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Gestational Day (gestational + day)

Distribution by Scientific Domains

Life Sciences	50%
Medical Sciences	38%
Chemistry	9%

Distribution within Life Sciences

Anatomy & Physiology	22%
Neuroscience	10%

Selected Abstracts

Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7

ALCOHOLISM, Issue 1 2010
Elizabeth A. Godin
Background:, This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:, C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 ,m isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:, Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:, Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development. [source]

Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8

ALCOHOLISM, Issue 6 2009
Scott E. Parnell
Background:, Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods:, For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance® solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 ,m (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results:, As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions:, This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. [source]

Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7

Dietary exposure to low doses of bisphenol A: Effects on reproduction and development in two generations of C57BL/6J mice

CONGENITAL ANOMALIES, Issue 3 2010
Kenichi Kobayashi
Abstract The present study was conducted to examine the effects of low-dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F0) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F1 and F2) from each F0 and F1 dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment-related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F0 dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F1 pups. No treatment-related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F1 and F2 adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F1 males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment-related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F1 or F2 males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice. [source]

Effects of in utero exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153) on somatic growth and endocrine status in rat offspring

CONGENITAL ANOMALIES, Issue 4 2008
Kenichi Kobayashi
ABSTRACT Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153), a di- ortho -substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose,anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153,treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153,treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10,16, 16,64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. [source]

Contractile activity of skeletal musculature involved in breathing is essential for normal lung cell differentiation, as revealed in Myf5,/,:MyoD,/, embryos

DEVELOPMENTAL DYNAMICS, Issue 3 2005
Mohammad Reza Inanlou
Abstract In the current study, the role of contractile activity of respiratory muscles in fetal lung growth and cell differentiation was examined using Myf5,/,:MyoD,/, mouse embryos. As previously found, Myf5,/,:MyoD,/, mouse embryos had no respiratory musculature. Consequently, they suffered from pulmonary hypoplasia and died shortly after birth. The hypoplastic lung had decreased proliferation and increased apoptotic index as early as embryonic day 14.5. By contrast, only at the last gestational day, the number of lung cells expressing platelet derived growth factor B and insulin growth factor I was decreased, while the gradient of the thyroid transcription factor 1 was not maintained. Type II pneumocytes had a failure in glycogen utilization and surfactant storage and secretion but were able to synthesize the surfactant-associated proteins. Type I pneumocytes were readily detectable using an early differentiation marker (i.e., Gp38). However, the late differentiation of type I pneumocytes never occurred, as revealed by transmission electron microscopy. Together, our findings suggest that pulmonary distension due to fetal breathing-like movements plays an important role not only in lung growth but also in lung cell differentiation. Developmental Dynamics 233:772,782, 2005. © 2005 Wiley-Liss, Inc. [source]

Amniotic fluid can act as an appetitive unconditioned stimulus in preweanling rats

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2007
Carlos Arias
Abstract Studies in humans and animals indicate that exposure to flavors in the amniotic fluid during the later gestational period may induce preferences for those flavors. Considering that during the last prenatal period the amniotic fluid contains substances that activate the opioid system, and that this system plays a critical role in the acquisition of olfactory preferences early in life, it has been hypothesized that the amniotic fluid may acquire appetitive unconditioned properties during this period. This has been tested in an experiment in which preweanling rats were exposed to alcohol odor (CS) paired or unpaired with the intraoral infusion of amniotic fluid (US) collected on gestational day 20. The pairing of these two stimuli induced an enhanced palatability of alcohol's flavor as well an increased intake of the drug. These results support the idea that amniotic fluid acquires appetitive unconditioned properties during the last days of gestation and suggest that associative mechanisms involving the amniotic fluid could be underlying odor and taste preferences acquired through fetal exposure. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 139,149, 2007. [source]

Ret deficiency in mice impairs the development of A5 and A6 neurons and the functional maturation of the respiratory rhythm

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2005
J. C. Viemari
Abstract Although a normal respiratory rhythm is vital at birth, little is known about the genetic factors controlling the prenatal maturation of the respiratory network in mammals. In Phox2a mutant mice, which do not express A6 neurons, we previously hypothesized that the release of endogenous norepinephrine by A6 neurons is required for a normal respiratory rhythm to occur at birth. Here we investigated the role of the Ret gene, which encodes a transmembrane tyrosine kinase receptor, in the maturation of norepinephrine and respiratory systems. As Ret -null mutants (Ret,/,) did not survive after birth, our experiments were performed in wild-type (wt) and Ret,/, fetuses exteriorized from pregnant heterozygous mice at gestational day 18. First, in wt fetuses, quantitative in situ hybridization revealed high levels of Ret transcripts in the pontine A5 and A6 areas. Second, in Ret,/, fetuses, high-pressure liquid chromatography showed significantly reduced norepinephrine contents in the pons but not the medulla. Third, tyrosine hydroxylase immunocytochemistry revealed a significantly reduced number of pontine A5 and A6 neurons but not medullary norepinephrine neurons in Ret,/, fetuses. Finally, electrophysiological and pharmacological experiments performed on brainstem ,en bloc' preparations demonstrated impaired resting respiratory activity and abnormal responses to central hypoxia and norepinephrine application in Ret,/, fetuses. To conclude, our results show that Ret gene contributes to the prenatal maturation of A6 and A5 neurons and respiratory system. They support the hypothesis that the normal maturation of the respiratory network requires afferent activity corresponding to the A6 excitatory and A5 inhibitory input balance. [source]

Metabolomics in the assessment of chemical-induced reproductive and developmental outcomes using non-invasive biological fluids: application to the study of butylbenzyl phthalate

JOURNAL OF APPLIED TOXICOLOGY, Issue 8 2009
Susan Sumner
Abstract This study was conducted to evaluate the use of metabolomics for improving our ability to draw correlations between early life exposures and reproductive and/or developmental outcomes. Pregnant CD rats were exposed by gavage daily during gestation to vehicle or to butylbenzyl phthalate (BBP) in vehicle at a level known to induce effects in the offspring and at a level previously not shown to induce effects. Urine was collected for 24,h (on dry ice using all glass metabolism chambers) from dams on gestational day 18 (during exposure) and on post natal day (pnd) 21, and from pnd 25 pups. Traditional phenotypic anchors were measured in pups (between pnd 0 and pnd 26). Metabolomics of urine collected from dams exposed to vehicle or BBP exhibited different patterns for endogenous metabolites. Even three weeks after gestational exposure, metabolic profiles of endogenous compounds in urine could differentiate dams that received the vehicle, low dose or high dose of BBP. Metabolic profiles could differentiate male from female pups, pups born to dams receiving the vehicle, low or high BBP dose, and pups with observable adverse reproductive effects from pups with no observed effects. Metabolites significant to the separation of dose groups and their relationship with effects measured in the study were mapped to biochemical pathways for determining mechanistic relevance. The application of metabolomics to understanding the mechanistic link between low levels of environmental exposure and disease/dysfunction holds huge promise, because this technology is ideal for the analysis of biological fluids in human populations. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Spatial and Temporal Ontogenies of Glutathione Peroxidase and Glutathione Disulfide Reductase During Development of the Prenatal Rat

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2001
Hyungsuk Choe
Abstract Spatial and temporal expression and regulation of the antioxidant enzymes, glutathione peroxidase (GSH-Px), glutathione disulfide reductase (GSSG-Rd) may be important in determining cell-specific susceptibility to embryotoxicants. Creation of tissue-specific ontogenies for antioxidant enzyme activities during development is an important first step in understanding regulatory relationships. Early organogenesis-stage embryos were grouped according to the somite number (GD 9,13), and fetuses were evaluated by gestational day (GD 14,21). GSH-Px activities in the visceral yolk sac (VYS) increased on consecutive days from GD 9 to GD 13, representing a 5.7-fold increase during this period of development. GSH-Px activities in VYS decreased after GD 13, ultimately constituting a 37% decrease at GD 21. Head, heart, and trunk specific activities generally increased from GD 9 to GD 13 albeit not to the same magnitude as detected in the VYS. GSSG-Rd activities showed substantial increases in the VYS from GD 9 to GD 13, 6.3-fold and decreased thereafter to 50% by GD 21. The greatest changes in enzyme activities were noted in the period between GD 10 and GD 11, where the embryo establishes an active cardiovascular system and begins to convert to aerobic metabolism. Generally, from GD 14,21, embryonic organ GSH-Px and GSSG-Rd activities either remained constant or increased as gestation progressed. These studies suggest the importance of the VYS in dealing with ROS and protecting the embryo. Furthermore, understanding the consequences of lower antioxidant activities during organogenesis may help to pinpoint periods of teratogenic susceptibility to xenobiotics and increased oxygen. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:197,206, 2001 [source]

Expression of nidogens in rat uterus and embryo during decidualization and implantation

JOURNAL OF MORPHOLOGY, Issue 7 2006
Hakan Öner
Abstract The purpose of this study was to demonstrate the expression of nidogen-1 and nidogen-2 and their possible role in decidualization and implantation events during early pregnancy in rats. The tissue samples were examined from pregnant animals between gestational days 1,8 using immunocytochemistry. The uterine luminal epithelium, the glandular epithelium, and the myometrial smooth muscle cells stained strongly from gestational days 1,8 with both nidogen antibodies. At day 4 the decidual reaction areas began to appear in the stromal matrix and immunostaining of both nidogens revealed that the basement membrane of the surface epithelium was discontinuous. The differentiation of stromal cells into decidual cells was seen at gestational day 5 and both nidogens were weakly expressed in the decidualizing cells. At day 6, nidogen-2 immunoreactivity was higher in the primary decidual cells close to the embryo than nidogen-1, and during development of the decidual tissue both nidogens appeared in the endometrial stromal cells. At day 7, while expression of both nidogens declined in the primary decidual cells, their expression was markedly observed in the secondary decidual cells close to the myometrium. At day 8, expression of both nidogens was also observed to increase in the primary decidual cells. While nidogen-2 expression was seen in the parietal endoderm and primary ectoderm of the rat embryos at this developmental stage, nidogen-1 expression was only detected in the parietal endoderm. These results indicate that nidogen-1 and nidogen-2 could play important roles during embryogenesis, decidualization, and implantation in the endometrium of rat uterus. J. Morphol. © 2006 Wiley-Liss, Inc. [source]

Chronic Prenatal Ethanol Exposure Increases Glucocorticoid-Induced Glutamate Release in the Hippocampus of the Near-Term Foetal Guinea Pig

JOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2006
U. Iqbal
Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and ,-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N -methyl- d -aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 µM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 µM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a consequence of increased GR expression. These effects of CPEE, coupled with increased glutamate release and increased NMDA receptor expression, may predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated neurodevelopmental toxicity. [source]

Central Regulation of the Hypothalamic-Pituitary-Adrenal Axis During Fetal Development in the Guinea-Pig

JOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2005
D. Owen
Abstract We have previously shown that the foetal guinea-pig hypothalamic-pituitary-adrenal (HPA) axis is activated near the time of parturition and that this is associated with changes in limbic glucocorticoid receptors (GR) and mineralocorticoid receptors. In the present study, we hypothesized that the foetal hypothalamic paraventricular nucleus (PVN) and pituitary contribute significantly to foetal HPA drive but that these areas remain sensitive to negative feedback by circulating glucocorticoids in late gestation. However, we observed decreased corticotrophin-releasing hormone mRNA expression in the PVN and decreased pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary with advanced gestational age. The reduction in POMC mRNA expression was likely the result of negative feedback via circulating glucocorticoids because GR mRNA was unchanged during development in the foetal pituitary. Furthermore, we found that maternally administered glucocorticoids significantly decreased foetal pituitary POMC mRNA expression in a dose-dependent manner at gestational day (gd) 62 with male foetuses being more sensitive to these effects. These findings show that the foetal HPA axis remains highly sensitive to glucocorticoid feedback even as plasma adrenocorticotropic hormone and cortisol levels are elevated at the end of gestation. [source]

Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7

Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8

Ethanol-Mediated Fetal Dysmorphology and its Relationship to the Ontogeny of Maternal Liver Metallothionein

ALCOHOLISM, Issue 6 2009
Peter Coyle
Background:, Fetal zinc (Zn) deficiency arising from ethanol-induction of the Zn-binding protein metallothionein (MT) in the mother's liver has been proposed as a mechanism of teratogenicity. Here, we determine the ontogeny of MT and Zn homeostasis in rats and mice and then examine the effect of acute ethanol exposure in early embryonic development on this relationship. The protective effect of Zn against ethanol-mediated fetal dysmorphology is also examined. Methods:, Study 1: Maternal liver MT and Zn homeostasis was determined in Sprague,Dawley rats and C57BL/6J mice throughout gestation. Study 2: Rats were administered ethanol (25% in saline, intraperitoneal 0.015 ml/g) or vehicle alone on gestational day (GD) 9. Maternal liver MT and Zn, and plasma Zn was determined over the ensuing 24 hours. Study 3: Pregnant rats were treated with ethanol and Zn (s.c. 2.5 ,g Zn/g) on GD9 and fetal dysmorphology was assessed on GD 19. Results:, Study 1: Maternal liver MT began to rise around GD 9 peaking on GD 15 before falling to nonpregnant levels around term. The pregnancy-related increase in MT was associated with a fall in plasma Zn which was significantly lower on GD 15 thereafter returning to nonpregnant levels by parturition. Study 2: Ethanol administered to pregnant rats on GD 9 resulted in a 10-fold induction of MT in the maternal liver and was associated with a 33% rise in liver Zn and a 30% fall in plasma Zn, 16 hours after treatment. Study 3: Ethanol treatment on GD 9 resulted in a significant increase in craniofacial malformations which were prevented by concurrent Zn treatment. Conclusions:, The findings indicate that maternal liver MT levels are lowest in early gestation (before GD 10) making this a sensitive period where ethanol-induction of MT can affect fetal Zn homeostasis and cause fetal dysmorphology. The study further provides evidence of a protective role for Zn against ethanol-mediated teratogenicity. [source]

Dietary Zinc Supplementation Throughout Pregnancy Protects Against Fetal Dysmorphology and Improves Postnatal Survival After Prenatal Ethanol Exposure in Mice

ALCOHOLISM, Issue 4 2009
Brooke L. Summers
Background:, We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Methods:, Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Results:, Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. Conclusions:, These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy. [source]

Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine Model

ALCOHOLISM, Issue 10 2007
Jayanth Ramadoss
Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. Methods: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. Results: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. Conclusions: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure. [source]

Maternal Oral Intake Mouse Model for Fetal Alcohol Spectrum Disorders: Ocular Defects as a Measure of Effect

ALCOHOLISM, Issue 10 2006
Scott E. Parnell
Background: This work was conducted in an effort to establish an oral intake model system in which the effects of ethanol insult that occur during early stages of embryogenesis can be easily examined and in which agents that may modulate ethanol's teratogenicity can be readily tested in vivo. The model system described utilizes the alcohol deprivation effect to obtain teratogenic levels of maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular defects including microphthalmia and uveal coloboma, which have previously been shown to result from ethanol administered by gavage or via intraperitoneal injection on these days, served as the developmental end point for this study. The ocular defects are readily identifiable and their degree of severity is expected to correlate with concurrently developing defects of the central nervous system (CNS). Methods: Female C57Bl/6J mice were maintained on an ethanol-containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th day of pregnancy. Fetuses were then weighed, measured for crown rump length, photographed, and analyzed for ocular abnormalities. Globe size, palpebral fissure length, and pupil size and shape were noted for both the right and left eyes of all fetuses and informative comparisons were made. Results: This exposure paradigm resulted in peak maternal blood alcohol concentrations that ranged from 170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from the normal control group, the pair-fed, acquisition controls, as well as the ethanol-exposed fetuses, were developmentally delayed and had reduced weights. Confirming previous studies, comparison of similarly staged control and treated GD 8 embryos illustrated reductions in the size of the forebrain in the latter. Subsequent ocular malformations were noted in 33% of the right eyes and 25% of the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence of defects is twice that observed in the control groups. Additionally, it was found that the palpebral fissure length is directly correlated with globe size. Conclusions: The high incidence of readily identifiable ocular malformations produced by oral ethanol intake in this model and their relevance to human fetal alcohol spectrum disorders (FASD) makes this an excellent system for utilization in experiments involving factors administered to the embryo that might alter ethanol's teratogenic effects. Additionally, the fact that early ethanol insult yields ocular and forebrain abnormalities that are developmentally associated allows efficient specimen selection for subsequent detailed analyses of CNS effects in this in vivo mammalian FASD model. [source]

Fetal Learning With Ethanol: Correlations Between Maternal Hypothermia During Pregnancy and Neonatal Responsiveness to Chemosensory Cues of the Drug

ALCOHOLISM, Issue 5 2004
Paula Abate
Abstract: Background: Fetuses learn about ethanol odor when the drug is present in the amniotic fluid. Prenatal learning comprising ethanol's chemosensory cues also suggests an acquired association between ethanol's chemosensory and postabsorptive properties. Ethanol-related thermal disruptions have been implicated as a significant component of the drug's unconditioned properties. In the present study, ethanol-induced thermal changes were analyzed in pregnant rats subjected to a moderate ethanol dose. This thermal response was later tested for its correlation with the responsiveness of the progeny to ethanol and nonethanol chemosensory stimuli. Methods: During gestational day (GD) 14, pregnant rats were subjected to a minor surgical procedure to place a subcutaneous telemetric thermal sensor in the nape of the neck. During GDs 17 to 20, females received a daily intragastric administration of ethanol (2 g/kg) or water, using solutions kept at room temperature. Maternal body temperatures were recorded before and after (4 consecutive hours) the administration of water or ethanol. Newborns representative of both prenatal treatments were tested in terms of behavioral activity elicited by the smell of ethanol or of a novel odorant (cineole). A third group of pups were tested in response to unscented air stimulation. Results: Ethanol administration during late gestation induced reliable maternal hypothermia, a thermal disruption greater than that observed in water-treated females. It was systematically observed that maternal ethanol-induced hypothermia negatively correlated with neonatal motor reactivity elicited by ethanol olfactory stimulation. No other significant correlations were observed in terms of responsiveness to cineole or to unscented air in animals prenatally exposed to ethanol or water. Conclusions: In conjunction with prior research, the present results indicate that fetal ethanol exposure may yield learning of an association between ethanol's sensory and unconditioned properties. Ethanol-induced hypothermia during late gestation seems to represent a significant component of ethanol's unconditioned consequences. Specifically, ethanol-related thermal disruptions in the womb are highly predictive of neonatal responsiveness to ethanol's chemosensory cues that are known to be processed by the near-term fetus. [source]

The effect of ethnic origin on nuchal translucency at 10,14,weeks of gestation

PRENATAL DIAGNOSIS, Issue 7 2002
Min Chen
Abstract Introduction Fetal nuchal translucency (NT) increases with gestation and is affected by fetal posture and fetal gender. A recent report suggested that there might also be ethnic differences. We investigated the effect of ethnic origin on NT in an Asian population. Methods NT was measured at 10,14,weeks. The measurements were converted into multiples of the median (MoM) for gestational day. The risk of Down syndrome was calculated by combining NT and maternal age. Cases affected by chromosomal and major structural abnormalities were excluded. NT measurements of different ethnic groups were compared. Results Between January 1997 and October 2001, 16,981 pregnancies with known ethnic origin and normal fetal outcome were analysed. Median NT MoM (95% CI) of the Filipinos was 1.07 (1.04,1.11). This was significantly higher than that of the Chinese, 1.01 (1.01,1.02); other Asians (Indians, Pakistanis and Nepalese), 0.96 (0.94,0.99), and Caucasians, 0.98 (0.93,1.06) (p<0.05, respectively; Mann,Whitney U-test). An NT risk cut-off of 1:180 would classify 5% of the Chinese, 4.6% of the Caucasians, 5.6% of the Filipinos and 4.2% of the other Asians as screen-positive. There were no statistically significant differences between these screen-positive rates (p>0.05, Chi-square test). Conclusion Although there were statistically significant differences in NT measurements between different ethnic groups, it was clinically insignificant, as reflected by similar screen-positive rates. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Atypical Fetal Prostate Development is Associated with Ipsilateral Hypoplasia of the Wolffian Ducts in the ACI Rat

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2010
Luke E. Hofkamp
Abstract For over a half century, the ACI (August × Copenhagen) rat has been a primary model for studying renal agenesis and ipsilateral hypoplasia (IHP) of the Wolffian-derived structures (WDS). Because the ACI rat is also used as a model for prostate research, it is important to examine the relationship of IHP and urogenital sinus (UGS) development. The prostate is dependent on androgens for proper growth and differentiation. Alteration in androgen production and/or delivery to the UGS has the potential to perturbate normal development. In this study, we investigate whether the ipsilateral loss of the WDS is associated with altered prostate development. Digital images of serial-sectioned fetal ACI rat UGS were used to create three-dimensional (3-D) surface-rendered models of the developing prostate, seminal vesicle, vas deferens, and utricle on gestational day 21. The number and volume of prostate ducts developing from the UGS were calculated from the 3-D model data. Animals exhibiting IHP had a significant decrease in total fetal prostate volume (40%; P < 0.005) with significant regional specific differences when compared with normal male ACI rats. Anatomical and histological differences in the utricle, abnormal histology of the ipsilateral testes, and a truncation of the ipsilateral Wolffian ductal mesenchyme were also seen in the animals with IHP. Additional research is needed to further understand the mechanisms and consequences of IHP on prostate growth and development. Alterations to normal prenatal development of the male accessory sex organs can have important consequences for the growth and morphology of the adult gland. Anat Rec, 2010. © 2010 Wiley-Liss, Inc. [source]

Comparison of chorionic gonadotropin expression in human and macaque (Macaca fascicularis) trophoblasts

AMERICAN JOURNAL OF PRIMATOLOGY, Issue 2 2002
Jason A. Wilken
Abstract We have designed novel DNA primers that allow us to detect the expression of the subunits of chorionic gonadotropin (CG) from a variety of species of the order Primates. Using these primers, reverse transcriptase-polymerase chain reaction (RT-PCR), and standard cloning techniques, we detected the expression of a single gene for the common glycoprotein hormone (GPH) ,-subunit and at least two genes for the CG ,-subunit in trophoblasts of Macaca fascicularis (cynomolgous macaque (cm)) at gestational day (GD) = 26 (± 2d). No cmCG expression was detected at GD = 35,40. When sequences of cmGPH-, and cmCG-, genes were compared to the corresponding genes of other primates, we found that the ,-subunit of M. fascicularis was highly conserved compared to other primate species. However, cmCG ,-subunits appeared to be less conserved, residing between those of human CG-, and baboon CG-, when analyzed phylogenetically. Of particular interest was a three amino acid stretch in one of the expressed cmCG-, genes that is distinct from all other primates studied. Our findings imply that not only does the expression of multiple CG ,-subunit genes appear to be common to Old World monkeys, but that the presented methodology will greatly facilitate our ability to understand primate evolution. Am. J. Primatol. 56:89,97, 2002. © 2002 Wiley-Liss, Inc. [source]

ORIGINAL ARTICLE: Can Sulfasalazine Prevent Infection-Mediated Pre-Term Birth in a Murine Model?

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
Carl A. Nath
Citation Nath CA, Ananth CV, Smulian JC, Peltier MR. Can sulfasalazine prevent infection-mediated pre-term birth in a murine model? Am J Reprod Immunol 2010; 63: 144,149 Problem, Sulfasalazine (SASP) blocks activation of nuclear factor-kappa B (NF-,B) in gestational tissues in vitro, one of the earliest signals in the inflammatory response. We hypothesized that the administration of SASP would reduce the rate of infection-mediated pre-term birth in a murine model. Method of study, CD-1 mice (n = 40) were assigned on gestational day (gd) 14.5 to 1 of 3 treatments: (1) Sham infection and vehicle; (2) 104 CFU Escherichia coli and vehicle; or (3) 104 CFU E. coli and SASP (150 mg/Kg daily). Mice were observed twice daily and deliveries prior to gd 18.5 were considered pre-term. Results, Significantly more mice delivered prior to gd 18.5 when infected with 104 CFU E. coli than sham-infected mice (P < 0.001) and this effect was significantly reduced in mice also treated with SASP (P = 0.002). SASP also tended to increase litter size (P = 0.060) and significantly increased weight of pups born to dams with intrauterine infections (P = 0.001). Conclusion, SASP reduced rates of pre-term delivery and improved pregnancy outcomes for mice infected with 104 CFU E. coli. This suggests that SASP has the potential to play a role in strategies to prevent pre-term birth in women. [source]

Development of Galanin-Containing Nerve Fibres in Rat Tibia

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2009
M. Gajda
Summary Galanin exerts tonic inhibition of nociceptive input to the central nervous system. Recently, this peptide was demonstrated in several neuronal and non-neuronal structures in bones and joints. In this study, the time of appearance and topographic localization of galanin-containing nerve fibres in bone were studied in rats from gestational day 16 (GD16) to postnatal day 21 (PD21). The tibia was chosen as a model of developing long bone and indirect immunofluorescence combined with confocal laser scanning microscopy was used to identify galanin-immunoreactive (GAL-IR) nerve fibres. The earliest, sparse GAL-IR fibres were observed on GD21 in the perichondrium of both epiphyses and in the periosteum of the diaphysis. From PD1 onwards, GAL-IR fibres were also seen in the bone marrow cavity and in the region of the inter-condylar eminence of the knee joint. Intramedullary GAL-IR fibres in proximal and distal metaphyses appeared around PD1. Some of them accompanied blood vessels, although free fibres were also seen. GAL-IR fibres located in the cartilage canals of both epiphyses were observed from PD7, in the secondary ossification centres from PD10 and in the bone marrow of both epiphyses from PD14. The time course and localization of galanin-containing nerve fibres resemble the development of substance P- and CGRP-expressing nerve fibres, thus suggesting their sensory origin. [source]

Morphological Examination of the Intraorbital Muscles (Musculi Bulbi) in Dogs in the Perinatal Period

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2006
J. Kle, kowska
Summary Twelve American Staffordshire terriers, gestational day 60, and 10 dogs de Bordeaux, gestational day 57 were examined in respect of the morphology and morphometry of their intraorbital muscles. The location of the retractor bulbi, recti and oblique muscles was described and the length of the muscles, the length and breadth of their tendons as well as the distance of the distal insertions of the muscle tendons from the corneal limbus were measured. Similarly, the shape of the line of distal insertions was investigated. The measurements were taken with an electronic caliper to the nearest 0.1 mm. The distance insertion,corneal limbus was measured by means of the Hifny and Misk method (1982). The following differences between the breeds in the morphometry of the intraorbital muscles and their tendons were found out. The distal insertions of the tendons of the dorsal, ventral and lateral recti muscles are further from the corneal limbus in American Staffordshire terriers than in dogs de Bordeaux. The muscular funiculi of the retractor bulbi muscle are further from the corneal limbus in dogs de Bordeaux, except the dorsolateral funiculus (1.96/1.94 mm). In addition, there are differences in the morphometry of the intraorbital muscles and their tendons. No differences, however, were found in the morphology of the intraorbital muscle tendons (their insertion line) and their location. The study can be applied to clinical sciences (surgery) and veterinary ophthalmology, in particular. [source]

Effects of Subchronic versus Acute in utero Exposure to Dexmedetomidine on Foetal Developments in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2008
Mohammad Tariq
This study was undertaken to investigate the effects of in utero exposure of dexmedetomidine on foetal development and postnatal behaviour in the offspring. Pregnant Sprague-Dawley rats were chronically treated with dexmedetomidine (0, 5, 10 and 20 µg/kg, subcutaneously) daily from gestation day 7 to day 19. Another group of animals received only a single acute dose of dexmedetomidine (20 µg/kg) on gestational day 19 to mimic a model for systemic analgesia during labour. Administration of dexmedetomidine did not affect the frequency of implantations. Chronic administration of 10 and 20 µg/kg of dexmedetomidine significantly reduced the body weight and crown-rump length of pups, whereas a single acute dose (20 µg/kg) did not affect these parameters. None of the pups exhibited any external malformations or skeletal abnormalities irrespective of treatment assigned. All the pups showed a normal postnatal weight gain during the developmental phase. No significant differences were observed among any of the groups with respect to behavioural performances of offspring in beam balance, grip strength and inclined plane tests as well as motor activity. In conclusion, acute exposure to dexmedetomidine at the anticipated delivery time does not exert any adverse effects on perinatal morphology of pups, their birth weight, crown-rump length, physical growth and postnatal behavioural performances. Since this study was conducted in rats, its clinical relevance in human beings remains to be unclear and warrants further studies. [source]

Effects of gestational exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats

BIOELECTROMAGNETICS, Issue 3 2009
Kumiko Ogawa
Abstract The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT-2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7,17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole-body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243,271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses. Bioelectromagnetics 30:205,212, 2009. © 2008 Wiley-Liss, Inc. [source]

Lack of adverse effects in pregnant/lactating female rats and their offspring following pre- and postnatal exposure to ELF magnetic fields

BIOELECTROMAGNETICS, Issue 4 2004
Moon-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]

Developmental toxicity evaluation of ELF magnetic fields in Sprague,Dawley rats

BIOELECTROMAGNETICS, Issue 4 2003
Moon-Koo Chung
Abstract To identify possible effects of horizontally polarized magnetic field (MF) exposure on maintenance of pregnancy and embryo-fetal development, an MF exposure system was designed and constructed and 96 time-mated female Sprague,Dawley (SD) rats (24/group) received continuous exposure to 60 Hz MF at field strengths of 0 (sham control) and 5, 83.3, or 500 ,T (50, 833, or 5000 mG). Dams received MF or sham exposures for 22 h/day on gestational day 6,20. MF was monitored continuously throughout the study. There were no evidences of maternal toxicity or developmental toxicity in any MF exposed groups. Mean maternal body weight, organ weights, and hematological and serum biochemical parameters in groups exposed to MF did not differ from those in sham control. No exposure related differences in fetal deaths, fetal body weight, and placental weight were observed between MF exposed groups and sham control. External, visceral, and skeletal examination of fetuses demonstrated no significant differences in the incidence of fetal malformations between MF exposed and sham control groups. In conclusion, exposure of pregnant rats to 60 Hz at MF strengths up to 500 ,T during gestation day 6,20 did not produce any biologically significant effect in either dams or fetuses. Bioelectromagnetics 24:231-240, 2003. © 2003 Wiley-Liss, Inc. [source]