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Pregnant Dams (pregnant + dam)
Selected AbstractsFoster mother care but not prenatal morphine exposure enhances cocaine self-administration in young adult male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2007I. Vathy Abstract The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11,18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 463-473, 2007. [source] Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11,-hydroxysteroid dehydrogenase type 2EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009P. J. Lucassen Abstract Prenatal stress (PS) produces persistent abnormalities in anxiety-related behaviors, stress responsivity, susceptibility to psychopathology and hippocampal changes in adult offspring. The hippocampus shows a remarkable degree of structural plasticity, notably in response to stress and glucocorticoids. We hypothesized that PS would differentially affect hippocampal neurogenesis in rats selectively bred for genetic differences in anxiety-related behaviors and stress responsivity. Pregnant dams of high anxiety-related behavior (HAB) and low anxiety-related behavior (LAB) strains were stressed between days 5 and 20 of pregnancy. The survival of newly generated hippocampal cells was found to be significantly lower in 43-day-old HAB than in LAB male offspring of unstressed pregnancies. PS further reduced newly generated cell numbers only in HAB rats, and this was paralleled by a reduction in doublecortin-positive cell numbers, indicative of reduced neurogenesis. As maternal plasma corticosterone levels during PS were similar in both strains, we examined placental 11,-hydroxysteroid dehydrogenase type 2 (11,-HSD2), which catalyses rapid inactivation of maternal corticosterone to inert 11-dehydrocorticosterone and thus serves as a physiological ,barrier' to maternal glucocorticoids. PS significantly increased placental 11,-HSD2 activity in LAB, but not HAB, rats. We conclude that PS differentially affects the number of surviving newly generated cells and neurogenesis in HAB and LAB rats. The high sensitivity of hippocampal neurogenesis to PS in HAB rats is paralleled by a failure to increase placental 11,-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11,-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis. [source] The Interaction of Gestational and Postnatal Ethanol Experience on the Adolescent and Adult Odor-Mediated Responses to Ethanol in Observer and Demonstrator RatsALCOHOLISM, Issue 10 2010Amber M. Eade Background:, Gestational ethanol exposure enhances the adolescent reflexive sniffing response to ethanol odor. Postnatal exposures of naïve animals as either an observer (i.e., conspecific) or demonstrator (i.e., intoxicated peer) using a social transmission of food odor preference paradigm also yields enhanced odor-mediated responses. Studies on the interaction of fetal and postnatal exposures using the social transmission paradigm have been limited to the responses of observers. When combined, the enhanced response is greater than either form of exposure alone and, in observer females, yields adult persistence. The absence of a male effect is noteworthy, given that chemosensory mechanisms are suggested to be an important antecedent factor in the progression of ethanol preference. Observers gain odor information on the breath of the demonstrator through social interaction. Demonstrators experience the pharmacologic properties of ethanol along with retronasal and hematogenic olfaction. Thus, we tested whether augmentation of the fetal ethanol-induced behavioral response with postnatal exposure as a demonstrator differed from that as an observer. We also examined whether re-exposure as a demonstrator yields persistence in both sexes. Methods:, Pregnant dams were fed an ethanol containing or control liquid diet throughout gestation. Progeny received four ethanol or water exposures: one every 48 hours through either intragastric infusion or social interaction with the infused peer beginning on P29. The reflexive behavioral sniffing response to ethanol odor was tested at postnatal (P) day 37 or P90, using whole-body plethysmography. Results:, When tested in either adolescence or adulthood - fetal ethanol exposed adolescent ethanol observers and demonstrators significantly differed in their odor-mediated response to ethanol odor both between themselves and from their respective water controls. Nonetheless, adolescent ethanol re-exposure as a demonstrator, like an observer, enhanced the reflexive sniffing response to ethanol odor at both testing ages by augmenting the known effects of prior fetal ethanol experience. At each age, the magnitude of the enhanced odor response in demonstrators was similar to that of observers. Interestingly, only re-exposure as a demonstrator resulted in persistence of the behavioral response into adulthood in both sexes. Conclusions:, The method of ethanol re-exposure plays an important role in prolonging the odor-mediated effects of fetal exposure. While ethanol odor-specific exposure through social interaction is important, additional factors such as the pairing of retronasal and hematogenic olfaction with ethanol's intoxicating properties appear necessary to achieve persistence in both sexes. [source] Ethanol Teratogenesis in Five Inbred Strains of MiceALCOHOLISM, Issue 7 2009Chris Downing Background:, Previous studies have demonstrated individual differences in susceptibility to the detrimental effects of prenatal ethanol exposure. Many factors, including genetic differences, have been shown to play a role in susceptibility and resistance, but few studies have investigated the range of genetic variation in rodent models. Methods:, We examined ethanol teratogenesis in 5 inbred strains of mice: C57BL/6J (B6), Inbred Short-Sleep, C3H/Ibg, A/Ibg, and 129S6/SvEvTac (129). Pregnant dams were intubated with either 5.8 g/kg ethanol (E) or an isocaloric amount of maltose,dextrin (MD) on day 9 of pregnancy. Dams were sacrificed on day 18 and fetuses were weighed, sexed, and examined for gross morphological malformations. Every other fetus within a litter was then either placed in Bouin's fixative for subsequent soft-tissue analyses or eviscerated and placed in ethanol for subsequent skeletal analyses. Results:, B6 mice exposed to ethanol in utero had fetal weight deficits and digit, kidney, brain ventricle, and vertebral malformations. In contrast, 129 mice showed no teratogenesis. The remaining strains showed varying degrees of teratogenesis. Conclusions:, Differences among inbred strains demonstrate genetic variation in the teratogenic effects of ethanol. Identifying susceptible and resistant strains allows future studies to elucidate the genetic architecture underlying prenatal alcohol phenotypes. [source] Distribution of carbon-14 labeled C60 ([14C]C60) in the pregnant and in the lactating dam and the effect of C60 exposure on the biochemical profile of urineJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2010Susan C. J. Sumner Abstract This study was conducted to determine the distribution of [14C]C60 in the pregnant rat and fetuses, and in the lactating rat and offspring. Pregnant rats were dosed on gestation day (gd) 15 and lactating rats were dosed on postnatal day (pnd) 8 via tail vein injection with a suspension of ,0.3,mg [14C]C60,kg,1 body weight prepared in polyvinylpyrrolidone (PVP), or with PVP alone. Tissues were collected at 24 and 48 h after dosing. The largest portion of the administered dose was detected in the liver (,43%, pregnant dam; ,35%, lactating dam) and lung (,25%, lactating dam). Radioactivity (,6%) was distributed to the reproductive tract, placenta and fetuses of the pregnant dam. Lactating rats had radioactivity distributed to the milk (3140,dpm,g,1 tissue, 24,h; 1620,dpm,g,1 tissue, 48,h), and to the pups' GI tract (2.8%, 24,h; 4.4% 48,h) and liver (<1%). Blood radioactivity was significant at 24,h (14,19%) and at 48,h (7%) after dosing; largely accounted for in the plasma fraction. Less that 4% of the dose was recovered in the maternal spleen, heart, brain, urine or feces. Metabolomics analysis of urine indicated that dams exposed to [14C]C60 had decreased metabolites derived from the Krebs cycle and increased metabolites derived from the urea cycle or glycolysis, as well as alterations in the levels of some sulfur-containing amino acids and purine/pyrimidine metabolites. This study demonstrated that [14C]C60 crosses the placenta and is transmitted to offspring via the dam's milk and subsequently systemically absorbed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Absence of tissue inhibitor of metalloproteinases 3 disrupts alveologenesis in the mouseDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2009Sean E. Gill Tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix (ECM) degradation by matrix metalloproteinases (MMPs) throughout lung development. We examined lungs from TIMP3 null mice and found significant air space enlargement compared with wild type (WT) animals during a time course spanning early alveologenesis (post-partum days 1, 5, 9 and 14). Trichrome staining revealed a similar pattern of collagen distribution in the walls of nascent alveoli; however, the alveolar walls of TIMP3 mutant mice appeared to be thinner than controls. Assessment of MMP2 and MMP9 activities by gelatin zymography demonstrated a significant elevation in the active form of MMP2 at post-partum days 1 and 5. Treatment of null pregnant dams with a broad spectrum synthetic metalloproteinase inhibitor, GM6001, on embryonic day 16.5 enhanced the formation of primitive alveoli during the saccular stage of lung development as evidenced by a partial, but significant, rescue of alveolar size in post-partum day 1 animals. We propose that increased MMP activity in the absence of TIMP3 enhances ECM proteolysis, upsetting proper formation of primitive alveolar septa during the saccular stage of alveologenesis. Therefore, TIMP3 indirectly regulates alveolar formation in the mouse. To our knowledge, ours is the first study to demonstrate that in utero manipulation of the TIMP/MMP proteolytic axis, to specifically inhibit proteolysis, significantly affects lung development. [source] Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome,DEVELOPMENTAL DYNAMICS, Issue 2 2007Maia L. Green Abstract Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613,631, 2007. © 2007 Wiley-Liss, Inc. [source] Lack of adverse effects in pregnant/lactating female rats and their offspring following pre- and postnatal exposure to ELF magnetic fieldsBIOELECTROMAGNETICS, Issue 4 2004Moon-Koo Chung Abstract We have recently reported that exposure of pregnant rats to 60 Hz at field strengths up to 0.5 mT during the entire period of pregnancy did not induce any biologically significant effects on both pregnant dams and embryo-fetal development. The present study was carried out to investigate the potential effects of gestational and lactational MF exposure on pregnancy, delivery, and lactation of dams and growth, behavior, and mating performance of their offspring in rats. Timed-pregnant female Sprague,Dawley (SD) rats (24/group) received continuous exposure to 60 Hz magnetic field (MF) at field strengths of 0 (sham control), 5 ,T, 83.3 ,T, or 0.5 mT. Dams received MF or sham exposures for 21 h/day from gestational day 6 through lactational day 21. Experimentally generated MF was monitored continuously throughout the study. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Parameters of growth, behavior, and reproductive performance of offspring showed no changes related to MF exposure. There were no adverse effects on embryo-fetal development of F2 offspring from dams exposed to MF. In conclusion, exposure of pregnant SD rats to 60 Hz at field strengths up to 0.5 mT from gestational day 6 to lactational day 21 did not produce biologically significant effects in dams, F1 offspring, or F2 fetuses. Bioelectromagnetics 25:236,244, 2004. © 2004 Wiley-Liss, Inc. [source] Embryonic development in the reduced folate carrier knockout mouse is modulated by maternal folate supplementation,,BIRTH DEFECTS RESEARCH, Issue 7 2008Janee Gelineau-van Waes Abstract BACKGROUND: The reduced folate carrier (RFC1) is a ubiquitously expressed integral membrane protein that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. In this study, embryonic/fetal development is characterized in an RFC1 knockout mouse model in which pregnant dams receive different levels of folate supplementation. METHODS:RFC1+/, males were mated to RFC1+/, females, and pregnant dams were treated with vehicle (control) or folic acid (25 or 50 mg/kg) by daily subcutaneous injection (0.1 mL/10 g bwt), beginning on E0.5 and continuing throughout gestation until the time of sacrifice. RESULTS: Without maternal folate supplementation, RFC1 nullizygous embryos die shortly postimplantation. Supplementation of pregnant dams with 25 mg/kg/day folic acid prolongs survival of mutant embryos until E9.5,E10.5, but they are developmentally delayed relative to wild-type littermates, display a marked absence of erythropoiesis, severe neural tube and limb bud defects, and failure of chorioallantoic fusion. Fgfr2 protein levels are significantly reduced or absent in the extraembryonic membranes of RFC1 nullizygous embryos. Maternal folate supplementation with 50 mg/kg/day results in survival of 22% of RFC1 mutants to E18.5, but they develop with multiple malformations of the eyelids, lungs, heart, and skin. CONCLUSIONS: High doses of daily maternal folate supplementation during embryonic/fetal development are necessary for early postimplantation embryonic viability of RFC1 nullizygous embryos, and play a critical role in chorioallantoic fusion, erythropoiesis, and proper development of the neural tube, limbs, lungs, heart, and skin. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||