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Utero
Terms modified by Utero Selected AbstractsEFFECT OF A HIGH PROTEIN DIET IN UTERO ON KIDNEY DEVELOPMENTNEPHROLOGY, Issue 1 2002M.A. Zimanyi [source] Body Dimensions of Infants Exposed to Antiepileptic Drugs In Utero: Observations Spanning 25 YearsEPILEPSIA, Issue 7 2000K. Wide Summary: Purpose: To investigate the influence of maternal antiepileptic drug (AED) treatment on pregnancy duration, birth weight, body length, head circumference, and intrauterine growth in infants exposed in utero to antiepileptic drugs in Sweden between 1973,1997, with 963 singleton infants. Methods: Data collected from (a) 1973,1981 (record linkage between a hospital discharge register and a medical birth register); (b) 1984,1995 (prospectively collected information in one defined catchment area with two delivery hospitals); and (c) 1995,1997 (medical birth register data). Observed numbers of infants below a defined size for body measurements compared with expected numbers calculated from all births in Sweden after stratification for year of birth, maternal age, parity, and education or smoking habits in early pregnancy. Standard deviation scores estimated with same stratification procedures. Results: Fraction of monotherapy exposures increased from ,40% to ,90% from 1973 to 1997. Significantly increased numbers of infants with small body measurements found in exposed group. Negative influence on body dimensions decreased over time. More marked effects found in infants exposed to polytherapy. In monotherapy, only infants exposed to carbamazepine consistently showed reduction in body dimensions. Significant effect on gestational age in girls and on number of small for gestational age (<2 SD) in boys. Conclusions: Polytherapy with antiepileptic drugs and negative influence on body dimensions decreased. In monotherapy, only carbamazepine has a negative influence on body dimensions in this study. [source] Reproductive Freedom, Self-Regulation, and the Government of Impairment in UteroHYPATIA, Issue 1 2006Shelley Tremain This article critically examines the constitution of impairment in prenatal testing and screening practices and various discourses that surround these technologies. While technologies to test and screen (for impairment) prenatally are claimed to enhance women's capacity to be self-determining, make informed reproductive choices, and, in effect, wrest control of their bodies from a patriarchal medical establishment, I contend that this emerging relation between pregnant women and reproductive technologies is a new strategy of a form of power that began to emerge in the late eighteenth century. Indeed, my argument is that the constitution of prenatal impairment, by and through these practices and procedures, is a widening form of modem government that increasingly limits the field of possible conduct in response to pregnancy. Hence, the government of impairment in utero is inextricably intertwined with the government of the maternal body. [source] Perspective: PTH/PTHrP Activity and the Programming of Skeletal Development In Utero,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2004Jonathan H Tobias First page of article [source] Twins and cerebral palsyACTA PAEDIATRICA, Issue 2001POD Pharoah In a national follow-up study of twin births, monozygous compared with dizygous twins were at significantly increased for both to die in utero, one to die in utero and the co-twin to die in infancy, or both to be livebirths but both die in infancy. The prevalence of cerebral palsy among survivors of a co-twin fetal death was 80.2 and other cerebral impairment was 107.0 per 1000. Many apparently singleton cases of cerebral palsy and impairment may be due to fetal death of a twin that has not been recognized or has been recognized but not registered. [source] Phagocyte activation in preterm infants following premature rupture of the membranes or chorioamnionitisACTA PAEDIATRICA, Issue 10 2000I Nupponen Phagocyte activation was studied in 48 preterm infants, gestational age 27.3 ± 0.3 wk, birthweight 968 ± 40 g, during the first postnatal week. Human neutrophil lipocalin as a marker of neutrophil activation was measured in plasma and tracheal aspirate fractions; and lysozyme, as a marker of monocyte and macrophage activation, in plasma. The concentration of plasma human neutrophil lipocalin was 69 (46,126) ,g/l (median and quartiles), tracheal aspirate fraction fluid 213 (71,433) (,g/l and plasma lysozyme 1337 (923,1764) ,g/l. Infants born to mothers with premature rupture of the membranes or clinical chorioamnionitis (group A, n 20) had significantly higher plasma [73 (58,151) vs 53 (38,108) ,g/l; p 0.027], and tracheal aspirate fraction human neutrophil lipocalin [319 (129,540) vs 190 (57,324) ,g/l; p= 0.019], and plasma lysozyme [1739 (1356,2021) vs 1140 (739,1557) ,g/l; p 0.0001] than did infants whose mothers had intact membranes and who had no suspicion of infection (Group B, n 28). In infants born to mothers receiving corticosteroids ante partum, correlations existed between time from treatment to delivery and plasma (r 0.322, p 0.0256) and tracheal aspirate fraction human neutrophil lipocalin (r= 0.314, p 0.0096). Infants born to mothers with at risk of infection are exposed to the potentially harmful effects of activated neutrophils. Premature rupture of the membranes, even without signs of clinical infection of the mother or the fetus, is associated with phagocyte activation that may begin already in utero. Corticosteroid treatment of the mother may cause transient inhibition of neutrophil activation in the newborn. [source] Childhood cancer,mainly curable so where next?ACTA PAEDIATRICA, Issue 4 2000AW Craft More than 70% of childhood cancer is now curable with best modern therapy. The treatment is expensive but in terms of cost per life year saved, USD 1750, compares very favourably with other major health interventions. The rate of improvement in survival is slowing down. New, "designer", treatments are needed and, better still, prevention. The causes of childhood cancer are beginning to emerge. The origin for many is probably in utero and may be initiated by dietary and other environmental exposures perhaps in susceptible individuals. However, one of the great challenges for the future must be to extend the benefits of modern treatment to the 80% of the world's children who currently have little or no access to it in economically disadvantaged and emerging nations. The International Paediatric Oncology Society (SIOP) is leading the way in bringing hope for children with cancer worldwide. In India, with the support of the WHO, there is a "train the trainers" programme. In Africa, pilot studies of cost-effective treatments for Burkitt's lymphoma are producing gratifying results in Malawi and there are several examples of twinning programmes between major centres in developed and less well-developed countries. Conclusions: The future for children with cancer is bright. Most are curable and prevention may be just over the horizon. [source] Hyperthermia in utero due to maternal influenza is an environmental risk factor for schizophreniaCONGENITAL ANOMALIES, Issue 3 2007Marshall J. Edwards ABSTRACT A hypothesis is presented that the association between maternal influenza and other causes of fever during the second trimester of pregnancy and the subsequent development of schizophrenia in the child is due to the damage caused by hyperthermia to the developing amygdalohippocampal complex and associated structures in the fetal brain. Hyperthermia is a known cause of congenital defects of the central nervous system and other organs after sufficiently severe exposures during early organogenesis. The pathogenic mechanisms include death of actively dividing neuroblasts, disruption of cell migration and arborization and vascular damage. In experimental studies, hyperthermia during later stages of central nervous system development also caused damage to the developing brainstem that was associated with functional defects. This damage usually results in hypoplasia of the parts undergoing active development at the time of exposure. Recent studies have shown no evidence of direct invasion of the fetus by the influenza virus. Factors that might interact with hyperthermia include familial liability to schizophrenia, season of birth, maternal nutrition, severe stress and medications used to alleviate the symptoms of fevers. The time of the development of the fetal amygdalohippocampal complex and the changes found in its structure and associated areas of the brain are compatible with the known effects of hyperthermia. [source] Developmental toxicity of estrogenic chemicals on rodents and other speciesCONGENITAL ANOMALIES, Issue 2 2002Taisen Iguchi ABSTRACT, Antenatal sex-hormone exposure induces lesions in mouse reproductive organs, which are similar to those in humans exposed in utero to a synthetic estrogen, diethylstilbestrol. The developing organisms including rodents, fish and amphibians are particularly sensitive to exposure to estrogenic chemicals during a critical window. Exposure to estrogens during the critical period induces long-term changes in reproductive as well as non-reproductive organs, including persistent molecular alterations. The antenatal mouse model can be utilized as an indicator of possible long-term consequences of exposure to exogenous estrogenic compounds including possible environmental endocrine disrupters. Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans, some of which exhibit estrogenic activity by binding to the estrogen receptors. Estrogen responsive genes, therefore, need to be identified to understand the molecular basis of estrogenic actions. In order to understand molecular mechanisms of estrogenic chemicals on developing organisms, we are identifying estrogen responsive genes using cDNA microarray, quantitative RT-PCR, and differential display methods, and genes related to the estrogen-independent vaginal changes in mice induced by estrogens during the critical window. In this review, discussion of our own findings related to endocrine distuptor issue will be provided. [source] Vascular endothelial growth factor in edematous mouse embryos induced by retinoic acid in uteroCONGENITAL ANOMALIES, Issue 2 2001Yoshiko Yasuda ABSTRACT, Vascular endothelial growth factor (VEGF) is induced by hypoxic environment and contributes to vascular formation in both developing embryos and adults. Exogenous retinoic acid (RA) induces avascular yolk sacs with anemic stunted embryos of day 9 and 10 of gestation when RA is given to pregnant mice on day 6, 6.5 or 7 of pregnancy (Yasuda et al., 1996). We undertook the present studies to find out whether VEGF is activated and plays any role in those RA-exposed embryos. Embryos were obtained from dams given 60 mg/kg of RA on day 6 or 7 of pregnancy and sacrificed three days later. Most RA-exposed embryos showed edematous swelling without prominent vascular nets, but had beating heart tubes on day 9 and day 10 of gestation. Microscopic examination of developing tissue components showed various degrees of degeneration, and distension of the dorsal aorta when the body cavity was dosed. Northern blot analysis revealed expression of VEGF mRNA in the RA-exposed and control embryos. The highest expression of VEGF mRNA was seen in the embryos of day 10 exposed to RA on day 7, and these embryos had a significantly lower ATP content than did the controls (p < 0.01). Immunoreactive VEGF was detectable in both experimental and control embryos; in the former it was especially visible in the distended neuroepithelium, endothelium and membranes. These VEGF-immunoreactive regions also expressed another permeability factor, bradykinin. These findings suggest that VEGF upregulated by hypoxic conditions in edematous embryos induced by RA exposure in utero acts as hyperpermeability. [source] Shb null allele is inherited with a transmission ratio distortion and causes reduced viability in uteroDEVELOPMENTAL DYNAMICS, Issue 9 2007Vitezslav Kriz Abstract SHB is an Src homology 2 domain-containing adapter protein that has been found to be involved in numerous cellular responses. We have generated an Shb knockout mouse. No Shb,/, pups or embryos were obtained on the C57Bl6 background, indicating an early defect as a consequence of Shb - gene inactivation on this genetic background. Breeding heterozygotes for Shb gene inactivation (Shb+/,) on a mixed genetic background (FVB/C57Bl6/129Sv) reveals a distorted transmission ratio of the null allele with reduced numbers of Shb+/+ and Shb,/, animals, but increased number of Shb+/, animals. The Shb, allele is associated with various forms of malformations, explaining the relative reduction in the number of Shb,/, offspring. Shb,/, animals that were born were viable, fertile, and showed no obvious defects. However, Shb+/, female mice ovulated preferentially Shb, oocytes explaining the reduced frequency of Shb+/+ mice. Our study suggests a role of SHB during reproduction and development. Developmental Dynamics 236:2485,2492, 2007. © 2007 Wiley-Liss, Inc. [source] Misregulation of gene expression in the redox-sensitive NF-,b-dependent limb outgrowth pathway by thalidomideDEVELOPMENTAL DYNAMICS, Issue 2 2002Jason M. Hansen Abstract Thalidomide is known to induce oxidative stress, but mechanisms have not been described through which oxidative stress could contribute to thalidomide-induced terata. Oxidative stress modulates intracellular glutathione (GSH) and redox status and can perturb redox-sensitive processes, such as transcription factor activation and/or binding. Nuclear factor-kappa B (NF-,B), a redox-sensitive transcription factor involved in limb outgrowth, may be modulated by thalidomide-induced redox shifts. Thalidomide-resistant Sprague-Dawley rat embryos (gestation day [GD] 13) treated with thalidomide in utero showed no changes in GSH distribution in the limb but thalidomide-sensitive New Zealand White rabbit embryos (GD 12) showed selective GSH depletion in the limb bud progress zone (PZ). NF-,B and regulatory genes that initiate and maintain limb outgrowth and development, such as Twist and Fgf-10, are selectively expressed in the PZ. Green fluorescent protein (GFP) reporter vectors containing NF-,B binding promoter sites were transfected into both rat and rabbit limb bud cells (LBCs). Treatment with thalidomide caused a preferential decrease in GFP expression in rabbit LBCs but not in rat LBCs. N-acetylcysteine and ,-N-t-phenylbutyl nitrone (PBN), a free radical trapping agent, rescued GFP expression in thalidomide-treated cultures compared with cultures that received thalidomide only. In situ hybridization showed a preferential decrease in Twist, Fgf-8, and Fgf-10 expression after thalidomide treatment (400 mg/kg per day) in rabbit embryos. Expression in rat embryos was not affected. Intravenous cotreatment with PBN and thalidomide (gavage) in rabbits restored normal patterns and localization of Twist, Fgf-8, and Fgf-10 expression. These findings show that NF-,B binding is diminished due to selective thalidomide-induced redox changes in the rabbit, resulting in the significant attenuation of expression of genes necessary for limb outgrowth. © 2002 Wiley-Liss, Inc. [source] Stress experienced in utero reduces sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampusDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2008Chitra D. Mandyam Abstract Hippocampal function and plasticity differ with gender, but the regulatory mechanisms underlying sex differences remain elusive and may be established early in life. The present study sought to elucidate sex differences in hippocampal plasticity under normal developmental conditions and in response to repetitive, predictable versus varied, unpredictable prenatal stress (PS). Adult male and diestrous female offspring of pregnant rats exposed to no stress (control), repetitive stress (PS-restraint), or a randomized sequence of varied stressors (PS-random) during the last week of pregnancy were examined for hippocampal proliferation, neurogenesis, cell death, and local microenvironment using endogenous markers. Regional volume was also estimated by stereology. Control animals had comparable proliferation and regional volume regardless of sex, but females had lower neurogenesis compared to males. Increased cell death and differential hippocampal precursor kinetics both appear to contribute to reduced neurogenesis in females. Reduced local interleukin-1beta (IL-1,) immunoreactivity (IR) in females argues for a mechanistic role for the anti-apoptotic cytokine in driving sex differences in cell death. Prenatal stress significantly impacted the hippocampus, with both stress paradigms causing robust decreases in actively proliferating cells in males and females. Several other hippocampal measures were feminized in males such as precursor kinetics, IL-1,-IR density, and cell death, reducing or abolishing some sex differences. The findings expand our understanding of the mechanisms underlying sex differences and highlight the critical role early stress can play on the balance between proliferation, neurogenesis, cell death, and hippocampal microenvironment in adulthood. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Similar and functionally typical kinematic reaching parameters in 7- and 15-month-old in utero cocaine-exposed and unexposed infantsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004E. Z. Tronick Abstract This study examined the effects of intrauterine cocaine exposure on the reaches of 19 exposed and 15 unexposed infants at 7 and 15 months using kinematic measures. Infants sat at a table and reached for a rattle, a toy doll, and a chair. Videotaped reaches were digitized using the Peak Performance system. Kinematic movement variables were extracted (e.g., reach duration, peak velocity, movement units, path length) and ratios computed (e.g., path length divided by number of movement units). Regardless of exposure status, reaches of older infants were faster, more direct, had fewer movement units, and covered more distance with the first movement unit. Exposed infants covered more distance per movement unit than unexposed infants, but there were no other significant differences. Reaches of exposed and unexposed infants were essentially similar. Importantly, reach parameters for these high-risk infants were similar to reach parameters for infants at lower social and biological risk. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 168,175, 2004. [source] Emergence of long-term memory for conditioned aversion in the rat fetusDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004Nadège Gruest Abstract Pregnant rats were subjected to garlic essential oil as the conditioned stimulus and 45 min later to LiCl as the unconditioned stimulus either on embryonic Days 15 and 16 (E15 and E16) or on 18 and 19 (E18 and E19). Control dams received only garlic, LiCl, or water. Progenies were tested on garlic drinking 6 weeks after the exposure to the stimuli via the mothers. In the E18 to 19 group, rats that were exposed to paired garlic,LiCl expressed a significant aversion for garlic. In the E15 to 16 group, no significant differences appeared between subgroups. These results confirm that an associative memory can be established before birth and suggests that this ability potentially emerges in a short time window of 3 days at the end of gestation. Moreover, it appears that a long-term memory can be acquired in utero and retained to be expressed postnatally when animals are autonomous. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 189,198, 2004. [source] Fetal Mouse Imaging Using Echocardiography: A Review of Current TechnologyECHOCARDIOGRAPHY, Issue 10 2006Christopher F. Spurney M.D. Advances in genetic research have led to the need for phenotypic analysis of small animal models. However, often these genetic alterations, especially when affecting the cardiovascular system, can result in fetal or perinatal death. Noninvasive ultrasound imaging is an ideal method for detecting and studying such congenital malformations, as it allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Two platforms for fetal mouse echocardiography exist, the clinical systems with 15-MHz phased array transducers and research systems with 20,55-MHz mechanical transducers. The clinical ultrasound system has limited two-dimensional (2D) resolution (axial resolution of 440 ,m), but the availability of color and spectral Doppler allows quick interrogations of blood flows, facilitating the detection of structural abnormalities. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. In comparison, the research biomicroscope system has significantly improved 2D resolution (axial resolution of 28 ,m). Spectral Doppler imaging is also available, but in the absence of color Doppler, imaging times are increased and the detection of flow abnormalities is more difficult. M-mode imaging is available and equivalent to the clinical ultrasound system. Overall, the research system, given its higher 2D resolution, is best suited for in-depth analysis of mouse fetal cardiovascular structure and function, while the clinical ultrasound systems, equipped with phase array transducers and color Doppler imaging, are ideal for high-throughput fetal cardiovascular screens. [source] A brief overview of mechanisms of mitochondrial toxicity from NRTIs,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007James J. Kohler Abstract Nucleoside reverse transcriptase inhibitors (NRTIs) in combinations with other antiretrovirals (highly active antiretroviral therapy, HAART) are the cornerstones of AIDS therapy, turning HIV infection into a manageable clinical entity. Despite the initial positive impact of NRTIs, therapeutic experience revealed serious side effects that appeared to originate in the mitochondria and which ultimately manifested as dysfunction of that organelle. It may be reasonable to consider that as the AIDS epidemic continues and as survival with HIV infection is prolonged by treatment with HAART, long-term side effects of NRTIs may become increasingly common. This consideration may be underscored in children who are born to HIV-infected mothers who received NRTI therapy in utero during gestation. The long-term effect of that NRTI exposure in utero is not clear yet. This review examines some proposed mechanisms of NRTI mitochondrial toxicity, including genetic predisposition, defects in mitochondria DNA replication, the encompassing "DNA pol-, hypothesis," the relationship between mitochondrial nucleotide and NRTI pools, mitochondrial DNA mutation and dysfunction, and oxidative stresses related to HIV infection and NRTIs. Mechanisms of mitochondrial toxicity are reviewed with respect to key cell biological, pathological, and pharmacological events. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] Transplacental mutagenicity of N -ethyl- N -nitrosourea at the hprt locus in T-lymphocytes of exposed B6C3F1 miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2001Hillary E. Sussman Abstract Previous studies have compared age-related differences in total mutagenic burden in mice of differing age (preweanling, weanling, or young adult) after single intraperitoneal (i.p.) injections of ethylnitrosourea (ENU). The purpose of the present investigation was to determine the effects of time elapsed since treatment on the frequency of hprt mutant T-cells (Mf) from mice treated transplacentally with single acute vs. multiple split doses of ENU. To this end, pregnant C57BL/6 mice (n = 13,16/group), which had been bred to C3H males, were given i.p. injections of 40 mg ENU/kg bw in a single dose on day 18 of gestation, in a split dose of 6 mg ENU/kg bw on days 12 through 18 of gestation, or DMSO vehicle alone. Groups of pups were necropsied on days 10, 13, 15 (single dose only), 17, 20, 40, and 70 postpartum for T-cell isolations and hprt Mf measurements using the T-cell cloning assay. The time required to reach maximum Mfs in T-cells isolated from thymus of transplacentally treated animals was 2 weeks, the same time span as previously observed after ENU treatment of adult, weanling, and preweanling mice. Mfs in T-cells isolated from spleens of control animals averaged 2.1 ± 0.3 (SE) × 10,6. In spleens of mice treated transplacentally with ENU in a single dose, Mfs reached a maximum at 15 days postpartum [84.7 ± 15.8 (SE) × 10,6] and decreased to lower but still elevated levels at 40 days postpartum. In spleens of mice treated transplacentally with ENU in a split dose, Mfs reached a maximum at 13 days postpartum [74.0 ± 16.3 (SE) × 10,6] and decreased to background levels at 40 days postpartum. The areas under the curves describing the change in hprt Mfs over time for ENU-treated vs. control mice estimate the mutagenic potency for transplacental single- and split-dose exposures to be 1.9 and 0.8 × 103, respectively. Comparison of the mutagenic potency estimates for mice exposed to ENU in utero to 4-week-old mice given a similar dose of the same lot number of ENU indicates that the mouse is more susceptible to ENU-induced mutagenesis during fetal life. Environ. Mol. Mutagen. 38:30,37, 2001 © 2001 Wiley-Liss, Inc. [source] Dietary exposure of mink (Mustela vison) to fish from the Housatonic River, Berkshire County, Massachusetts, USA: Effects on reproduction, kit growth, and survivalENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2006Steven J. Bursian Abstract We evaluated the effects of feeding farm-raised mink (Mustela vison) diets containing polychlorinated biphenyl (PCB)-contaminated fish from the Housatonic River (HR; Berkshire County, MA, USA) on adult reproductive performance and kit growth and survival. Diets contained 0.22,3.54% HR fish, providing 0.34,3.7 ,g total PCBs (TPCB)/g feed wet wt (3.5,68.5 pg toxic equivalence [TEQ]/g). Female mink were fed diets before breeding through weaning of kits. Twelve kits from each treatment were maintained on their respective diets for an additional 180 d. Dietary PCBs had no effect on the number of offspring produced, gestation period, or other measures of adult reproductive performance. Mink kits exposed to 3.7 ,g TPCB/g feed (68.5 pg TEQ/g) in utero and during lactation had reduced survivability between three and six weeks of age. The lethal concentrations to 10 and 20% of the population (LC10 and LC20, respectively) were estimated to be 0.231 and 0.984 ,g TPCB/g feed, respectively. Because inclusion of PCB-contaminated fish that composed approximately 1% of the diet would reduce mink kit survival by 20% or more, it is likely that consumption of up to 30-fold that quantity of HR fish, as could be expected for wild mink, would have an adverse effect on wild mink populations. [source] In utero exposure to vigabatrin: No indication of visual field lossEPILEPSIA, Issue 2 2009Charlotte Lawthom Summary The purpose of the study was to determine whether in utero exposure to vigabatrin caused visual field loss. Three mothers with four children who had been exposed to vigabatrin in utero and who were subsequently formula fed were identified. All seven individuals underwent perimetry and imaging of the retinal nerve fiber layer (RNFL). All individuals yielded reliable outcomes to perimetry and RNFL images of acceptable quality. Two of the three mothers exhibited vigabatrin-attributed visual field loss and an abnormally attenuated RNFL. The third exhibited an upper left quadrantanopia, consistent with previous temporal lobe surgery, and a normal RNFL. All four children yielded normal visual fields and RNFL thicknesses. The presence of the normal findings for the children is reassuring and, if representative, suggests a lack of vigabatrin visual toxicity and therefore obviates the need for ophthalmological examination of those exposed to vigabatrin prenatally. [source] Electroencephalographic Characterization of an Adult Rat Model of Radiation-Induced Cortical DysplasiaEPILEPSIA, Issue 10 2001Shinji Kondo Summary: ,Purpose: Cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The mechanisms of CD-induced epileptogenicity remain unknown. The difficulty in obtaining and testing human tissue warrants the identification and characterization of animal model(s) of CD that share most of the clinical, electroencephalographic (EEG), and histopathologic characteristics of human CD. In this study, we report on the in vivo EEG characterization of the radiation-induced model of CD. Methods: Timed-pregnant Sprague,Dawley rats were irradiated on E17 using a single dose of 145 cGy or left untreated. Their litters were identified and implanted with bifrontal epidural and hippocampal depth electrodes for prolonged continuous EEG recordings. After prolonged EEG monitoring, animals were killed and their brains sectioned and stained for histologic studies. Results: In utero,irradiated rats showed frequent spontaneous interictal epileptiform spikes and spontaneous seizures arising independently from the hippocampal or the frontal neocortical structures. No epileptiform or seizure activities were recorded from age-matched control rats. Histologic studies showed the presence of multiple cortical areas of neuronal clustering and disorganization. Moreover, pyramidal cell dispersion was seen in the CA1>CA3 areas of the hippocampal formations. Conclusions: Our results further characterize the in vivo EEG characteristics of the in utero radiation model of CD using long-term EEG monitoring. This model may be used to study the molecular and cellular changes in epileptogenic CD and to test the efficacy of newer antiepileptic medications. [source] Teratogenic Effects of Antiepileptic Drugs: Use of an International Database on Malformations and Drug Exposure (MADRE)EPILEPSIA, Issue 11 2000Carla Arpino Summary: Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. Methods: Information on all malformed infants (1990,1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries. Results: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid. Conclusions: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports. [source] Body Dimensions of Infants Exposed to Antiepileptic Drugs In Utero: Observations Spanning 25 YearsEPILEPSIA, Issue 7 2000K. Wide Summary: Purpose: To investigate the influence of maternal antiepileptic drug (AED) treatment on pregnancy duration, birth weight, body length, head circumference, and intrauterine growth in infants exposed in utero to antiepileptic drugs in Sweden between 1973,1997, with 963 singleton infants. Methods: Data collected from (a) 1973,1981 (record linkage between a hospital discharge register and a medical birth register); (b) 1984,1995 (prospectively collected information in one defined catchment area with two delivery hospitals); and (c) 1995,1997 (medical birth register data). Observed numbers of infants below a defined size for body measurements compared with expected numbers calculated from all births in Sweden after stratification for year of birth, maternal age, parity, and education or smoking habits in early pregnancy. Standard deviation scores estimated with same stratification procedures. Results: Fraction of monotherapy exposures increased from ,40% to ,90% from 1973 to 1997. Significantly increased numbers of infants with small body measurements found in exposed group. Negative influence on body dimensions decreased over time. More marked effects found in infants exposed to polytherapy. In monotherapy, only infants exposed to carbamazepine consistently showed reduction in body dimensions. Significant effect on gestational age in girls and on number of small for gestational age (<2 SD) in boys. Conclusions: Polytherapy with antiepileptic drugs and negative influence on body dimensions decreased. In monotherapy, only carbamazepine has a negative influence on body dimensions in this study. [source] Maternal Effort is State Dependent: Energetic Limitation or Regulation?ETHOLOGY, Issue 4 2008Anke Rehling Many small altricial rodents have a postpartum oestrus and are often simultaneously pregnant and lactating. Negative influences of concurrent pregnancy and lactation on both lactational performance and the litter in utero are commonly observed and have been interpreted as resulting from high simultaneous energetic demands of gestation and lactation. We studied these effects in the precocial guinea-pig (Cavia aperea f. porcellus) that, like many altricial rodents, has a postpartum oestrus, but in which the peaks of energy expenditure on lactation and gestation are widely separated. This life history allowed to investigate whether physiological regulation other than by energetic limitations may be responsible for allocation conflicts arising when lactation and gestation overlap. By comparing simultaneously pregnant and lactating females with lactating non-pregnant females, we show that females in the former group nurse less and wean earlier than females of the latter group. In a comparison of litter size, litter mass, and pup mortality of females that had not been lactating during pregnancy with females that had been simultaneously pregnant and lactating, we show that the latter do not reduce investment in the following litter. In our study, energetic constraints on ad libitum fed females are unlikely and we therefore suggest that the results must be explained by regulatory constraints on lactational effort. We point out that this explanation has not been excluded for the effects observed in altricial small mammals. [source] Age-dependent effect of prenatal stress on hippocampal cell proliferation in female ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Muriel Koehl Abstract Stressors occurring during pregnancy can alter the developmental trajectory of offspring and lead to, among other deleterious effects, cognitive deficits and hyperactivity of the hypothalamo-pituitary-adrenal axis. A recent feature of the prenatal stress (PS) model is its reported influence on structural plasticity in hippocampal formation, which sustains both cognitive functions and stress responsiveness. Indeed, we and others have previously reported that males exposed to stress in utero are characterized by a decrease in hippocampal cell proliferation, and consequently neurogenesis, from adolescence to senescence. Recent studies in females submitted to PS have reported conflicting results, ranging from no effect to a decrease in cell proliferation. We hypothesized that changes in cell proliferation in PS female rats are age dependent. To address this issue, we examined the impact of PS on hippocampal cell proliferation in juvenile, young, middle-aged and old females. As hypothesized, we found an age-dependent effect of PS in female rats as cell proliferation was significantly decreased only when animals reached senescence, a time when adrenal gland weight also increased. These data suggest that the deleterious effects of PS on hippocampal cell proliferation in females are either specific to senescence or masked during adulthood by protective factors. [source] Hormones as epigenetic signals in developmental programmingEXPERIMENTAL PHYSIOLOGY, Issue 6 2009Abigail L. Fowden In mammals, including man, epidemiological and experimental studies have shown that a range of environmental factors acting during critical periods of early development can alter adult phenotype. Hormones have an important role in these epigenetic modifications and can signal the type, severity and duration of the environmental cue to the developing feto-placental tissues. They affect development of these tissues both directly and indirectly by changes in placental phenotype. They act to alter gene expression, hence the protein abundance in a wide range of different tissues, which has functional consequences for many physiological systems both before and after birth. By producing an epigenome specific to the prevailing condition in utero, hormones act as epigenetic signals in developmental programming, with important implications for adult health and disease. This review examines the role of hormones as epigenetic signals by considering their responses to environmental cues, their effects on phenotypical development and the molecular mechanisms by which they programme feto-placental development, with particular emphasis on the glucocorticoids. [source] Reproductive modes in lizards: measuring fitness consequences of the duration of uterine retention of eggsFUNCTIONAL ECOLOGY, Issue 2 2008R. S. Radder Summary 1One of the primary axes of life-history variation involves the proportion of embryonic development for which the offspring is retained within its parent's body; understanding trade-offs associated with prolonging that period thus is a critical challenge for evolutionary ecology. 2Prior to oviposition, most oviparous squamate reptiles retain developing eggs in utero for about one-third of embryogenesis; the strong conservatism in this trait is a major puzzle in reptilian reproduction. To clarify fitness consequences of this prolonged uterine retention, we need to experimentally modify the trait and examine the effects of our manipulation. 3We used transdermal application of corticosterone to induce gravid scincid lizards (Bassiana duperreyi) to lay their eggs ,prematurely', with relatively undeveloped embryos. Corticosterone application induced females to oviposit sooner (mean of 5·41 ± 0·51 days post-treatment) at earlier embryonic developmental stage (27 ± 0·21) than did controls (13·2 ± 1·22 days; embryonic stage 30·4 ± 0·16). 4Corticosterone levels in the egg yolk were unaffected by maternal treatment, so effects of earlier oviposition should not be confounded by endocrine disruption of embryogenesis. Nonetheless, early oviposition reduced hatchling fitness. Hatching success was lower, incubation periods post-laying were increased, and neonates from eggs laid at earlier embryonic stages were smaller and slower. 5These results suggest that retention of developing eggs in utero by oviparous squamates enhances maternal fitness, and does so via modifications to offspring phenotypes rather than (for example) due to accelerated developmental rates of eggs in utero compared to in the nest. 6More generally, our data support optimality models that interpret interspecific variation in the duration of maternal,offspring contact in terms of the selective forces that result from earlier vs. later termination of that maternal investment. [source] Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression,HEPATOLOGY, Issue 6 2009Kimberley D. Bruce Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring. Conclusion: Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis. (HEPATOLOGY 2009.) [source] New school in liver development: Lessons from zebrafish,HEPATOLOGY, Issue 5 2009Jaime Chu There is significant overlap in the genes and pathways that control liver development and those that regulate liver regeneration, hepatic progenitor cell expansion, response to injury, and cancer. Additionally, defects in liver development may underlie some congenital and perinatal liver diseases. Thus, studying hepatogenesis is important for understanding not only how the liver forms, but also how it functions. Elegant work in mice has uncovered a host of transcription factors and signaling molecules that govern the early steps of hepatic specification; however, the inherent difficulty of studying embryogenesis in utero has driven developmental biologists to seek new systems. The rapidly developing vertebrate zebrafish is a favorite model for embryology. The power of forward genetic screens combined with live real-time imaging of development in transparent zebrafish embryos has highlighted conserved processes essential for hepatogenesis and has uncovered some exciting new players. This review presents the advantages of zebrafish for studying liver development, underscoring how studies in zebrafish and mice complement each other. In addition to their value for studying development, zebrafish models of hepatic and biliary diseases are expanding, and using these small, inexpensive embryos for drug screening has become de rigueur. Zebrafish provide a shared platform for developmental biology and translational research, offering innovative methods for studying liver development and disease. The story of hepatogenesis has something for everyone. It involves transcriptional regulation, cell-cell interaction, signaling pathways, control of cell proliferation and apoptosis, plus morphogenic processes that sculpt vasculature, parenchymal cells, and mesenchyme to form the multifaceted liver. Decades of research on liver development in mice and other vertebrates offer valuable lessons in how the multipotent endoderm is programmed to form a functional liver. Of equal importance are insights that have illuminated the mechanisms by which hepatic progenitors are activated in a damaged liver, how the adult liver regenerates, and, possibly, the basis for engineering liver cells in vitro for cell transplantation to sustain patients with liver failure. Moreover, processes that are key to liver development are often co-opted during pathogenesis. Therefore, reviewing hepatogenesis is informative for both basic and translational researchers. In this review, we bring to light the many advantages offered by the tropical freshwater vertebrate zebrafish (Danio rerio) in studying hepatogenesis. By comparing zebrafish and mice, we highlight how work in each system complements the other and emphasize novel paradigms that have been uncovered using zebrafish. Finally, we highlight exciting efforts using zebrafish to model hepatobiliary diseases. (HEPATOLOGY 2009.) [source] MR-determined hippocampal asymmetry in full-term and preterm neonatesHIPPOCAMPUS, Issue 2 2009Deanne K. Thompson Abstract Hippocampi are asymmetrical in children and adults, where the right hippocampus is larger. To date, no literature has confirmed that hippocampal asymmetry is evident at birth. Furthermore, gender differences have been observed in normal hippocampal asymmetry, but this has not been examined in neonates. Stress, injury, and lower IQ have been associated with alterations to hippocampal asymmetry. These same factors often accompany preterm birth. Therefore, prematurity is possibly associated with altered hippocampal asymmetry. There were three aims of this study: First, we assessed whether hippocampi were asymmetrical at birth, second whether there was a gender effect on hippocampal asymmetry, and third whether the stress of preterm birth altered hippocampal asymmetry. This study utilized volumetric magnetic resonance imaging to compare left and right hippocampal volumes in 32 full-term and 184 preterm infants at term. Full-term infants demonstrated rightward hippocampal asymmetry, as did preterm infants. In the case of preterm infants, hippocampal asymmetry was proportional to total hemispheric asymmetry. This study is the first to demonstrate that the normal pattern of hippocampal asymmetry is present this early in development. We did not find gender differences in hippocampal asymmetry at term. Preterm infants tended to have less asymmetrical hippocampi than full-term infants, a difference which became significant after correcting for hemispheric brain tissue volumes. This study may suggest that hippocampal asymmetry develops in utero and is maintained into adulthood in infants with a normal neurological course. © 2008 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||