs) of embryonic day (E) 17.5 rat fetuses with spina bifida aperta induced by retinoic acid (RA). We identified five proteins differentially expressed in AFSs of spina bifida aperta, including three upregulated proteins (transferrin, alpha-1 antiproteinase and signal recognition particle receptor, B subunit [SRPRB] 55 kDa), two downregulated proteins (apolipoprotein A IV [APO A4] and Srprb 77 kDa). Specifically, we found 11 alpha-1 fetoprotein (AFP) fragments that were downregulated and 35 AFP fragments that were upregulated in AFSs from embryos with spina bifida aperta. Of the downregulated AFP fragments, 72.7% (8/11) were confined to the AFP N-terminus (amino acids [aas] 25-440) and 77.1% (27/35) of upregulated AFP fragments were confined to the AFP C-terminus (aas 340-596). We also confirmed APO A4 and AFP by immunoblot analysis. This is the first comparative proteomic study of AFSs from rat fetuses with spina bifida aperta. We demonstrate proteomic alterations in the AFS of spina bifida aperta, which may provide new insights in neural tube defects and contribute to the prenatal screening. PMID:22108047

Shan, Liping; Fan, Yang; Li, Hui; Liu, Wei; Gu, Hui; Zhou, Fenghua; Yuan, Zhengwei



Disposition of styrene-acrylonitrile (SAN) trimer in female rats: Single dose intravenous and gavage studies  

Microsoft Academic Search

Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [3H]SAN Trimer following a single intravenous administration (26mg\\/kg) to nonpregnant rats; a single gavage administration (nominal

Michael L. Gargas; Brad Collins; Timothy R. Fennell; Norman F. Gaudette; Lisa M. Sweeney



Prenatal Exposure to Methylmercury during Late Gestation Affects Cerebral Opiatergic System in Rat Offspring  

Microsoft Academic Search

Pregnant female rats were orally administered a single dose (8 mg\\/kg) of methylmercury chloride (MMC) on Day 15 of gestation. The binding characteristics of opioid receptors were studied in the brain of developing rats at different stages of age. An increased density of opioid receptors was found in whole brain of MMC-exposed rats at 21 days (? receptors) and 60

Paola Zanoli; Cristina Truzzi; Cristina Veneri; Cinzia Brandoli; Mario Baraldi



Effect of prenatal exposure to bisphenol A on the serum testosterone concentration of rats at birth  

Microsoft Academic Search

In the rat, testosterone (T) in the neonatal period plays an important role in sexual differentiation and there is a serum T surge in male rats 2 hours after birth. Pregnant female rats were exposed to various doses of bisphenol A (BPA) from gestational day 1 (GD1) through 2 hours after parturition. About half of the BPA-exposed and control dams

M Tanaka; S Nakaya; M Katayama; H Leffers; S Nozawa; R Nakazawa; T Iwamoto; S Kobayashi



The toxicity mechanism of sodium fluoride on fertility in female rats.  


Recognition of the harmful effects of sodium fluoride (NaF) on human reproduction is increasing, especially as it relates to female reproduction. However, the mechanism by which NaF interferes with female reproduction is unclear. The aims of the present study were to investigate the effects of fluoride exposure on female fertility and to elucidate the mechanisms underlying these effects. Female Sprague-Dawley rats were divided into three groups: one control group and two NaF-treated groups (100 and 200 mg/L in the drinking water for 12 weeks). Several parameters were evaluated, including: (i) fluoride concentrations; (ii) estrogen (E2) and progesterone (P) concentrations; (iii) estrogen receptor alpha protein (ER?); (iv) progesterone receptor (PgR) protein; (v) follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) protein. The results indicated that administration of NaF lead to significant decreases in E2 and P levels in the serum and in the expression of FSHR protein. In addition, fluoride exposure significantly increased Er? and PgR protein expression levels and LHR protein expression. These results suggest that the reproductive hormone reduction and the abnormalities of related receptor proteins expression are important factors underlying the decreased fertility observed in female rats that have been exposed to NaF. PMID:24071475

Zhou, Yongjiang; Qiu, Yiwen; He, Junlin; Chen, Xuemei; Ding, Yubing; Wang, Yingxiong; Liu, Xueqing




PubMed Central

Premature infants are routinely exposed to invasive medical procedures during neonatal intensive care treatment that are largely performed in the absence of anesthetics or analgesics. Data collected to date suggest that exposure to early insult during this time of increased plasticity alters the development of the CNS and influences future pain responses. As previous studies examining the impact of neonatal injury on nociception have been conducted primarily in males, the potential adverse effects on females is not known. Therefore, the present studies were conducted to determine whether neonatal injury differentially impacts male and female sensory thresholds in adulthood. A short lasting inflammatory response was evoked in male and female rats on the day of birth with an injection of carrageenan (CGN; 1% or 2%) into the right hind paw. Nociceptive thresholds were assessed using a noxious thermal stimulus at both adolescence (P40) and adulthood (P60). A more persistent inflammation was subsequently evoked in adult rats with an intraplantar injection of Complete Freund's adjuvant (CFA). Neonatally injured females exhibited significantly greater hypoalgesia at P60, and displayed enhanced inflammatory hyperalgesia following re-injury in adulthood compared to neonatally injured males and controls. These results demonstrate that the long-term adverse effects of neonatal injury are exacerbated in females, and may contribute to the higher prevalence, severity and duration of pain syndromes noted in women compared to men. PMID:17904745

LaPrairie, Jamie L.; Murphy, Anne Z.



Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.  


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

Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban



Female spontaneously hypertensive rats have greater renal anti-inflammatory T lymphocyte infiltration than males  

PubMed Central

T cells contribute to hypertension in male experimental models; data in females is lacking even though women are more likely to develop immune disorders. The goal of this study was to determine whether immune cells contribute to hypertension in female spontaneously hypertensive rats (SHR) and define the T cell profile in whole blood and kidneys of male and female SHR. We hypothesized that inflammatory cells contribute to hypertension in female SHR; however, male SHR have a higher blood pressure so we hypothesize they will have a heightened inflammatory profile. The lymphocyte inhibitor mycophenolate mofetil (MMF) was administered in a dose-dependent manner to SHR. At the highest dose (50 mg·kg?1·day?1), blood pressure was significantly decreased in both sexes, yet the percent decrease in blood pressure was greater in females (female: 12 ± 1%; males: 7 ± 1%, P = 0.01). Circulating and renal T cell profiles were defined using analytical flow cytometry. Female SHR had more circulating CD3+, CD4+, and pro-inflammatory CD3+CD4+ROR?+ Th17 cells, whereas males had more immune-suppressive CD3+CD4+Foxp3+ T regulatory cells. In the kidney, females had greater numbers of CD8+ and T regulatory cells than males, whereas males had greater CD4+ and Th17 cell infiltration. MMF decreased circulating and renal T cells in both sexes (P < 0.0001), although the effect of MMF on T cell subtypes was sex specific with females having greater sensitivity to MMF-induced decreases in lymphocytes. In conclusion, there is a lymphocyte contribution to the maintenance of hypertension in the female SHR and sex of the animal impacts the T cell profile. PMID:22761180

Tipton, Ashlee J.; Baban, Babak



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


To evaluate maternal transfer of decabromodiphenyl ether (BDE-209), Sprague-Dawley rats were given daily oral doses of 5 ?mol/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

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



Spontaneous harderian gland adenocarcinoma in a female f344 rat: a case report.  


Harderian gland tumors are extremely rare in female F344 rats. An expansive enlarging lesion of the Harderian gland with compression, distortion and invasion of the surrounding muscle was found in a 110-week-old female F344/DuCrj rat, which was diagnosed as a Harderian gland adenocarcinoma. Epithelial growth patterns such as glandular, lobular, papillary and duct forming patterns were exhibited in most areas of the tumor. The tumor cells were pleomorphic and atypical. In one part of the tumor, poorly differentiated areas were found. This case was observed in the middle dose group of a carcinogenicity study of diphenylamine, which was not carcinogenic, we determine to be this case was a spontaneous tumor. PMID:25352715

Senoh, Hideki; Katagiri, Taku; Takanobu, Kenji; Umeda, Yumi; Aiso, Shigetoshi; Fukushima, Shoji



Spontaneous Harderian Gland Adenocarcinoma in a Female F344 Rat: A Case Report  

PubMed Central

Harderian gland tumors are extremely rare in female F344 rats. An expansive enlarging lesion of the Harderian gland with compression, distortion and invasion of the surrounding muscle was found in a 110-week-old female F344/DuCrj rat, which was diagnosed as a Harderian gland adenocarcinoma. Epithelial growth patterns such as glandular, lobular, papillary and duct forming patterns were exhibited in most areas of the tumor. The tumor cells were pleomorphic and atypical. In one part of the tumor, poorly differentiated areas were found. This case was observed in the middle dose group of a carcinogenicity study of diphenylamine, which was not carcinogenic, we determine to be this case was a spontaneous tumor. PMID:25352715

Senoh, Hideki; Katagiri, Taku; Takanobu, Kenji; Umeda, Yumi; Aiso, Shigetoshi; Fukushima, Shoji



Humoral (immunological) responses in female albino rats during rotating magnetic field exposures  

NASA Astrophysics Data System (ADS)

Experiments were designed to evaluate the primary and secondary humoral responses to a rotating magnetic field configuration, which is known to evoke significant biobehavioral changes. Ten days after inoculation with human serum albumin and 10 days before a booster, female rats were exposed to eigher a 0.5 Hz rotating magnetic field (RMF) or to room conditions (control). The lighting schedule was either continuous or involved a light-dark cycle (LD) of 12:12h. A third group of rats served as colony room controls. Group differences of low statistical significance were found when females were exposed to continuous lighting rather than the LD 12:12 light-dark cycle. However, the effects were considered trivial and not sufficient to explain the previously reported biobehavioral changes evoked by this field configuration.

Reid, K.; Falter, H.; Persinger, M. A.



Early maternal separation increases symptoms of activity-based anorexia in male and female rats.  


Running activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing the release of stress hormones known to exert anorexic effects. HPA axis reactivity is strongly influenced by early postnatal manipulations, including removal of pups from the dam for short (handling) or prolonged (maternal separation) durations during the preweaning period. The authors examined the effects of handling and maternal separation on food intake, body weight loss, and running rates of young adult male and female rats in the activity-based anorexia (ABA) paradigm. Postnatal treatment did not affect adaptation to a 1-hr restricted feeding schedule before the introduction of wheel running. During the ABA paradigm, maternally separated animals lost weight faster, ate less, ran more, and required fewer days to reach removal criterion compared with handled rats. Females were particularly vulnerable. These findings indicate that early postnatal treatment and sex influence ABA. PMID:19594284

Hancock, Stephanie; Grant, Virginia



Synergism of diethylstilbestrol and radiation in mammary carcinogenesis in female F344 rats.  


One compressed 20-mg pellet containing cholesterol only or cholesterol mixed with 0.98, 1.6, 2.6, or 3.9 mg of diethylstilbestrol (DES) was implanted into each of 203 female F344 rats. Two days later, half the animals in each group were exposed to 150 R of X-rays, and the other half were sham irradiated. The rats were maintained until 350 days post implantation. Mortality increased with the higher doses of DES, with or without X-rays. DES at all dose levels, with or without X-rays, produced pituitary tumors and pyometritis. Only rats that received both DES and X-rays had mammary adenocarcinomas (AC). A synergistic AC response was found in the group that received 2.6 mg DES plus X-rays. Synergism was defined as a significantly greater incidence of rats with mammary neoplasia resulting from DES plus X-ray treatment when compared to the summed incidence from comparable individual treatments. For all other groups of rats that received both treatments, synergism was detected only when their data were combined. Synergism was not detected among rats that had fibroadenomas (FA). Both types of neoplasms were independent phenomena because no significant relationship was found between the incidences of FA and AC. PMID:480380

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



Protective effect of curcuminoids on age-related mitochondrial impairment in female Wistar rat brain.  


The present study demonstrated the neuroprotective effect of curcuminoids, the active polyphenols of Curcuma longa (L.) rhizomes on mitochondrial dysfunctioning in middle aged and aged female Wistar rat brain. Rats were orally treated with curcuminoids (100 mg/kg) for 3 months and their brain was collected for evaluation of mitochondrial enzymes and complexes activity, ultra structural changes in mitochondria, neuronal nitric oxide synthase (nNOS) protein expression, adenosine triphosphate (ATP) and lipofuscin content. Significant alterations were observed in all the tested parameters in highly aged rat brain when compared with young control. Long term curcuminoids administration prevented this age associated loss of mitochondrial enzymes and complexes activity in middle aged rat brain except for malate dehydrogenase, Complex II and IV activity when compared with young control. Among aged rats, curcuminoids treatment specifically elevated isocitrate and NADH dehydrogenase, cytochrome c oxidase, Complex I and total ATP content. A significant down-regulation of nNOS protein expression along with reduced lipofuscin content was also observed in curucminoids treated middle aged and aged rats. Thus, it was suggested that curcuminoids may act as a putative drug candidate for the prevention of deleterious effects of ageing and age associated neurodegenerative disorders through amelioration of aberrant mitochondrial functioning. PMID:24048922

Rastogi, Manisha; Ojha, Rudra P; Sagar, Chandrasekhar; Agrawal, Aruna; Dubey, Govind P



Melatonin Treatment Delays Reproductive Aging of Female Rat via the Opiatergic System  

Microsoft Academic Search

In female rat age-related reproductive decline is accompanied by progressive impairment of the neuroendocrine mechanisms that regulate LH secretion. The biosynthetic activity of the pineal gland is markedly depressed and the nocturnal secretion of melatonin decreases significantly. The aim of the present study was to evaluate whether the nocturnal administration of melatonin via the drinking water (0.4 ?g\\/ml) throughout the

Gian Paolo Trentini; Andrea R. Genazzani; Mario Criscuolo; Felice Petraglia; Carmela de Gaetani; Guido Ficarra; Bosena Bidzinska; Mario Migaldi; Alessandro D. Genazzani



Inducing effect of testosterone on the hepatic reduction of zearalenone in the female prepubertal rat  

Microsoft Academic Search

The prepubertal responsiveness of 3?-hydroxysteroid dehydrogenase and zeara-lenone-reducing activity to either a large subcutaneous\\u000a dose of testosterone or dietary zearalenone was investigated in female rats. Testosterone induced both the activity of the\\u000a 3?-hydroxysteroid dehydrogenase, with androsterone as substrate, and zearalenone reduction to ?- and (?-zearalenol. Zearalenone\\u000a had no effect on the activity of 3?-hydroxysteroid dehydrogenase, but had a slight inducing

Monica Olsen



Spatial matching and nonmatching in male and female Wistar rats: Effects of delay-interval duration  

Microsoft Academic Search

Male and female Wistar rats were trained in a delayed matching-to-position procedure in which one of the two levers (sample)\\u000a was presented. Pressing this lever resulted in its retraction and began a delay interval of random variable duration, which\\u000a terminated with the occurrence of the first nose poke in the pellet retrieval unit after the delay interval had expired. Both

Frans Van Haaren; Annemieke Van Hest



Effects of Neonatally-Administered DDT Homologs on Reproductive Function in Male and Female Rats  

Microsoft Academic Search

The possibility of altering neuroendocrine differentiationby administering homologs of the pesticide DDT to neonatal male and female rats was investigated. The estrogenic isomer o, p’-DDT pro-duced precocious puberty with an inverse relationship between age at vaginal opening and dose of DDT. 0.1 mg o, p’-DDT on the 2nd, 3rd, and 4th days of life was the minimum effective dose for

R. J. Gellert; W. L. Heinrichs; R. Swerdloff



Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats  

PubMed Central

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 Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. 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



Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams  

NASA Technical Reports Server (NTRS)

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.

Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)



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


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 ?1-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

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



Serum lipoprotein composition, lecithin cholesterol acyltransferase and tissue lipase activities in pregnant diabetic rats and their offspring receiving enriched n-3 PUFA diet.  


The effects of dietary n-3 polyunsaturated fatty acids on lipoprotein concentrations and on lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL) and lecithin cholesterol acyltransferase (LCAT) activities were studied in streptozotocin-induced diabetic rats during pregnancy and in their macrosomic offspring from birth to adulthood. Pregnant diabetic and control rats were fed Isio-4 diet (vegetable oil) or EPAX diet (concentrated marine omega-3 EPA/DHA oil), the same diets were consumed by pups at weaning. Compared with control rats, diabetic rats showed, during pregnancy, a significant elevation in very low density lipoprotein (VLDL) and low and high density lipoprotein (LDL-HDL(1))-triglyceride, cholesterol and apoprotein B100 concentrations and a reduction in apoprotein A-I levels. HTGL activity was high while LPL and LCAT activities were low in these rats. The macrosomic pups of Isio-4-fed diabetic rats showed a significant enhancement in triglyceride and cholesterol levels at birth and during adulthood with a concomitant increase in lipase and LCAT activities. EPAX diet induces a significant diminution of VLDL and LDL-HDL(1) in mothers and in their macrosomic pups, accompanied by an increase in cholesterol and apoprotein A-I levels in HDL(2-3) fraction. It also restores LPL, HTGL and LCAT activities to normal range. EPAX diet ameliorates considerably lipoprotein disorders in diabetic mothers and in their macrosomic offspring. PMID:18436977

Soulimane-Mokhtari, N A; Guermouche, B; Saker, M; Merzouk, S; Merzouk, H; Hichami, A; Madani, S; Khan, N A; Prost, J



Proliferative retinopathy and neovascularization of the anterior segment in female type 2 diabetic rats  

PubMed Central

Background To examine the presence of diabetic retinopathy in a female rat model of type 2 diabetes fed on a high-fat diet (HFD). Methods Wistar rats were injected with streptozotocin (STZ) at the age of two days and fed on an HFD from eight weeks onwards. Five diabetic animals were euthanized at 110 weeks of disease, together with a control group of age-matched, non-diabetic animals. A group of diabetic animals at 57 weeks of disease was included for comparison. Cross sections of the rats’ corneas, iris and retinas were histologically examined and analysed by immunohistochemistry and immunofluorescence, using glial-fibrillary-acidic-protein (GFAP), the vascular endothelial growth factor (VEGF) and the Von Willebrand factor (vWF). The trypsine digestive technique was used for the pericytes count. Results Neovascularization was only found in the retinas, irises and corneas of the diabetic animals of 110 weeks of disease. There was also a significantly lower number of pericytes in these animals than in the controls. Conclusion The female rat model of type 2 diabetes fed on an HFD may prove useful in evaluating the mechanisms involved in diabetic retinopathy, together with strategies to reduce its severity. PMID:24499599



Acute Oral Administration of Cytosine Arabinoside Triacetate to Male Albino Rats and Male and Female Rhesus Monkeys.  

National Technical Information Service (NTIS)

The acute toxicity of cytosine arabinoside triacetate was evaluated following single oral administration in male albino rats and in male and female rhesus monkeys. Methyl cellulose suspensions of the compound were prepared at concentrations ranging from 4...

H. Feinman, T. W. Tusing, E. R. Homan, D. P. Rall



The role of constrictor prostanoids in the development of aortic coarctation-induced hypertension in male and female rats  

E-print Network

Vascular reactivity to vasopressin and phenylephrine is potentiated by constrictor prostanoids (CP) in normotensive female (F) but not male (M) rat aorta and CP function is estrogen-dependent. This study investigated the effects of estrogen on CP...

Baltzer, Wendy Irene




EPA Science Inventory

RTD-03-031 Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations in Circulating Estradiol: Effects in Both Cycling and Ovariectomized/Steroid-primed Female Rats. Reproductive Toxicology (in press). Abstract Oral exposures to high concentrations of th...


Amphetamine effects on startle gating in normal women and female rats  

PubMed Central

Background Dopamine agonists disrupt prepulse inhibition (PPI) of startle in male rodents. In humans, this is observed only in some studies. We reported that PPI was disrupted by D-amphetamine in men, but only among those with high basal PPI levels. Here, amphetamine effects on PPI were tested in normal women and female rats. Materials and methods Acoustic startle and PPI were tested in normal women after placebo or 20 mg amphetamine, in a double-blind, crossover design, and in female rats after vehicle or 4.5 mg/kg amphetamine. Rats were from Sprague–Dawley (SD) and Long Evans (LE) strains that differ significantly in gene expression in PPI-regulatory circuitry, including levels of nucleus accumbens (NAC) catechol-O-methyl transferase (COMT) mRNA. Results Amphetamine was bioactive in humans based on quantitative autonomic and self-rating measures, but did not significantly change startle magnitude or PPI across all subjects. Amphetamine’s effects on PPI in women correlated significantly (p<0.0008) with placebo PPI levels (reducing PPI only in women whose basal PPI levels exceeded the sample median) and with measures of novelty and sensation seeking. Amphetamine decreased PPI in SD rats that have relatively low NAC COMT gene expression and increased PPI in LE rats that have relatively high NAC COMT gene expression. Conclusion The dopaminergic regulation of PPI in humans is related to basal levels of sensorimotor gating and to specific personality traits in normal men and women. In rats, the effects of amphetamine on PPI differ significantly in strains with low vs. high NAC COMT expression. PMID:19148623

Talledo, Jo A.; Sutherland Owens, Ashley N.; Schortinghuis, Tijmen



Effects of Stimulation and Blockade of D2 Receptor on Depression-Like Behavior in Ovariectomized Female Rats  

PubMed Central

The aim of the present study was to explore the hedonic effects of D2 receptor agonist, quinpirole and D2 receptor antagonist, and sulpiride alone or in combination with a low dose of 17?-E2-estradiol (17?-E2) in the adult ovariectomized female rats (OVX). OVX rats of Wistar strain were used in all experiments. Two weeks after surgery rats were chronically treated with vehicle, a low dose of 17?-E2 (5.0??g/rat), quinpirole (0.1?mg/kg), sulpiride (10.0?mg/kg), quinpirole plus 17?-E2, or sulpiride plus 17?-E2 for 14 days before the forced swimming test. We found that sulpiride significantly decreased immobility time in the OVX females. A combination of sulpiride with a low dose of 17?-E2 induced more profound decrease of immobility time in the OVX rats compared to the rats treated with sulpiride alone. On the contrary, quinpirole failed to modify depression-like behavior in the OVX rats. In addition, quinpirole significantly blocked the antidepressant-like effect of 17?-E2 in OVX rats. Thus, the D2 receptor antagonist sulpiride alone or in combination with a low dose of 17?-E2 exerted antidepressant-like effect in OVX female rats, while the D2 receptor agonist quinpirole produced depressant-like profile on OVX rats. PMID:22530139

Fedotova, Julia



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

PubMed Central

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

Karami, Manizheh; Zarrindast, Mohammad Reza



An inter-gender effect on ethanol drinking in rats: Proximal females increase ethanol drinking in males  

Microsoft Academic Search

Three groups of male Long–Evans hooded rats were assessed for effects of social opportunity on drinking of ethanol or water. The ethanol\\/female group received intermittent presentations of a sipper containing ethanol that was followed by 15 s of social interaction opportunity with a female rat. The ethanol\\/male group received similar training except the social interaction opportunity was with a male

Arthur Tomie; Reka Hosszu; Rachel H. Rosenberg; Jennifer Gittleman; Patricia Patterson-Buckendahl; Larissa A. Pohorecky



Deficits in Progesterone-Facilitated Sexual Behaviors and Forebrain Estrogen and Progestin Receptors in Obese Female Zucker Rats  

Microsoft Academic Search

Obese female Zucker rats (fa\\/fa) are sterile. Among their reproductive abnormalities is hyporesponsiveness to the stimulatory effects of ovarian steroid hormones on sexual behaviors. This study was designed to test the hypothesis that obese Zucker females are deficient in hypothalamic\\/preoptic area estrogen receptors (ERs) and\\/or estradiol-induced progestin receptors (PRs). Ovariectomized (OVX) lean and obese Zucker rats were tested for the

Deborah H. Olster; Ilene D. Auerbach



Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens  

PubMed Central

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

Lund, Trent D; West, Timothy W; Tian, Lilyan Y; Bu, Lihong H; Simmons, Daniel L; Setchell, Kenneth DR; Adlercreutz, Herman; Lephart, Edwin D



Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats  

PubMed Central

We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women. PMID:18391188

Park, Collin R.; Zoladz, Phillip R.; Conrad, Cheryl D.; Fleshner, Monika; Diamond, David M.



A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase  

SciTech Connect

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.

Seppen, Jurgen, E-mail:



Appetite Regulation in the Rat Under Various Physiological Conditions: The Role of Dietary Protein and Calories1  

Microsoft Academic Search

Rat dams fed isocaloric diets either high (25%) or low (8%) in protein content demonstrated three distinct phases of appetite regulation. During periods of mature growth (250-g female rats neither pregnant nor lactating) food intake was regu lated by the caloric content of the diet alone. During pregnancy a 50% increase in food intake was seen in those rats fed



Characteristics of 106 spontaneous mammary tumours appearing in Sprague-Dawley female rats.  

PubMed Central

Pathological studies were undertaken on 106 mammary tumours (89 benign, 17 malignant) appearing spontaneously in 95 normal female Sprague-Dawley rats which were killed at Day 756. The benign tumours comprised those with a predominant acinar hyperplasia and those with adenomatous or fibroadenomatous pattern. No significant differences were found histochemically between the acinar cells of the benign tumours and of the lactating gland, except that the amount of fibrous interstitial connective tissue was larger in the former. 3H- or 35S-glycosaminoglycan synthesis by the benign tumours was found to be much higher. The prolactin value in the plasma of the benign-tumour-bearing rats was about 27 times that of 6-month-old virgin rats, and similar to that of rats on the 7th day post partum. Carcinomatous proliferation of tubuloacinar cells could be seen in 5 of the 89 benign tumours. The incidence of benign tumours increases with the age of the rats. Images Fig. 1 Fig. 2 Fig. 3 PMID:7248153

Okada, M.; Takeuchi, J.; Sobue, M.; Kataoka, K.; Inagaki, Y.; Shigemura, M.; Chiba, T.



c-fos Expression in the Forebrain after Mating in the Female Rat Is Altered by Adrenalectomy  

Microsoft Academic Search

In rats of both sexes, mating stimulates neuronal activity in forebrain areas that are also activated by stress. Hypothalamic cells in the arcuate (ARC) and paraventricular (PVN) nuclei synthesize hormones or peptides whose levels are altered by adrenalectomy. In this experiment, we examined whether the mating-induced expression of c-fos in the forebrain is altered by adrenalectomy (Adx) in female rats.

Nicole Cameron; Mary S. Erskine



The Serotonin Reuptake Inhibitor Fluoxetine Reduces Sex Steroid-Related Aggression in Female Rats: An Animal Model of Premenstrual Irritability?  

Microsoft Academic Search

The aggressive behavior displayed by some (but not all) female Wistar rats when an unfamiliar rat is being introduced into their home cage (the resident intruder paradigm) was found to be higher in non-receptive phases (metestrus, diestrus) than in the receptive phases (proestrus, estrus) of the estrus cycle, and effectively reduced by ovariectomy. When removal of the ovaries was followed

Hoi-Por Ho; Marie Olsson; M Pharm; Lars Westberg; Jonas Melke; Elias Eriksson



Assessment of anxiety-like behaviors in female rats bred for differences in kindling susceptibility and amygdala excitability  

Microsoft Academic Search

Two rat lines bred for kindling susceptibility were previously observed to engage in different behavioral strategies in tests of emotionality. In order to extend past research on defensive behaviors in these strains which largely used males, Fast- and Slow-kindling females were assessed for anxiety-like behaviors in a number of aversive paradigms. Fast rats entered and spent more time in the

Dwayne Runke; Dan C. McIntyre



Effects of different concentrations of sugarcane alcohol on food intake and nutritional status of male and female periadolescent rats  

Microsoft Academic Search

The present study evaluated the effects of food and alcohol intake on the nutritional and metabolic status of male and female periadolescent rats submitted to single (15%) and multiple (10%, 20%, 30%) concentrations of hydroalcoholic solutions of sugar-based alcohol associated with a feed mixture. Thirty-six periadolescent Wistar rats were used and randomly arranged into three groups: Group A (control; 0%

Luciana Gonçalves de Orange; Francisca Martins Bion; Cybelle Rolim de Lima



Lack of Correlation between paraAminophenol Toxicity in Vivoand in Vitroin Female Sprague–Dawley Rats  

Microsoft Academic Search

The present study was designed to test the hypothesis thatpara-aminophenol (PAP) nephrotoxicity is due to autooxidation. We compared renal functional responses following PAP administration to female Sprague–Dawley rats and following incubation of renal proximal tubules with PAP. The concentrations of PAP selected forin vitroincubations produced cytotoxicity (for example, a decrease in oxygen consumption or adenine nucleotide concentration) in rat renal

Rong Shao; Joan B. Tarloff



Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane  

Microsoft Academic Search

Background: Aromatase inhibition has been proposed as a potential approach for growth enhancement in children with short stature, but detailed animal studies are lacking. Aim: To assess the effect and potential adverse effects of aromatase inhibition on growth in female rats. Methods: Prepubertal Wistar rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10,

Sandy A. van Gool; Jan M. Wit; Tineke De Schutter; Nora De Clerck; Andreï A. Postnov; Sandra Kremer Hovinga; Jaap van Doorn; Sergio J. Veiga; Luis Miguel Garcia-Segura; Marcel Karperien



Loss of Ovarian Estrogens Causes Only Mild Deterioration of Glucose Homeostasis in Female ZDF Rats Preventable by Voluntary Running Exercise.  


Studies on normoglycemic ovariectomized Sprague-Dawley rats have provided insights about the effects of estrogen deficiency on insulin resistance in lean individuals. It is not completely clear if subjects with pre-established obesity and insulin resistance are at greater risk of developing type 2 diabetes when ovarian estrogens are no longer secreted, and if physical activity can protect against this susceptibility. Contrasting with their male counterparts, obese and insulin resistant female ZDF (Zucker diabetic fatty) rats do not become hyperglycemic when fed a standard diet. The aim of the study was to evaluate the hypothesis that withdrawal of ovarian estrogens in insulin resistant female ZDF rats would trigger overt hyperglycemia, provided they remain physically inactive. Female ZDF rats underwent either an ovariectomy (OVX) or a simulated surgery (SHAM). Thereafter, OVX rats engaged either in voluntary wheel cage running (OVX-Active), or like the Sham rats, remained sedentary (OVX-Sed) for 6 weeks. Fasting glycemia, insulinemia, and glucose tolerance were not altered in OVX-Sed as compared to SHAM-Sed rats. However, OVX-Sed rats showed altered liver triglyceride and glycogen contents, increased pancreatic insulin content and reduced insulin-stimulated muscle pAKT as compared to SHAM-Sed rats. Physical activity in OVX rats lowered fasting glucose and insulin levels, improved glucose tolerance and insulin-stimulated skeletal muscle glucose uptake as compared to OVX-Sed rats. OVX-induced alterations in pancreatic insulin content and liver glycogen and triglyceride contents were significantly improved by physical activity. Loss of ovarian estrogens did not cause overt hyperglycemia in insulin-resistant female ZDF rats. Physical activity improved glucose homeostasis despite estrogen deficiency. PMID:24983383

Bergeron, R; Mentor, J S; Côté, I; Ngo Sock, E T; Rabasa-Lhoret, R; Lavoie, J M



Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats.  


Each year, 75 million pounds of the broadleaf herbicide atrazine (ATR) are applied to crops in the United States. Despite limited solubility, ATR is common in ground and surface water, making it of regulatory concern. ATR suppresses the immunomodulatory hormones prolactin (PRL) and the thyroid hormones (THs), with developmental exposure to ATR permanently disrupting PRL regulation. We hypothesized that ATR may cause developmental immunotoxicity through its disruption of PRL or THs. To test this hypothesis, pregnant Sprague-Dawley (SD) rats were exposed to 35-mg ATR/kg/d from gestational day (GD) 10 through postnatal day (PND) 23. Separate groups were exposed to bromocryptine (BCR) at 0.2 mg/kg/2x/day to induce hypoprolactinemia or to propylthiouracil (PTU) at 2 mg/kg/day to induce hypothyroidism. After the offspring reached immunologic maturity (at least 7 weeks old), the following immune functions were evaluated: natural killer (NK) cell function; delayed-type hypersensitivity (DTH) responses; phagocytic activity of peritoneal macrophages; and antibody response to sheep erythrocytes (SRBC). ATR decreased the primary antibody and DTH responses in male offspring only. Neither PTU nor BCR caused immunosuppression in any measured variable, although PTU increased phagocytosis by peritoneal macrophages. These results demonstrate that developmental exposure to ATR produced gender-specific changes in immune function in adult rats and suggest that immune changes associated with ATR are not mediated through the suppression of PRL or THs. PMID:14514952

Rooney, Andrew A; Matulka, Raymond A; Luebke, Robert W



Effects of aqueous extract of Aspilia africana on reproductive functions of female Wistar rats.  


Effects of Aspilia africana leaf extract on oestrous cycle and ovulation were studied in adult female Wistar strain rats. Cyclic female rats weighing 150 to 200 g were divided into two study groups: the oestrous study and ovulation study group. For the oestrous study, the experimental group received 500 mg kg(-1) b. wt. of the extract for 14 days while the control group received distilled water for the same period. In both groups, vaginal lavage was taken daily from the 5th day to monitor the oestrous cycle. For the ovulation study, there was a control group and two experimental groups. The control group received distilled water while group 1 and 2 received 500 and 1000 mg kg(-1) b.wt. of Aspilia africana leaf extract for 16 days, respectively. The animals were sacrificed on the estrous following the treatment. The results showed a significant decrease in the body weight of the treated rats (p = 0.01) and the oestrous cycle was altered after the commencement of extract. This was indicated by the prolonged proestrous and a reduced dioestrus and estrus. There was a dose-dependent reduction in the ovulation s shown by the reduced number of ova observed in the oviduct from the treated rats compared with control (p<0.05). The extract caused inflammation of the fallopian tube, degeneration in the ovarian cortex in the stroma cells of the ovary and disruption of the endometrium of the uterus. Results suggest that aqueous extract of Aspilia africana leaf has antifertility effect by altering oestrous cycle and causing a dose dependent adverse effect on ovulation in Wistar strain rats. PMID:20437701

Oyesola, T O; Oyesola, O A; Okoye, C S



Ovariectomy Results in Variable Changes in Nociception, Mood and Depression in Adult Female Rats  

PubMed Central

Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way. PMID:24710472

Li, Li-Hong; Wang, Zhe-Chen; Yu, Jin; Zhang, Yu-Qiu



Effects of ovariectomy and growth hormone administration on body composition and vascular function and structure in old female rats  

Microsoft Academic Search

Aging and estrogen-deprivation induce deleterious effects on body composition and vascular function in females. On the other hand, growth hormone (GH), whose production is reduced by age, exerts several vascular effects. The aim of this study was to investigate the effect of long-term estrogen deprivation and GH administration on body composition, vascular function and structure in aged female rats. Methods:

C. Castillo; M. Cruzado C. Ariznavarreta; V. Lahera; V. Cachofeiro; P. Gil-Loyzaga; Jesús A. F. Tresguerres



Response of ER -IR and ER -IR cells in the forebrain of female rats to mating stimuli  

E-print Network

Response of ER -IR and ER -IR cells in the forebrain of female rats to mating stimuli Be´atrice Gre on estrogen receptors (ERs) found in particular brain regions. While hormonal regulation of female sexual behavior requires ER , the possible functions of ER remain to be clarified. Mating stimulation has several

Blaustein, Jeffrey D.


Antispasmodic Effects of Aqueous and Hydroalcoholic Punica granatum Flower Extracts on the Uterus of Non-pregnant Rats  

PubMed Central

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 ?-adrenoceptors or potassium channels. PMID:23926538

Ahangarpour, Akram; Heidari, Razieh; Abdolahzadeh, Mahsa; Oroojan, Ali Akbar



Levels of DNA damage in blood leukocyte samples from non-diabetic and diabetic female rats and their fetuses exposed to air or cigarette smoke.  


The objective of the present study was to evaluate DNA damage level in blood leukocytes from diabetic and non-diabetic female Wistar rats exposed to air or to cigarette smoke, and to correlate the findings with levels of DNA damage detected in blood leukocyte samples from their fetuses. A total of 20 rats were distributed into four experimental groups: non-diabetic (control; G1) and diabetic exposed to filtered air (G2); non-diabetic (G3) and diabetic (G4) exposed to cigarette smoke. Rats placed into whole-body exposure chambers were exposed for 30min to filtered air (control) or to tobacco smoke generated from 10 cigarettes, twice a day, for 2 months. Diabetes was induced by a pancreatic beta-cytotoxic agent, streptozotocin (40mg/kgb.w.). At day 21 of pregnancy, each rat was anesthetized and humanely killed to obtain maternal and fetal blood samples for genotoxicity analysis using the alkaline comet assay. G2, G3 and G4 dams presented higher DNA damage values in tail moment and tail length as compared to G1 group. There was a significant positive correlation between DNA damage levels in blood leukocyte samples from G2 and G3 groups (tail moment); G3 and G4 groups (tail length) and G3 group (tail intensity) and their fetuses. Thus, this study showed the association of severe diabetes and tobacco cigarette smoke exposure did not exacerbate levels of maternal and fetal DNA damages related with only diabetes or cigarette smoke exposure. Based on the results obtained and taking into account other published data, maternal diabetes requires rigid clinical control and public health and education campaigns should be increased to encourage individuals, especially pregnant women, to stop smoking. PMID:18455954

Lima, Paula Helena Ortiz; Damasceno, Débora Cristina; Sinzato, Yuri Karen; de Souza, Maricelma da Silva Soares; Salvadori, Daisy Maria Fávero; Calderon, Iracema de Mattos Paranhos; Rudge, Marilza Vieira Cunha



Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats  

NASA Technical Reports Server (NTRS)

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.

Allen, Matthew R.; Bloomfield, Susan A.



In utero exposure to the environmental androgen trenbolone masculinizes female Sprague-Dawley rats.  


Recently, the occurrence of environmental contaminants with androgenic activity has been described from pulp and paper mill effluents and beef feedlot discharges. A synthetic androgen associated with beef production is trenbolone acetate, which is used to promote growth in cattle. A primary metabolite, 17beta Trenbolone (TB), has been characterized as a potent androgen in both in vitro and in vivo studies with rats. The current study was designed to characterize the permanent morphological and functional consequences of prenatal TB exposure on female rats compared with those produced in an earlier study with testosterone propionate (TP). Female rat offspring were exposed to 0mg/day, 0.1mg/day, 0.5mg/day, 1.0mg/day, or 2.0mg/day TB on gestational days 14-19. The 0.5mg/day, 1.0mg/day, or 2.0mg/day TB groups displayed increases in neonatal anogenital distance (AGD) which persisted in the high dose group. Puberty was delayed in the high dose group and there were increased incidences of external genital malformations and the presence of male prostatic tissue in the 0.5mg/day, 1.0mg/day, or 2.0mg/day groups. These changes were associated with amniotic fluid concentrations of TB that compare favorably with concentrations known to be active in both in vitro systems and in fish. PMID:17931805

Hotchkiss, A K; Furr, J; Makynen, E A; Ankley, G T; Gray, L E



Comparison of Dexamethasone Pharmacokinetics in Female Rats after Intravenous and Intramuscular Administration  

PubMed Central

This study seeks a route of drug administration that would produce a pharmacokinetic profile for dexamethasone not significantly different from the intravenous route in female rats and would offer reproducible drug input with minimal stress to the animals. The intramuscular (IM) route of drug administration vs intravenous (IV) injection were compared in three female Wistar rats administered 1 mg/kg dexamethasone phosphate. Dexamethasone plasma concentrations were measured by a normal phase HPLC assay for 12 h after drug administration. Dexamethasone exhibited monoexponential behavior after intravenous dosing and was absorbed rapidly after intramuscular dosing (absorption half-life of 14 min) with 86% bioavailability. Dexamethasone had a terminal half-life of 2.3 h after drug administration by either route. The volume of distribution of 0.78 l/kg and the clearance of 0.23 l/h/kg are in good agreement with reported pharmacokinetic parameters in male rats. Intravenous dosing can be replaced by intramuscular dosing without causing any marked difference in dexamethasone pharmacokinetics. PMID:15654687

Samtani, Mahesh N.; Jusko, William J.



Single trial nicotine conditioned place preference in pre-adolescent male and female rats.  


The mean age of first voluntary tobacco inhalation is 12.3years (DiFranza et al., 2004). 60% of smokers start smoking before the age of 14 and 90% are dependent before reaching the age of 19. Females are typically more sensitive to nicotine than males yet few studies examine the effects of nicotine on the reward systems in pre-adolescent female subjects. This study utilized the single trial conditioned place preference (CPP) test in very young (postnatal day 25-27) rats of both sexes. Latent effects on anxiety and amphetamine response were determined 5 and 7days following a second nicotine exposure. Results show that 0.05mg/kg nicotine induced CPP in females following a single trial while both sexes showed CPP following the 0.5mg/kg dose. Five days later, rats dosed with 0.05mg/kg show increased time on the open arm of the elevated plus maze, an anxiolytic response. While baseline activity was increased in nicotine-exposed males 7days following dosing, amphetamine response was not affected by the treatments in either sex. Therefore, our data suggest that young females are more sensitive to nicotine reward than males supporting a heightened sensitivity of the mesolimbic dopamine system in very young females. However, alterations in baseline activity were only seen in males suggesting that different components of the system are affected by nicotine in each sex. An anxiolytic response to nicotine 5days after dosing may suggest that this very young age group is uniquely affected by this very low nicotine dose. Clearly, nicotine has substantial acute and lasting effects during pre-adolescence at doses substantially lower than seen at older ages as reported by others. These effects, which could potentially result from cigarette or e-cigarette smoking by 11-12year old children , focus attention on the vulnerability of this age group to nicotine. PMID:25109273

Edwards, Alexander W; Konz, Nathan; Hirsch, Zahava; Weedon, Jeremy; Dow-Edwards, Diana L



Percutaneous absorption of triadimefon in the adult and young male and female rat  

SciTech Connect

The percutaneous absorption of /sup 14/C-phenoxy ring labeled triadimefon was studied in adult and young male and female Sprague-Dawley rats. Triadimefon was applied (41.1 to 46.4 micrograms/cm2) in 0.2 ml of acetone to areas comprising 3% of the body surface (7.0 to 14.5 cm2). Thirty-six animals were treated at the initiation of each study. Groups of three animals were subsequently killed at 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hr after treatment. Skin from the treated area as well as blood, heart, liver, kidneys, remaining carcass, urine, and feces were analyzed for /sup 14/C by scintillation counting techniques. Based on /sup 14/C counts, triadimefon was lost more rapidly from the skin of young animals (t 1/2, 20 to 25 hr) than from the skin of adult animals (t 1/2, 29 to 53 hr). Recovery studies indicated that adult males, adult females, young males, and young females, respectively, absorbed 53, 82, 57, and 52% of the dose. The rest of the dose based on material balance was presumably lost by evaporation. Approximately 2.5 to 3.9% of the dose penetrated the skin in one hour and was available for absorption. The rate of entry triadimefon into blood was 2 to 2.5 times faster for young than that observed in adult animals. Elimination of it from blood was faster in the case of the young animals. Triadimefon was absorbed through the skins of the adult male, adult female, young male, and young female rats, respectively, at rates of 0.20, 0.50, 0.58, and 0.48 micrograms/hr/cm2 of skin.

Knaak, J.B.; Yee, K.; Ackerman, C.R.; Zweig, G.; Wilson, B.W.



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


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

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



Effects of perinatal ethinyl estradiol exposure in male and female Wistar rats.  


Perinatal exposure to endocrine disrupting chemicals with estrogenic activity can adversely affect reproductive development, but few studies evaluating estrogen-sensitive endpoints have been performed in Wistar rats. Therefore, time-mated Wistar rats (n=10) were gavaged during gestation and lactation with 0, 5, 15 or 50?g/kg bw/day of ethinyl estradiol. This potent estrogen was found to induce an increased number of nipples and reduced ovary weight in female offspring. Malformations of female genitalia were found in young as well as adult offspring, as an increased AGD was seen at birth and a deeper urethral slit length was seen in adulthood. In prepubertal male offspring, estrogen-regulated gene expression in ventral prostate was increased dose-dependently and a decreased ventral prostate weight was seen at 15?g/kg. Female external sexual characteristics and prostate development were found to be targets for exposure to estrogenic compounds and may be of interest in studies on estrogenic environmental compounds. PMID:24036065

Mandrup, Karen Riiber; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Axelstad, Marta; Dreisig, Karin; Hadrup, Niels; Vinggaard, Anne Marie; Hass, Ulla; Boberg, Julie



Hepatic enzyme induction potential of acitretin in male and female Sprague-Dawley rats.  


Certain retinoids have been shown in rats and mice to induce the hepatic cytochrome P-450 enzyme system, and evidence from our laboratory suggested that acitretin, the active primary metabolite of etretinate (a retinoid used in the treatment of psoriasis) may induce its own metabolism. To test this hypothesis, male and female Sprague-Dawley rats were orally pretreated with acitretin for 18 days (10 mg/kg/day) and intravenously dosed with acitretin on day 20 (0.8-0.9 mg/kg). Serial blood samples were taken through 24 h, after which the hepatic microsomal proteins were harvested. Plasma concentrations of acitretin and its main metabolite isoacitretin were determined by HPLC, and total hepatic cytochrome P-450 concentrations and activities were determined using standard methods. Systemic clearance (17.4 +/- 2.5 and 12.1 +/- 1.6 mL/min per kg in control males and females, respectively), volume of distribution at steady state (Vss = 1568 +/- 353 and 1589 +/- 488 mL in control males and females, respectively), and mean residence time (MRT = 1.50 +/- 0.23 and 2.22 +/- 0.70 h in control males and females, respectively) were unchanged by acitretin pretreatment. Systemic clearance was 44% higher in control males than females. Concentrations of total microsomal protein (13.8 +/- 1.6 and 8.4 +/- 1.2 mg/g of liver in control males and females, respectively) and total P-450 (0.433 +/- 0.041 and 0.425 +/- 0.104 nmol/mg microsomal protein in control males and females, respectively) were also unchanged by acitretin pretreatment, as were microsomal levels of methoxy-, ethoxy-, pentoxy-, and (benzyloxy)resorufin O-dealkylation (MROD, EROD, PROD, and BROD, respectively) (control males and females, respectively, expressed as pmol of resorufin formed/min per mg of microsomal protein: MROD = 37.7 +/- 4.5 and 30.6 +/- 4.2; EROD 276 +/- 40 and 208 +/- 59; PROD = 15.2 +/- 4.5 and 5.8 +/- 1.2; and BROD 93.7 +/- 24.4 and 15.5 +/- 3.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8071817

Small, D S; McNamara, P J



Amygdala activation by corticosterone alters visceral and somatic pain in cycling female rats.  


Irritable bowel syndrome (IBS) is often seen in women, and symptom severity is known to vary over the menstrual cycle. In addition, activation of the hypothalamic-pituitary-adrenal (HPA) axis enhances symptomology and patients with IBS have increased activation of the amygdala, a brain region known to facilitate HPA output. However, little is known about the effects of amygdala activation during different stages of the menstrual cycle. We therefore investigated the effects of amygdala activation on somatic and visceral pain perception over the rat estrous cycle. Female Wistar rats were implanted with either corticosterone (Cort) or cholesterol as a control onto the dorsal margin of the central amygdala. Visceral sensitivity was quantified by recording the visceromotor response (VMR) to colorectal distension (CRD) and somatic sensitivity was assessed via the Von Frey test. In cholesterol controls, both visceral and somatic sensitivity varied over the estrous cycle. Rats in proestrus/estrus responded to CRD with an increased VMR compared with rats in metestrus/diestrus. Somatic sensitivity followed a similar pattern with enhanced sensitivity during proestrus/estrus compared with metestrus/diestrus. Elevated amygdala Cort induced visceral hypersensitivity during metestrus/diestrus but had no effect during proestrus/estrus. In contrast, elevated amygdala Cort increased somatic sensitivity during both metestrus/diestrus and proestrus/estrous. These results suggests that amygdala activation by Cort eliminates spontaneously occurring differences in visceral and somatic pain perception, which could explain the lowered pain thresholds and higher incidence of somatic pain observed in women with IBS. PMID:21454447

Gustafsson, Jenny K; Greenwood-Van Meerveld, Beverley



Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats.  


Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats. PMID:15204037

Hamann, Scott R; Malik, Hammad; Sloan, Jewell W; Wala, Elzbieta P



Effects of pyperonyl butoxide on the female reproductive tract in rats.  


This study was investigated the effects of piperonyl butoxide (PBO) on the female reproductive tract. Female Crj:Donryu rats were fed a basal diet containing 5,000, 10,000 or 20,000 ppm PBO for 28 days, and compared with food-restricted rats of comparable body weights to those in the PBO 10,000 or 20,000 ppm groups. Although treatment with 20,000 ppm PBO for 28 days depressed body weight gain, the abnormal estrous cyclicity, mainly prolonged diestrus, was also induced by the PBO treatment which was not correlated with body weight change. 20,000 ppm PBO treatment markedly decreased uterine weights and slightly decreased ovarian weights. 10,000 and 20,000 ppm PBO treatment increased liver weights. These cycle and organ weight changes were linked to atrophic uterus and increased atretic follicles in the ovary. In hormone assays, PBO at both doses reduced serum E2 levels, but did not affect corticosterone levels. An anti-uterotrophic assay showed a slight but significant decrease in absolute uterine weight and a reduction of endometrial epithelium height in the 20,000 ppm group. PBO was positive in an ER ? antagonist reporter gene assay, although the activity was much weaker than that of 4-hydroxytamoxifen. These results indicate that high-dose PBO treatment directly induces atrophic changes in the female reproductive tract in rats, and these effects are likely the result of a hypoestrogenic state and the anti-estrogenic activity of PBO. PMID:24213009

Hayashi, Seigo; Taketa, Yoshikazu; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Irie, Kaoru; Watanabe, Gen; Yoshida, Midori



Estrous cycle affects the neurochemical and neurobehavioral profile of carvacrol-treated female rats  

SciTech Connect

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.

Trabace, L., E-mail: [Department of Biomedical Sciences, University of Foggia, V. le Luigi Pinto 1, 71121 Foggia (Italy); Zotti, M.; Morgese, M.G.; Tucci, P.; Colaianna, M.; Schiavone, S. [Department of Biomedical Sciences, University of Foggia, V. le Luigi Pinto 1, 71121 Foggia (Italy); Avato, P. [Department of Pharmaco-Chemistry, University of Bari, 'A. Moro', Via Orabona 4, 70125, Bari (Italy); Cuomo, V. [Department of Human Physiology and Pharmacology, Vittorio Erspamer, University of Rome 'La Sapienza', P. le Aldo Moro 5, 00185, Rome (Italy)



Low-dose effects of bisphenol A on early sexual development in male and female rats.  


Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50?mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25?mg/kg bw per day). Time-mated Wistar rats (n=22) were gavaged during pregnancy and lactation from gestation day 7 to pup day 22 with 0, 0.025, 0.25, 5 or 50?mg/kg bw per day BPA. From 0.250?mg/kg and above, male anogenital distance (AGD) was significantly decreased, whereas decreased female AGD was seen from 0.025?mg/kg bw per day and above. Moreover, the incidence of nipple retention in males appeared to increase dose relatedly and the increase was statistically significant at 50?mg/kg per day. No significant changes in reproductive organ weights in the 16-day-old males and females and no signs of maternal toxicity were seen. The decreased AGD at birth in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5?mg/kg for BPA, which is used as the basis for establishment of the current tolerable daily intake (TDI) by EFSA; thus a reconsideration of the current TDI of BPA appears warranted. PMID:24298045

Christiansen, Sofie; Axelstad, Marta; Boberg, Julie; Vinggaard, Anne Marie; Pedersen, Gitte Alsing; Hass, Ulla



Effects of induced precocious puberty on cranial growth in female Wistar rats.  


This investigation examined the effects of pharmacologically induced precocious puberty on cranial growth in Wistar rats. Forty-eight female newborn Wistar rats were divided into two groups: a control group (C) and an experimental group (E), with four subgroups of six animals each. The time interval from birth until sacrifice differed between the subgroups, and was set at 30, 60, 90, and 120 days. An intramuscular single dose (300 ?g) of steroid hormone danazol was administered on day 5 after birth, as a means of inducing precocious puberty. Alizarin (2 mg/100 g) was administered to three animals in each subgroup three days prior to sacrifice. Body mass and dates corresponding to the beginning of the oestrous cycle were recorded. Craniometric measurements were undertaken. Histological analysis using light and fluorescence microscopy was then carried out to qualitatively and quantitatively evaluate the spheno-occipital synchondrosis and to visualize bone deposition patterns. The results were analysed with a Student's t-test and analysis of variance. Precocious puberty was effectively induced and differences between groups denoted an earlier maturation in the experimental rats. In qualitative analysis, a significant increase of total synchondrosis width was noted only in group E60, in comparison with C60, and an increase in the E90 subgroup cortical bone width compared with the C90 subgroup. Histomorphometrically, a statistical difference between total width values of subgroups E60 (434.3 ?m) and C60 (323.5 ?m) was detected. However, body mass and macroscopic measurements did not show statistically significant differences. An appropriate model for studying bone growth associated with precocious puberty in Wistar female rats was not achieved using steroid hormone danazol, when evaluated at 30 day intervals. PMID:21808074

Izquierdo, Antonio de Moraes; Mishima, Fernanda Danielle; Carrard, Vinícius Coelho; Farina, Marcos; Nojima, Matilde da Cunha Gonçalves



Evaluation of reproductive function of female rats exposed to radiofrequency fields (27. 12 MHz) near a shortwave diathermy device  

SciTech Connect

In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

Brown-Woodman, P.D.; Hadley, J.A.; Richardson, L.; Bright, D.; Porter, D.



Amphetamine effects on startle gating in normal women and female rats  

Microsoft Academic Search

Background  Dopamine agonists disrupt prepulse inhibition (PPI) of startle in male rodents. In humans, this is observed only in some studies.\\u000a We reported that PPI was disrupted by d-amphetamine in men, but only among those with high basal PPI levels. Here, amphetamine effects on PPI were tested in normal\\u000a women and female rats.\\u000a \\u000a \\u000a \\u000a Materials and methods  Acoustic startle and PPI were tested

Jo A. Talledo; Ashley N. Sutherland Owens; Tijmen Schortinghuis; Neal R. Swerdlow



Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction  

PubMed Central

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy. PMID:22345570

Johnson, Megan S.; Ma, Lixin; Pulakat, Lakshmi; Mugerfeld, Irina; Hayden, Melvin R.; Garro, Mona; Knight, William; Britton, Steven L.; Koch, Lauren G.; Sowers, James R.



Age-specific features of estrous cycles and folliculogenesis in GC female rats selected by catatonic reactivity.  


A decrease in the total count of follicles in the diestrus and proestrus and higher incidence of permanent estruses were found in 3-month-old females of the catatonic GC rat strain in comparison with Wistar females (control). At the age of 6-12 months, GC females had lower incidence of long estrus and diestrus. The estrous cycle of GC females was shorter than of Wistar rats. With aging (at the age of 18 months), the counts of growing and maturing follicles significantly decreased. Higher counts of growing single-layer and bilayer follicles were found in 18-month-old GC females. Differences in the length of estrus and diestrus and in the incidence of abnormal phases in the two strains also disappeared at this age. Selection by high catatonic reactivity was associated with a decrease in body weight. PMID:22238754

Klochkov, D V; Alekhina, T A; Prokudina, O I



A new slow releasing, H?S generating compound, GYY4137 relaxes spontaneous and oxytocin-stimulated contractions of human and rat pregnant myometrium.  


Better tocolytics are required to help prevent preterm labour. The gaseotransmitter Hydrogen sulphide (H(2)S) has been shown to reduce myometrial contractility and thus is of potential interest. However previous studies used NaHS, which is toxic and releases H(2)S as a non-physiological bolus and thus alternative H(2)S donors are sought. GYY4137 has been developed to slowly release H(2)S and hence better reflect endogenous physiological release. We have examined its effects on spontaneous and oxytocin-stimulated contractility and compared them to NaHS, in human and rat myometrium, throughout gestation. The effects on contractility in response to GYY4137 (1 nM-1 mM) and NaHS (1 mM) were examined on myometrial strips from, biopsies of women undergoing elective caesarean section or hysterectomy, and from non-pregnant, 14, 18, 22 day (term) gestation or labouring rats. In pregnant rat and human myometrium dose-dependent and significant decreases in spontaneous contractions were seen with increasing concentrations of GYY4137, which also reduced underlying Ca transients. GYY4137 and NaHS significantly reduced oxytocin-stimulated and high-K depolarised contractions as well as spontaneous activity. Their inhibitory effects increased as gestation advanced, but were abruptly reversed in labour. Glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of GYY4137. These data suggest (i) H(2)S contributes to uterine quiescence from mid-gestation until labor, (ii) that H(2)S affects L-type calcium channels and K(ATP) channels reducing Ca entry and thereby myometrial contractions, (iii) add to the evidence that H(2)S plays a physiological role in relaxing myometrium, and thus (iv) H(2)S is an attractive target for therapeutic manipulation of human myometrial contractility. PMID:23029460

Robinson, Hayley; Wray, Susan



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


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 17?-estradiol and the atypical APD clozapine, whereas the typical APD haloperidol was ineffective unless co-administered with 17?-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 17?-estradiol (150 ?g/kg) and clozapine (2.5mg/kg), but not by haloperidol (0.1mg/kg) or lower doses of 17?-estradiol (10 and 50 ?g/kg). However, co-administration of haloperidol with 17?-estradiol (50 ?g/kg) was effective. In sham rats low 17?-estradiol (10 ?g/kg) produced rapid reversal, while high 17?-estradiol (150 ?g/kg), haloperidol alone, or haloperidol-17?-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

Arad, Michal; Weiner, Ina



Renoprotective effect of hydroalcoholic extract of Rheum ribes root in diabetic female rats  

PubMed Central

Objective: Medical plants, as rich sources of natural antioxidants with antidiabetic effects, are used worldwide to diminish a variety of symptoms and many diseases. R. ribes L., which belongs to the family of polygonaceae, can provide symptomatic relief and assist in the prevention of the secondary complications of the diabetes. Material and Methods: 36 female adult rats were randomly divided into 6 groups of 6. Normal Control groups treated with normal saline. Positive control groups treated with hydroalcohlic extract of R. ribes root (150 mg/kg) daily by gavages for 4 consecutive weeks. Diabetes was inducedby injection of 120 mg/kg alloxan monohydrate intraperitoneally. Two diabetic groups were treated with different doses of R. ribes root extract. The sixth diabetic groups were treated with glibenclamide (0.6 mg/kg). At the end of 28 days, blood samples were collected and their kidney tissues were processed for light microscopy. Results: The results showed that hydro-alcoholic extract of R. ribes decreased the level of glucose, cholesterol, triglyceride, urea and creatinine in diabetic rats (p<0.05) in compared with diabetic rats, while the level of HDL increased at the same group (p<0.05). Histopathological changes of kidney samples were comparable with respective control. In diabetic rats, kidney sections showed atrophy of glomerular capillaries with increased Bowman's space and acute tubular necrosis. The groups that were treated with R. ribes root were improved towards normal condition. Conclusion: It is interesting to note that hydroalcohlic extract of R. ribes root improves renal dysfunction in alloxan-induced diabetic rats through controlling blood glucose and renal protective effects. PMID:25386403

Hamzeh, Shokri; Farokhi, Farah; Heydari, Reza; Manaffar, Ramin



Preliminary assessment of the oral toxicity of 1,5-diazido-3-nitrazapentane, 2- and 6-week feeding study, male and female rats. Final report  

SciTech Connect

A 2 and 6 week gavage feeding of DANPE caused testicular hypospermatogenesis in male rats and pneumonitis in female rats. A NOAEL was not achieved in male rats but was achieved in female rats at the 56.00 mg/kg/day dose level.... 1,5-Diazido-3-Nitrazapentane (DANPE), Gavage, Testicular hypospermatogenesis, Insterstitual Inflammation No-observed-Adverse-Effect-Level(NOAEL), Feeding study.

Haight, E.A.; Harvey, J.G.; Bell, P.A.



Teratologic Evaluation of Hydrochlorothiazide (CAS No. 58-93-5) Administered to CD (Trade Name) Rats on Gestational Days 6 through 15.  

National Technical Information Service (NTIS)

Hydrochlorothiazide (HCTZ) is a widely used thiazide diuretic. HCTZ (0, 100, 300 and 1000 mg/kg/day, po) was administered to timed-pregnant CD rats on gestational days (gd) 6 through 15. At sacrifice (gd 20), confirmed-pregnant females (36-39 per group) w...

C. A. Kimmel, C. J. Price, J. D. George, M. C. Marr, R. Wolkowski-Tyl



Immediate early gene activity-regulated cytoskeletal-associated protein regulates estradiol-induced lordosis behavior in female rats.  


Sensory feedback is an important component of any behavior, with each instance influencing subsequent activity. Female sexual receptivity is mediated both by the steroid hormone milieu and interaction with the male. We tested the influence of repeated mating on the level of sexual receptivity in ovariectomized rats treated with estradiol benzoate (EB) once every fourth day to mimic the normal phasic changes of circulating estradiol. Females were divided into two groups: naïve, which were tested for lordosis behavior once, and experienced rats, which were tested for lordosis after each EB injection. To monitor the effect of mating, the number of neurons expressing the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) were counted in the mediobasal hypothalamus. Females were unreceptive following the first EB treatment, but the mating induced Arc expression. In naïve rats, each subsequent EB injection increased the levels of sexual receptivity. This ramping was not observed in experienced rats, which achieved only a moderate level of sexual receptivity. However, experienced females treated with EB and progesterone were maximally receptive and did not have Arc expression. To test whether the expression of Arc attenuated lordosis, Arc antisense oligodeoxynucleotides (asODN) were microinjected into experienced females' arcuate nuclei. Arc expression was attenuated, and the experienced EB-treated females achieved maximal sexual receptivity. These results demonstrate that Arc expression in the hypothalamus might influence future sexual receptivity and provides evidence of learning in the arcuate nucleus. The loss of Arc results in unrestrained sexual receptivity. © 2014 Wiley Periodicals, Inc. PMID:25088303

Christensen, Amy; Dewing, Phoebe; Micevych, Pavel




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....


[Morphological changes induced by valproate and its administration concomitant with folinic acid or S-adenosylmethionine in pregnant rats].  


Neural tube defects (NTD) are serious congenital abnormalities that have a multifactorial etiology, including both genetic and environmental effectors (for example, diet and/or drugs). Valproic acid (VPA) is a frequently used anti-epileptic drug that has a potentially teratogenic character, as well as the capacity for inducing NTD and other less serious malformations. However, the mechanism of action of VPA has not been clearly established, and it has been suggested that it interferes in the folate cycle and therefore, with the methionine/methylation, possibly through a metabolic blocking of some biomarker that is a key of the cycle, such as for example S-adenosylmethionine (SAM) and folic acid (FA). The objective of the present study is to analyze the morphological and histological changes, which can occur in a high risk experimental model after the administration of VPA as well as for the induction of NTD and other malformations. In addition, the protective roles of the administration of folic acid, 5-formyltetrahydrofolate (FOL) and S-adenosylmethionine (SAM) are assessed. For this pregnant "Wistar" rats classified according to the following treatments: 1) VPA (300 mg/kg/day on days 8, 9, and 10 of the pregnancy); II) VPA (300 mg/kg/day on days 8, 9, and 10 of the pregnancy) and FOL (4 mg/kg/day i.p. on days 8, 9, and 10 of the pregnancy); III) VPA (300 mg/kg/day on days 8, 9, and 10 of the pregnancy) + SAM (10 mg/kg/day, on days 1-10 of the pregnancy); IV) CONTROL (no treatment). VPA decreases the fertility index by 25% compared to the control group, it increases the number of reabsorptions by mother (1.3 +/- 0.5 vs 1.0 +/- 0.5), and decreases the number of fetuses compared to the control (9.0 +/- 1.4 vs. 12.6 +/- 0.9). In the VPA + FOL group, the numbers for these parameters approach those of the control group and the VPA + SAM group is no different from the VPA group, showing no protective factors. With respect to the bone alterations observed, when these are grouped according to whether they affect the skull, trunk, and extremities, it is seen that there are no significant differences between the groups. The histological study and the immunohistochemical analysis show liver alterations in all groups treated, and a lower number of lymphocytes in the VPA group, and a greater number of Kupffer cells, The results are discussed in relation to, first, the effect of VPA per se in the interference of the methionine/methylation cycle, and secondly, with regard to how folic acid and/or S-adenosylmethionine can improve or not some of the harmful effects induced by VPA. PMID:9578686

Ubeda-Martín, N; Alonso-Aperte, E; Achón, M; Varela-Moreiras, G; Puerta, J; Pérez de Miguelsanz, J



Disposition and acute toxicity of imidacloprid in female rats after single exposure.  


Single dose of imidacloprid (IMI-20mg/kg bodyweight) was orally administered in female rats. Its disposition along with two metabolites 6-chloro nicotinic acid (6-CNA) and 6-hydroxy nicotinic acid (6-HNA) was monitored in organs (brain, liver, kidney, and ovary) and bodily fluids (blood, urine) at 6, 12, 24 and 48h and faeces at 24 and 48h. Maximum concentration (Cmax) of IMI and metabolites in each organ and bodily fluid occurred after 12h. Area under curve (AUC) of IMI ranged from 35 to 358?g/ml/h; 6-CNA: 27.12-1006.42?g/ml/h and 6-HNA: 14.98-302.74?g/ml/h in different organs and bodily fluids. Clearance rate of IMI was maximum in ovary followed by kidney, liver, brain, faeces, blood and urine. Percent inhibition of acetyl-cholinesterase (AChE) was comparable in brain and Red Blood Cells (RBC) at 6-48h which suggests the RBC-AChE as valid biomarker for assessing IMI exposure. It is evident that IMI was absorbed, metabolized, and excreted showing increased level of serum enzymes like Glutamic oxaloacetic transaminase (GOT), Glutamic pyruvic transaminase (GPT) and biochemical constituents like billirubin and Blood Urea Nitrogen (BUN) at 48h. These data suggest that IMI is widely distributed, metabolized and induced toxicology effects at 20mg/kg bodyweight to female rats. PMID:24662525

Kapoor, Upasana; Srivastava, M K; Trivedi, Purushottam; Garg, Veena; Srivastava, L P



Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage  

PubMed Central

Aim: To investigate the effect of excess genistein on the extracellular matrix in mandibular condylar cartilage of female rats in vivo. Methods: Female SD rats were administered through oral gavage with genistein (50 mg/kg) or placebo daily for 6 weeks. The morphological changes of temporomandibular joints were studied with HE staining. The expression of cartilage matrix compounds (aggrecan and collagen type II), estrogen-related molecules (aromatase, estradiol, ER? and ER?) and proliferating cell nuclear antigen (PCNA) in mandibular condylar cartilage was detected using immunohistochemistry, ELISA and real-time PCR. Results: The genistein treatment significantly reduced the thickness of the posterior and middle regions of mandibular condylar cartilage, and decreased the expression of collagen type II, aggrecan and PCNA. Compared with the control group, the estradiol content and expression levels of the key estradiol-synthesizing enzyme aromatase in the genistein-treatment group were significantly decreased. The genistein treatment significantly increased the expression of ER?, but decreased the expression of ER?. Conclusion: Excess genistein suppresses extracellular matrix synthesis and chondrocytes proliferation, resulting in thinner mandibular condylar cartilage. These effects may be detrimental to the ability of mandibular condylar cartilage to adapt to mechanical loads. PMID:22705728

Yu, Shi-bin; Xing, Xiang-hui; Dong, Guang-ying; Weng, Xi-li; Wang, Mei-qing



Maternal separation exaggerates spontaneous recovery of extinguished contextual fear in adult female rats.  


Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD. PMID:24746487

Xiong, Gui-Jing; Yang, Yuan; Wang, Li-Ping; Xu, Lin; Mao, Rong-Rong



Unpredictable chronic mild stress induced behavioral deficits: a comparative study in male and female rats.  


Stress is an important precipitant factor for depression. Changes in various body systems that occur in depression are similar to those observed in response to stress. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Unpredictable chronic mild stress (UCMS) also produces alteration in the serotonergic (5-HT; 5-hydroxytryptamine) neurotransmission. Unpredictable chronic mild stress (UCMS) could be used as an animal model of depression. Neurochemical and behavioral effects of UCMS can be reversed by antidepressant agents, suggesting an important role of serotonin. In rodents, UCMS can elicit depression-like symptoms. The objective of the present study was to evaluate and compare the behavioral deficits induced by chronic mild stress in male and female rats and finding out the vulnerability of the two groups. Male and female rats exposed to UCMS exhibited a significant decrease in cumulative food intake as well as in growth rate. Loco motor activity in home cage and open field was also decreased. Results may contribute to our understanding of the interaction between stress and behavioral functions have to depressive disorders. PMID:25015455

Farhan, Muhammad; Ikram, Huma; Kanwal, Sumera; Haleem, Darakhshan Jabeen



Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats  

PubMed Central

Background Atrazine (ATR), a widely used chlorotriazine herbicide, inhibits a number of endocrine-dependent processes, including gonadotrophin surges and mammary gland development in rats. Chlorotriazine herbicides are rapidly metabolized in plants and animals to form a group of metabolites that are detected both in the environment and in exposed animals. The extent to which these metabolites are responsible directly for the observed health effects is not understood. Objectives Our goal was to determine if a mixture of ATR metabolites, in proportions found in the environment, might produce developmental effects in Long-Evans rats following exposure late in pregnancy. Methods We administered an ATR metabolite mixture (AMM) containing ATR, hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine orally to pregnant Long-Evans rats at 0.09, 0.87, or 8.73 mg/kg body weight (bw)/day, on gestation days 15–19, using 0 and 100 mg ATR/kg bw/day as negative and positive controls, respectively. Results We observed no significant effect of acute AMM exposure on body weight gain in dams during the dosing period, weight loss in pups on postnatal day (PND)4, or pubertal timing, as is seen with ATR alone. However, as with ATR, we detected delayed mammary gland development, evaluated by whole mount analysis, as early as PND4 in all treatment groups. Conclusions Our data suggest that acute exposure to AMM at levels as low as 0.09 mg/kg bw during late pregnancy causes persistent alterations in mammary gland development of female offspring, and that these effects do not appear to be related to bw or associated with pubertal timing. PMID:17450222

Enoch, Rolondo R.; Stanko, Jason P.; Greiner, Sara N.; Youngblood, Geri L.; Rayner, Jennifer L.; Fenton, Suzanne E.



Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure  

NASA Technical Reports Server (NTRS)

This experiment contains the crucial data for the lose, restore, and maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses anabolic agents to restore bone mass and architecture (+ phase) and then switches to an agent with the established ability to maintain bone mass, to keep the new bone (+/- phase). The purpose of this study was to learn whether switching to an agent known chiefly for its ability to maintain existing bone mass preserves new bone induced by PGE2 in osteopenic, estrogen-depleted rats. The current study had three phases, the bone loss (-), restore (+), and maintain (+/-) phases. We ovariectomized (OX) or sham ovariectomized (sham-OX) 5.5-month-old female rats (- phase). The OX rats were treated 5 months postovariectomy with 1-6 mg PGE2 per kg/day for 75 days to restore lost cancellous bone mass (+ phase), and then PGE2 treatment was stopped and treatment began with 1 or 5 micrograms/kg of risedronate, a bisphosphonate, twice a week for 60 days (+/- phase). During the loss (-) phase, the cancellous bone volume of the proximal tibial metaphysis in the OX rat fell to 19% of initial and 30% of age-matched control levels. During the restore (+) phase, the cancellous bone volume in OX rats doubled. When PGE2 treatment was stopped, however, and no special maintenance efforts were made during the maintain (+/-) phase, the PGE2-induced cancellous bone disappeared. In contrast, the PGE2-induced cancellous bone persisted when the PGE2 treatment was followed by either a 1 or 5 micrograms treatment of risedronate per kg given twice a week for 60 days during the maintain (+/-) phase. The tibial shaft demonstrated very little cortical bone loss during the loss (-) phase in OX rats. The tibial shaft cortical bone fell some 8%. During the restore (+) phase, new cortical bone in OX rats increased by 22%. When PGE2 treatment was stopped and nothing was given during the maintain (+/-) phase, however, all but the PGE2-induced subperiosteal bone disappeared. In contrast, when PGE2 treatment was stopped and 1 micron risedronate per kg twice a week for 60 days was administered during the maintenance (+/-) phase, the PGE2-induced subperiosteal bone and some of the subendocortical bone and marrow trabeculae persisted.(ABSTRACT TRUNCATED AT 400 WORDS).

Tang, L. Y.; Jee, W. S.; Ke, H. Z.; Kimmel, D. B.



Amelioration of Collagen-Induced Arthritis in Female Dark Agouti Rats by Glucosamine Treatment  

PubMed Central

The present study assessed the therapeutic efficacy of glucosamine hydrochloride against collagen-induced arthritis in female Dark Agouti rats (DA). Arthritis was induced by intradermaly injecting a collagen and complete Freund's adjuvant suspension at multiple sites in the rat at a dose of 4?mg/kg of body weight and thereafter followed by two more boosters of the same dose, after the 1st week and 2nd week of primary immunization. After 21 days from the day of primary immunization, the arthritic group rats were given oral supplementation of glucosamine hydrochloride at a dose of 300?mg/kg of body weight until day 45. The arthritic group treated with glucosamine hydrochloride from day 21 to day 45 showed significant reduction in arthritic histopathological changes of the joints, reduction in paw thickness and also a significant decrease in C-reactive protein and TNF-alpha in the serum. Treatment with 300?mg/kg of glucosamine hydrochloride was able to reverse the arthritic changes, hence suggesting that glucosamine has a therapeutic effect against collagen-induced arthritis. PMID:23476804

Haleagrahara, Nagaraja; Tudawe, Dulanthi; Chakravarthi, Srikumar; Kutty Radhakrishnan, Ammu



Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating in Female Rats  

PubMed Central

Purpose. The present study evaluated the effect of Hypericum perforatum dry extract in an experimental model of binge eating (BE). Methods. BE for highly palatable food (HPF) was evoked in female rats by three 8-day cycles of food restriction/re-feeding and acute stress on the test day (day 25). Stress was induced by preventing access to HPF for 15?min, while rats were able to see and smell it. Hypericum perforatum dry extract was given by gavage. Results. Only rats exposed to both food restrictions and stress exhibited BE. The doses of 250 and 500?mg/kg of Hypericum perforatum extract significantly reduced the BE episode, while 125?mg/kg was ineffective. The same doses did not affect HPF intake in the absence of BE. The dose of 250?mg/kg did not significantly modify stress-induced increase in serum corticosterone levels, suggesting that the effect on BE is not due to suppression of the stress response The combined administration of 125?mg/kg of Hypericum perforatum together with Salidroside, active principle of Rhodiola rosea, produced a synergic effect on BE. Conclusions. The present results indicate for the first time that Hypericum perforatum extracts may have therapeutic properties in bingeing-related eating disorders. PMID:22997570

Micioni Di Bonaventura, Maria Vittoria; Vitale, Giovanni; Massi, Maurizio; Cifani, Carlo



Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats  

PubMed Central

Background Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood. Methods At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n?=?10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n?=?6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p?rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered. Conclusions In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels. PMID:24499555



Hypothalamic molecular changes underlying natural reproductive senescence in the female rat.  


The role of the hypothalamus in female reproductive senescence is unclear. Here we identified novel molecular neuroendocrine changes during the natural progression from regular reproductive cycles to acyclicity in middle-aged female rats, comparable with the perimenopausal progression in women. Expression of 48 neuroendocrine genes was quantified within three hypothalamic regions: the anteroventral periventricular nucleus, the site of steroid positive feedback onto GnRH neurons; the arcuate nucleus (ARC), the site of negative feedback and pulsatile GnRH release; and the median eminence (ME), the site of GnRH secretion. Surprisingly, the majority of changes occurred in the ARC and ME, with few effects in anteroventral periventricular nucleus. The overall pattern was increased mRNA levels with chronological age and decreases with reproductive cycle status in middle-aged rats. Affected genes included transcription factors (Stat5b, Arnt, Ahr), sex steroid hormone receptors (Esr1, Esr2, Pgr, Ar), steroidogenic enzymes (Sts, Hsd17b8), growth factors (Igf1, Tgfa), and neuropeptides (Kiss1, Tac2, Gnrh1). Bionetwork analysis revealed region-specific correlations between genes and hormones. Immunohistochemical analyses of kisspeptin and estrogen receptor-? in the ARC demonstrated age-related decreases in kisspeptin cell numbers as well as kisspeptin-estrogen receptor-? dual-labeled cells. Taken together, these results identify unexpectedly strong roles for the ME and ARC during reproductive decline and highlight fundamental differences between middle-aged rats with regular cycles and all other groups. Our data provide evidence of decreased excitatory stimulation and altered hormone feedback with aging and suggest novel neuroendocrine pathways that warrant future study. Furthermore, these changes may impact other neuroendocrine systems that undergo functional declines with age. PMID:24914937

Kermath, Bailey A; Riha, Penny D; Woller, Michael J; Wolfe, Andrew; Gore, Andrea C



Estradiol modulates medial prefrontal cortex and amygdala activity during fear extinction in women and female rats  

PubMed Central

Background Men and women differ in their ability to extinguish fear. Fear extinction requires the activation of brain regions including the ventromedial prefrontal cortex (vmPFC) and amygdala. Could estradiol modulate the activity of these brain regions during fear extinction? Methods All rat experiments were conducted in naturally cycling females. Rats underwent fear conditioning on day 1. On day 2, they underwent extinction training during the metestrus phase of the cycle (low estrogen and progesterone). Extinction recall was assessed on day 3. Systemic injections of estrogen-receptor beta and alpha agonists, and estradiol were administered at different time points to assess their influence on extinction consolidation and c-fos expression in the vmPFC and amygdala. In parallel, healthy naturally cycling women underwent an analogous fear conditioning extinction training while in a 3T fMRI scanner. Measurement of their estradiol levels and skin conductance responses were obtained throughout the experiment. Results In female rats, administration of the estrogen-receptor beta (but not alpha) agonist facilitated extinction recall. Immediate (but not delayed) post-extinction training administration of estradiol facilitated extinction memory consolidation and increased c-fos expression in the vmPFC while reducing it in the amygdala. In parallel, natural variance in estradiol in pre-menopausal cycling women modulated vmPFC and amygdala reactivity and facilitated extinction recall. Conclusion We provide translational evidence that demonstrates the influence of endogenous and exogenous estradiol on the fear extinction network. Our data suggest that women’s endogenous hormonal status should be considered in future neurobiological research related to anxiety and mood disorders. PMID:21762880

Zeidan, Mohamed A.; Igoe, Sarah A.; Linnman, Clas; Vitalo, Antonia; Levine, John B.; Klibanski, Anne; Goldstein, Jill M.; Milad, Mohammed R.



Effect of Silitidil, a standardized extract of milk thistle, on the serum prolactin levels in female rats.  


The aim of this study was to assess the effect of Silitidil, a standardized extract of milk thistle, on the serum levels of prolactin in female rats. A 14-day treatment with Silitidil (25-200 mg/kg, per os), a standardized extract of Silybum marianum fruits (milk thistle), increased, in a dose dependent manner, the serum prolactin levels in female rats. Galega (200 mg/kg, per os) given alone neither modified the basal levels of prolactin nor increased further serum prolactin levels when associated with Silitidil. Bromocriptine (1 mg/kg, per os) significantly reduced the high serum prolactin levels induced by Silitidil (200 mg/kg, per os). The results show that the extract of S. marianum fruits significantly increases prolactin levels in female rats; this effect is not potentiated by galega and seems to involve, at least in part, dopamine D2 receptors. PMID:25230499

Capasso, Raffaele



Age-Dependent Reductions in Mitochondrial Respiration are Exacerbated by Calcium in the Female Rat Heart  

PubMed Central

Cardiovascular disease mortality increases rapidly following menopause by poorly defined mechanisms. Since mitochondrial function and Ca2+ sensitivity are important regulators of cell death following myocardial ischemia, we sought to determine if aging and/or estrogen deficiency (ovx) increased mitochondrial Ca2+ sensitivity. Mitochondrial respiration was measured in ventricular mitochondria isolated from adult (6mo; n=26) and aged (24mo; n=25), intact or ovariectomized female rats using the substrates: ?-ketoglutarate/malate (Complex I); succinate/rotenone (Complex II); ascorbate/TMPD/Antimycin (Complex IV). State 2 and State 3 respiration was initiated by sequential addition of mitochondria and ADP. Ca2+ sensitivity was assessed by Ca2+-induced swelling of de-energized mitochondria and reduction in state 3 respiration. Propylpyrazole triol (PPT) was administered i.p. 45 min prior to euthanasia to assess mitochondrial protective effects through estrogen receptor (ER) ? activation. Aging decreased the respiratory control index (RCI; state 3/state 2) for Complexes I and II by 12% and 8%, respectively, independent of ovary status (p<0.05). Of interest, Ca2+ induced a greater decrease (18–30%; p<0.05) in Complex I state 3 respiration in aged and ovx animals, and mitochondrial swelling occurred twice as quickly in aged (vs. adult) female rats (p<0.05). Pretreatment with PPT increased RCI by 8% and 7% at Complexes I and II, respectively (p<0.05) but surprisingly increased Ca2+ sensitivity. Age-dependent decreases in RCI and sensitization to Ca2+ may explain in part the age-associated reductions in female ischemic tolerance; however protection afforded by ER agonism involves more complex mechanisms. PMID:22555015

Hunter, J. Craig; Machikas, Alexandra M.; Korzick, Donna H.



Flaxseed oil during lactation changes milk and body composition in male and female suckling pups rats.  


We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation. PMID:24727050

Guarda, Deysla Sabino; Lisboa, Patricia Cristina; de Oliveira, Elaine; Nogueira-Neto, José Firmino; de Moura, Egberto Gaspar; Figueiredo, Mariana Sarto



Distribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats?  

PubMed Central

The ventral premammillary nucleus (PMV) expresses dense collections of sex steroid receptors and receptors for metabolic cues, including leptin, insulin and ghrelin. The PMV responds to opposite sex odor stimulation and projects to areas involved in reproductive control, including direct innervation of gonadotropin releasing hormone neurons. Thus, the PMV is well positioned to integrate metabolic and reproductive cues, and control downstream targets that mediate reproductive function. In fact, lesions of PMV neurons blunt female reproductive function and maternal aggression. However, although the projections of PMV neurons have been well documented, little is known about the neuronal inputs received by PMV neurons. To fill this gap, we performed a systematic evaluation of the brain sites innervating the PMV neurons of male and female rats using the retrograde tracer subunit B of the cholera toxin (CTb). In general, we observed that males and females show a similar pattern of afferents. We also noticed that the PMV is preferentially innervated by neurons located in the forebrain, with very few projections coming from brainstem nuclei. The majority of inputs originated from the medial nucleus of the amygdala, the bed nucleus of the stria terminalis and the medial preoptic nucleus. A moderate to high density of afferents was also observed in the ventral subiculum, the arcuate nucleus and the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus. Our findings strengthen the concept that the PMV is part of the vomeronasal system and integrates the brain circuitry controlling reproductive functions. PMID:25084037

Cavalcante, Judney Cley; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti



Distribution of the neuronal inputs to the ventral premammillary nucleus of male and female rats.  


The ventral premammillary nucleus (PMV) expresses dense collections of sex steroid receptors and receptors for metabolic cues, including leptin, insulin and ghrelin. The PMV responds to opposite sex odor stimulation and projects to areas involved in reproductive control, including direct innervation of gonadotropin releasing hormone neurons. Thus, the PMV is well positioned to integrate metabolic and reproductive cues, and control downstream targets that mediate reproductive function. In fact, lesions of PMV neurons blunt female reproductive function and maternal aggression. However, although the projections of PMV neurons have been well documented, little is known about the neuronal inputs received by PMV neurons. To fill this gap, we performed a systematic evaluation of the brain sites innervating the PMV neurons of male and female rats using the retrograde tracer subunit B of the cholera toxin (CTb). In general, we observed that males and females show a similar pattern of afferents. We also noticed that the PMV is preferentially innervated by neurons located in the forebrain, with very few projections coming from brainstem nuclei. The majority of inputs originated from the medial nucleus of the amygdala, the bed nucleus of the stria terminalis and the medial preoptic nucleus. A moderate to high density of afferents was also observed in the ventral subiculum, the arcuate nucleus and the ventrolateral subdivision of the ventromedial nucleus of the hypothalamus. Our findings strengthen the concept that the PMV is part of the vomeronasal system and integrates the brain circuitry controlling reproductive functions. PMID:25084037

Cavalcante, Judney Cley; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti



Isoflurane exposure in newborn rats induces long-term cognitive dysfunction in males but not females.  


Volatile anesthetics are used widely for achieving a state of unconsciousness, yet these agents are incompletely understood in their mechanisms of action and effects on neural development. There is mounting evidence that children exposed to anesthetic agents sustain lasting effects on learning and memory. The explanation for these behavioral changes remains elusive, although acute neuronal death after anesthesia is commonly believed to be a principal cause. Rodent models have shown that isoflurane exposure in newborns induces acute neuroapoptosis and long-term cognitive impairment. However, the assessment of predisposing factors is lacking. We investigated the role of sex by delivering isoflurane to postnatal day (P)7 male and female Sprague Dawley rats for 4 h. Brain cell death was assessed 12 h later using FluoroJade C staining in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. Behavior was assessed separately using a series of object recognition tasks and a test of social memory beginning at P38. We found that isoflurane exposure significantly increased neuronal death in each brain region with no difference between sexes. Behavioral outcome was also equivalent in simple novel object recognition. However, only males were impaired in the recognition of objects in different locations and contexts. Males also exhibited deficient social memory while females were intact. The profound behavioral impairment in males relative to females, in spite of comparable cell death, suggests that males are more susceptible to long-term cognitive effects and this outcome may not be exclusively attributed to neuronal death. PMID:24704083

Lee, Bradley H; Chan, John Thomas; Kraeva, Ekaterina; Peterson, Katherine; Sall, Jeffrey W



Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats.  


Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mgMPH/kgbodyweight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2mgMPH/kgbodyweight3×/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior. PMID:25132048

Panos, John J; O'Callaghan, James P; Miller, Diane B; Ferguson, Sherry A



Role of Tissue Repair in Carbon Tetrachloride Hepatotoxicity in Male and Female Sprague-Dawley and Wistar Rats  

Microsoft Academic Search

This study was designed to assess the hypothesis that large differences between male and female Wistar and Sprague-Dawley rats in susceptibility to carbon tetrachloride (CCl4)-induced hepatotoxicity are related to the differential capacity to repair tissue damage. This hypothesis was evaluated via two complementary approaches, (a) Separate groups of rats were administered a minimum lethal dose (LD10) of CC14, with colchicine

Edward J. Calabrese; Denise A. Leonard; Xiaoqiang Zhao; Kamala Lakshmanan



Oxidative stress induced by gibberellic acid on kidney tissue of female rats and their progeny: biochemical and histopathological studies  

Microsoft Academic Search

Gibberellic acid (GA3) is an endogenous plant growth regulator used worldwide in agriculture. The objective of this study was to investigate the\\u000a effects of GA3 on the kidney function of adult rats and their pups. Female Wistar rats were given daily 200 ppm GA3 in drinking water from the 14th day of pregnancy until day 14 after delivery. GA3 induced nephrotoxicity, as

Afef Troudi; Ibtissem Ben Amara; Nejla Soudani; Amira Mahjoubi Samet; Najiba Zeghal


2,2,4-Trimethylpentane-induced nephrotoxicity. I. Metabolic disposition of TMP in male and female Fischer 344 rats  

SciTech Connect

2,2,4-Trimethylpentane (TMP), a component of unleaded gasoline, causes nephrotoxicity in male, but not in female, rats. In the present study, male and female Fischer 344 rats were treated with a single oral dose of (/sup 14/C)TMP (4.4 mmol/kg; 2 microCi/mmol). Radiolabeled material in kidney, liver, and plasma was determined at 4, 8, 12, 24, and 48 hr after dosing. Maximum concentration of TMP-derived radioactivity in kidney, liver, and plasma of male rats was found after 12 hr (1252, 1000, and 403 nmol eq/g, respectively), whereas those measured in females were found after 8 hr (577, 1163, and 317 nmol eq/g, respectively). A selective retention of the TMP-derived radiolabel in the kidneys of male rats was noted when peak tissue concentration was expressed as a percentage of administered dose. Kidney concentrations of TMP-derived radiolabel increased in a nonlinear, but dose-dependent, manner; the kidney to plasma ratio was greater at low doses than at higher doses. Increased retention of radiolabel material in the kidney was associated with a significant increase in renal concentration of the male-rat-specific protein, alpha 2u-globulin, 24 and 48 hr after TMP administration. Total radioactivity collected in urine 48 hr after TMP administration was similar in males and females (32 and 31% of dose). Identification and quantitation of the urinary metabolites of TMP showed that both male and female rats metabolize TMP via the same pathway and at a similar rate. Female rats, however, excreted more conjugates of 2,4,4-trimethyl-2-pentanol in urine than males. 2,4,4-Trimethyl-2-pentanol was the major metabolite present in the male rat kidney, but was absent in the female rat kidney. The renal retention of 2,4,4-trimethyl-2-pentanol appears to account for the delayed clearance observed in the disposition of (/sup 14/C)TMP-derived radiolabel.

Charbonneau, M.; Lock, E.A.; Strasser, J.; Cox, M.G.; Turner, M.J.; Bus, J.S.



Dehydroepiandrosterone administration increased trabecular mass and dihydrotestosterone levels in the cancellous region of the tibia in young female rats.  


The aim of the present study was to determine whether dehydroepiandrosterone (DHEA) administration affects bone mass and local sex hormone levels in the cancellous region of young female rats. Eleven female rats (6 weeks old) were randomly divided into 2 groups: control rats (CON, n=5) and rats treated with DHEA (DHEA, n=6). DHEA dissolved in sesame oil was administered to the DHEA group intraperitoneally at 20?mg DHEA/kg body weight, and the CON group was treated with vehicle only (sesame oil, 0.5?ml). The rats were treated with DHEA or vehicle for 3 consecutive days, followed by 1 day of no treatment. The experimental period was 8 weeks. According to dual-energy X-ray absorptiometry and high-resolution microcomputed tomography data, the DHEA group exhibited increased trabecular bone mineral density (BMD), bone volume, and tibial thickness compared to the findings in the CON group, whereas no effect was observed on cortical BMD or morphometry. The concentrations of free testosterone and estradiol in the cancellous region of the tibia did not differ between the 2 groups, but the DHT concentration was significantly higher in the DHEA group than in the CON group. These findings suggest that an increase in local DHT levels may stimulate an increase in trabecular bone mass during growth phases in female rats. PMID:24867140

Park, J; Aizawa, K; Akimoto, T; Iemitsu, M; Agata, U; Maeda, S; Lim, K; Omi, N



An Enriched Rearing Environment Calms Adult Male Rat Sexual Activity: Implication for Distinct Serotonergic and Hormonal Responses to Females  

PubMed Central

Early life events induce alterations in neural function in adulthood. Although rearing in an enriched environment (EE) has a great impact on behavioral development, the effects of enriched rearing on sociosexual behavior remain unclear. In this study, we investigated the effects of rearing in an EE on male copulatory behavior and its underlying neurobiological mechanisms in Wistar-Imamichi rats. Three-week-old, recently weaned rats were continuously subjected to a standard environment (SE) or an EE comprised of a large cage with several objects, such as toys, tunnels, ladders, and a running wheel. After 6 weeks, rats reared in an EE (EE rats) showed decreased sexual activity compared with rats reared in a SE (SE rats). This included a lower number of ejaculations and longer latencies in three consecutive copulatory tests. In addition, EE rats showed decreased emotional responsiveness and less locomotor behavior in an open field. In a runway test, on the other hand, sexual motivation toward receptive females in EE males was comparable to that of SE males. Furthermore, following exposure to a female, increases in serotonin levels in the nucleus accumbens and the striatum were significantly suppressed in EE males, whereas dopaminergic responses were similar between the groups. Female-exposure-induced increases in the levels of plasma corticosterone and testosterone were also suppressed in EE rats compared to SE rats. These data suggest that rearing in an EE decreases male copulatory behavior, and serotonin and hormonal regulating systems may regulate the differences in sociosexual interactions that result from distinct rearing environments. PMID:24505330

Urakawa, Susumu; Mitsushima, Dai; Shimozuru, Michito; Sakuma, Yasuo; Kondo, Yasuhiko



An enriched rearing environment calms adult male rat sexual activity: implication for distinct serotonergic and hormonal responses to females.  


Early life events induce alterations in neural function in adulthood. Although rearing in an enriched environment (EE) has a great impact on behavioral development, the effects of enriched rearing on sociosexual behavior remain unclear. In this study, we investigated the effects of rearing in an EE on male copulatory behavior and its underlying neurobiological mechanisms in Wistar-Imamichi rats. Three-week-old, recently weaned rats were continuously subjected to a standard environment (SE) or an EE comprised of a large cage with several objects, such as toys, tunnels, ladders, and a running wheel. After 6 weeks, rats reared in an EE (EE rats) showed decreased sexual activity compared with rats reared in a SE (SE rats). This included a lower number of ejaculations and longer latencies in three consecutive copulatory tests. In addition, EE rats showed decreased emotional responsiveness and less locomotor behavior in an open field. In a runway test, on the other hand, sexual motivation toward receptive females in EE males was comparable to that of SE males. Furthermore, following exposure to a female, increases in serotonin levels in the nucleus accumbens and the striatum were significantly suppressed in EE males, whereas dopaminergic responses were similar between the groups. Female-exposure-induced increases in the levels of plasma corticosterone and testosterone were also suppressed in EE rats compared to SE rats. These data suggest that rearing in an EE decreases male copulatory behavior, and serotonin and hormonal regulating systems may regulate the differences in sociosexual interactions that result from distinct rearing environments. PMID:24505330

Urakawa, Susumu; Mitsushima, Dai; Shimozuru, Michito; Sakuma, Yasuo; Kondo, Yasuhiko



Gene Expression, Function and Ischemia Tolerance in Male and Female Rat Hearts After Sub-Toxic Levels of Angiotensin II  

Microsoft Academic Search

To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with\\u000a respect to gene expression and ischemic injury. Female and male litter–matched rats were treated with 400 ng kg?1 min?1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional\\u000a monitoring and thereafter harvested for gene

M. B. Aljabri; T. Lund; A. C. Höper; T. V. Andreasen; S. Al-Saad; S. Lindal; K. Ytrehus



Role of Mas receptor in renal blood flow response to angiotensin (1-7) in male and female rats.  


Epidemiologic and clinical studies have shown that progression of renal disease in male is faster than that in female. However, the exact mechanisms are not well recognized. Angiotensin (1-7) (Ang 1-7) receptor, called "Mas", is an element in the depressor arm of renin angiotensin system (RAS), and its expression is enhanced in females. We test the hypothesis that Mas receptor (MasR) blockade (A779) attenuates renal blood flow (RBF) in response to infusion of graded doses of Ang 1-7 in female rats. Male and female Wistar rats were anesthetized and catheterized. Then, the mean arterial pressure (MAP), RBF, and controlled renal perfusion pressure (RPP) responses to infusion of graded doses of Ang 1-7 (100-1000 ng/kg/min i.v.) with and without A779 were measured in the animals. Basal MAP, RPP, RBF, and renal vascular resistance (RVR) were not significantly different between the two groups. After Ang 1-7 administration, RPP was controlled at a constant level. However, RBF increased in a dose-related manner in response to Ang 1-7 infusion in both male and female rats (Pdose<0.0001), but masR blockade significantly attenuated this response only in female (Pgroup=0.04) and not male (Pgroup=0.23). In addition, A779 increased the RBF response to Ang 1-7 to a greater extent. This is while the increase in male was not significant when compared with that in female (Pgender=0.08). RVR response to Ang 1-7 was insignificantly attenuated by A779 in both genders. The masR differently regulated RBF response to Ang 1-7 in the two genders, and the effect was greater in female rats. The masR may be a target for improvement of kidney circulation in renal diseases. PMID:24968411

Nematbakhsh, Mehdi; Safari, Tahereh



Exposure to dexamethasone during late gestation causes female-specific decreases in core body temperature and prepro-thyrotropin-releasing hormone expression in the paraventricular nucleus of the hypothalamus in rats.  


Synthetic glucocorticoids (GC) have been used to promote lung development in preterm infants, thereby decreasing respiratory distress syndrome and mortality, yet, concern has arisen from reports that such treatment predisposes individuals to disease in adulthood. Given the variety of preclinical studies that show metabolic and behavioral abnormalities in adulthood following fetal exposure to synthetic GC, we examined the effect of in utero exposure to the synthetic GC, dexamethasone (DEX), on hypothalamic expression of thyrotropin-releasing hormone (TRH) a central neuropeptide involved in mediating behavior and metabolic balance. Pregnant Sprague-Dawley rats were administered 0.4mg/kg DEX on gestational days 18-21. As adults (postnatal day (PD) 60), the offspring were fitted with temperature sensing transmitters allowing real-time monitoring of core body temperature (CBT) across the 24h light dark period. This revealed a significant decrease in CBT throughout the day in prenatal DEX-treated females on estrus and diestrus, but not in male offspring. The reduction in CBT by prenatal DEX exposure was accompanied by a significant decrease in the expression of Trh transcript in the paraventricular nucleus of the hypothalamus (PVN) of female rats at PD 60 and this effect was also present on PD7. There was also a female-specific reduction in the number of preproTRH-immunoreactive (ir) neurons in the PVN, with ppTRH-ir nerve fibers decreases that were present in both male and female offspring. No changes in thyroid hormone (triiodothyronine, T3; thyroxine, T4) were observed in adult offspring, but during development, both males and females (PD14) had lower T3 and T4 levels. These data indicate abnormal expression of TRH results from fetal DEX exposure during late gestation, possibly explaining the decreased CBT observed in the female offspring. PMID:22884559

Carbone, David L; Zuloaga, Damian G; Lacagnina, Anthony F; McGivern, Robert F; Handa, Robert J




EPA Science Inventory

7,12-dimethylbenz(a)anthracene (DMBA) is a powerful carcinogen to the mammary gland of the pubescent female Sprague-Dawley (S.D.) rat but is a much less potent inducer of mammary adenocarcinoma in the female Long-Evans (L.E.) rat of the same age. The livers of both strains are re...


Abortifacient activity of Plumeria rubra (Linn) pod extract in female albino rats.  


To evaluate the potential abortifacient activity of the aqueous, alcohol, ethyl acetate and chloroform extracts of P. rubra pod in female albino rats 50, 100 and 200 mg/kg body weight doses of each extract were administered from day 11 to 15 of pregnancy and animals were allowed to go full-term. The phytochemical screening revealed the presence of alkaloids, flavonoids, simple phenolics, steroids, tannins and saponins. Clinical toxicity symptoms such as respiratory distress, salivation, weight loss, dull eyes, diarrhea, and change in the appearance of fur as well as mortality were not observed in the animals at any period of the experiment. All the four extracts of P. rubra pods exhibited abortifacient activity (8-100%). The extracts significantly reduced the number of live fetuses, whereas the resorption index and post implantation losses increased significantly. The % of abortion was found to be highest (100%) with 200 mg/kg dose of alcoholic extract of P. rubra pods. PMID:23214263

Dabhadkar, Dinesh; Zade, Varsha



Estradiol Synthesis and Release in Cultured Female Rat Bone Marrow Stem Cells  

PubMed Central

Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity for de novo synthesis of Estradiol-17? (E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency. PMID:23484106

Zhang, Dalei; Yang, Bei; Zou, Weiying; Lu, Xiaying; Xiong, Mingdi; Wu, Lei; Wang, Jinglei; Gao, Junhong; Xu, Sifan; Zou, Ting



Lipid-Lowering Effects of Tetradecylthioacetic Acid in Antipsychotic-Exposed, Female Rats: Challenges with Long-Term Treatment  

PubMed Central

Background Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. Aims In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Methods Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. Results The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. Conclusion TTA is a promising candidate for prophylactic treatment of antipsychotic-induced dyslipidemic effects, but a more valid long-term rat model for antipsychotic-induced metabolic adverse effects is required. PMID:23226405

Skrede, Silje; Fern?, Johan; Bj?rndal, Bodil; Brede, Wenche R?dseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin



Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats.  


Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% wt/vol) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-s presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age. PMID:21534648

Doremus-Fitzwater, Tamara L; Spear, Linda P



Quantification of neurological and other contributors to continence in female rats.  


Smooth muscle, striated muscle, their central and peripheral innervations and control, and mucosal coaptation contribute to maintenance of continence. We used manual leak point pressure (mLPP) testing and electrical stimulation LPP (eLPP) testing in female rats to quantify the contribution of these factors to urethral resistance, a measure of continence. Abdominal muscles were electrically stimulated to induce leakage for eLPP. A Crede maneuver was applied for mLPP. These were repeated after complete T8 spinal cord injury (SCI) and/or bilateral pudendal nerve transection (PNT). After euthanasia, mLPP was repeated. MLPP was not significantly affected by opening the abdomen, suggesting that intra-abdominal pressure transmission contributes little to continence during slow pressure changes. ELPP was significantly higher than mLPP in intact rats, after PNT, and after SCI+PNT, suggesting that abdominal pressure transmission contributes to continence during rapid increases in intra-abdominal pressure. MLPP decreased significantly after PNT, indicating that urethral striated muscles contribute significantly to continence. ELPP decreased significantly after PNT with and without SCI, suggesting that supraspinal control significantly affects continence during rapid pressure changes, but not during slow pressure changes. MLPP after euthanasia was significantly decreased compared to mLPP after SCI+PNT, suggesting that urethral mucosal seal coaptation and tissue elasticity also contribute to continence. The urethra is a complex organ that maintains continence via a highly organized and hierarchical system involving both the central and peripheral nervous systems. PMID:21295013

Jiang, Hai-Hong; Salcedo, Levilester B; Damaser, Margot S



Extraskeletal Osteosarcoma with Pulmonary Metastasis in a Female F344 Rat  

PubMed Central

A subcutaneous mass in the right femoral region of a female F344 Slc/N rat was examined histopathologically. At 83 weeks of age, the animal showed symptoms of severe anemia and nasal bleeding. Necropsy revealed that the mass had invaded the skeletal muscles but did not affect the bones. Multicentric nodules were also observed in the lung. Histopathology revealed a sheet-like growth pattern of polygonal tumor cells with round or comma-shaped nuclei and pale eosinophilic cytoplasm. Osteoid tissue was observed in not only the original lesion but also the metastatic foci in the lung. Each tumor cell was surrounded by argentophil fibers and few collagen fibers. Immunohistochemically, the tumor cells were positive for proliferating cell nuclear antigen (PCNA), vimentin, osterix and osteocalcin, but negative for keratin, S-100, von Willebrand factor, CD-31, CD-34, desmin, ?-smooth muscle actin, lysozyme, ?1-antitrypsin and rat malignant fibrous histiocytoma (MFH) antigen. CD-68-positive cells were considered to be infiltrated macrophages because they were negative for PCNA. On the basis of these findings, we diagnosed the present case as extraskeletal osteosarcoma. PMID:22272046

Nagaike, Mika; Sakai, Kimie; Tsuchiya, Seiichiro; Shimada, Fumi; Inui, Kosei; Uratani, Mamoru



Assessment of Genotoxic Potential of Arsenic in Female Albino Rats at Permissible Dose Levels  

PubMed Central

Background: Arsenic is a wide spread environmental contaminant and has been recognized as a genotoxic element which is of major public health concern. Aim: The present study evaluates the genotoxic potential of arsenic at low permissible dose levels. Materials and Methods: Forty-eight mature female rats were divided into four groups of 12 animals each. Group I animals received distilled water and served as control. Group II-IV animals received sodium arsenite dissolved in distilled water continuously for a period of 60 days at the dose of 10, 30 and 50 ?g/L (ppb) respectively. Six rats from each group were sacrificed after 30 days of arsenic exposure and the remaining animals were sacrificed after 60 days. Liver was excised from the sacrificed animals to study the probable advent signs of carcinogenicity measured through microsomal degranulation test. Assessment of mutagenic potential of arsenic was evaluated through chromosomal aberrations observed in the bone marrow cells. Results: The levels of RNA and proteins decreased significantly (P ? 0.01) in all the three doses administered along with an increase in % microsomal degranulation in hepatic fraction when compared to control at both 30 and 60 days time period. A dose-dependent increase in chromosome aberrations like fragmentation, breakage has been observed in all the treated animals. Conclusion: The results of present study revealed that chronic exposure of arsenic even at its low permissible dose limits results in carcinogenic and mutagenic effects which emphasize its genotoxic possibility. PMID:24748731

Mehta, Madhuri; Hundal, Swarndeep Singh




EPA Science Inventory

PERINATAL EXPOSURE TO ATRAZINE SUPPRESSES JUVENILE IMMUNE FUNCTION IN MALE, BUT NOT FEMALE SPRAGUE-DAWLEY RATS. AA Rooney1 and RW Luebke2. 1NCSU/USEPA CVM, Department of Anatomy, Physiological Sciences, and Radiology, Raleigh, NC;2USEPA, NHEERL, RTP, NC. The ability of the ...



EPA Science Inventory



Intervention with environmental enrichment after experimental brain trauma enhances cognitive recovery in male but not female rats  

Microsoft Academic Search

Environmental enrichment (EE) has been repeatedly shown to affect multiple aspects of brain function, and is known to enhance cognitive recovery after experimental traumatic brain injury (TBI) in males. However, the impact of gender on how EE affects behavioral performance after experimental TBI have not been studied. Male and normally cycling female Sprague–Dawley rats underwent controlled cortical impact injury or

Amy K Wagner; Anthony E Kline; Joshua Sokoloski; Ross D Zafonte; Edwin Capulong; C. Edward Dixon



C omparative behavioral changes between male and female postpubertal rats following neonatal excitotoxic lesions of the ventral  

Microsoft Academic Search

Neonatal ventral hippocampal (nVH) lesioned male rat has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. There are significant gender differences in schizophrenia with male and female individuals differing in the age of onset, course and outcome of the disorder. In order to assess whether the behavioral

Adriana B. Silva-Gomez; Martha Bermudez; Lalit K. Srivastava; Ofir Picazo; Gonzalo Flores



Proteins Regulated by Gonadal Steroids in the Medial Preoptic and Ventromedial Hypothalamic Nuclei of Male and Female Rats  

Microsoft Academic Search

Protein profiles of brain areas mediating effects of steroid hormones on copulation were compared between animals in gonadal steroid states predictive of either the presence or absence of copulatory activity. A broad range of proteins present in micropunches of tissue from the medial preoptic area (MPO) and from the ventromedial hypothalamus (VMH) were compared between male and female rats with

Charles W. Scouten; William E. Heydorn; G. Joseph Creed; Charles W. Malsbury; David M. Jacobowitz



Comparative behavioral changes between male and female postpubertal rats following neonatal excitotoxic lesions of the ventral hippocampus  

Microsoft Academic Search

Neonatal ventral hippocampal (nVH) lesioned male rat has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. There are significant gender differences in schizophrenia with male and female individuals differing in the age of onset, course and outcome of the disorder. In order to assess whether the behavioral

Adriana B. Silva-Gómez; Martha Bermudez; Lalit K. Srivastava; Ofir Picazo; Gonzalo Flores




EPA Science Inventory

Effects of Prenatal Testosterone Propionate and Vinclozolin on Perinatal and Infantile Development of Male and Female Rats Cynthia Wolf1,2, Jonathan Furr1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1 1USEPA, NHEERL, RTD, EB, RTP, NC 27711, 2Dept. of Environmental and Molecu...


Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine  

PubMed Central

Objective: Lamotrigine is an antiepileptic drug, widely used in the treatment of epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber officinale Roscoe (ginger) possesses antioxidant properties. In present research, the effect ofhydroalcoholic extract of ginger (HEG) on the liver of lamotrigine-treated epileptic rats was investigated Material and Methods: Forty-eight female Wistar rats were selected and allocated to 8 groups of 6 each. Group 1: Negative controls were treated with normal saline. Group 2: Positive controls were treated with lamotrigine (LTG) (10 mg/kg) daily by gavages for 4 consecutive weeks. Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol (PTZ) (40 mg/kg). Group 3: Epileptic group received normal saline (10 ml/kg). Group 4: Epileptic group was treated with LTG (10 mg/kg). Groups 5 and 6: Epileptic groups received HEG (50 and 100 mg/kg). Groups 7 and 8: Epileptic groups received LTG and HEG (50 and 100 mg/kg). At the end of 28 days, blood samples were drawn and their livers were processed for light microscopy. Results: The mean values of TG, CHOL, AST, and ALT activity significantly rose (p<0.01) in groups 2, 3, and 4, while in rats treated with HEG (groups 5, 6, 7, and 8), the levels of liver enzymes significantly decreased (p<0.05) compared with epileptic group treated with lamotrigine (group 4). Histopathological changes of liver samples were comparable with respective control. Conclusion: These results suggest that hydroalcoholic extract of ginger improves liver function in lamotrigine-induced hepatotoxicity. PMID:25068142

Poorrostami, Ameneh; Farokhi, Farah; Heidari, Reza



The opioid system and excitatory amino acids in the onset of puberty in female rats.  


The control of sexual maturation by the hypothalamus is incompletely understood. The activation and/or removal of inhibition of gonadotropin-releasing hormone (GnRH) secretion at puberty involves several neurotransmitters. Excitatory amino acids (EAA), such as L-glutamic acid (L-GLU), may increase gonadotropin secretion acting on N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Endogenous opiates peptides (EOP) play an inhibitory role on gonadotropin secretion, and the opiate antagonist naloxone (NAL) increases serum LH levels. We tested the effect of drugs acting on the opiate and EAA systems. We treated prepubertal rats with intraperitoneal injections of NAL, NMDA antagonist dextromethorphan (DMT) and non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX), alone and in combinations among them. The onset of puberty was assessed by the vaginal opening (VO). Female Wistar rats (25 days old), weaned at 21 days of age, were randomly assigned to one of seven groups (15 rats each). The groups were treated with 1) DMT (18 mg/kg b.w.), 2) DNQX (17 micrograms/kg), 3) NAL (0.5 mg/kg), 4) NAL plus DMT, 5) NAL plus DNQX, 6) DMT plus DNQX and 7) control vehicle: distilled water). The age at VO among groups was significant by survival time analysis (x2 = 15.18, p = 0.018). Analysis of covariance controlling for weight and length at 21 days showed that the groups treated with NAL alone (p = 0.003) or combined with DMT (p = 0.012) and DNQX (p = 0.005) had earlier age at VO. NMDA and non-NMDA antagonist used alone or combined were not different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8580679

Mena-Valdivia, M A; Nava-Espinosa, L E; Malacara-Hernández, J M



Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats  

SciTech Connect

Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17{beta}-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca{sup 2+} delaying the opening of the permeability transition pore. The presence of 25 {mu}M E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H{sub 2}O{sub 2} in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

Moreira, Paula I. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Physiology, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Custodio, Jose B.A. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3005-504 Coimbra (Portugal); Nunes, Elsa [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Physiology, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Moreno, Antonio [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Department of Zoology, Faculty of Sciences and Technology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Marine Research, University of Coimbra, 3005-504 Coimbra (Portugal); Seica, Raquel [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Physiology, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Oliveira, Catarina R. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Santos, Maria S. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal) and Department of Zoology, Faculty of Sciences and Technology, University of Coimbra, 3005-504 Coimbra (Portugal)]. E-mail:



Developmental lead exposure induces depressive-like behavior in female rats.  


The involvement of neurotoxicants in the etiology of emotional pathologies is becoming an issue in neurotoxicology. Lead (Pb) exposure during childhood has been associated with increased impulsivity, aggressivity, and delinquency. Considering the paucity of experimental studies investigating the involvement of developmental Pb exposure in emotional disorders, our objective was to investigate whether Pb exposure during pregnancy and/or lactation could be related to depressive symptoms in adult male and female rats. Wistar dams received 10 mg of Pb, as Pb acetate, or 13.4 mg of Na acetate, by gavage, daily, during pregnancy and lactation. By cross-fostering at the time of birth, pups were either exposed to Pb or Na acetate during pregnancy only, lactation only, or during both pregnancy and lactation. At 70 days of age, animals were submitted to the open-field test followed by the forced swimming test. Pb levels were measured in the blood of dams (weaning) and pups (after behavioral evaluation). The results demonstrated that exposure to Pb during both pregnancy and lactation induced, in males, an increased emotionality state detected in the open-field test, and in females, depressive-like behavior detected in the forced swimming test. These alterations were observed at residual blood Pb levels (i.e., around 5 microg/dL). PMID:15720036

de Souza Lisboa, Sabrina Francesca; Gonçalves, Gisele; Komatsu, Fernanda; Queiroz, Carlos Alfredo Salci; Almeida, Alaor Aparecido; Moreira, Estefânia Gastaldello



Influence of an alpha-1-adrenoceptor antagonist, nicergoline, on placental prostanoid production in streptozotocin-induced diabetic pregnant rats.  


The aim of this study was to determine if placental prostanoids could mediate the vasodilating action of an alpha-1-adrenoceptor antagonist, nicergoline (400 micrograms/kg i.p.), during late pregnancy in streptozotocin-induced diabetic rats (40 mg/kg i.v.). Placental prostanoid concentrations were evaluated by radioimmunoassay. Prostaglandin E2 levels showed a highly significant increase in diabetic and nondiabetic rats treated with nicergoline (p less than 0.001). 6-Keto-PGF1 alpha concentrations were slightly increased in diabetic rats compared to controls, and this increase was reversed by both nicergoline and insulin treatments. In all groups studied thromboxane B2 levels were comparable. It is concluded that prostaglandin E2 could mediate the vasodilating action of nicergoline on the placental irrigation and, therefore, improved the hemodynamic state of this organ in diabetic rats. PMID:1969751

Chartrel, N; Clabaut, M; Boismare, F; Schrub, J C



Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte contractile function in female rats  

PubMed Central

Aim To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat. Methods Non-ovariectomized (control, n?=?8) and ovariectomized (OVX, n?=?8) female rats were kept under normal conditions or were exposed to stress (control-S, n?=?8 and OVX-S, n?=?8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca2+-dependent active force (Factive), Ca2+-independent passive force (Fpassive), and Ca2+-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings. Results Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6?±?4.8 ng/mL and OVX-S, 21.9?±?4.0 ng/mL) compared to control (10?±?2.9 ng/mL) and OVX (2.8?±?0.5 ng/mL) groups. Factive was higher in the OVX groups (OVX, 25.9?±?3.4 kN/m2 and OVX-S, 26.3?±?3.0 kN/m2) than in control groups (control, 16.4?±?1.2 kN/m2 and control-S, 14.4?±?0.9 kN/m2). Regarding the potential molecular mechanisms, Factive correlated with MyBP-C phosphorylation, while myofilament Ca2+-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. Fpassive was unaffected by any treatment. Conclusion Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca2+-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca2+-dependent cardiomyocyte contractile force production, which may have pathophysiological importance during stress conditions affecting postmenopausal women. PMID:24891282

Kalasz, Judit; Toth, Eniko Pasztor; Bodi, Beata; Fagyas, Miklos; Toth, Attila; Pal, Bhattoa Harjit; Vari, Sandor G.; Balog, Marta; Blazetic, Senka; Heffer, Marija; Papp, Zoltan; Borbely, Attila



Female spontaneously hypertensive rats have a compensatory increase in renal regulatory T cells in response to elevations in blood pressure.  


Female spontaneously hypertensive rats (SHR) have more regulatory T cells (Tregs) in their kidneys than males. The goal of this study was to determine the impact of blood pressure (BP) on the renal immune profile. We hypothesize that increases in BP promote a proinflammatory renal T cell and cytokine profile in SHR, although females will have greater hormone-dependent increases in Tregs and males will have greater increases in Th17 cells. Renal T cell and cytokine profiles were assessed in male and female Wistar-Kyoto rats and male and female SHR treated with vehicle or hydrochlorothiazide and reserpine (HCTZ) from 6 to 12 (6-HCTZ) or 11 to 13 weeks of age (2-HCTZ). Regardless of sex, SHR had a more proinflammatory renal immune profile than Wistar-Kyoto rats. 6-HCTZ attenuated age-related increases in BP and 2-HCTZ reversed hypertension compared with vehicle-treated SHR. Neither 6-HCTZ nor 2-HCTZ altered CD3(+), CD4(+), or CD8(+) T cells in either sex. Both treatments decreased Tregs only in female SHR abolishing sex differences in Tregs. 6-HCTZ has no impact on Th17 cells in either sex and 2-HCTZ had a minimal impact on renal Th17 cells. To further assess mechanisms mediating sex differences in the renal immune profile, male and female SHR were gonadectomized to determine the impact of sex hormones. Gonadectomy increased proinflammatory markers in both sexes, suggesting that both male and female sex hormones are anti-inflammatory. In conclusion, BP contributes to sex differences in the renal T-cell profile of SHR; female SHR increase renal Tregs in response to increases in BP. PMID:24914200

Tipton, Ashlee J; Baban, Babak; Sullivan, Jennifer C



Toxicological Features of Catha edulis (Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study  

PubMed Central

Hepato- and nephrotoxicity of Khat consumption (Catha edulis Forskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120?g) were distributed randomly into four groups of males and female (n = 12). Normal controls (NCs) received distilled water, whereas test groups received 500?mg/kg (low dose (LD)), 1000?mg/kg (medium dose (MD)), or 2000?mg/kg (high dose (HD)) of crude extract of Catha edulis orally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats. PMID:23259000

Alsalahi, Abdulsamad; Abdulla, Mahmood Ameen; Al-Mamary, Mohammed; Noordin, Mohamed Ibrahim; Abdelwahab, Siddig Ibrahim; Alabsi, Aied M.; Shwter, Abdrabuh; Alshawsh, Mohammed A.



Female temperament, tumor development and life span: Relation to glucocorticoid and tumor necrosis factor ? levels in rats  

PubMed Central

Behavioral characteristics closely associated with specific physiological profiles present an important area of research in understanding health disparities. In particular, glucocorticoid overproduction may be an important factor moderating disease progression; natural variance in production of this steroid has been proposed as one mechanism underlying individual differences in health and disease. In the current paper, we examined immune parameters in female rats of two different behavioral types previously shown to have differential glucocorticoid production and life spans. We categorized young female rats according to their behavioral response to novelty (high- or low-locomotion), and compared their glucocorticoid production, adrenal size, thymus size, tumor necrosis factor-? (TNF-?) production, tumor development and life span. As expected, high-locomotion females produced more glucocorticoids and had larger adrenal glands during young adulthood than did low-locomotion females. High-locomotion females had significantly smaller thymuses and reduced TNF-? levels compared to low-locomotion, suggesting altered immune function in young adulthood. Finally, high-locomotion females had shorter life spans than did low-locomotion females, and this was particularly true in females that developed pituitary tumors, but not in those that developed mammary tumors. These results, along with other published findings, suggest that high-locomotion rodent females experience life-long elevations in glucocorticoid responses to novelty, and that these elevated levels may be comparable to chronic stress. This naturally-occurring endocrine profile may influence immune responses which in turn could affect disease susceptibility. Variance in immune function across personality types may be partially moderated by natural variance in glucocorticoid production. PMID:18155400

Cavigelli, Sonia A.; Bennett, Jeanette M.; Michael, Kerry C.; Klein, Laura Cousino



2-bromo-alpha-ergocryptine mesylate (CB-154) inhibits prolactin and luteinizing hormone secretion in the prepubertal female rat.  


Treatment of immature female rats with 100 micrograms 2-bromo-alpha-ergocryptine mesylate (CB-154) per ml drinking water beginning on Day 30 of age until vaginal opening delayed puberty by 6 days. Rats treated with CB-154 exhibited vaginal opening at 43.3 +/- 0.6 days whereas controls exhibited vaginal opening at 37.9 +/- 0.8 days. Most interestingly, serum levels of luteinizing hormone (LH) and prolactin (PRL) on Days 31-35, determined by a homologous radioimmunoassay were significantly lower in treated rats than in controls. The ovarian concentrations of progesterone (P) and androstenedione (A) were lower in rats treated with CB-154 than in controls; ovarian estradiol (E2) concentrations were low in both groups. Serum levels of P (but not A and E2) were reduced on Days 31-35 of the treatment period. Cessation of the CB-154 treatment on the morning of Day 35 returned the onset of puberty to normal values; steroid and gonadotropin levels also returned to normal values within 2 days after removal of the CB-154 from the drinking water. Near the time of onset of puberty, serum levels of LH in rats treated with CB-154 returned to control values. These data indicate that in the female rat the delay in puberty induced by CB-154 might be due to a reduction in the secretion of LH, especially since the onset of delayed puberty in rats treated with CB-154 correlates with an increase in the serum level of LH. Further studies are needed to elucidate the specific effects of hypoprolactinemia on ovarian function and the onset of puberty in the rat. PMID:3089338

Shaban, M A; Terranova, P F



Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease  

Microsoft Academic Search

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were

Eric E Nilsson; Matthew D Anway; Jacob Stanfield; Michael K Skinner



Improving Active and Passive Avoidance Memories Deficits Due to Permanent Cerebral Ischemia by Pomegranate Seed Extract in Female Rats  

PubMed Central

Background: This study aimed to evaluate the effect of two weeks oral administration of pomegranate seed extract (PGSE) on active and passive avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO) to induce permanent cerebral ischemia in adult female rats. Methods: Seventy adult female Wistar rats (250 ± 20 g) were used. Animals were divided randomly into seven groups with 10 in each: 1) Sham-operated; 2) Ischemic; 3–6) Ischemic received PGSE (100, 200, 400, and 800 mg/2mL/kg, orally) for 14 days; 7) Ischemic received vehicle. In order to create 2CCAO, carotid arteries were ligatured and then cut bilaterally. Active and passive avoidance task were measured using criterion condition responses (CCRs) in Y-maze and step-through latency (STL) in two-way shuttle box in all female rats. Results: Both active and passive avoidance memories were significantly impaired in rats after cerebral hypoxia-ischemia (CHI) (P < 0.001). PGSE treatment significantly improved passive and active memory impairments with 2CCAO (P < 0.05, P < 0.01, and P < 0.001). No toxicity was observed even with high-dose PGSE consumption (800 mg/kg, for 14 days). Conclusion: PGSE exhibits therapeutic potential for avoidance memories, which is most likely related at least in part to its antioxidative and free radical scavenging actions. PMID:23983574

Sarkaki, Alireza; Rezaiei, Moslem; Gharib naseri, MohammadKazem; Rafieirad, Maryam



Spatial working memory and hippocampal size across pregnancy in rats.  


The present experiments investigated the effects of pregnancy on performance in the Morris water maze and on hippocampal volume. In the first study, pregnant rats (in between the first and second trimester) outperformed nonpregnant rats on the Morris water maze on 1 day of testing. In the second study, rats were tested in a working memory variation of the maze in which the spatial location of the platform varied. Pregnant females traveled shorter distances than nonpregnant females during the first two trimesters, but performed worse than nonpregnant females during the third trimester. Latency measures showed a similar profile. Group differences in performance were not related to changes in swim speed. However, changes in performance in pregnant females may be related to estrogen, progesterone, and/or corticosterone levels during pregnancy, with low levels of estradiol and high levels of progesterone being associated with better performance. There were no significant differences between pregnant and nonpregnant animals on any of the brain measures, although pregnant animals tended to have a smaller hippocampus than nonpregnant animals. These results indicate that pregnancy can affect performance, possibly related to the hormonal changes that accompany pregnancy. PMID:10712861

Galea, L A; Ormerod, B K; Sampath, S; Kostaras, X; Wilkie, D M; Phelps, M T



Neonatal ventral hippocampal lesions in male and female rats: effects on water maze, locomotor activity, plus-maze and prefrontal cortical GABA and glutamate release in adulthood.  


Schizophrenia is characterized by diverse behavioural and neurochemical abnormalities that may be differentially expressed in males and females. Male rats with neonatal ventral hippocampal lesions (nVHL) have commonly demonstrated behavioural and neurochemical abnormalities similar to those in schizophrenia. Fewer studies have used female rats. We investigated the hypothesis that male and female nVHL rats will demonstrate behavioural abnormalities accompanied by decreased GABA and l-glutamate release in the prefrontal cortex (PFC). On postnatal day (P) 7 rats received VH injections of ibotenate (3.0 microg/0.3 microl/side; n=18) or saline (n=21) or no injections (n=22). On P56, rats began water-maze, locomotor activity and elevated plus maze testing, and were then sacrificed for potassium-evoked GABA and l-glutamate release from PFC slices. nVHL rats showed impaired performance in water maze acquisition and match-to-sample tasks, increased spontaneous and amphetamine-induced locomotor activity and increased percent open-arm time. These behavioural changes were similar in males and females. These effects were accompanied by significantly reduced potassium-evoked l-glutamate release in male and female nVHL rats relative to controls, and non-significantly lower GABA release. Findings support the notion that behavioural abnormalities in post-pubertal male and female nVHL rats are associated with decreases in PFC neurotransmitter release. PMID:19463702

Beninger, Richard J; Tuerke, Katharine J; Forsyth, Jennifer K; Giles, Andrew; Xue, Lihua; Boegman, Roland J; Jhamandas, Khem



Age-associated alterations in sympathetic noradrenergic innervation of primary and secondary lymphoid organs in female Fischer 344 rats.  


Normal aging processes, as well as, psychological stress affect the immune system; each can act alone, or interact with each other, to cause dysregulation of immune function substantially altering physical and mental health. The sympathetic nervous system (SNS), a major mediator of stress effects on immune function, is significantly affected by normal aging process, and stress can affect aging of the SNS. Previously, we have shown age-associated changes in sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents that affect immune regulation. The purpose of this study was to investigate sympathetic innervation of lymphoid organs and associated alterations in immune responses in young and aging female Fischer 344 (F344) rats. Histofluorescence and immunocytochemistry for NA innervation, and neurochemistry for norepinephrine (NE) levels were performed in the thymus, spleen, and mesenteric lymph nodes (MLN) isolated from 3-month-old young (normal estrous cycle), 8- to 9-month-old (onset of irregular estrous cycling), and 24-25 month, and 30-31 month female F344 rats (acyclic) at diestrus based on vaginal smears. Age-related alterations in natural killer (NK) cell activity, interleukin-2 (IL-2) and interferon-? (IFN-?) production, T and B lymphocyte proliferation were examined in splenocytes. Sympathetic NA innervation and NE levels increased with aging in the thymus, declined in spleen and MLN, and was accompanied by significant reductions in NK cell activity, IL-2 and IFN-? production, and T and B cell proliferation in old female rats. In 8-9 mo rats, NE levels in the hilar region of the spleen and IFN-? production were unaltered, while NE levels in the end region of the spleen and IL-2 production were reduced. Collectively, these results suggest that aging is characterized by significant alterations in sympathetic NA innervation in the thymus, spleen, and MLN associated with immunosuppression, and that there is a marked shift in NA activity and immune reactivity occurring during middle-aged female rats. PMID:21186063

ThyagaRajan, Srinivasan; Madden, Kelley S; Teruya, Brian; Stevens, Suzanne Y; Felten, David L; Bellinger, Denise L




PubMed Central

Normal aging processes, as well as, psychological stress affect the immune system; each can act alone, or interact with each other, to cause dysregulation of immune function substantially altering physical and mental health. The sympathetic nervous system (SNS), a major mediator of stress effects on immune function, is significantly affected by normal aging process, and stress can affect aging of the SNS. Previously, we have shown age-associated changes in sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents that affect immune regulation. The purpose of this study was to investigate sympathetic innervation of lymphoid organs and associated alterations in immune responses in young and aging female Fischer 344 (F344) rats. Histofluorescence and immunocytochemistry for NA innervation, and neurochemistry for norepinephrine (NE) levels were performed in the thymus, spleen, and mesenteric lymph nodes (MLN) isolated from 3-month-old young (normal estrous cycle), 8- to 9-month-old (onset of irregular estrous cycling), and 24–25 month, and 30–31 month female F344 rats (acyclic) at diestrus based on vaginal smears. Age-related alterations in natural killer (NK) cell activity, interleukin-2 (IL-2) and interferon-? (IFN-?) production, T and B lymphocyte proliferation were examined in splenocytes. Sympathetic NA innervation and NE levels increased with aging in the thymus, declined in spleen and MLN, and was accompanied by significant reductions in NK cell activity, IL-2 and IFN-? production, and T and B cell proliferation in old female rats. In 8–9 mo rats, NE levels in the hilar region of the spleen and IFN-? production were unaltered, while NE levels in the end region of the spleen and IL-2 production were reduced. Collectively, these results suggest that aging is characterized by significant alterations in sympathetic NA innervation in the thymus, spleen, and MLN associated with immunosuppression, and that there is a marked shift in NA activity and immune reactivity occurring during middle-aged female rats. PMID:21186063

ThyagaRajan, Srinivasan; Madden, Kelley S.; Teruya, Brian; Stevens, Suzanne Y.; Felten, David L.; Bellinger, Denise L.



Protective role of thymoquinone against liver damage induced by tamoxifen in female rats.  


One of the major reasons for terminating a clinical trial is the liver toxicity induced by chemotherapy. Tamoxifen (TAM) is an anti-estrogen used in the treatment and prevention of hormone-dependent breast cancer. Tamoxifen therapy may cause hepatic injury. The seeds of Nigella sativa, which contain the active ingredient thymoquinone (TQ), have been used in folk medicine for diverse ailments. TQ is reported to possess anticancer and hepatoprotective effects. In this study, the protective effects of TQ against TAM-induced hepatotoxicity in female rats were evaluated. Four groups of rats were used: control; TAM; TQ; TAM+TQ. TAM (45 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection (i.p.), for 10 consecutive days) resulted in elevated serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, and gamma glutamyl transferase, as well as depletion of reduced glutathione in the liver and accumulation of lipid peroxides. Also, TAM treatment inhibited the hepatic activity of superoxide dismutase. Further, it raised the levels of tumor necrosis factor alpha in the liver and induced histopathological changes. Pretreatment with TQ (50 mg·(kg body mass)(-1)·day(-1); orally, for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. TQ significantly inhibited TAM-induced hepatic GSH depletion and LPO accumulation. Consistently, TQ normalized the activity of SOD, inhibited the rise in TNF-? and ameliorated the histopathological changes. In conclusion, TQ protects against TAM-induced hepatotoxicity. PMID:24941454

Suddek, Ghada M



External urethral sphincter motoneuron properties in adult female rats studied in vitro.  


The external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate = 12-27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulator-independent mechanisms. PMID:20573976

Carp, Jonathan S; Tennissen, Ann M; Liebschutz, Jennifer E; Chen, Xiang Yang; Wolpaw, Jonathan R



External Urethral Sphincter Motoneuron Properties in Adult Female Rats Studied In Vitro  

PubMed Central

The external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate = 12–27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulator-independent mechanisms. PMID:20573976

Tennissen, Ann M.; Liebschutz, Jennifer E.; Chen, Xiang Yang; Wolpaw, Jonathan R.



Induction of liver monooxygenases by annatto and bixin in female rats.  


Annatto or urucum is an orange-yellow dye obtained from Bixa orellana seeds. It has been used as a natural dye in a variety of food products, drugs and cosmetics, and also in Brazilian cuisine as a condiment ('colorau'). Bixin, a carotenoid devoid of provitamin A activity, is the main pigment found in annatto. Some carotenoids (canthaxanthin, astaxanthin and beta-Apo-8'-carotenal) are known to be potent inducers of CYP1A1, a property not shared by others (beta-carotene, lycopene and lutein). Little is known, however, about the CYP1A1-inducing properties of bixin and annatto. The present study was performed to determine the effects of an annatto extract (28% bixin) and bixin (95% pure) on rat liver monooxygenases. Adult female Wistar rats were treated by gavage with daily doses of annatto (250 mg/kg body weight, which contains approximately 70 mg bixin/kg body weight), bixin (250 mg/kg body weight) or the vehicle only (corn oil, 3.75 g/kg body weight) for 5 consecutive days, or were not treated (untreated control). The activities of aniline-4-hydroxylase (A4H), ethoxycoumarin-O-deethylase (ECOD), ethoxy- (EROD), methoxy- (MROD), pentoxy- (PROD) and benzyloxy- (BROD) resorufin-O-dealkylases were measured in liver microsomes. Annatto (250 mg/kg containing 70 mg bixin/kg) induced EROD (3.8x), MROD (4.2x), BROD (3.3x) and PROD (2.4x). Bixin (250 mg/kg) was a weaker inducer of EROD (2.7x), MROD (2.3x) and BROD (1.9x) and did not alter PROD, A4H or ECOD activities. These results suggest that constituents of the extract other than bixin play an important role in the induction of CYP1A and CYP2B observed with annatto food colorings. PMID:12532234

De-Oliveira, A C A X; Silva, I B; Manhaes-Rocha, D A; Paumgartten, F J R



Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine.  


Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted. PMID:24140931

Boyda, Heidi N; Procyshyn, Ric M; Asiri, Yahya; Wu, Claire; Wang, Cathy K; Lo, Ryan; Pang, Catherine C Y; Honer, William G; Barr, Alasdair M



Induction of malignant fibrous histiocytoma in female Fisher rats by implantation of cyanoacrylate, zirconia, polyvinyl chloride or silicone.  


Five kinds of foreign bodies (silicone, cellulose, polyvinyl chloride, zirconia and alkyl-alpha cyanoacrylate) were implanted into subcutaneous tissue of female Fisher rats. Subcutaneous tumors were induced in 27.3, 54.5, 100, 63.6% of rats by silicone rubber, polyvinyl chloride, zirconia and alkyl-alpha-cyanoacrylate, respectively, but not by cellulose. Almost all tumors were composed of a mixture of cells that resembled fibroblasts characterized by the presence of numerous rough-surfaced endoplasmic reticulum and Golgi apparatus, histiocytes characterized by developed endoplasmic reticulum and abundant lysosome, myofibroblasts characterized by the presence of both myofibrils and fibroblast-like structures, and immature mesenchymal cells. In some tumors, the cells exhibited a storiform pattern. Some tumor cells were positively stained by ED2 or anti-muscle actin antibody. The features of induced tumors in rats were consistent with those of human malignant fibrous histiocytoma. A rat malignant fibrous histiocytoma transplanted into the subcutaneous tissue of the syngeneic female Fisher rats grew and metastasized to the lungs. PMID:8395906

Hatanaka, S; Oneda, S; Okazaki, K; Shong, L J; Yoshida, A; Isaka, H; Yoshida, H



L-arginine improves endothelial function, independently of arginine uptake, in aortas from chronic renal failure female rats.  


Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. Decreased activity of cationic amino acid transporter-1 (CAT-1), the selective arginine transporter of eNOS, has been shown to inhibit eNOS in uremia. Recently, we failed to demonstrate a decrease in glomerular arginine transport in uremic female rats (Schwartz IF, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, Ingbir M, Shtabski A, Weinstein T, Chernin G, Shashar M, Hershkoviz R, Schwartz D. Am J Physiol Renal Physiol 303: F396-F404, 2012). The current experiments were designed to determine whether sexual dimorphism which characterizes glomerular arginine transport system in uremia involves the systemic vasculature as well and to assess the effect of L-arginine in such conditions. Contractile and vasodilatory responses, ultrastructural changes, and measures of the L-arginine-NO system were performed in thoracic aortas of female rats subjected to 5/6 nephrectomy. The contractile response to KCl was significantly reduced, and acetylcholine-induced vasodilation was significantly impaired in aortas from CRF dames compared with healthy rats. Both of these findings were prevented by the administration of arginine in the drinking water. The decrease in both cGMP generation, a measure of eNOS activity, and aortic eNOS and phosphorylated eNOS abundance observed in CRF rats was completely abolished by l-arginine, while arginine transport and CAT-1 protein were unchanged in all experimental groups. Arginine decreased both serum levels of advanced glycation end products and the asymmetrical dimethylarginine/arginine ratio and restored the endothelial ultrastructure in CRF rats. In conclusion. arginine administration has a profound beneficial effect on ECD, independently of cellular arginine uptake, in CRF female rats. PMID:24338824

Nesher, Nachum; Frolkis, Inna; Schwartz, Doron; Chernichovski, Tamara; Levi, Sharon; Pri-Paz, Yael; Chernin, Gil; Shtabsky, Alexander; Ben-Gal, Yanai; Paz, Yossi; Schwartz, Idit F



Female-Specific Induction of Rat Pituitary Dentin Matrix Protein-1 by GnRH  

PubMed Central

Hypothalamic GnRH is the primary regulator of reproduction in vertebrates, acting via the G protein-coupled GnRH receptor (GnRHR) in pituitary gonadotrophs to control synthesis and release of gonadotropins. To identify elements of the GnRHR-coupled gene network, GnRH was applied in a pulsatile manner for 6 hours to a mixed population of perifused pituitary cells from cycling females, mRNA was extracted, and RNA sequencing analysis was performed. This revealed 83 candidate-regulated genes, including a large number coding for secreted proteins. Most notably, GnRH induces a greater than 600-fold increase in expression of dentin matrix protein-1 (Dmp1), one of five members of the small integrin-binding ligand N-linked glycoprotein gene family. The Dmp1 response is mediated by the GnRHR, not elicited by other hypothalamic releasing factors, and is approximately 20-fold smaller in adult male pituitary cells. The sex-dependent Dmp1 response is established during the peripubertal period and independent of the developmental pattern of Gnrhr expression. In vitro, GnRH-induced expression of this gene is coupled with release of DMP1 in extracellular medium through the regulated secretory pathway. In vivo, pituitary Dmp1 expression in identified gonadotrophs is elevated after ovulation. Cell signaling studies revealed that the GnRH induction of Dmp1 is mediated by the protein kinase C signaling pathway and reflects opposing roles of ERK1/2 and p38 MAPK; in addition, the response is facilitated by progesterone. These results establish that DMP1 is a novel secretory protein of female rat gonadotrophs, the synthesis and release of which are controlled by the hypothalamus through the GnRHR signaling pathway. This advance raises intriguing questions about the intrapituitary and downstream effects of this new player in GnRH signaling. PMID:24085820

Kucka, Marek; Bjelobaba, Ivana; Clokie, Samuel J. H.; Klein, David C.



Effects of cadmium, calcium, age and parity on bone mineral, density and strength in female rats  

SciTech Connect

Weanling female rats were fed diets containing one of three levels of Ca (0.3, 0.6, or 0.9%) and one of four levels of Cd (0, 1, 5, or 10 ppm) in the drinking water. One half of each group was fed first as adolescents (55 days) and the other half as mature (110 days) females. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppm Cd were smaller at birth than offspring of dams treated with 0 or 1 ppm Cd. After the fourth pregnancy, the decreased birth weight was evident only in offspring of dams treated with 10 ppm Cd. Offspring of dams fed 5 or 10 ppm Cd or the 0.3% Ca diet had decreased weaning weight regardless of parity. A 0.3% Ca diet superimposed upon a 5 or 10 ppm Cd intake decreased weaning weight of the male offspring after the first, but not the fourth, pregnancy with the offspring of adolescent dams affected more than those of mature dams. Offspring of dams fed the 0.9% Ca diet did not differ in weaning weight from the offspring of dams fed the 0.6% Ca diet. The 0.3% Ca diet depressed the plasma Ca and the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet.

Hammond, B.F.



Malignant amelanotic melanoma behind the left eye in a female Crj:CD(SD)IGS rat: a case report.  


A tumor behind the left eye in a female Crj:CD(SD)IGS rat was investigated histopathologically, immunohistopathologically, and electron microscopically. The tumor invaded and destroyed orbital tissues and bones. It consisted of various tumor cells; namely, spindle-shaped, epithelioid, anaplastic melanoma cells, and had prominent eosinophilic cytoplasm and nuclei with a greater variation in size. Immunohistochemically, almost all of the tumor cells were positive for antimelanoma, PNL2 antibody. Ultrastructurally, the tumor cells were rich in small vesicles containing fine granules and filamentous structures. This is the first report describing an amelanotic melanoma in the head of an albino rat. PMID:18725473

Kurotaki, T; Tomonari, Y; Kanno, T; Wako, Y; Tsuchitani, M



Factors affecting mammary tumor incidence in chlorotriazine-treated female rats: hormonal properties, dosage, and animal strain.  


Chlorotriazines are widely used in agriculture as broadleaf herbicides. The compounds specifically inhibit photosynthesis, and, as such, display little interaction with animal systems. However, a 24-month feeding study with atrazine (ATR) revealed a significant dose-related increase of mammary tumors in female Sprague-Dawley (SD) rats. Because numerous studies indicated that ATR had a low mutagenic and oncogenic potential, it was decided to test a hypothesis that the herbicide possessed endocrine activity. Among tests for estrogenic action, oral dosing of ATR up to 300 mg/kg did not stimulate uterine weight of ovariectomized rats. However, ATR administration did reduce estrogen-stimulated uterine weight gain. Further evidence of inhibition came from measures of [3H]-thymidine incorporation into uterine DNA of ATR-treated immature rats. Again, no intrinsic estrogenic activity was observed up to a 300-mg/kg dose. In vitro, ATR competed poorly against estradiol binding to cytosolic receptors, with an approximate IC50 of 10(-5) M. Atrazine administration to SD and Fischer-344 (F-344) rats for 12 months, up to 400 ppm in food, was correlated with significant alterations of estrous cycling activity; but there was a divergent strain response. SD rats showed an increased number of days in vaginal estrus, increased plasma estradiol, and decreased plasma progesterone by 9 to 12 months of treatment. F-344 rats did not demonstrate treatment-related affects. A study of ultrastructure in the hypothalamic arcuate nucleus of female SD rats that were fed diaminochlorotriazine (DACT), an ATR metabolite, suggested that age-associated glial pathology was enhanced by treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7737039

Eldridge, J C; Tennant, M K; Wetzel, L T; Breckenridge, C B; Stevens, J T



Hypothalamic IGF-I gene therapy prolongs estrous cyclicity and protects ovarian structure in middle-aged female rats.  


There is substantial evidence that age-related ovarian failure in rats is preceded by abnormal responsiveness of the neuroendocrine axis to estrogen positive feedback. Because IGF-I seems to act as a permissive factor for proper GnRH neuronal response to estrogen positive feedback and considering that the hypothalamic content of IGF-I declines in middle-aged (M-A) rats, we assessed the effectiveness of long-term IGF-I gene therapy in the mediobasal hypothalamus (MBH) of M-A female rats to extend regular cyclicity and preserve ovarian structure. We used 3 groups of M-A rats: 1 group of intact animals and 2 groups injected, at 36.2 weeks of age, in the MBH with either a bicistronic recombinant adeno-associated virus (rAAV) harboring the genes for IGF-I and the red fluorescent protein DsRed2, or a control rAAV expressing only DsRed2. Daily vaginal smears were taken throughout the study, which ended at 49.5 weeks of age. We measured serum levels of reproductive hormones and assessed ovarian histology at the end of the study. Although most of the rats injected with the IGF-I rAAV had, on the average, well-preserved estrous cyclicity as well as a generally normal ovarian histology, the intact and control rAAV groups showed a high percentage of acyclic rats at the end of the study and ovaries with numerous enlarged cysts and scarce corpora lutea. Serum LH was higher and hyperprolactinemia lower in the treated animals. These results suggest that overexpression of IGF-I in the MBH prolongs normal ovarian function in M-A female rats. PMID:23584855

Rodríguez, Silvia S; Schwerdt, José I; Barbeito, Claudio G; Flamini, Mirta A; Han, Ye; Bohn, Martha C; Goya, Rodolfo G



Effects of a selectively bred novelty-seeking phenotype on the motivation to take cocaine in male and female rats  

Microsoft Academic Search

Background  Gender and enhanced novelty reactivity can predispose certain individuals to drug abuse. Previous research in male and female\\u000a rats selectively bred for high or low locomotor reactivity to novelty found that bred High Responders (bHRs) acquire cocaine\\u000a self-administration more rapidly than bred Low Responders (bLRs) and that bHR females in particular self-administered more\\u000a cocaine than the other groups. The experiments

Jennifer A Cummings; Brooke A Gowl; Christel Westenbroek; Sarah M Clinton; Huda Akil; Jill B Becker



Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.  


We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity. PMID:16224581

Trofimov, S S; Voronina, T A; Guzevatykh, L S



Development of gonadotropin-releasing hormone (GnRH) neuron regulation in the female rat.  


1. After reaching its final destination the GnRH neuronal network develops under the influence of both excitatory and inhibitory inputs. 2. In the first 2 weeks of life, the immaturity of the GnRH neuronal system is reflected in sporadic unsynchronized bursts of the decapeptide, which determine the pattern of serum gonadotropin levels observed in female rats: high FSH levels and transient bursts of LH. The main inhibitory neuronal systems that operate in this period are the opioid and dopaminergic systems. A decrease in their inhibitory effectiveness may not be sufficient correctly to activate and synchronize the GnRH neuronal system. 3. There is a concomitant increase in excitatory inputs, mainly noradrenaline, excitatory amino acids, and NPY, which increase the synthesis and release of GnRH at the beginning of the juvenile period and participate in the coupling of GnRH neural activity to the ongoing rhythmic activity of a hypothalamic circadian oscillator. 4. The morphological changes of GnRH neurons which take place during the third and fourth weeks of life, and which are probably related to increasing estradiol levels, reflects the increasing complexity of the GnRH neuronal network, which establishes synaptic contacts to enable the expression of pulsatility and of the positive feedback of estradiol, both necessary components for the occurrence of puberty. PMID:7648607

Becú-Villalobos, D; Libertun, C



Different modes of hippocampal plasticity in response to estrogen in young and aged female rats  

PubMed Central

Estrogen regulates hippocampal dendritic spine density and synapse number in an N-methyl-d-aspartate (NMDA) receptor-dependent manner, and these effects may be of particular importance in the context of age-related changes in endocrine status. We investigated estrogen's effects on axospinous synapse density and the synaptic distribution of the NMDA receptor subunit, NR1, within the context of aging. Although estrogen induced an increase in axospinous synapse density in young animals, it did not alter the synaptic representation of NR1, in that the amount of NR1 per synapse was equivalent across groups. Estrogen replacement in aged female rats failed to increase axospinous synapse density; however, estrogen up-regulated synaptic NR1 compared with aged animals with no estrogen. Therefore, the young and aged hippocampi react differently to estrogen replacement, with the aged animals unable to mount a plasticity response generating additional synapses, yet responsive to estrogen with respect to additional NMDA receptor content per synapse. These findings have important implications for estrogen replacement therapy in the context of aging. PMID:11427724

Adams, Michelle M.; Shah, Ravi A.; Janssen, William G. M.; Morrison, John H.



[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].  


Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test