Consequences of intrauterine growth restriction on ventilatory and thermoregulatory responses to asphyxia and hypercapnia in the newborn guinea-pig.

PubMed

Tolcos, Mary; Rees, Sandra; McGregor, Hugh; Walker, David

2002-01-01

The purpose of this study was to determine the effects of prenatal growth restriction on the ventilatory and thermoregulatory responses to asphyxia and hypercapnia in the newborn guinea-pig. Spontaneously growth-restricted (SGR) animals born to unoperated dams, and growth-retarded (GR) neonates born to dams in which a uterine artery had been ligated at mid gestation, were studied and compared with control neonates. Ventilatory responses to progressive asphyxia and steady-state hypercapnia were tested at 3-6 days of age using a barometric plethysmograph. The animals were then killed and the brains prepared for histological and immunohistochemical analysis. During progressive asphyxia, SGR neonates (n = 5) had a significantly increased minute ventilation compared with both control (n = 6) and GR (n = 5) neonates. Rectal temperature fell significantly in GR and SGR neonates after progressive asphyxia, but was unchanged in control neonates. The ventilatory responses to steady-state hypercapnia were not different in the GR, SGR and control neonates. The immunoreactive expression of glial fibrillary acidic protein, tyrosine hydroxylase, substance P and met-enkephalin in the medulla was also not different between the three groups. It was concluded that prenatal growth restriction is associated with alterations in the respiratory and thermoregulatory responses to asphyxia and hypercapnia, with greater effects observed when in utero growth restriction arises spontaneously, compared with that produced experimentally over approximately the last half of gestation.

Infant Head Growth and Cognitive Status at 36 Months in Children with In-Utero Drug Exposure

ERIC Educational Resources Information Center

Butz, Arlene M.; Pulsifer, Margaret; Belcher, Harolyn M. E.; Leppert, Mary; Donithan, Michele; Zeger, Scott

2005-01-01

Previous studies of children with in-utero drug exposure (IUDE) raise concerns that decreased head circumference (HC) at birth increases the child's risk for later compromised cognitive functioning. The purpose of this study was to determine if HC at birth and HC growth change are associated with cognitive functioning (IQ) at 36 months of age in…

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses.

PubMed

Bouyssi-Kobar, Marine; du Plessis, Adré J; McCarter, Robert; Brossard-Racine, Marie; Murnick, Jonathan; Tinkleman, Laura; Robertson, Richard L; Limperopoulos, Catherine

2016-11-01

Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks' GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI. Copyright © 2016 by the American Academy of Pediatrics.

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses

PubMed Central

Bouyssi-Kobar, Marine; du Plessis, Adré J.; McCarter, Robert; Brossard-Racine, Marie; Murnick, Jonathan; Tinkleman, Laura; Robertson, Richard L.

2016-01-01

BACKGROUND AND OBJECTIVES: Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. METHODS: Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. RESULTS: We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks’ GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. CONCLUSIONS: These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI. PMID:27940782

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed

Buchhorn, Reiner; Meint, Sebastian; Willaschek, Christian

2016-01-01

Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed Central

Buchhorn, Reiner; Meint, Sebastian

2016-01-01

Introduction Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Results Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. Conclusion It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children—allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)—have the highest risk for ‘stress diseases’ such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children. PMID:27861527

Bartsocas-papas syndrome: unusual findings in the first reported egyptian family.

PubMed

Abdalla, E M; Morsy, H

2011-01-01

Bartsocas-Papas syndrome (BPS) is an autosomal recessive syndrome with severe craniofacial, limb, and genital abnormalities. As of 2011, 24 published cases and families were registered in the Orphanet Report Series. Compared to other disorders characterized by pterygia, the condition is usually more severe and often lethal: most affected patients die in utero or shortly after birth. We report the first Egyptian family with Bartsocas-Papas syndrome comprising three cases; our proband who was a female infant with severe craniofacial and limb anomalies typical of Bartsocas-Papas syndrome, a similarly affected female fetus which died in utero at the 7th gestational month, and a 16-year-old mentally retarded uncle who presented with some of the typical features of Bartsocas-Papas syndrome, including syndactyly, thumb hypoplasia, and microphthalmia. This male patient actually did not present with pterygia, however, we find his clinical description noteworthy.

Placental morphometry and Doppler flow velocimetry in cases of chronic human fetal hypoxia.

PubMed

Kuzmina, Irina Y; Hubina-Vakulik, Galina I; Burton, Graham J

2005-06-01

To investigate the structural basis of abnormal Doppler waveforms in the utero-placental circulations in cases of chronic fetal hypoxia. Morphometric analysis was performed on placental samples from 58 pregnancies with abnormal Doppler waveforms in the uterine, placental and umbilical circulations at 32-34 weeks, and 10 pregnancies with normal waveforms. The volume of placental villi reduced from 350.5 cm3 in controls to 286.4 cm3 (P<0.05) in the severest cases. The volume of the fetal capillaries reduced from 59.7 cm3 to 20.5 cm3 (P<0.05). These reductions were associated with increased placental infarction. The myometrial segments of the spiral arteries were severely constricted, demonstrating failure of physiological conversion secondary to deficient trophoblast invasion. The placental vascular bed is greatly reduced in cases of chronic fetal hypoxia. We propose impaired placental perfusion causes oxidative stress and regression of the fetal vasculature, leading to fetal growth retardation and distress.

Placental heat shock proteins: no immunohistochemical evidence for a differential stress response in preterm labour.

PubMed

Divers, M J; Bulmer, J N; Miller, D; Lilford, R J

1995-01-01

The aetiology of idiopathic preterm labour remains obscure. The hypothesis that a stress response induced by low-grade bacterial infection in utero-placental tissues was investigated. Distribution of cognate and inducible isoforms of heat shock proteins (HSP) 70 kD, HSP 60 kD and HSP 90 kD were investigated in an immunohistochemical study of placental and decidual tissues before and after labour at varying gestations. Subjects were pregnant women undergoing singleton delivery after idiopathic preterm labour at less than 34 weeks' gestation (n = 23); spontaneous term labour at 37-42 weeks' gestation (n =24); preterm caesarean sections at less than 34 weeks' gestation for preeclampsia or intrauterine growth retardation (n=14); elective caesarean section at 37-42 weeks' gestation for cephalopelvic disproportion (n = 6). HSP expression was constant throughout the third trimester of pregnancy and did not change following the onset of labour, regardless of gestational age. A stress response in decidual tissues as determined by immunohistochemical analysis is apparently not associated with preterm labour.

[Review on application of plant growth retardants in medicinal plants cultivation].

PubMed

Zhai, Yu-Yao; Guo, Bao-Lin; Cheng, Ming

2013-09-01

Plant growth retardants are widely used in cultivation of medicinal plant, but there is still lack of scientific guidance. In order to guide the use of plant growth retardants in medicinal plant cultivation efficiently and reasonably, this paper reviewed the mechanism, function characteristic, plant and soil residue of plant growth retardants, such as chlorocholine chloride, mepiquat chloride, paclobutrazol, unicnazle and succinic acid, and summarized the application of plant growth retardants in medicinal plants cultivation in recent years, with focus on the effect of growth and yield of the officinal organs and secondary metabolites.

[Advantages and limitations of chorionic villous sampling].

PubMed

Carles, Dominique; Pelluard, Fanny; Mangione, Raphalle; Liquier, Alain; Horovitz, Jacques; Saura, Robert

2009-03-01

Chorionic villous sampling (CVS) has been available for more than twenty years. Together with amniocentesis, it helps the cytogenetician to determine the fetal karyotype for prenatal diagnosis. The choice between these two methods depends on the team and the indication. CVS can now provide sufficient material for both histopathologic and cytogenetic analyses. We evaluated the accuracy of microscopic examination of CVS for detecting primary ovular, uteroplacental vascular (preeclampsia) and inflammatory disorders. Four hundred CVS were examined in the pathology laboratory of Pellegrin Hospital, Bordeaux, France, from January 1995 to February 2008. The results were analyzed according to the indication, the karyotype, the results of placental examination, pregnancy outcome and, when available (following spontaneous or medical termination), fetoplacental findings. The sample was representative of patients requiring CVS for prenatal diagnosis, with respect to maternal age, the stage of pregnancy, and the indications. When used to screen for preeclamsia (prevalence 29.6% in the sample), the sensitivity and specificity of placental biopsy were respectively 56.8% and 87.2% (76.9% in case of intra-uterine growth retardation). When used to screen for chromosomal aberrations (prevalence 7.4%), the specificity was 14.3% and the sensitivity 93.2%. The prevalence of other disorders, and particularly chronic intervillitis, was too low for meaningful analysis. This study shows that histopathologic analysis of chorionic villous samples is useful for detecting the utero-placental vascular origin of intrauterine growth retardation in the absence of other clinical, biological or ultrasound signs, and that it is complementary to cytogenetic analysis. Being a simple and inexpensive examination, histopathologic analysis of CVS could be performed systematically in this indication. Its value and diagnostic signs in other settings need to be determined in larger series.

Intrauterine growth retardation (IUGR): epidemiology and etiology.

PubMed

Romo, Agustín; Carceller, Raquel; Tobajas, Javier

2009-02-01

Intrauterine growth retardation (IUGR) is mainly due to a pathologic slow-down in the fetal growth pace, resulting in a fetus that is unable to reach its growth potential. IUGR frequency will vary depending on the discrimination criteria adopted. It is extremely important to use local or national fetal growth graphs in order to avoid some confounding factors. IUGR incidence in newborns would be between 3% and 7% of the total population. In our experience it is 5.13% a figure similar to the one obtained by other authors but with a progressively higher incidence during the last decade. There are multiple maternal factors that can generally be grouped into constitutional and general factors given that they affect age, weight, race, maternal cardiac volume, etc, socioeconomic factors with key incidence in the mother's nutrition level, where a poor maternal nutrition level would be the key factor in this group. We have evaluated multiple factors as possible contributors to the IUGR risk: race, parents' age, mother's height (cm), mother's birth weight and before pregnancy (kg), ponderal gain and blood pressure during pregnancy, and previous SGA newborns. Socioeconomic factors like social class, parents' profession, habitual residence, salary, immigration, and diet were also evaluated. We also included variables such as total daily working time and time mothers spent standing up, daily sleeping time (hrs), stress self-perception test at work and primiparity age. Toxic factors during pregnancy: tobacco (active and passive), alcohol, drugs and coffee consumption. Fetal or utero-placental factors were considered. In our study, the most significant etiologic factors were: Active and passive tobacco consuming, mother's stress level, increase of total months worked during pregnancy, total daily working hours and time mothers spent standing up and finally, the parent's height. Our data support the main objective of reducing the incidence of SGA newborns after IUGR by fighting against tobacco from all fields, including the passive smoking habit, and improving the laboral conditions of the pregnant mother, lowering the number of daily hours worked, the physical activity and trying to avoid and to cope with stressful situations.

Utero-placental perfusion Doppler indices in growth restricted fetuses: effect of sildenafil citrate.

PubMed

El-Sayed, Mohamed Adel; Saleh, Said Abdel-Aty; Maher, Mohammad Ahmed; Khidre, Asmaa Mohamed

2018-04-01

To assess efficacy and tolerability of sildenafil citrate on utero-placental blood flow and fetal growth in pregnancies complicated by fetal growth restriction (FGR). From March 2015, a randomized controlled trial of 54 patients at 24 weeks or more complicated by FGR and abnormal Doppler indices were randomly allocated 1:1 into an intervention arm (receive sildenafil citrate, 50 mg) or a control arm (receive placebo). The primary outcomes were changes occurred in the Doppler parameters 2 h following drug administration. Baseline characteristics were similar between groups. Significant difference was observed in the Delta uterine and umbilical Doppler indices among sildenafil group as compared to placebo group (p < 0.001). Middle cerebral Doppler indices, however, decreased significantly after sildenafil, which could be the result of shifting more blood to improve the utero-placental perfusion. No difference regarding Delta cerebro-placental ratio among both groups (p = 0.979). Sildenafil was also associated with pregnancy prolongation (p = .0001), increased gestational age at delivery (p = .004), improved neonatal weight (p = .0001), and less admission to neonatal intensive care unit (p = .03). No adverse effects reported in both treatment arms. Sildenafil citrate, by its vasodilator effect, can improve utero-placental blood flow in pregnancies complicated by FGR and abnormal Doppler. gov Registry: NCT02362399.

Effects of late-gestation heat stress on immunity and performance of calves.

PubMed

Dahl, G E; Tao, S; Monteiro, A P A

2016-04-01

Lactating cows that experience heat stress will have reduced dry matter intake and milk yield and shift metabolism, which ultimately reduces the efficiency of milk production. Dry cows that are heat stressed similarly experience lower intake, reduced mammary growth, and compromised immune function that ultimately results in a poorer transition into lactation and lower milk yield in the next lactation. A recent focus in our laboratory is on the effects of late gestation, in utero heat stress on calf survival and performance. We have completed a series of studies to examine preweaning growth and health, and later reproductive and productive responses, in an attempt to quantify acute and persistent effects of in utero heat strain. Late gestation heat stress results in calves with lower body weight at birth, shorter stature at weaning, and failure to achieve the same weight or height at 12 mo of age observed in calves from dams that are cooled when dry. A portion of the reduced growth may result from the lower immune status observed in calves heat stressed in utero, which begins with poorer apparent efficiency of immunoglobulin absorption and extends to lower survival rates through puberty. Heat-stressed calves, however, have permanent shifts in metabolism that are consistent with greater peripheral accumulation of energy and less lean growth relative to those from cooled dams. Comparing reproductive performance in calves heat stressed versus those cooled in utero, we observe that the cooled heifers require fewer services to attain pregnancy and become pregnant at an earlier age. Tracking the milk production in calves that were heat stressed in utero versus those cooled in late gestation revealed a significant reduction of yield in the first lactation, approximately 5 kg/d through 35 wk of lactation, despite similar body weight and condition score at calving. These observations indicate that a relatively brief period of heat stress in late gestation dramatically alters the health, growth, and ultimate performance of dairy calves. Thus, it is critical to effectively manage heat stress of dry cows to avoid negative effects on the calf. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

GROWTH AND DEVELOPMENT OF MICE OFFSPRING AFTER IRRADIATION IN UTERO WITH 2,450-MHZ MICROWAVES

EPA Science Inventory

Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm. sq. (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, ...

Maternal exposure to brominated flame retardants and infant Apgar Scores

PubMed Central

Terrell, Metrecia L.; Hartnett, Kathleen P.; Lim, Hyeyeun; Wirth, Julie; Marcus, Michele

2014-01-01

Brominated flame retardants (BFRs) and other persistent organic pollutants have been associated with adverse health outcomes in humans and may be particularly toxic to the developing fetus. We investigated the association between in utero polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB) exposures and infant Apgar scores in a cohort of Michigan residents exposed to PBB through contaminated food after an industrial accident. PBB and PCB concentrations were measured in serum at the time the women were enrolled in the cohort. PBB concentrations were also estimated at the time of conception for each pregnancy using a validated elimination model. Apgar scores, a universal measure of infant health at birth, measured at 1 and 5 minutes, were taken from birth certificates for 613 offspring born to 330 women. Maternal PCB concentrations at enrollment were not associated with below–median Apgar scores in this cohort. However, maternal PBB exposure was associated with a dose–related increase in the odds of a below–median Apgar score at 1 minute and 5 minutes. Among infants whose mothers had an estimated PBB at conception above the limit of detection of 1 part per billion, the odds ratio was 2.32 (95 % CI: 1.22– 4.40); for those with PBB ≥ 2.5 ppb the OR=2.62 (95% CI: 1.38-4.96; test for trend p< 0.01). Likewise, the odds of a below–median 5–minute Apgar increased with higher maternal PBB at conception. It remains critical that future studies examine possible relationships between in utero exposures to brominated compounds and adverse health outcomes. PMID:25203650

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

PubMed Central

2011-01-01

Background Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Methods Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. Results We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. Conclusions In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood. PMID:21702915

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats.

PubMed

Toledo, Fabíola C; Perobelli, Juliana E; Pedrosa, Flávia P C; Anselmo-Franci, Janete A; Kempinas, Wilma D G

2011-06-24

Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.

PERK eIF2alpha kinase regulates neonatal growth by controlling the expression of circulating insulin-like growth factor-I derived from the liver.

PubMed

Li, Yulin; Iida, Kaori; O'Neil, Jeff; Zhang, Peichuan; Li, Sheng'ai; Frank, Ami; Gabai, Aryn; Zambito, Frank; Liang, Shun-Hsin; Rosen, Clifford J; Cavener, Douglas R

2003-08-01

Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2alpha kinase) show severe postnatal growth retardation. In mice, growth retardation in Perk-/- mutants is manifested within the first few days of neonatal development. Growth parameters of Perk-/- mice, including comparison of body weight to length and organ weights, are consistent with proportional dwarfism. Tibia growth plates exhibited a reduction in proliferative and hypertrophic chondrocytes underlying the longitudinal growth retardation. Neonatal Perk-/- deficient mice show a 75% reduction in liver IGF-I mRNA and serum IGF-I within the first week, whereas the expression of IGF-I mRNA in most other tissues is normal. Injections of IGF-I partially reversed the growth retardation of the Perk-/- mice, whereas GH had no effect. Transgenic rescue of PERK activity in the insulin- secreting beta-cells of the Perk-/- mice reversed the juvenile but not the neonatal growth retardation. We provide evidence that circulating IGF-I is derived from neonatal liver but is independent of GH at this stage. We propose that PERK is required to regulate the expression of IGF-I in the liver during the neonatal period, when IGF-I expression is GH-independent, and that the lack of this regulation results in severe neonatal growth retardation.

Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs.

PubMed

Kliegman, R M

1989-03-01

Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth-retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth-retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels.

[How to intervene and prevent stunting of children from homes belonging to the Sisbén in Caldas].

PubMed

Benjumea, María Victoria; Parra, José Hernán; Jaramillo, Juan Felipe

2017-12-01

Growth retardation or chronic malnutrition (low height for age) indicates a failure in the natural genetic potential that allows us to growth. To estimate predictive models of growth retardation in households with children younger than five years in the department of Caldas and registered in the identification system of potential beneficiaries of social programs (Sistema de Identificación de Potenciales Beneficiarios de Programas Sociales, Sisbén). We conducted an analytical study in all households (N=56,987) included in the Sisbén III database with the presence of children younger than five years (N=33,244). The variables under study were demographic and socioeconomic characteristics, health service access, housing, poverty, education, job market, and growth retardation. The multivariate analysis was done in two phases: first, an exploratory analysis of households using hierarchical classification (cluster), then estimation of a nonlinear predictive model (probit) with growth retardation as the dependent variable. The largest proportion of growth retardation in children younger than five years was found in southcentral Caldas, in urban centers, and households with monthly income lower than USD$ 65. Poverty in Caldas women-headed households with children younger than five years registered in the Sisbén was the main predictor of growth retardation.

Chemical Mowing: Effect of Plant Growth Retardants on Plant Roots

DTIC Science & Technology

1991-08-01

nature of the turf. The retardation effects of mefluidide in this case ( field -treated) are consistent with other researchers (Nielsen and Wakefield...CONTRACT REPORT EL-91-1 CHEMICAL MOWING: EFFECT OF PLANT Of 5,’’ ’,i em GROWTH RETARDANTS ON PLANT ROOTS AD-A2 4 0 88 byI/l!ll//I, I/ll/lil/l///l/o.P...Chemical Mowing: Effect of Plant Growth Retardants on Plant Roots 6. AUTHOR(S) DACW39-88-C-0043 0. P. Vadhwa DACW39-88-C-0043-P 00002 7. PERFORMING

Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

PubMed

Satterfield, M Carey; Bazer, Fuller W; Spencer, Thomas E; Wu, Guoyao

2010-02-01

Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

Melatonin regulates delayed embryonic development in the short-nosed fruit bat, Cynopterus sphinx.

PubMed

Banerjee, Arnab; Meenakumari, K J; Udin, S; Krishna, A

2009-12-01

The aim of the present study was to evaluate the seasonal variation in serum melatonin levels and their relationship to the changes in the serum progesterone level, ovarian steroidogenesis, and embryonic development during two successive pregnancies of Cynopterus sphinx. Circulating melatonin concentrations showed two peaks; one coincided with the period of low progesterone synthesis and delayed embryonic development, whereas the second peak coincided with regressing corpus luteum. This finding suggests that increased serum melatonin level during November-December may be responsible for delayed embryonic development by suppressing progesterone synthesis. The study showed increased melatonin receptors (MTNR1A and MTNR1B) in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed that a high dose of melatonin suppressed progesterone synthesis, whereas a lower dose of melatonin increased progesterone synthesis by the ovary. The effects of melatonin on ovarian steroidogenesis are mediated through changes in the expression of peripheral-type benzodiazepine receptor, P450 side chain cleavage enzyme, and LH receptor proteins. This study further showed a suppressive impact of melatonin on the progesterone receptor (PGR) in the utero-embryonic unit; this effect might contribute to delayed embryonic development in C. sphinx. The results of the present study thus suggest that a high circulating melatonin level has a dual contribution in retarding embryonic development in C. sphinx by impairing progesterone synthesis as well as by inhibiting progesterone action by reducing expression of PGR in the utero-embryonic unit.

[The laboratory evaluation of pathogenic factors under retarded consolidation of fractures of bones of lower extremities].

PubMed

Stogov, V M; Kireeva, E A; Karasev, A G

2014-12-01

The study was carried out to comparatively analyze metabolic profile and content of growth factors in blood serum of patients with retarded consolidation of fractures of bones of lower extremities. The evaluation was applied to concentration of metabolites, growth factors and enzyme activity of blood serum in 13 patients with retarded consolidation of fractures of thigh and shank bones (main group). The comparative group included 14 patients with solid fractures of thigh and shank bones. The analysis established that as compared to patients with solid fractures of bones, in patients with retarded consolidation of fractures blood serum contained reliably higher concentration of triglycerides, products of glycolysis, epidermal growth factor and transforming growth factors TGF-α and TGF-β2. The content of vitamin E and insullin-like growth factor (IGF-1) was decreased The given markers can be labeled as potential markers of diagnostic and prognosis of development of retarded consolidation of fractures.

Maternal exposure to brominated flame retardants and infant Apgar scores.

PubMed

Terrell, Metrecia L; Hartnett, Kathleen P; Lim, Hyeyeun; Wirth, Julie; Marcus, Michele

2015-01-01

Brominated flame retardants (BFRs) and other persistent organic pollutants have been associated with adverse health outcomes in humans and may be particularly toxic to the developing fetus. We investigated the association between in utero polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB) exposures and infant Apgar scores in a cohort of Michigan residents exposed to PBB through contaminated food after an industrial accident. PBB and PCB concentrations were measured in serum at the time the women were enrolled in the cohort. PBB concentrations were also estimated at the time of conception for each pregnancy using a validated elimination model. Apgar scores, a universal measure of infant health at birth, measured at 1 and 5min, were taken from birth certificates for 613 offspring born to 330 women. Maternal PCB concentrations at enrollment were not associated with below-median Apgar scores in this cohort. However, maternal PBB exposure was associated with a dose-related increase in the odds of a below-median Apgar score at 1min and 5min. Among infants whose mothers had an estimated PBB at conception above the limit of detection of 1 part per billion (ppb) to <2.5ppb, the odds ratio=2.32 (95% CI: 1.22-4.40); for those with PBB⩾2.5ppb the OR=2.62 (95% CI: 1.38-4.96; test for trend p<0.01). Likewise, the odds of a below-median 5min Apgar score increased with higher maternal PBB at conception. It remains critical that future studies examine possible relationships between in utero exposures to brominated compounds and adverse health outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

PubMed

King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

1993-05-01

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

PubMed Central

King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

1993-01-01

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. Images PMID:8486767

Growth retardation induced by avian leukosis virus subgroup J associated with down-regulated Wnt/β-catenin pathway.

PubMed

Feng, Weiguo; Zhou, Defang; Meng, Wei; Li, Gen; Zhuang, Pingping; Pan, Zhifang; Wang, Guihua; Cheng, Ziqiang

2017-03-01

Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, induces growth retardation and neoplasia in chickens, leading to enormous economic losses in poultry industry. Increasing evidences showed several signal pathways involved in ALV-J infection. However, what signaling pathway involved in growth retardation is largely unknown. To explore the possible signaling pathway, we tested the cell proliferation and associated miRNAs in ALV-J infected CEF cells by CCK-8 and Hiseq, respectively. The results showed that cell proliferation was significantly inhibited by ALV-J and three associated miRNAs were identified to target Wnt/β-catenin pathway. To verify the Wnt/β-catenin pathway involved in cell growth retardation, we analyzed the key molecules of Wnt pathway in ALV-J infected CEF cells. Our data demonstrated that protein expression of β-catenin was decreased significantly post ALV-J infection compared with the normal (P < 0.05). The impact of this down-regulation caused low expression of known target genes (Axin2, CyclinD1, Tcf4 and Lef1). Further, to obtain in vivo evidence, we set up an ALV-J infection model. Post 7 weeks infection, ALV-J infected chickens showed significant growth retardation. Subsequent tests showed that the expression of β-catenin, Tcf1, Tcf4, Lef1, Axin2 and CyclinD1 were down-regulated in muscles of growth retardation chickens. Taken together, all data demonstrated that chicken growth retardation caused by ALV-J associated with down-regulated Wnt/β-catenin signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aflatoxin exposure in utero causes growth faltering in Gambian infants.

PubMed

Turner, Paul C; Collinson, Andrew C; Cheung, Yin Bun; Gong, Yunyun; Hall, Andrew J; Prentice, Andrew M; Wild, Christopher P

2007-10-01

Growth faltering in West African children has previously been associated with dietary exposure to aflatoxins, particularly upon weaning. However, in animal studies in utero exposure to low levels of aflatoxin also results in growth faltering. This study investigated the effect of in utero aflatoxin exposure on infant growth in the first year of life in The Gambia. Height and weight were measured for 138 infants at birth and at regular monthly intervals for one year. Aflatoxin-albumin (AF-alb) adduct level was measured in maternal blood during pregnancy, in cord blood and in infants at age 16 weeks. The geometric mean AF-alb levels were 40.4 pg/mg (range 4.8-260.8 pg/mg), 10.1 pg/mg (range 5.0-189.6 pg/mg) and 8.7 pg/mg (range 5.0-30.2 pg/mg) in maternal, cord and infant blood, respectively. AF-alb in maternal blood was a strong predictor of both weight (P = 0.012) and height (P = 0.044) gain, with lower gain in those with higher exposure. A reduction of maternal AF-alb from 110 pg/mg to 10 pg/mg would lead to a 0.8 kg increase in weight and 2 cm increase in height within the first year of life. This study shows a strong effect of maternal aflatoxin exposure during pregnancy on growth in the first year of life and thus extends earlier observations of an association between aflatoxin exposure during infancy and growth faltering. The findings imply value in targeting intervention strategies at early life exposures.

Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation.

PubMed

Bottini, E; Lucarelli, P; Amante, A; Saccucci, P; Gloria-Bottini, F

2002-01-01

We studied 101 growth-retarded children from the population of Ancona (Italy). Plasma growth hormone (GH) levels at the end of insulin and clonidine tests were considered for classification of children into 3 categories according to severity of GH deficit: total deficit of GH (TD), partial deficit (PD, and familiar short stature (FSS; no deficit of GH). The BGLIIA*2/BGLIIB*1 haplotype of GH cluster that was previously found to be negatively associated with severe glucose intolerance in non-insulin-dependent diabetes mellitus (NIDDM) is negatively associated with GH deficit in growth-retarded children. The hypothesis that intrauterine growth retardation and glucose intolerance in adult life could be phenotypes of the same underlying genotype has been recently put forward. The present observation suggests that genes influencing both growth and glucose tolerance are encoded in the GH cluster. Copyright 2002 by W.B. Saunders Company

In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

USDA-ARS?s Scientific Manuscript database

Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

[Epigenetics of childhood obesity and diabetes].

PubMed

Valladares-Salgado, Adán; Suárez-Sánchez, Fernando; Burguete-García, Ana I; Cruz, Miguel

2014-01-01

Obesity and type 2 diabetes mellitus (T2DM) result from sedentary lifestyle, high-carbohydrate diets and genetic predisposition. Epigenetics is a form of genetic regulation in specialized cells that does not involve changes in the deoxyribonucleic acid (DNA) sequence, but it can be inherited to one or more generations through mitosis or meiosis. Children whose mothers develop gestational diabetes are more likely to become obese and diabetic in adult life. DNA methylation is a major mechanism in the regulation of transcription and gene expression of several genes. High levels of glucose and insulin during pregnancy modify the risk of developing T2DM, suggesting that the expression pattern is modified due to cell memory in a specific tissue. If T2DM is linked to adaptation in utero, the obvious primary prevention is to protect the fetal development. Future epidemiological studies need to employ more accurate indicators or markers of development to show the relationship between a specific disease and the exposure to environmental factors. The mechanisms by which malnutrition, and intrauterine growth retardation produce changes in the metabolism of glucose and insuline are worth to explore in order to control obesity and T2DM.

Pregnancy and contraception in systemic and cutaneous lupus erythematosus.

PubMed

Guettrot-Imbert, G; Morel, N; Le Guern, V; Plu-Bureau, G; Frances, C; Costedoat-Chalumeau, N

2016-10-01

A causal link has long been described between estrogen and systemic lupus erythematosus activity. Contraceptive and pregnancy management is now common for lupus patients, but pregnancy continues to be associated with higher maternal and fetal mortality/morbidity in systemic lupus erythematosus patients than among the general population. Potential complications include lupus flares, obstetric complications (fetal loss, in utero growth retardation, premature birth) and neonatal lupus syndrome. Association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetric complications. Anti-SSA and/or anti-SSB antibodies put fetuses at risk for neonatal lupus. Improving the outcome of such pregnancies depends upon optimal systematic planning of pregnancy at a preconception counseling visit coupled with a multidisciplinary approach. Absence of lupus activity, use of appropriate medication during pregnancy based on the patient's medical history and risk factors, and regular monitoring constitute the best tools for achieving a favorable outcome in such high-risk pregnancies. The aim of this review is to provide an update on the management of contraception and pregnancy in systemic lupus erythematosus, cutaneous lupus and/or antiphospholipid syndrome in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Does acute maternal stress in pregnancy affect infant health outcomes? Examination of a large cohort of infants born after the terrorist attacks of September 11, 2001.

PubMed

Endara, Skye M; Ryan, Margaret A K; Sevick, Carter J; Conlin, Ava Marie S; Macera, Caroline A; Smith, Tyler C

2009-07-20

Infants in utero during the terrorist attacks of September 11, 2001 may have been negatively affected by maternal stress. Studies to date have produced contradictory results. Data for this retrospective cohort study were obtained from the Department of Defense Birth and Infant Health Registry and included up to 164,743 infants born to active-duty military families. Infants were considered exposed if they were in utero on September 11, 2001, while the referent group included infants gestating in the same period in the preceding and following year (2000 and 2002). We investigated the association of this acute stress during pregnancy with the infant health outcomes of male:female sex ratio, birth defects, preterm birth, and growth deficiencies in utero and in infancy. No difference in sex ratio was observed between infants in utero in the first trimester of pregnancy on September 11, 2001 and infants in the referent population. Examination of the relationship between first-trimester exposure and birth defects also revealed no significant associations. In adjusted multivariable models, neither preterm birth nor growth deficiencies were significantly associated with the maternal exposure to the stress of September 11 during pregnancy. The findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes.

Rescue of neonatal cardiac dysfunction in mice by administration of cardiac progenitor cells in utero

PubMed Central

Liu, Xiaoli; Hall, Sean R. R.; Wang, Zhihong; Huang, He; Ghanta, Sailaja; Di Sante, Moises; Leri, Annarosa; Anversa, Piero; Perrella, Mark A.

2015-01-01

Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family. We previously showed that disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy with immature-appearing cardiomyocytes. Here we show that cardiomyopathy of Speg−/− mice arises as a consequence of defects in cardiac progenitor cell (CPC) function, and that neonatal cardiac dysfunction can be rescued by in utero injections of wild-type CPCs into Speg−/− foetal hearts. CPCs harvested from Speg−/− mice display defects in clone formation, growth and differentiation into cardiomyocytes in vitro, which are associated with cardiac dysfunction in vivo. In utero administration of wild-type CPCs into the hearts of Speg−/− mice results in CPC engraftment, differentiation and myocardial maturation, which rescues Speg−/− mice from neonatal heart failure and increases the number of live births by fivefold. We propose that in utero administration of CPCs may have future implications for treatment of neonatal heart diseases. PMID:26593099

In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered Lxra DNA methylation.

PubMed

Martínez, Débora; Pentinat, Thais; Ribó, Sílvia; Daviaud, Christian; Bloks, Vincent W; Cebrià, Judith; Villalmanzo, Nuria; Kalko, Susana G; Ramón-Krauel, Marta; Díaz, Rubén; Plösch, Torsten; Tost, Jörg; Jiménez-Chillarón, Josep C

2014-06-03

Obesity and type 2 diabetes have a heritable component that is not attributable to genetic factors. Instead, epigenetic mechanisms may play a role. We have developed a mouse model of intrauterine growth restriction (IUGR) by in utero malnutrition. IUGR mice developed obesity and glucose intolerance with aging. Strikingly, offspring of IUGR male mice also developed glucose intolerance. Here, we show that in utero malnutrition of F1 males influenced the expression of lipogenic genes in livers of F2 mice, partly due to altered expression of Lxra. In turn, Lxra expression is attributed to altered DNA methylation of its 5' UTR region. We found the same epigenetic signature in the sperm of their progenitors, F1 males. Our data indicate that in utero malnutrition results in epigenetic modifications in germ cells (F1) that are subsequently transmitted and maintained in somatic cells of the F2, thereby influencing health and disease risk of the offspring. Copyright © 2014 Elsevier Inc. All rights reserved.

Keap1-Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring.

PubMed

Chapple, Sarah J; Puszyk, William M; Mann, Giovanni E

2015-11-01

Intrauterine exposure to gestational diabetes, pre-eclampsia or intrauterine growth restriction alters the redox status of the developing fetus. Such pregnancy-related diseases in most cases do not have a readily identifiable genetic cause, and epigenetic 'priming' mechanisms in utero may predispose both mother and child to later-life onset of cardiovascular and metabolic diseases. The concept of 'fetal programing' or 'developmental priming' and its association with an increased risk of disease in childhood or adulthood has been reviewed extensively. This review focuses on adaptive changes in the in utero redox environment during normal pregnancy and the consequences of alterations in redox control associated with pregnancies characterized by oxidative stress. We evaluate the evidence that the Keap1-Nrf2 pathway is important for protecting the fetus against adverse conditions in utero and may itself be subject to epigenetic priming, potentially contributing to an increased risk of vascular disease and insulin resistance in later life. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

PubMed

Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

2015-02-12

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.

[Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation].

PubMed

Cai, Yue-Ju; Song, Yan-Yan; Huang, Zhi-Jian; Li, Jian; Qi, Jun-Ye; Xiao, Xu-Wen; Wang, Lan-Xiu

2015-09-01

To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well. Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

In Utero Influences, Breast Stem Cells, and Breast Cancer Risk Factors

DTIC Science & Technology

2011-08-01

predictor of human breast cancer risk. Our hypothesis is that the in utero levels of mitogens, such as insulin -like growth factor-1 (IGF-1), drive an...by histological assays and in vivo and explant imaging. Histologically, we stained mammary glands from virgin and pregnant C57BL/6J mice using whole...that of a E16 pregnant (right panel); both glands are from 8 week-old mice. Second, we performed preliminary studies to quantitate and validate

Nutritional status and growth in pediatric Crohn's disease: a population-based study.

PubMed

Vasseur, Francis; Gower-Rousseau, Corinne; Vernier-Massouille, Gwenola; Dupas, Jean Louis; Merle, Veronique; Merlin, Beatrice; Lerebours, Eric; Savoye, Guillaume; Salomez, Jean Louis; Cortot, Antoine; Colombel, Jean Frederic; Turck, Dominique

2010-08-01

Growth retardation and malnutrition are major features of pediatric Crohn's disease (CD). We examined nutritional and growth parameters from diagnosis to maximal follow-up in a population-based pediatric cohort, and we determined predictive factors. A total of 261 patients (156 boys, 105 girls) with onset of CD before the age of 17 were identified from 1988 to 2004 through the EPIMAD registry (Registre des Maladies Inflammatoires Chroniques de l'Intestin) in northern France. Median age at diagnosis was 13 years (11.2-15.4) and median follow-up was 73 months (46-114). Z-scores of height/age, weight/age, and body mass index (BMI)/age were determined. Multivariate stepwise regression analysis identified predictive factors for malnutrition and growth retardation at maximal follow-up. At diagnosis, 25 children (9.5%) showed height less than -2 s.d., 70 (27%) weight less than -2 s.d., and 84 (32%) BMI less than -2 s.d. At maximal follow-up, growth retardation was present in 18 children (6.9%), whereas 40 (15%) had malnutrition. Nutritional status was more severely impaired in children with stricturing disease. Growth and nutritional retardation at diagnosis, young age, male gender, and extraintestinal manifestations at diagnosis were indicators of poor prognosis. A significant compensation was observed for weight and BMI in both genders and for height in girls. No treatment was associated with height, weight, or BMI at maximal follow-up. In our pediatric population-based study, growth retardation and severe malnutrition were still present at maximal follow-up in 6.9 and 15% of CD children, respectively. Young boys with substantial inflammatory manifestations of CD have a higher risk of subsequent growth failure, especially when growth retardation is present at diagnosis.

Intrauterine growth restriction is associated with persistent aortic wall thickening and glomerular proteinuria during infancy

PubMed Central

Zanardo, Vincenzo; Fanelli, Tiziana; Weiner, Gary; Fanos, Vassilios; Zaninotto, Martina; Visentin, Silvia; Cavallin, Francesco; Trevisanuto, Daniele; Cosmi, Erich

2011-01-01

Low birth weight, caused either by preterm birth or by intrauterine growth restriction, has recently been associated with increased rates of adult renal and cardiovascular disease. Since aortic intima–media thickening is a noninvasive marker of preclinical vascular disease, we compared abdominal aortic intima–media thickness among intrauterine growth restricted and equivalent gestational age fetuses in utero and at 18 months of age. The relationship between intrauterine growth restriction, fetal aortic thickening, and glomerular function during infancy was measured by enrolling 44 mothers with single-fetus pregnancies at 32 weeks gestation: 23 growth restricted and 21 of appropriate gestational age as controls. Abdominal aortic intima–media thickness was measured by ultrasound at enrollment and again at 18 months of age. Fetuses with intrauterine growth restriction had significantly higher abdominal aortic intima–media thickness compared with age controls when measured both in utero and at 18 months. At 18 months, the median urinary microalbumin and median albumin–creatinine ratio were significantly higher in those infants who experienced intrauterine growth restriction compared to the controls. Our results show that intrauterine growth restriction is associated with persistent aortic wall thickening and significantly higher microalbuminuria during infancy. PMID:21490588

Growth status of children in well-baby outpatient clinics and related factors.

PubMed

Çelik, Sercan Bulut; Şahin, Figen; Beyazova, Ufuk; Can, Hüseyin

2014-06-01

The aim of this study was to determine the state of growth during follow-up of healthy children and the factors affecting growth. The patient cards of the infants who were born in 2002 and followed up in the well-baby outpatient clinic in Gazi University, Medical Faculty regularly for at least 18 months were examined retrospectively. Their sociodemographic properties including age, education level, occupation of the parents, if the mother was working, caretakers and gender, gestational week, birth weight, birth height and mode of nutrition (breastmilk, formula, cow's milk, period of feeding, etc.) and growth of the babies (month, percentile) were recorded. Number of siblings and ages of the siblings were also recorded and the children with and without growth problems were compared in terms of these properties. It was found that 290 (39.3%) of 739 children who were followed up continued to grow up in the percentile in which they started (normal growth), 188 (25.4%) lost 2 or more percentiles in any month (growth retardation) and 261 (35.3%) lost less than 2 percentiles (decelerated growth). Deceleration/retardation in growth was observed most commonly in the 9(th) month. Deceleration in growth was found in the 6(th) month in 23.6% of the group with deceleration in growth, in the 9(th) month in 50.2%, in the 12(th) month in 15.8% and in the 18(th) month in 3.9%. Growth retardation was found in the 6(th) month in 35.8% of the group with growth retardation, in the 9(th) month in 38.0% and in the 18(th) month in 4.3%. It was found that receiving formula and presence of infection were the main risk factors in terms of deceleration of growth and unemployed mother, the lenght of the total time of breastfeeding and presence of infection were the main risk factors in terms of growth retardation. This study shows the importance of follow-up of growth of children in outpatient clinics for healthy children. It was found that detailed examination and recording of non-organic causes is necessary in addition to investigation of pathological causes of growth retardation. Since it was observed that elimination of the defects determined and educating the family about nutrition and supporting growth had a positive impact on growth retardation, it was concluded that all children should be followed up regularly especially in the first years of life.

Striatal but not frontal cortical up-regulation of the epidermal growth factor receptor in rats exposed to immune activation in utero and cannabinoid treatment in adolescence.

PubMed

Idrizi, Rejhan; Malcolm, Peter; Weickert, Cynthia Shannon; Zavitsanou, Katerina; Suresh Sundram

2016-06-30

In utero maternal immune activation (MIA) and cannabinoid exposure during adolescence constitute environmental risk factors for schizophrenia. We investigated these risk factors alone and in combination ("two-hit") on epidermal growth factor receptor (EGFR) and neuregulin-1 receptor (ErbB4) levels in the rat brain. EGFR but not ErbB4 receptor protein levels were significantly increased in the nucleus accumbens and striatum of "two-hit" rats only, with no changes seen at the mRNA level. These findings support region specific EGF-system dysregulation as a plausible mechanism in this animal model of schizophrenia pathogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Retardation analytical model to extend service life

NASA Technical Reports Server (NTRS)

Matejczyk, D.

1984-01-01

A fatigue crack growth model that incorporates crack growth retardation effects and is applicable to the materials characteristics and service environments of high performance LH2/LO2 engine systems was developed and tested.

Does acute maternal stress in pregnancy affect infant health outcomes? Examination of a large cohort of infants born after the terrorist attacks of September 11, 2001

PubMed Central

Endara, Skye M; Ryan, Margaret AK; Sevick, Carter J; Conlin, Ava Marie S; Macera, Caroline A; Smith, Tyler C

2009-01-01

Background Infants in utero during the terrorist attacks of September 11, 2001 may have been negatively affected by maternal stress. Studies to date have produced contradictory results. Methods Data for this retrospective cohort study were obtained from the Department of Defense Birth and Infant Health Registry and included up to 164,743 infants born to active-duty military families. Infants were considered exposed if they were in utero on September 11, 2001, while the referent group included infants gestating in the same period in the preceding and following year (2000 and 2002). We investigated the association of this acute stress during pregnancy with the infant health outcomes of male:female sex ratio, birth defects, preterm birth, and growth deficiencies in utero and in infancy. Results No difference in sex ratio was observed between infants in utero in the first trimester of pregnancy on September 11, 2001 and infants in the referent population. Examination of the relationship between first-trimester exposure and birth defects also revealed no significant associations. In adjusted multivariable models, neither preterm birth nor growth deficiencies were significantly associated with the maternal exposure to the stress of September 11 during pregnancy. Conclusion The findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes. PMID:19619310

Consequences of in utero exposure to Zika virus in offspring of AG129 mice.

PubMed

Julander, Justin G; Siddharthan, Venkatraman; Park, Albert H; Preston, Elizabeth; Mathur, Pranav; Bertolio, Michael; Wang, Hong; Zukor, Katherine; Van Wettere, Arnaud J; Sinex, Donal G; Morrey, John D

2018-06-20

Zika virus (ZIKV) can cause various diseases in offspring after congenital infection. The purpose of this study was to identify disease phenotypes in pups exposed to ZIKV in utero. Female interferon-α/β, -γ receptor knockout mice (AG129) were infected intraperitoneally with ZIKV 7.5 days' post coitus (dpc). Viral RNA, antigen and infectious virus were detected in some, but not all, maternal and fetal tissues at various times during gestation. Fetuses of infected dams had significant intrauterine growth restriction (IUGR), which was more pronounced as females neared parturition. Pups born to infected dams were significantly smaller and had significantly shortened skull lengths, as determined by measurement with a caliper and by micro-CT analysis, as compared with age-matched controls. Growth rates of exposed pups after birth, however, was similar to sham-exposed offspring. Viral RNA was detected in pups of infected dams after birth. A lower survival rate was observed in neonates exposed to ZIKV in utero. A mortality rate of over 50%, attributed to consequences of ZIKV infection, occurred after birth in pups born to infected dams. A transient hearing loss was observed in some animals exposed to virus in utero. No motor deficits or cognitive deficits were detected using running wheel or viral paresis scoring assays. Abnormalities in offspring included smaller size, shorter skull length and increased neonatal mortality, while the only functional deficit we could detect was a low incidence of transient hearing loss.

Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat

USDA-ARS?s Scientific Manuscript database

Perinatal skeletal muscle growth rates are a function of protein and myonuclear accretion. Precocious exposure of the fetus to glucocorticoids (GLC) in utero impairs muscle growth. Reduced muscle protein synthesis rates contribute to this response, but the consequences for myonuclear hyperplasia are...

Fetal Genotype for the Xenobiotic Metabolizing Enzyme "NQO1" Influences Intrauterine Growth among Infants Whose Mothers Smoked during Pregnancy

ERIC Educational Resources Information Center

Price, Thomas S.; Grosser, Tilo; Plomin, Robert; Jaffee, Sara R.

2010-01-01

Maternal smoking during pregnancy retards fetal growth and depresses infant birth weight. The magnitude of these effects may be moderated by fetal genotype. The current study investigated maternal smoking, fetal genotype, and fetal growth in a large population sample of dizygotic twins. Maternal smoking retarded fetal growth in a dose-dependent…

Retardation analytical model to extend service life

NASA Technical Reports Server (NTRS)

Matejczyk, J.

1984-01-01

A fatigue crack growth model that incorporates crack growth retardation effects and is applicable to the materials characteristics and service environments of high performance LH2/LO2 engine systems is discussed. Future Research plans are outlined.

Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring.

PubMed

Beauchamp, Brittany; Thrush, A Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y; Patti, Mary-Elizabeth; Harper, Mary-Ellen

2015-04-10

Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. © 2015 Authors.

Transplacental cocaine exposure. 1: A rodent model.

PubMed

Wilkins, A S; Genova, L M; Posten, W; Kosofsky, B E

1998-01-01

To characterize the transplacental effects of cocaine on the developing brain, we have developed a mouse model of gestational cocaine exposure. Pharmacokinetic analysis revealed that cocaine and its metabolites (BE, BNE, and NC) were found in fetal brain and plasma at 30 and 120 min following SC administration to embryonic day (E) 17 pregnant Swiss Webster mice. Pregnant dams injected twice daily with cocaine HCl at 20 mg/kg SC from gestational day E8 to E17 (COC) demonstrated less food intake and lower percentage weight gain than vehicle-injected dams allowed access to food ad lib (SAL). A nutritionally paired control group of dams injected with saline vehicle and pair-fed with the COC dams (SPF) demonstrated the lowest percentage weight gain of all three groups. The surrogate fostered offspring of COC and SPF dams demonstrated persistent growth retardation [on postnatal days (P) 1, P9, and P50] and transient brain growth retardation (on P1 and P9) when compared to pups born to SAL dams. We conducted behavioral tests that allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all three groups were tested for first-order Pavlovian conditioning on P9 or P12, or for the ability to ignore redundant information in a blocking paradigm on P50 or P100. Unlike the SPF and SAL controls, COC mice (i.e., mice born to COC dams) were unable to acquire an aversion to an odor previously paired with shock on P9. This learning deficit was transient because on P12, COC mice trained on the same conditioning task displayed an aversion to the odor that was indistinguishable from the SPF and SAL controls. P50 and P100 COC mice (and to a lesser extent, SPF mice) demonstrated a persistent behavioral deficit in the blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

Nocturnal growth hormone and gonadotrophin secretion in growth retarded children with Crohn's disease.

PubMed Central

Farthing, M J; Campbell, C A; Walker-Smith, J; Edwards, C R; Rees, L H; Dawson, A M

1981-01-01

Although impaired growth hormone secretion in response to pharmacological stimuli occurs in some growth retarded children with Crohn's disease, its relationship to past and future th is uncertain. We have therefore determined the growth hormone and gonadotrophin response to the physiological stimulus of sleep by continuous venous sampling in five severely gonadotrophin profiles, the mean plasma hormone concentrations during the first five hours of sleep were determined. In three of the five patients, five hour mean growth hormone levels were reduced (3.8, 5.0, and 8.5 mU/l) compared with levels reported previously in normal short children (10-43 mU/l), although the pulsatile pattern of growth hormone secretion was preserved in all. Nocturnal growth hormone secretion was unrelated to the growth velocities of these children during both pre- and post-treatment assessment periods but a significant correlation was found between growth hormone concentration and a disease activity score (r = 0.79, P less than 0.05), suggesting that growth hormone release by the pituitary was influenced by the severity of the disease. Nocturnal growth hormone secretion was also correlated with gonadotrophin secretion (luteinising hormones, r = 0.99, and follicle stimulating hormone, r = 0.96; p less than 0.01) indicating more extensive hypothalamic-pituitary disturbance. These findings suggest that hypothalamic-pituitary function is depressed in growth retarded children with Crohn's disease, but that abnormalities of growth hormone secretion are unlikely to be directly involved in the growth retardation seen in this condition. PMID:7308847

Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA).

PubMed

Roth, Christian L; Sathyanarayana, Sheela

2012-06-01

Signaling peptides produced in peripheral tissues such as gut, adipose tissue, and pancreas communicate with brain centers, such as hypothalamus and hindbrain to manage energy homeostasis. These regulatory mechanisms of energy intake and storage have evolved during long periods of hunger in the evolution of man to protect the species from extinction. It is now clear that these circuitries are influenced by prenatal and postnatal environmental factors including endocrine disruptive chemicals. Hypothalamic appetite regulatory systems develop and mature in utero and early infancy, and involve signaling pathways that are important also for the regulation of puberty onset. Recent studies in humans and animals have shown that metabolic pathways involved in regulation of growth, body weight gain and sexual maturation are largely affected by epigenetic programming that can impact both current and future generations. In particular, intrauterine and early infantile developmental phases of high plasticity are susceptible to factors that affect metabolic programming that therefore, affect metabolic function throughout life. In children born small for gestational age, poor nutritional conditions during gestation can modify metabolic systems to adapt to expectations of chronic undernutrition. These children are potentially poorly equipped to cope with energy-dense diets and are possibly programmed to store as much energy as possible, leading to later obesity, metabolic syndrome, disturbed regulation of normal puberty and early onset of cardiovascular disease. Most cases of disturbed energy balance are likely a result of a combination of genetics, epigenetics and environment. This review will discuss potential mechanisms linking intrauterine growth retardation with changes in growth, energy homeostasis and sexual maturation.

Language development in preschool children born after asymmetrical intrauterine growth retardation.

PubMed

Simić Klarić, Andrea; Kolundžić, Zdravko; Galić, Slavka; Mejaški Bošnjak, Vlatka

2012-03-01

After intrauterine growth retardation, many minor neurodevelopmental disorders may occur, especially in the motor skills domain, language and speech development, and cognitive functions. The assessment of language development and impact of postnatal head growth in preschool children born with asymmetrical intrauterine growth retardation. Examinees were born at term with birth weight below the 10th percentile for gestational age, parity and gender. Mean age at the time of study was six years and four months. The control group was matched according to chronological and gestational age, gender and maternal education with mean age six years and five months. There were 50 children with intrauterine growth retardation and 50 controls, 28 girls and 22 boys in each group. For the assessment of language development Reynell Developmental Language Scale, the Naming test and Mottier test were performed. There were statistically significant differences (p < 0.05) in language comprehension, total expressive language (vocabulary, structure, content), naming skills and non-words repetition. Statistically significant positive correlations were found between relative growth of the head [(Actual head circumference - head circumference at birth)/(Body weight - birth weight)] and language outcome. Children with neonatal complications had lower results (p < 0.05) in language comprehension and total expressive language. Intrauterine growth retardation has a negative impact on language development which is evident in preschool years. Slow postnatal head growth is correlated with poorer language outcome. Neonatal complications were negatively correlated with language comprehension and total expressive language. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Clinical, cytogenetic and molecular investigation in a fetus with Wolf-Hirschhorn syndrome with paternally derived 4p deletion. Case report and review of the literature.

PubMed

Dietze, Ilona; Fritz, Barbara; Huhle, Dagmar; Simoens, Wouter; Piecha, Ernestine; Rehder, Helga

2004-01-01

Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping. Chromosome analysis after amniocentesis revealed a de novo terminal deletion of chromosome 4p [karyotype: 46,XX,del(4) (p16)] which was confirmed by FISH. Analyses of a set of polymorphic markers mapping in 4pter->4p15.3 showed absence of paternal haplotypes. These observations corroborate the preferential paternal origin of the de novo 4p deletion in WHS patients. Furthermore, the distal breakpoint could be narrowed to band 4p16.1. At autopsy, the fetus showed typical craniofacial dysmorphic signs of WHS, severe IUGR and delayed bone age. This report suggests the possibility of recognising the particular phenotype of WHS in utero by prenatal ultrasound and emphasises the importance of karyotyping fetuses with severe IUGR, especially when the amount of amniotic fluid is normal. Copyright 2004 S. Karger AG, Basel

Intervention for individuals with fetal alcohol spectrum disorders: treatment approaches and case management.

PubMed

Paley, Blair; O'Connor, Mary J

2009-01-01

Exposure to alcohol in utero is considered to be the leading cause of developmental disabilities of known etiology. The most severe consequence of such exposure, fetal alcohol syndrome (FAS), is characterized by a distinct constellation of characteristic facial anomalies, growth retardation, and central nervous system (CNS) dysfunction. Some individuals with prenatal alcohol exposure (PAE) do not meet the full criteria for FAS, but instead are diagnosed with partial FAS, alcohol related neurodevelopmental disorder (ARND), or alcohol related birth defects (ARBD). The entire continuum of effects from PAE is increasingly being referred to under the umbrella term of fetal alcohol spectrum disorders (FASDs). An extensive body of research has documented major cognitive, behavioral, adaptive, social, and emotional impairments among individuals with FASDs. Although FAS was identified in the U.S. over 35 years ago, the development, evaluation, and dissemination of evidence-based interventions for individuals with FASDs have lagged behind significantly. Encouragingly, however, in recent years there has been a marked increase in efforts to design and test interventions to remediate the impairments associated with prenatal alcohol exposure. This article will review treatment needs and considerations for individuals with FASDs and their families, current empirically tested treatment approaches, case management issues, and suggestions for future directions in research on the treatment of FASDs. (c) 2009 Wiley-Liss, Inc.

Biallelic UNC80 mutations caused infantile hypotonia with psychomotor retardation and characteristic facies 2 in two Chinese patients with variable phenotypes.

PubMed

He, Yunjuan; Ji, Xing; Yan, Hui; Ye, Xiantao; Liu, Yu; Wei, Wei; Xiao, Bing; Sun, Yu

2018-06-20

Biallelic UNC80 mutations cause infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2), which is characterized by hypotonia, developmental delay (DD)/intellectual disability (ID), intrauterine growth retardation, postnatal growth retardation and characteristic facial features. We report two unrelated Chinese patients with compound heterozygous UNC80 mutations inherited from their parents, as identified by whole-exome sequencing (WES). Mutations c.3719G>A (p.W1240*)/c.4926_4937del (p.N1643_L1646del) and c.4963C>T (p.R1655C)/c.8385C>G (p.Y2795*) were identified in patient 1 and patient 2, respectively. Although both patients presented with DD/ID and hypotonia, different manifestations also occurred. Patient 1 presented with infantile hypotonia, epilepsy and hyperactivity without growth retardation, whereas patient 2 presented with persistent hypotonia, growth retardation and self-injury without epilepsy. Furthermore, we herein summarize the genotypes and phenotypes of patients with UNC80 mutations reported in the literature, revealing that IHPRF2 is a phenotypically heterogeneous disease. Common facial dysmorphisms include a thin upper lip, a tented upper lip, a triangular face, strabismus and microcephaly. To some extent, the manifestations of IHPRF2 mimic those of Angelman syndrome (AS)-like syndromes. Copyright © 2018 Elsevier B.V. All rights reserved.

Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep.

PubMed

Manikkam, Mohan; Crespi, Erica J; Doop, Douglas D; Herkimer, Carol; Lee, James S; Yu, Sunkyung; Brown, Morton B; Foster, Douglas L; Padmanabhan, Vasantha

2004-02-01

Alterations in the maternal endocrine, nutritional, and metabolic environment disrupt the developmental trajectory of the fetus, leading to adult diseases. Female offspring of rats, subhuman primates, and sheep treated prenatally with testosterone (T) develop reproductive/metabolic defects during adult life similar to those that occur after intrauterine growth retardation. In the present study we determined whether prenatal T treatment produces growth-retarded offspring. Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16; prenatal T, n = 32). Newborn weight and body dimensions were measured the day after birth, and postnatal weight gain was monitored for 4 months in all females and in a subset of males. Consistent with its action, prenatal T treatment produced females and males with greater anogenital distances relative to controls. Prenatal T treatment reduced body weights and heights of newborns from both sexes and chest circumference of females. Prenatally T-treated females, but not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of prenatally T-treated females were elevated in the first month of life, a period when the prenatally T-treated females were not exhibiting catch-up growth. This is suggestive of reduced IGF availability and potential contribution to growth retardation. These findings support the concept that fetal growth retardation and postnatal catch-up growth, early markers of future adult diseases, can also be programmed by prenatal exposure to excess sex steroids.

Intrauterine growth restriction in infants of less than thirty-two weeks' gestation: associated placental pathologic features.

PubMed

Salafia, C M; Minior, V K; Pezzullo, J C; Popek, E J; Rosenkrantz, T S; Vintzileos, A M

1995-10-01

Our purpose was to describe placental lesions associated with normal and abnormal fetal growth in infants delivered for obstetric indications at < 32 weeks' gestation. Maternal and neonatal charts and placental tissues from 420 consecutive nonanomalous live-born singleton infants delivered at < 32 weeks' gestation with accurate gestational dates were retrospectively studied. Excluded were cases with maternal diabetes, chronic hypertension, hydrops fetalis, diagnosed congenital viral infection, and placenta previa, leaving four primary indications for delivery: preeclampsia, preterm labor, premature rupture of membranes, and nonhypertensive abruptio placentae. The presence and severity of placental lesions was scored by a pathologist blinded to clinical data. Birth weight and length percentiles were calculated from published nomograms. Asymmetric intrauterine growth retardation (n = 32) was defined as birth weight < 10th percentile with length > 10th percentile and symmetric intrauterine growth retardation (n = 48) as both weight and length < 10th percentile for gestational age. A "growth restriction index" was developed to express a continuum of growth in both length and weight. Contingency tables, analyses of variance, and multiple regression analysis defined significance as p < 0.05 (with corrections for multiple comparisons). A greater proportion of cases with intrauterine growth retardation had lesions of uteroplacental insufficiency (p < 0.001) or chronic villitis (p < 0.02) than did appropriately grown preterm infants. Cases with asymmetric intrauterine growth retardation tended to have more lesions than did cases with appropriate-for-gestational-age infants. Four multiple regression analyses used the growth restriction index as outcome and the histologic lesion that had significant relationships to fetal growth as independent predictors in univariate analyses. Overall, uteroplacental fibrinoid necrosis, circulating nucleated erythrocytes, avascular terminal villi, and villous infarct were significant independent predictors of fetal growth (adjusted R2 = 0.312). With addition of preeclampsia as a variable, villous fibrosis, avascular villi, infarct, and preeclampsia were independent predictors of fetal growth (adjusted R2 = 0.341). In the 65 preeclampsia cases no histologic lesion was an independent predictor of fetal growth, whereas in the nonpreeclampsia cases, villous fibrosis and avascular villi were independent predictors of fetal growth (adjusted R2 = 0.075). In nonanomalous preterm infants intrauterine growth retardation is most commonly symmetric and is primarily related to the cumulative number and severity of lesions reflecting abnormal uteroplacental or fetoplacental blood flow. The growth restriction index may contribute to the study of the biologic range of fetal growth. The statistical relationship of most placental lesions to intrauterine growth retardation depends on the presence or absence of preeclampsia.

Growth patterns in children with intrauterine growth retardation and their correlation to neurocognitive development.

PubMed

Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Leitner, Yael; Geva, Ronny; Eshel, Rina; Harel, Shaul

2009-07-01

The relationship between somatic growth and neurocognitive outcome was studied in a cohort of 136 children with intrauterine growth retardation. The children were followed up from birth to 9 to 10 years of age by annual measurements of growth parameters, neurodevelopmental evaluations, and IQ. The rate of catch-up for height between 1 and 2 years of age was significantly higher than the catch-up for weight (P < .001). The cognitive outcome at 9 to 10 years correlated with head circumference at all ages. The neurodevelopmental outcome at 9 to 10 years correlated with weight at all ages. Correlation with head circumference was more significant with IQ, while with weight it was stronger with the neurodevelopmental score. Height at 1 year was a significant predictor for IQ and neurodevelopmental outcome at 9 to 10 years. These findings are of distinct importance for prediction of subsequent neurodevelopmental outcome in children with intrauterine growth retardation.

Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.

PubMed Central

Woods, C G; Leversha, M; Rogers, J G

1995-01-01

We report an infant with pre- and postnatal microcephaly and growth retardation, a distinctive face, and developmental delay. The initial diagnosis was of Seckel syndrome. He became pancytopenic at 16 months and died soon after. His bone marrow was of normal cellularity but had a small lymphocyte infiltration. Increased spontaneous chromosome breakage was seen in blood and fibroblasts. Mitomycin C induced chromosome damage was increased and comparable to that seen in Fanconi anaemia. Reports of similar patients are reviewed. This entity of severe intrauterine growth retardation and increased mitomycin C sensitivity is hypothesised to be a distinct chromosome breakage syndrome. Images PMID:7643362

Bisphenol A (BPA) Exposure In Utero Leads to Immunoregulatory Cytokine Dysregulation in the Mouse Mammary Gland: A Potential Mechanism Programming Breast Cancer Risk.

PubMed

Fischer, Catha; Mamillapalli, Ramanaiah; Goetz, Laura G; Jorgenson, Elisa; Ilagan, Ysabel; Taylor, Hugh S

2016-08-01

Bisphenol-A (BPA) is a ubiquitous estrogen-like endocrine disrupting compound (EDC). BPA exposure in utero has been linked to breast cancer and abnormal mammary gland development in mice. The recent rise in incidence of human breast cancer and decreased age of first detection suggests a possible environmental etiology. We hypothesized that developmental programming of carcinogenesis may involve an aberrant immune response. Both innate and adaptive immunity play a role in tumor suppression through cytolytic CD8, NK, and Th1 T-cells. We hypothesized that BPA exposure in utero would lead to dysregulation of both innate and adaptive immunity in the mammary gland. CD1 mice were exposed to BPA in utero during gestation (days 9-21) via osmotic minipump. At 6 weeks, the female offspring were ovariectomized and estradiol was given at 8 weeks. RNA and protein were extracted from the posterior mammary glands, and the mRNA and protein levels were measured by PCR array, qRT-PCR, and western blot. In mouse mammary tissue, BPA exposure in utero significantly decreased the expression of members of the chemokine CXC family (Cxcl2, Cxcl4, Cxcl14, and Ccl20), interleukin 1 (Il1) gene family (Il1β and Il1rn), interleukin 2 gene family (Il7 receptor), and interferon gene family (interferon regulatory factor 9 (Irf9), as well as immune response gene 1 (Irg1). Additionally, BPA exposure in utero decreased Esr1 receptor gene expression and increased Esr2 receptor gene expression. In utero exposure of BPA resulted in significant changes to inflammatory modulators within mammary tissue. We suggest that dysregulation of inflammatory cytokines, both pro-inflammatory and anti-inflammatory, leads to a microenvironment that may promote disordered cell growth through inhibition of the immune response that targets cancer cells.

Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

PubMed

Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

2006-12-01

Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P < .01). In addition, alpha-phenyl-N-t-butylnitrone significantly reversed lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation. However, aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, had little effect. Furthermore, lipopolysaccharide-induced intrauterine fetal death, intrauterine fetal growth restriction, and skeletal development retardation were associated with lipid peroxidation and glutathione depletion in maternal liver, placenta, and fetal liver. Alpha-phenyl-N-t-butylnitrone significantly attenuated lipopolysaccharide-induced lipid peroxidation and glutathione depletion in maternal liver, placenta, and fetal liver. Maternal lipopolysaccharide exposure at late gestational stages results in intrauterine fetal growth restriction and skeletal development retardation in mice. Reactive oxygen species might be, at least in part, involved in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation.

Exposure to electromagnetic fields during pregnancy with emphasis on electrically heated beds: association with birthweight and intrauterine growth retardation.

PubMed

Bracken, M B; Belanger, K; Hellenbrand, K; Dlugosz, L; Holford, T R; McSharry, J E; Addesso, K; Leaderer, B

1995-05-01

Several animal and human studies indicate that fetal growth may be retarded following exposure to electromagnetic fields (EMF). We conducted a prospective study (N = 2,967) to evaluate the relation of birthweight and fetal growth retardation with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. A "nested" study design allowed monitoring of exposure at different stages of pregnancy using both direct and indirect methods. We assessed EMF exposure using personal monitors, home measurement, video display terminal use, and wire code. Exposure to EMF during pregnancy, either at conception, at < or = 16 weeks, or in the third trimester, showed no important relation to risk of low birth-weight or fetal growth retardation. This result was the same whether we used subjective measures of exposure or direct measurement. Use of video display terminals at home or work, exposure to > or = 2.0-milligauss fields as measured by home or personal monitors, and home wire code were unrelated to the reproductive outcomes studied. A time-weighted analysis of electric bed use, which accounted for strength of EMF exposure and hours of use, also showed evidence of no meaningful increase in risk. None of the exposure measures showed a dose response relation to risk. We conclude that risk of low birth-weight and intrauterine growth retardation is not increased after electrically heated bed use during pregnancy.

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice.

PubMed

Wang, Yongan; Yang, Qing; Liu, Wei; Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu

2016-09-15

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

PubMed

Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

2015-04-01

Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

Psychomotor retardation in a girl with complete growth hormone deficiency.

PubMed

Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

2013-01-01

Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

PubMed

Gibb, Diana M; Kizito, Hilda; Russell, Elizabeth C; Chidziva, Ennie; Zalwango, Eva; Nalumenya, Ruth; Spyer, Moira; Tumukunde, Dinah; Nathoo, Kusum; Munderi, Paula; Kyomugisha, Hope; Hakim, James; Grosskurth, Heiner; Gilks, Charles F; Walker, A Sarah; Musoke, Phillipa

2012-01-01

Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens. Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children. www.controlled-trials.com ISRCTN13968779

Experimental intrauterine growth retardation.

PubMed

van Marthens, E; Harel, S; Zamenshof, S

1975-01-01

The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.

Fetal Onset of Aberrant Gene Expression Relevant to Pulmonary Carcinogenesis in Lung Adenocarcinoma Development Induced by In Utero Arsenic Exposure

PubMed Central

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A.; Waalkes, Michael P.

2009-01-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-α (ER-α) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-β-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. in utero arsenic exposure also induced overexpression of α-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-α expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-α expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-α activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. PMID:17077188

Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

PubMed

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A; Waalkes, Michael P

2007-02-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

Genetic and epigenetic insights into fetal alcohol spectrum disorders

PubMed Central

2010-01-01

The magnitude of the detrimental effects following in utero alcohol exposure, including fetal alcohol syndrome and other fetal alcohol spectrum disorders (FASD), is globally underestimated. The effects include irreversible cognitive and behavioral disabilities as a result of abnormal brain development, pre- and postnatal growth retardation and facial dysmorphism. Parental alcohol exposure and its effect on offspring has been recognized for centuries, but only recently have we begun to gain molecular insight into the mechanisms involved in alcohol teratogenesis. Genetic attributes (susceptibility and protective alleles) of the mother and the fetus contribute to the risk of developing FASD and specific additional environmental conditions, including malnutrition, have an important role. The severity of FASD depends on the level of alcohol exposure, the developmental stage at which exposure occurs and the nature of the exposure (chronic or acute), and although the most vulnerable period is during the first trimester, damage can occur throughout gestation. Preconception alcohol exposure can also have a detrimental effect on the offspring. Several developmental pathways are affected in FASD, including nervous system development, growth and remodeling of tissues, as well as metabolic pathways that regulate glucocorticoid signaling and balanced levels of retinol, insulin and nitric oxide. A body of knowledge has accumulated to support the role of environmentally induced epigenetic remodeling during gametogenesis and after conception as a key mechanism for the teratogenic effects of FASD that persist into adulthood. Transgenerational effects are likely to contribute to the global burden of alcohol-related disease. FASD results in lifelong disability and preventative programs should include both maternal alcohol abstention and preconception alcohol avoidance. PMID:20423530

Chemistry and toxicity of flame retardants for plastics.

PubMed Central

Liepins, R; Pearce, E M

1976-01-01

An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products. PMID:1026419

Counting the stunted children in a population: a criticism of old and new approaches and a conciliatory proposal.

PubMed

Monteiro, C A

1991-01-01

Two methods for estimating the prevalence of growth retardation in a population are evaluated: the classical method, which is based on the proportion of children whose height is more than 2 standard deviations below the expected mean of a reference population; and a new method recently proposed by Mora, which is based on the whole height distribution of observed and reference populations. Application of the classical method to several simulated populations leads to the conclusion that in most situations in developing countries the prevalence of growth retardation is grossly underestimated, and reflects only the presence of severe growth deficits. A second constraint with this method is a marked reduction of the relative differentials between more and less exposed strata. Application of Mora's method to the same simulated populations reduced but did not eliminate these constraints. A novel method for estimating the prevalence of growth retardation, which is based also on the whole height distribution of observed and reference populations, is also described and evaluated. This method produces better estimates of the true prevalence of growth retardation with no reduction in relative differentials.

Abscinazole-F1, a conformationally restricted analogue of the plant growth retardant uniconazole and an inhibitor of ABA 8'-hydroxylase CYP707A with no growth-retardant effect.

PubMed

Todoroki, Yasushi; Kobayashi, Kyotaro; Shirakura, Minaho; Aoyama, Hikaru; Takatori, Kokichi; Nimitkeatkai, Hataitip; Jin, Mei-Hong; Hiramatsu, Saori; Ueno, Kotomi; Kondo, Satoru; Mizutani, Masaharu; Hirai, Nobuhiro

2009-09-15

To develop a specific inhibitor of abscisic acid (ABA) 8'-hydroxylase, a key enzyme in the catabolism of ABA, a plant hormone involved in stress tolerance, seed dormancy, and other various physiological events, we designed and synthesized conformationally restricted analogues of uniconazole (UNI), a well-known plant growth retardant, which inhibits a biosynthetic enzyme (ent-kaurene oxidase) of gibberellin as well as ABA 8'-hydroxylase. Although most of these analogues were less effective than UNI in inhibition of ABA 8'-hydroxylase and rice seedling growth, we found that a lactol-bridged analogue with an imidazole is a potent inhibitor of ABA 8'-hydroxylase but not of plant growth. This compound, abscinazole-F1, induced drought tolerance in apple seedlings upon spray treatment with a 10 microM solution.

Public health implications of components of plastics manufacture. Flame retardants.

PubMed Central

Pearce, E M; Liepins, R

1975-01-01

The four processes involved in the flammability of materials are described and related to the various flame retardance mechanisms that may operate. Following this the four practical approaches used in improving flame retardance of materials are described. Each approach is illustrated with a number of typical examples of flame retardants or synthetic procedures used. This overview of flammability, flame retardance, and flame retardants used is followed by a more detailed examination of most of the plastics manufactured in the United States during 1973, their consumption patterns, and the primary types of flame retardants used in the flame retardance of the most used plastics. The main types of flame retardants are illustrated with a number of typical commercial examples. Statistical data on flame retardant market size, flame retardant growth in plastics, and price ranges of common flame retardants are presented. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. PMID:1175568

Growth failure, somatomedin and growth hormone levels in juvenile diabetes mellitus--a pilot study.

PubMed

Nash, H

1979-06-01

Growth hormone (hGH) responsiveness to exercise and somatomedin C (SmC) activity were measured in ten children with insulin-deficient diabetes mellitus. Four of the ten children showed a significant degree of growth retardation. Normal SmC activity was found in association with elevated hGH levels. The hypothesis that growth-retarded diabetics have a failure of Sm production despite high hGH levels (analogous to malnutrition and Laron dwarfism) was not substantiated by this study. Chronic deficiency of insulin, itself a somatomedin, may play a major role in diabetic growth failure.

Nutrition and Mental Retardation. An Annotated Bibliography, 1964-1970.

ERIC Educational Resources Information Center

Springer, Ninfa Saturnino

This annotated bibliography is primarily organized for nutritionists. It presents selected articles published from 1964 to the present. All aspects of nutrition in mental retardation are covered excepting inborn errors of metabolism. Sections are included on: (1) nutrition, birthweight, and mental retardation; (2) nutrition, growth, and mental…

Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Yu; Cao, Hong; Cu, Fenglong

Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotinemore » exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.« less

Postnatal Prevention of Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now?

PubMed Central

Dugas, Camille; Perron, Julie; Kearney, Michèle; Mercier, Roxanne; Tchernof, André; Marc, Isabelle; Weisnagel, S. John; Robitaille, Julie

2017-01-01

Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing many health problems such as obesity. There is an urgent need to find new strategies to prevent obesity development among high-risk populations such as those children. Accordingly, the aim of this review was to summarize current knowledge on the postnatal prevention of childhood obesity in offspring born from mothers with GDM. Specifically, this review addresses the impact of breastfeeding, complementary feeding practices as well as dietary intake and physical activity during childhood on obesity risk of children exposed to GDM in utero. Furthermore, breast milk composition of diabetic mothers and its potential impact on growth is discussed. According to the available literature, breastfeeding may reduce obesity risk in children exposed to GDM in utero but a longer duration seems necessary to achieve its protective effect against obesity. Detailed analysis of breast milk composition of mothers with GDM will be necessary to fully understand the relationship between breastfeeding and obesity in this specific population. This review highlights the need for more studies addressing the impact of complementary feeding practices and lifestyle habits during childhood on obesity risk of children exposed to GDM in utero. PMID:28848122

Postnatal Prevention of Childhood Obesity in Offspring Prenatally Exposed to Gestational Diabetes mellitus: Where Are We Now?

PubMed

Dugas, Camille; Perron, Julie; Kearney, Michèle; Mercier, Roxanne; Tchernof, André; Marc, Isabelle; Weisnagel, S John; Robitaille, Julie

2017-01-01

Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing many health problems such as obesity. There is an urgent need to find new strategies to prevent obesity development among high-risk populations such as those children. Accordingly, the aim of this review was to summarize current knowledge on the postnatal prevention of childhood obesity in offspring born from mothers with GDM. Specifically, this review addresses the impact of breastfeeding, complementary feeding practices as well as dietary intake and physical activity during childhood on obesity risk of children exposed to GDM in utero. Furthermore, breast milk composition of diabetic mothers and its potential impact on growth is discussed. According to the available literature, breastfeeding may reduce obesity risk in children exposed to GDM in utero but a longer duration seems necessary to achieve its protective effect against obesity. Detailed analysis of breast milk composition of mothers with GDM will be necessary to fully understand the relationship between breastfeeding and obesity in this specific population. This review highlights the need for more studies addressing the impact of complementary feeding practices and lifestyle habits during childhood on obesity risk of children exposed to GDM in utero. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Overload retardation due to plasticity-induced crack closure

NASA Technical Reports Server (NTRS)

Fleck, N. A.; Shercliff, H. R.

1989-01-01

Experiments are reported which show that plasticity-induced crack closure can account for crack growth retardation following an overload. The finite element method is used to provide evidence which supports the experimental observations of crack closure. Finally, a simple model is presented which predicts with limited success the retardation transient following an overload.

Facilitative Effects of Forgetting from Short-Term Memory on Growth of Long-Term Memory in Retardates

ERIC Educational Resources Information Center

Sperber, Richard D.

1976-01-01

Competing explanations of the beneficial effect of spacing in retardate discrimination learning were tested. Results are inconsistent with consolidation and rehearsal theories but support the prediction of the Geber, Greenfield, and House spacing model that forgetting from short-term memory facilities retardate learning. (Author/SB)

Toxicity of water and sediment from stormwater retarding basins to Hydra hexactinella.

PubMed

Rosenkrantz, Rikke T; Pollino, Carmel A; Nugegoda, Dayanthi; Baun, Anders

2008-12-01

Hydra hexactinella was used to assess the toxicity of stormwater and sediment samples from three retarding basins in Melbourne, Australia, using an acute test, a sublethal test, and a pulse test. Stormwater from the Avoca St retarding basins resulted in a LC50 of 613 ml/L, NOEC and LOEC values of 50 ml/L and 100 ml/L, while the 7h pulse exposure caused a significant increase in the mean population growth rate compared to the control. Water samples from the two other retarding basins were found non-toxic to H. hexactinella. This is the first study to employ sediment tests with Hydra spp. on stormwater sediments and a lower population growth rate was observed for organisms exposed to sediment from the Avoca St retarding basins. The behavioral study showed that H. hexactinella tended to avoid the sediment-water interface when exposed to sediment from all retarding basins, compared to the reference sediment. Further work is needed to determine the long-term effects of stormwater polluted sediments and acute effects due to organism exposure to short-term high concentrations during rain events.

Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.

PubMed Central

Ray, P; Tang, W; Wang, P; Homer, R; Kuhn, C; Flavell, R A; Elias, J A

1997-01-01

Standard overexpression transgenic approaches are limited in their ability to model waxing and waning diseases and frequently superimpose development-dependent and -independent phenotypic manifestations. We used the clara cell 10-kD protein (CC10) promoter and the reverse tetracycline transactivator (rtTA) to create a lung-specific, externally regulatable, overexpression transgenic system and used this system to express human interleukin 11 (IL-11) in respiratory structures. Gene induction could be achieved in utero, in neonates and in adult animals. Moreover, gene expression could be turned off by removal of the inducing stimulus. When gene activation was initiated in utero and continued into adulthood, subepithelial airway fibrosis, peribronchiolar mononuclear nodules, and alveolar enlargement (emphysema) were noted. Induction in the mature lung caused airway remodeling and peribronchiolar nodules, but alveolar enlargement was not appreciated. In contrast, induction in utero and during the first 14 d of life caused alveolar enlargement without airway remodeling or peribronchiolar nodules. Thus, IL-11 overexpression causes abnormalities that are dependent (large alveoli) and independent (airway remodeling, peribronchiolar nodules) of lung growth and development, and the CC10-rtTA system can be used to differentiate among these effector functions. The CC10-rtTA transgenic system can be used to model waxing and waning, childhood and growth and development-related biologic processes with enhanced fidelity. PMID:9366564

Genetic selection of embryos that later develop the metabolic syndrome.

PubMed

Edwards, M J

2012-05-01

THE BARKER HYPOTHESIS: Is an excellent explanation of the process where human and animal foetuses exposed to malnutrition, either by maternal malnutrition or placental insufficiency, are metabolically programmed, with selective stunting of cell differentiation and organ growth. With the postnatal excess of nutrition observed in developed countries, this irreversible programming causes metabolic syndrome, including obesity, type 2 diabetes, and hypertension. Metabolic programming involves epigenetic changes including imprinting which might be transmitted through more than one generation rather than being completely re-set or erased during reproduction. The Barker hypothesis was supported by epidemiological data that recognised no excess fetal or postnatal mortality when pregnant women were starved during the Dutch famine in World War II. This argued against the "thrifty genotype" theory introduced in 1962, which proposed that starvation selected against members of the population with less "thrifty" genes, but the survivors who had "thrifty" genes developed metabolic syndrome if they were subsequently over-nourished. EMBRYONIC/FETAL SELECTION: Embryos or early foetuses could be selected very early in pregnancy on the basis of their genotype, by maternal malnutrition, hypertension, obesity or other causes of placental insufficiency. The genotype that allows embryos, or cells within them, to survive a less hospitable environment in the decidua after implantation might contribute to the later development of metabolic syndrome. This article hypothesises that an adverse intrauterine environment, caused by maternal malnutrition or placental insufficiency, kills a proportion of embryos and selects a surviving population of early embryos whose growth in utero is retarded by their genotype, their environment or a combination of both. The metabolic syndrome follows if the offspring is over-nourished later in life. The embryonic selection hypothesis presented here could be tested by using single nucleotide polymorphism (SNP) microarrays to study adults who had a history of intrauterine growth retardation (IUGR) and subsequent metabolic syndrome. Their SNP array could be compared with their parents and unaffected unrelated or related controls. If there were no selection based on a "thrifty genotype", all parental sequences would be expected to appear in their surviving children, whether or not they had IUGR or developed metabolic syndrome. SNP sequences present in parents or controls but missing from adult offspring with metabolic syndrome who had IUGR, could be associated with or linked to genes that influence susceptibility to metabolic syndrome. This hypothesis proposes that missing genotypes would be lost if the embryos that inherited them died very early in pregnancy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Retardation of ice crystallization by short peptides

NASA Astrophysics Data System (ADS)

Kim, Jun Soo; Yethiraj, Arun

2009-03-01

The effect of short peptides on the growth of ice crystals is studied using molecular dynamics simulations. The simulations focus on two sequences (Gly-Pro-Ala-Gly and Gly-Gly-Ala-Gly) that are found in collagen hydrolysate, a substance that is known to retard crystal growth. In the absence of peptides, the growth of ice crystal in the solution with the ice/water interface is observed in at a rate comparable to the experimental data. When peptides are present in the liquid phase, the crystal growth is retarded to a significant extent compared to the pure water. It is found that Gly-Pro-Ala-Gly is more effective (crystallization is up to 5 times slower than in its absence) than Gly-Gly-Ala-Gly (up to 3 times slower) implying that the role of the proline residue is important. The mechanism can be understood in the nature of binding of the peptides to the growing crystal.

Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome.

PubMed

Kramer, M S; Olivier, M; McLean, F H; Willis, D M; Usher, R H

1990-11-01

Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Plant growth retardation and conserved miRNAs are correlated to Hibiscus chlorotic ringspot virus infection.

PubMed

Gao, Ruimin; Wan, Zi Yi; Wong, Sek-Man

2013-01-01

Virus infection may cause a multiplicity of symptoms in their host including discoloration, distortion and growth retardation. Hibiscus chlorotic ringspot virus (HCRSV) infection was studied using kenaf (Hibiscus cannabinus L.), a non-wood fiber-producing crop in this study. Infection by HCRSV reduced the fiber yield and concomitant economic value of kenaf. We investigated kenaf growth retardation and fluctuations of four selected miRNAs after HCRSV infection. Vegetative growth (including plant height, leaf size and root development) was severely retarded. From the transverse and radial sections of the mock and HCRSV-infected kenaf stem, the vascular bundles of HCRSV-infected plants were severely disrupted. In addition, four conserved plant developmental and defence related microRNAs (miRNAs) (miR165, miR167, miR168 and miR171) and their respective target genes phabulosa (PHB), auxin response factor 8 (ARF8), argonaute 1 (AGO1) and scarecrow-like protein 1 (SCL1) displayed variation in expression levels after HCRSV infection. Compared with the mock inoculated kenaf plants, miR171 and miR168 and their targets SCL1 and AGO1 showed greater fluctuations after HCRSV infection. As HCRSV upregulates plant SO transcript in kenaf and upregulated AGO1 in HCRSV-infected plants, the expression level of AGO1 transcript was further investigated under sulfite oxidase (SO) overexpression or silencing condition. Interestingly, the four selected miRNAs were also up- or down-regulated upon overexpression or silencing of SO. Plant growth retardation and fluctuation of four conserved miRNAs are correlated to HCRSV infection.

Plant Growth Retardation and Conserved miRNAs Are Correlated to Hibiscus Chlorotic Ringspot Virus Infection

PubMed Central

Gao, Ruimin; Wan, Zi Yi; Wong, Sek-Man

2013-01-01

Virus infection may cause a multiplicity of symptoms in their host including discoloration, distortion and growth retardation. Hibiscus chlorotic ringspot virus (HCRSV) infection was studied using kenaf (Hibiscus cannabinus L.), a non-wood fiber-producing crop in this study. Infection by HCRSV reduced the fiber yield and concomitant economic value of kenaf. We investigated kenaf growth retardation and fluctuations of four selected miRNAs after HCRSV infection. Vegetative growth (including plant height, leaf size and root development) was severely retarded. From the transverse and radial sections of the mock and HCRSV-infected kenaf stem, the vascular bundles of HCRSV-infected plants were severely disrupted. In addition, four conserved plant developmental and defence related microRNAs (miRNAs) (miR165, miR167, miR168 and miR171) and their respective target genes phabulosa (PHB), auxin response factor 8 (ARF8), argonaute 1 (AGO1) and scarecrow-like protein 1 (SCL1) displayed variation in expression levels after HCRSV infection. Compared with the mock inoculated kenaf plants, miR171 and miR168 and their targets SCL1 and AGO1 showed greater fluctuations after HCRSV infection. As HCRSV upregulates plant SO transcript in kenaf and upregulated AGO1 in HCRSV-infected plants, the expression level of AGO1 transcript was further investigated under sulfite oxidase (SO) overexpression or silencing condition. Interestingly, the four selected miRNAs were also up- or down-regulated upon overexpression or silencing of SO. Plant growth retardation and fluctuation of four conserved miRNAs are correlated to HCRSV infection. PMID:24386476

Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission.

PubMed

Kumar, Surender B; Rice, Cara E; Milner, Danny A; Ramirez, Nilsa C; Ackerman, William E; Mwapasa, Victor; Turner, Abigail Norris; Kwiek, Jesse J

2012-03-27

To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT). We designed a case-control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum. After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio-Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit. Levels of interleukin (IL) 4, IL-5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP-10) were significantly elevated in placental plasma isolated from cases of in-utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4(+) T-cell count, every log(10) increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT. Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV-replication, was robustly and independently associated with prevalent, in-utero MTCT.

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yongan

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposuremore » levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla follicular atresia potentially leading to precocious puberty.« less

Skeletal demineralization and growth retardation in inflammatory bowel disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genant, H.K.; Mall, J.C.; Wagonfeld, J.B.

1976-01-01

Skeletal growth and mineralization in 54 adolescent and adult patients with inflammatory bowel disease have been analyzed comprehensively. Quantitative and qualitative radiologic techniques consisted of conventional roentgenography, photon absorptiometry, and radiographic morphometry. The data are correlated with the type, duration, and severity of disease, and with several modes of therapy. The results indicate that osteopenia and retardation of growth are common in patients with inflammatory bowel disease, particularly in adolescents, in whom the effects of corticosteroids on the skeleton are most deleterious.

The Kenny-Caffey syndrome: growth retardation and hypocalcemia in a young boy.

PubMed

Lee, W K; Vargas, A; Barnes, J; Root, A W

1983-04-01

A 2-year-old black boy with the Kenny-Caffey syndrome was first evaluated because of growth retardation and hypocalcemia. Hypothalamic-pituitary function was normal. Basal serum somatomedin C levels were normal for age, but did not increase during short-term administration of human growth hormone. Serum immunoreactive parathyroid hormone levels remained inappropriately low during spontaneous and induced hypocalcemia, indicating that hypocalcemia was the consequence of hypoparathyroidism. The manifestations of 15 patients with this syndrome are tabulated.

In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-Exposed Uninfected Children in Brazil

PubMed Central

Hofer, Cristina Barroso; Keiser, Olivia; Zwahlen, Marcel; Lustosa, Carla Sepulveda; CisneFrota, Ana Cristina; de Oliveira, Ricardo Hugo; Abreu, Thalita F; Carvalho, Alice Weber; Araujo, Lucia Evangelista; Egger, Matthias

2015-01-01

Context There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV exposed but uninfected (HEU) children. Objectives To evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first two years of life. Design Cohort study of HEU infants. Setting Tertiary children's hospital in Rio de Janeiro, Brazil. Study population HEU infants born 1996-2010. Main outcome measures Weight measured by mechanical scale, height measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. Results A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared to infants exposed later: adjusted differences were −0.52 (95% CI −0.99 to −0.04, P=0.02) at birth and −0.22 (95% CI −0.47 to 0.04, P=0.10) during follow-up. LAZ were lower during follow-up: −0.35 (95% CI −0.63 to −0.08, P=0.01). There were no differences in WLZ scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. Conclusions In HEU children early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely. PMID:26741583

Preliminary analysis of in utero low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports.

PubMed

Davis, Matthew A; Higgins, John; Li, Zhigang; Gilbert-Diamond, Diane; Baker, Emily R; Das, Amar; Karagas, Margaret R

2015-03-30

Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value < 0.05). Although, associations were attenuated in adjusted analyses - among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: -0.151, 0.007) decrease in biparietal head diameter Z-score. Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation.

Effect of parathyroidectomy on bone growth and composition in the young rat

NASA Technical Reports Server (NTRS)

Keil, L. C.; Prinz, J. A.; Evans, J. W.

1974-01-01

In an effort to determine the influence of the parathyroids on bone growth and composition, 28-day-old male Sprague-Dawley rats were sacrificed 28, 56, and 84 days after parathyroidectomy or sham parathyroidectomy. Body growth as well as femur growth were retarded following parathyroidectomy. Hypocalcemia and hyperphosphatemia occurred in all parathyroidectomized rats; no alterations in plasma magnesium levels were noted. Femur magnesium was increased by 22-30% in the parathyroidectomized rats whereas femur calcium remained unchanged. Bone phosphorus was increased 56 and 84 days following parathyroidectomy. Results of this study indicate that parathyroidectomy retards growth while increasing bone magnesium and phosphorus content.

Improvement in Growth After 1 Year of Growth Hormone Therapy in Well-Nourished Infants with Growth Retardation Secondary to Chronic Renal Failure: Results of a Multicenter, Controlled, Randomized, Open Clinical Trial

PubMed Central

Moreno, M. Llanos; Neto, Arlete; Ariceta, Gema; Vara, Julia; Alonso, Angel; Bueno, Alberto; Afonso, Alberto Caldas; Correia, António Jorge; Muley, Rafael; Barrios, Vicente; Gómez, Carlos; Argente, Jesús

2010-01-01

Background and objectives: Our aim was to evaluate the growth-promoting effect of growth hormone (GH) treatment in infants with chronic renal failure (CRF) and persistent growth retardation despite adequate nutritional and metabolic management. Design, setting, participants, & measurements: The study design included randomized, parallel groups in an open, multicenter trial comparing GH (0.33 mg/kg per wk) with nontreatment with GH during 12 months. Sixteen infants who had growth retardation, were aged 12 ± 3 months, had CRF (GFR ≤60 ml/min per 1.73 m2), and had adequate nutritional intake and good metabolic control were recruited from eight pediatric nephrology departments from Spain and Portugal. Main outcome measures were body length, body weight, bone age, biochemical and hormonal analyses, renal function, bone mass, and adverse effects. Results: Length gain in infants who were treated with GH was statistically greater (P < 0.05) than that of nontreated children (14.5 versus 9.5 cm/yr; SD score 1.43 versus −0.11). The GH-induced stimulation of growth was associated with no undesirable effects on bone maturation, renal failure progression, or metabolic control. In addition, GH treatment improved forearm bone mass and increased serum concentrations of total and free IGF-I and IGF-binding protein 3 (IGFBP-3), whereas IGF-II, IGFBP-1, IGFBP-2, GH-binding protein, ghrelin, and leptin were not modified. Conclusions: Infants with CRF and growth retardation despite good metabolic and nutritional control benefit from GH treatment without adverse effects during 12 months of therapy. PMID:20522533

Placenta: chronicle of intrauterine growth restriction.

PubMed

Dicke, Jeffrey M

2010-09-23

The foundation for adult health is laid in utero and requires a healthy placenta. A common manifestation of abnormal placental development is impaired fetal growth. While placental pathology is the final common denominator in many cases of fetal growth restriction, a variety of discreet lesions have been described involving both the maternal and fetal circulations at their confluence in the placenta. Detailed examination of the placenta provides a means of elucidating the pathophysiology of poor fetal growth. This is an essential step in developing effective strategies for the prediction, prevention, and possible treatment of the growth restricted fetus.

Evaluation of the Reproductive and Developmental Risks of Caffeine

PubMed Central

Brent, Robert L; Christian, Mildred S; Diener, Robert M

2011-01-01

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the “pregnancy signal,” which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 µg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the “caffeine teratogenic syndrome.” Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses. Birth Defects Res (Part B) 92:152–187, 2011. © 2011 Wiley-Liss, Inc. PMID:21370398

Brain heparan sulphate proteoglycans are altered in developing foetus when exposed to in-utero hyperglycaemia.

PubMed

Sandeep, M S; Nandini, C D

2017-08-01

In-utero exposure of foetus to hyperglycaemic condition affects the growth and development of the organism. The brain is one of the first organs that start to develop during embryonic period and glycosaminoglycans (GAGs) and proteoglycans (PGs) are one of the key molecules involved in its development. But studies on the effect of hyperglycaemic conditions on brain GAGs/PGs are few and far between. We, therefore, looked into the changes in brain GAGs and PGs at various developmental stages of pre- and post-natal rats from non-diabetic and diabetic mothers as well as in adult rats induced with diabetes using a diabetogenic agent, Streptozotocin. Increased expression of GAGs especially that of heparan sulphate class in various developmental stages were observed in the brain as a result of in-utero hyperglycaemic condition but not in that of adult rats. Changes in disaccharides of heparan sulphate (HS) were observed in various developmental stages. Furthermore, various HSPGs namely, syndecans-1 and -3 and glypican-1 were overexpressed in offspring from diabetic mother. However, in adult diabetic rats, only glypican-1 was overexpressed. The offsprings from diabetic mothers became hyperphagic at the end of 8 weeks after birth which can have implications in the long run. Our results highlight the likely impact of the in-utero exposure of foetus to hyperglycaemic condition on brain GAGs/PGs compared to diabetic adult rats.

Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

PubMed

Buscariollo, Daniela L; Fang, Xiefan; Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A; Wendler, Christopher C

2014-01-01

Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

Transforming growth factor- 1 C-509T polymorphism, oxidant stress, and early-onset childhood asthma.

PubMed

Salam, Muhammad T; Gauderman, W James; McConnell, Rob; Lin, Pi-Chu; Gilliland, Frank D

2007-12-15

Transforming growth factor (TGF)-beta1 is involved in airway inflammation and remodeling, two key processes in asthma pathogenesis. Tobacco smoke and traffic emissions induce airway inflammation and modulate TGF-beta1 gene expression. We hypothesized that the effects of functional TGF-beta1 variants on asthma occurrence vary by these exposures. We tested these hypotheses among 3,023 children who participated in the Children's Health Study. Tagging single-nucleotide polymorphisms rs4803457 C>T and C-509T (a functional promoter polymorphism) accounted for 94% of the haplotype diversity of the upstream region. Exposure to maternal smoking in utero was based on smoking by biological mother during pregnancy. Residential distance from nearest freeway was calculated based on residential address at study entry. Children with the -509TT genotype had a 1.8-fold increased risk of early persistent asthma (95% confidence interval [CI], 1.11-2.95). This association varied marginally significantly by in utero exposure to maternal smoking. Compared with children with the -509CC/CT genotype with no in utero exposure to maternal smoking, those with the -509TT genotype with such exposure had a 3.4-fold increased risk of early persistent asthma (95% CI, 1.46-7.80; interaction, P = 0.11). The association between TGF-beta1 C-509T and lifetime asthma varied by residential proximity to freeways (interaction P = 0.02). Children with the -509TT genotype living within 500 m of a freeway had over three-fold increased lifetime asthma risk (95% CI, 1.29-7.44) compared with children with CC/CT genotype living > 1500 m from a freeway. Children with the TGF-beta1 -509TT genotype are at increased risk of asthma when they are exposed to maternal smoking in utero or to traffic-related emissions.

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth

PubMed Central

Black, Laurel; Bennfors, Grace; Parsons, Trish E.; Elsalanty, Mohammed E.; Yu, Jack C.; Weinberg, Seth M.; Cray, James J.

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology. PMID:27959899

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

PubMed

Howie, R Nicole; Durham, Emily L; Black, Laurel; Bennfors, Grace; Parsons, Trish E; Elsalanty, Mohammed E; Yu, Jack C; Weinberg, Seth M; Cray, James J

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

PubMed

Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

2013-11-12

Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

USDA-ARS?s Scientific Manuscript database

Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wi...

Improved bone status by the beta-blocker propranolol in an animal model of nutritional growth retardation.

PubMed

Lezón, Christian E; Olivera, María I; Bozzini, Clarisa; Mandalunis, Patricia; Alippi, Rosa M; Boyer, Patricia M

2009-06-01

The aim of the present research was to study if the beta-blocker propranolol, which is known to increase bone mass, could reverse the adverse skeletal effects of mild chronic food restriction in weanling rats. Male Wistar rats were divided into four groups: control, control+propranolol (CP), nutritional growth retardation (NGR) and nutritional growth retardation+propranolol (NGRP). Control and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80 % of the amount of food consumed by the control and CP rats, respectively. Results were expressed as mean values and sem. Food restriction induced detrimental effects on body and femur weight and length (P < 0.05) and bone structural and geometrical properties (P < 0.001), confirming results previously shown in our laboratory. However, the beta-blocker overcame the deleterious effect of nutritional stress on load-bearing capacity, yielding load, bone stiffness, cross-sectional cortical bone area and second moment of inertia of the cross-section in relation to the horizontal axis without affecting anthropometric, histomorphometric and bone morphometric parameters. The results suggest that propranolol administration to mildly chronically undernourished rats markedly attenuates the impaired bone status in this animal model of growth retardation.

Effects of Colonization of the Roots of Domestic Rice (Oryza sativa L. cv. Amaroo) by Burkholderia pseudomallei

PubMed Central

Constantinoiu, Constantin; Gardiner, Christopher; Warner, Jeffrey

2015-01-01

Burkholderia pseudomallei is a saprophytic bacterium that causes melioidosis and is often isolated from rice fields in Southeast Asia, where the infection incidence is high among rice field workers. The aim of this study was to investigate the relationship between this bacterium and rice through growth experiments where the effect of colonization of domestic rice (Oryza sativa L. cv Amaroo) roots by B. pseudomallei could be observed. When B. pseudomallei was exposed to surface-sterilized seeds, the growth of both the root and the aerosphere was retarded compared to that in controls. The organism was found to localize in the root hairs and endodermis of the plant. A biofilm formed around the root and root structures that were colonized. Growth experiments with a wild rice species (Oryza meridionalis) produced similar retardation of growth, while another domestic cultivar (O. sativa L. cv Koshihikari) did not show retarded growth. Here we report B. pseudomallei infection and inhibition of O. sativa L. cv Amaroo, which might provide insights into plant interactions with this important human pathogen. PMID:25911477

Modelling and measurement of crack closure and crack growth following overloads and underloads

NASA Technical Reports Server (NTRS)

Dexter, R. J.; Hudak, S. J.; Davidson, D. L.

1989-01-01

Ignoring crack growth retardation following overloads can result in overly conservative life predictions in structures subjected to variable amplitude fatigue loading. Crack closure is believed to contribute to the crack growth retardation, although the specific closure mechanism is dabatable. The delay period and corresponding crack growth rate transients following overload and overload/underload cycles were systematically measured as a function of load ratio and overload magnitude. These responses are correlated in terms of the local 'driving force' for crack growth, i.e. the effective stress intensity factor range. Experimental results are compared with the predictions of a Dugdale-type (1960) crack closure model, and improvements in the model are suggested.

[Detection of agent "zhuanggenling" and investigation of utilization of plant growth retardants in traditional Chinese medicine cultivation].

PubMed

Zhai, Yu-yao; Guo, Bao-lin; Huang, Wen-hua

2015-02-01

Plant growth retardant as one of plant growth regulator can inhibit the cell division, elongation and growth rate in shoot apical meristem (SAM), which can be reversed by gibberellin regulate the product of photosynthesis transfer to the root and rhizome part. As commonly used plant growth retardant, paclobutrazol, uniconazole, chlorocholine chloride, mepiquat chloride, choline chloride and daminozide are used to promote the growth of root and rhizome, call as "zhuanggenling", "pengdasu", "pengdaji" etc. Single or recombination of plant growth regulator is registered as pesticide, and called as pesticide "zhuanggenling" in this paper. Growth regulator which registered as a foliar fertilizer or fertilization was called agricultural fertilizer "zhuanggenling" in this paper. The author investigate the usage of "zhuanggenling" in the root and rhizome of medicinal plants cultivation from 2012 to 2014 in Sichuan province, Huangyuan town, Mianyang (Ophiopogonis Radix); Pengzhou Aoping town (Chuanxiong Rhizoma); Pengshan Xiejia town (Alismatis Rhizoma); Jiangyou Taiping town and Zhangming town (Aconiti Lateralis Radix Praeparata); Yunnan Wenshan (Notoginseng Radix et Rhizoma); Henan province, Wuzhidafeng Town (Rehmanniae Radix, Achyranthis Bidentatae Radix, Dioscoreae Rhizoma); Gansu Min county (Codonopsis Radix, Angelicae Sinensis Radix); Gansu Li county (Rhei Radix et Rhizoma). The result showed that "zhuanggenling" were applied in the most medicinal plant cultivation except Rhei Radix et Rhizoma. It has been applied widespreadly in Ophiopogonis Radix, Alismatis Rhizoma, Achyranthis Bidentatae Radix, Codonopsis Radix; Rehmanniae Radix, commonly in Angelicae Sinensis Radix application, and occasionally in Chuanxiong Rhizoma, Aconiti Lateralis Radix Praeparata, Notoginseng Radix et Rhizoma and Dioscoreae Rhizoma. In 53 collected sample from plantation areas, fifteen (28%) were pesticide "zhuanggenling", thirty-eight (72%) were pesticide "zhuanggenling". UPLC analysis results showed that 38 farmers fertilizer "zhuanggenling" content of 6 kinds of plant growth retardant. It is regarded that fertilizer "zhuanggenling" was dominant in medicinal plant cultivation, and that the plant growth retardant is added widespreadly in farm fertilizer "zhuanggenling". All evidence proves conclusively that "zhuanggenling" have been used in the proper way, whereas some others have been misused or even abused in the use regarding to type, number, use frequency. The root or rhizoma are increased to 20%-200%. But there is lack of evaluation to appraise the quality of medicinal materials from the aspects of research or industry. "zhuanggenling" has become a important Chemical control material besides fertilizer, insecticidal sterilization of pesticide

Examining triclosan-induced potentiation of the estrogen uterotrophic effect

EPA Science Inventory

Triclosan (TCS), a widely used antibacterial, has been shown to be an endocrine disruptor. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats orally administered 3 μg/kg EE and TCS (2 to 18 mg/kg) in the utero...

Effects of maternal and pre-weaning undernutrition in rat offspring: Age at reproductive senescence and intergenerational pup growth and viability

EPA Science Inventory

Maternal and/or postnatal undernutrition are widespread in human populations and are components of many experimental developmental and reproductive toxicology bio-assays. This study investigated in utero and/or pre-weaning undernutrition effects on reproductive maturation and se...

Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo.

PubMed

Wang, Yanhua; Hao, Hang; Liu, Haoming; Wang, Yifan; Li, Yan; Yang, Gaojie; Ma, Jun; Mao, Chuanbin; Zhang, Shengmin

2015-08-26

Selenite-doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation-mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evolution of Residual-Strain Distribution through an Overload-Induced Retardation Period during Fatigue Crack Growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S. Y.; Sun, Yinan; An, Ke

2010-01-01

Neutron diffraction was employed to investigate the crack-growth retardation phenomenon after a single tensile overload by mapping both one-dimensional and two-dimensional residual-strain distributions around the crack tip in a series of compact-tension specimens representing various crack-growth stages through an overload-induced retardation period. The results clearly show a large compressive residual-strain field near the crack tip immediately after the overload. As the fatigue crack propagates through the overload-induced plastic zone, the compressive residual strains are gradually relaxed, and a new compressive residual-strain field is developed around the propagating crack tip, illustrating that the subsequent fatigue-induced plastic zone grows out of themore » large plastic zone caused by the overloading. The relationship between the overload-induced plastic zone and subsequent fatigue-induced plastic zone, and its influence on the residual-strain distributions in the perturbed plastic zone are discussed.« less

Growth, Hypothalamic Function, and Brain Ventricle Size in Mentally Retarded Subjects

ERIC Educational Resources Information Center

Leisti, S.; Iianainen, M.

1978-01-01

To determine whether moderate enlargement of the third brain ventricle or the temporal horns of the lateral ventricles was associated with hypothalamic dysfunction, 15 mentally retarded Ss (ages 12-25 years) with such characteristics were studies. (DLS)

Growth hormone in intra-uterine growth retarded newborns.

PubMed

Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Latha

2007-11-01

To study growth hormone levels in IUGR and healthy controls and its association with birth weight and ponderal index. We studied 50 Intra uterine growth retarded (IUGR) and 50 healthy newborns born at term by vaginal delivery in JIPMER, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of growth hormone. When compared with healthy newborns, IUGR newborns had higher growth hormone levels (mean +/- SD, 23.5 +/- 15.6 vs 16.2 +/- 7.61 ngm/ml, P = 0.019). A negative correlation was identified between growth hormone levels and birth weight (r2 = - 0.22, P = 0.03) and ponderal index (r2 = - 0.36, P = 0.008). Correlation of growth hormone levels was much more confident with ponderal index than with birth weight. At birth IUGR infants display increased growth hormone levels which correlate with ponderal index much more confidently than with birth weight.

Delayed growth

MedlinePlus

Growth - slow (child 0 - 5 years); Weight gain - slow (child 0 - 5 years); Slow rate of growth; Retarded growth and development; ... A child should have regular, well-baby check-ups with a health care provider. These checkups are usually scheduled ...

[DENTAL STATUS OF PATIENTS WITH INTRAUTERINE GROWTH RESTRICTION IN PAST HISTORY DURING PERIOD OF REMOVABLE AND PERMANENT DENTITION].

PubMed

Garmash, O V; Ryabokon, E N

2014-12-01

The analysis of the dental status in patients with IUGR in past history in period of removable and permanent dentition was conducted. 39 patients with intrauterine growth retardation in past history were examined. The clinical, statistical methods were held. Concluded that the child, who was born with IUGR, later in future life, has a great risk of dental diseases. The most considerable violations were found in patients with "symmetrical" form of intrauterine growth retardation. It is proposed to use clinical markers as possible predictors of periodontal diseases.

Paternally Expressed, Imprinted Insulin-Like Growth Factor-2 in Chorionic Villi Correlates Significantly with Birth Weight

PubMed Central

Demetriou, Charalambos; Abu-Amero, Sayeda; Thomas, Anna C.; Ishida, Miho; Aggarwal, Reena; Al-Olabi, Lara; Leon, Lydia J.; Stafford, Jaime L.; Syngelaki, Argyro; Peebles, Donald; Nicolaides, Kypros H.; Regan, Lesley; Stanier, Philip; Moore, Gudrun E.

2014-01-01

Context Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. Objective The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Design Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11–13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Results Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3·6×10−7). Interpretation Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth. PMID:24454871

[Anemia in public school first graders in the city of Maceió, Alagoas, Brazil].

PubMed

Santos, Célia Dias dos; Santos, Leonor Maria Pacheco; Figueiroa, José Natal; Marroquim, Pajuçara Maria Guimarães; Oliveira, Maria Alice Araújo

2002-01-01

A cross-sectional study was conducted in a representative sample of 426 randomly selected first graders (ages 6 to 10 years) from public schools in Maceió, State of Alagoas, Brazil. The aim was to determine the prevalence of anemia, as well as its association with growth retardation. Data were collected from May to July 2000, and determination of hemoglobin (HGB) employed an STKS Coulter counter. Two cut-off points were used to classify anemia, both established by the World Health Organization: HGB < 11.5g/dl and HGB < 12.0g/dl. The indicators height/age (H/A), weight/age (W/A), and weight/height (W/H) below -2.0 standard deviations from the NCHS reference were diagnosed as growth retardation. Prevalence of anemia was 9.9% when HGB < 11.5g/dl was used, and 25.4% when the cut-off point was HGB < 12.0g/dl. Growth retardation was detected in 6.2% of children according to H/A, 4.0% for W/A, and 3.0% for W/H. There was no statistically significant association between the variables in the study. These findings confirm results of previous surveys where prevalence of anemia was much higher than that of growth retardation. The severe consequences of anemia in this age group justify the implementation of broad public policies to overcome this nutritional deficiency.

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice.

PubMed

Rozhdestvensky, Timofey S; Robeck, Thomas; Galiveti, Chenna R; Raabe, Carsten A; Seeger, Birte; Wolters, Anna; Gubar, Leonid V; Brosius, Jürgen; Skryabin, Boris V

2016-02-05

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5'HPRT-LoxP-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p-/m5'LoxP)), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p-/m5'LoxP) mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases.

Circulatory Responses to Asphyxia Differ if the Asphyxia Occurs In Utero or Ex Utero in Near-Term Lambs

PubMed Central

Sobotka, Kristina S.; Morley, Colin; Ong, Tracey; Polglase, Graeme R.; Aridas, James D. S.; Miller, Suzanne L.; Schmölzer, Georg M.; Klingenberg, Claus; Moss, Timothy J. M.; Jenkin, Graham; Hooper, Stuart B.

2014-01-01

Background A cornerstone of neonatal resuscitation teaching suggests that a rapid vagal-mediated bradycardia is one of the first signs of perinatal compromise. As this understanding is based primarily on fetal studies, we investigated whether the heart rate and blood pressure response to total asphyxia is influenced by whether the animal is in utero or ex utero. Methods Fetal sheep were instrumented at ∼139 days of gestation and then asphyxiated by umbilical cord occlusion until mean arterial blood pressure decreased to ∼20 mmHg. Lambs were either completely submerged in amniotic fluid (in utero; n = 8) throughout the asphyxia or were delivered and then remained ex utero (ex utero; n = 8) throughout the asphyxia. Heart rate and arterial blood pressure were continuously recorded. Results Heart rate was higher in ex utero lambs than in utero lambs. Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero lambs initially increased following cord occlusion (for ∼1.5 min) before they started to decrease. Mean arterial pressure initially increased then decreased in both groups. Conclusions Heart rate response to asphyxia was markedly different depending upon whether the lamb was in utero or ex utero. This indicates that the cardiovascular responses to perinatal asphyxia are significantly influenced by the newborn's local environment. As such, based solely on heart rate, the stage and severity of a perinatal asphyxic event may not be as accurate as previously assumed. PMID:25393411

Circulatory responses to asphyxia differ if the asphyxia occurs in utero or ex utero in near-term lambs.

PubMed

Sobotka, Kristina S; Morley, Colin; Ong, Tracey; Polglase, Graeme R; Aridas, James D S; Miller, Suzanne L; Schmölzer, Georg M; Klingenberg, Claus; Moss, Timothy J M; Jenkin, Graham; Hooper, Stuart B

2014-01-01

A cornerstone of neonatal resuscitation teaching suggests that a rapid vagal-mediated bradycardia is one of the first signs of perinatal compromise. As this understanding is based primarily on fetal studies, we investigated whether the heart rate and blood pressure response to total asphyxia is influenced by whether the animal is in utero or ex utero. Fetal sheep were instrumented at ∼ 139 days of gestation and then asphyxiated by umbilical cord occlusion until mean arterial blood pressure decreased to ∼ 20 mmHg. Lambs were either completely submerged in amniotic fluid (in utero; n = 8) throughout the asphyxia or were delivered and then remained ex utero (ex utero; n = 8) throughout the asphyxia. Heart rate and arterial blood pressure were continuously recorded. Heart rate was higher in ex utero lambs than in utero lambs. Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero lambs initially increased following cord occlusion (for ∼ 1.5 min) before they started to decrease. Mean arterial pressure initially increased then decreased in both groups. Heart rate response to asphyxia was markedly different depending upon whether the lamb was in utero or ex utero. This indicates that the cardiovascular responses to perinatal asphyxia are significantly influenced by the newborn's local environment. As such, based solely on heart rate, the stage and severity of a perinatal asphyxic event may not be as accurate as previously assumed.

Unbalanced translocation 6p/16q (partial monosomy 6p and trisomy 16q): prenatal diagnosis and cytogenetics.

PubMed

Puhl, Alexander G; Zelazny, Julia; Galetzka, Danuta; Skala, Christine; Frey-Mahn, Gabriele; Wellek, Brigitte; Koelbl, Heinz

2010-06-01

Unbalanced translocation 6p/16q in one fetus is a very rare event and the prenatal sonographic findings have never been published before. We will give a short overview of the literature along with a case report focussing on prenatal ultrasound features and molecular cytogenetic analysis. A 21-year-old primigravid woman presented with a singleton pregnancy at 19 weeks' gestation. The fetus revealed a mild hydrocephalus, a ventricular septal defect (VSD), a Dandy-Walker malformation as well as an intrauterine growth retardation (IUGR) and limb anomalities. MLPA analysis from amniotic fluid cells showed an unbalanced translocation from the subtelomeric region of chromosome 6p to the subtelomeric region of chromosome 16q. Karyotype of the fetus was 46, XX.ishder(6)t(6;16)(p2?5;q?13)(pVYS246A+, pVYS228B-, pVYS229A+). Despite the karyotype the mother decided not to interrupt pregnancy. The fetus died in utero within the 39th week of gestation and was delivered vaginally after labour induction, with a birth weight of 1815g. Prenatal FISH and MLPA studies can be very important to help outline the chromosomal area of deletion and duplication and the sonographic findings forebode the cytogenetic region of interest. Subsequent to the processing of the case, a complete Medline search was conducted to review previous cases with similar genetic alterations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

The effects of own fetal growth on reported hypertension in parous women aged 33.

PubMed

Hennessy, E; Alberman, E

1997-06-01

Data from the study of the British 1958 birth cohort, National Child Development Study (NCDS), has allowed wider investigation of the relationship between retarded fetal growth and risk of adult hypertension. A history of self-reported hypertension was related to fetal growth in 3308 parous cohort members. Fetal growth, the measure used, is the difference in actual birthweight from that expected for the gestational age and subsequent adult height. The relationships were investigated both linearly and non-linearly adjusting for potential confounders. After adjustment for confounding factors, including adult weight for height, retarded fetal growth was associated with reported hypertension particularly when not confined to pregnancy. The latter was also associated with accelerated fetal growth, moderate or severe hypertension in the mother when pregnant with the cohort member, being relatively taller than your mother, and lack of educational qualifications. Hypertension confined to pregnancy was more likely among women who were themselves firstborn or older at childbirth. Neither maternal smoking during cohort's gestation nor cohort member's gestational age had a significant effect. The results are consistent with previous reports that fetal growth effects are less marked if gestation is short. The relationships between fetal growth and subsequent hypertension are extremely complex and variable, and need to be studied allowing for deviations from growth potential. Adult weight for height remains the strongest predictor of hypertension. The results suggest that losing weight is likely to have the same proportional benefit in women with and without a history of retarded fetal growth.

DNA Damage as a Driver for Growth Delay: Chromosome Instability Syndromes with Intrauterine Growth Retardation

PubMed Central

Hernández-Gómez, Mariana

2017-01-01

DNA is constantly exposed to endogenous and exogenous mutagenic stimuli that are capable of producing diverse lesions. In order to protect the integrity of the genetic material, a wide array of DNA repair systems that can target each specific lesion has evolved. Despite the availability of several repair pathways, a common general program known as the DNA damage response (DDR) is stimulated to promote lesion detection, signaling, and repair in order to maintain genetic integrity. The genes that participate in these pathways are subject to mutation; a loss in their function would result in impaired DNA repair and genomic instability. When the DDR is constitutionally altered, every cell of the organism, starting from development, will show DNA damage and subsequent genomic instability. The cellular response to this is either uncontrolled proliferation and cell cycle deregulation that ensues overgrowth, or apoptosis and senescence that result in tissue hypoplasia. These diverging growth abnormalities can clinically translate as cancer or growth retardation; both features can be found in chromosome instability syndromes (CIS). The analysis of the clinical, cellular, and molecular phenotypes of CIS with intrauterine growth retardation allows inferring that replication alteration is their unifying feature. PMID:29238724

Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

PubMed

Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

2015-01-01

Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

Progression of Prostate Carcinogenesis and Dietary Methyl Donors: Temporal Dependence

PubMed Central

Shabbeer, Shabana; Williams, Simon A.; Simons, Brian W.; Herman, James G.; Carducci, Michael A.

2011-01-01

Insufficient dose of dietary methyl groups are associated with a host of conditions ranging from neural tube defects to cancer. On the other hand, it is not certain what effect excess dietary methyl groups could have on cancer. This is especially true for prostate cancer (PCa), a disease that is characterized by increasing DNA methylation changes with increasing grade of the cancer. In this three-part study in animals, we look at (i) the effect of excess methyl donors on the growth rate of PCa in vivo, (ii) the ability of 5-aza-2'-deoxycytidine, a demethylating agent, to demethylate in the presence of excess dietary methyl donors and (iii) the effect of in utero feeding of excess methyl donors to the later onset of PCa. The results show that when mice are fed a dietary excess of methyl donors, we do not see (i) an increase in the growth rate of DU-145 and PC-3 xenografts in vivo, or (ii) interference in the ability of 5-aza-2'-deoxycytidine to demethylate the promoters of Androgen Receptor or Reprimo of PCa xenografts but (iii) a protective effect on the development of higher grades of PCa in the “Hi-myc” mouse model of PCa which were fed the increased methyl donors in utero. We conclude that the impact of dietary methyl donors on PCa progression depends upon the timing of exposure to the dietary agents. When fed before the onset of cancer, i.e. in utero, excess methyl donors can have a protective effect on the progression of cancer. PMID:22139053

Growth and differentiation of mammalian embryonic tissues exposed to hypergravity in vivo and in vitro

NASA Technical Reports Server (NTRS)

Duke, J.; Janer, L.; Moore, J.

1985-01-01

Decreased cartilage areas in embryonic limbs developing under excess g in vitro, is reported, as well as delayed skeletal development in embryos and fetuses exposed to excess g in utero. 12.5-day mouse limb buds were cultured at 2.6 g, and fixed at two days and six days of culture. In vivo experiments used alizarin-stained 18-day fetuses exposed to 2.3 g. In all studies, cartilage areas were determined using a digitized tablet. Form factor analysis determined that the main effect of in vitro centrifugation was a reduction in length of the limb elements, probably due to the precocious chondrogenesis seen in the upper regions of centrifuged limbs. Similar reductions in length of ossified areas was seen in the in utero studies.

Effects of gestational exposure to PFOA on PPAR protein and mRNA expression in vital organs of fetal and postnatal mice

EPA Science Inventory

Perfluorooctanoic acid (PFOA) is developmentally toxic, causing in utero and neonatal mortality, and altering development and growth in mice. PFOA activates peroxisome proliferator-activated receptor (PPAR)a and PPARa signaling is required for toxicity. This study examines the ex...

Prebiotic effects of bovine lactoferrin on specific probiotic bacteria.

PubMed

Chen, Po-Wen; Liu, Zhen-Shu; Kuo, Tai-Chen; Hsieh, Min-Chi; Li, Zhe-Wei

2017-04-01

Bovine lactoferrin (bLf) is a natural iron-binding protein and it has been suggested to be a prebiotic agent, but this finding remains inconclusive. This study explores the prebiotic potential of bLf in 14 probiotics. Initially, bLf (1-32 mg/mL) treatment showed occasional and slight prebiotic activity in several probiotics only during the late experimental period (48, 78 h) at 37 °C. We subsequently supposed that bLf exerts stronger prebiotic effects when probiotic growth has been temperately retarded. Therefore, we incubated the probiotics at different temperatures, namely 37 °C, 28 °C, room temperature (approximately 22-24 °C), and 22 °C, to retard or inhibit their growth. As expected, bLf showed more favorable prebiotic activity in several probiotics when their growth was partially retarded at room temperature. Furthermore, at 22 °C, the growth of Bifidobacterium breve, Lactobacillus coryniformis, L. delbrueckii, L. acidophilus, B. angulatum, B. catenulatum, and L. paraplantarum were completely blocked. Notably, these probiotics started regrowing in the presence of bLf (1-32 mg/mL) in a significant and dose-dependent manner. Accordingly, bLf significantly increased the growth of Pediococcus pentosaceus, L. rhamnosus, and L. paracasei (BCRC 17483; a locally isolated strain) when their growth was retarded by incubation at 22 °C. In conclusion, bLf showed inconsistent prebiotic activity in the 14 probiotics at 37 °C, but revealed strong prebiotic activity in 10 probiotic strains at 22 °C. Therefore, this study enables determining additional roles of Lf in probiotic strains, which can facilitate developing novel combinational approaches by simultaneously using Lf and specific probiotics.

Horseshoe kidney with growth retardation: Don't forget Turner syndrome.

PubMed

Arslansoyu-Çamlar, Seçil; Soylu, Alper; Abacı, Ayhan; Türkmen, Mehmet Atilla; Ülgenalp, Ayfer; Kavukçu, Salih

2016-01-01

Horseshoe kidney is the most frequent renal fusion anomaly that is usually asymptomatic and isolated malformation. However it can be seen with various syndromes and chromosomal anomalies. It was reported that 15-35% of Turner syndrome cases (TS) also display horseshoe kidney condition. TS is a chromosomal anomaly that had been characterized by delayed puberty, short body height and gonadal dysgenesis. In this report a five-year-old girl with horseshoe kidney, which has growth retardation during follow-up as only symptom of Turner syndrome.

Growth hormone stimulation test (image)

MedlinePlus

... test is performed by administering the amino acid arginine in a vein to raise hGH levels. The ... to secrete growth hormone in response to the arginine. Lack of hGH can cause growth retardation in ...

Studies on the growth of the fetal guinea pig. The effects of ligation of the uterine artery on organ growth and development.

PubMed

Lafeber, H N; Rolph, T P; Jones, C T

1984-12-01

The effects of reduced maternal placental blood flow on the growth and development of the fetal guinea pig have been studied by unilateral ligation of the uterine artery at day 30 of pregnancy. Fetal guinea pigs were investigated about 20 or 30 days later. In about one-third of cases fetal death occurred, in another third fetuses less than 60% of normal weight were observed and in the remainder all fetuses were in the normal weight range. In the growth retarded fetuses prenatal growth occurred at about 50% of the rate in control. There was no postnatal 'catch up' as growth still remained lower than in controls. Restricted fetal growth affected particularly development of the visceral tissues in which case size declined in proportion to body weight. Brain and adrenal by comparison were less affected as their contribution to total body weight increased, but even so in the severely retarded fetuses the mass of both fell. The responses of the liver were in general consistent with a delay in the pattern of development. Thus DNA, RNA, protein and haematopoietic cell content changes occurred later than normal. In contrast an enhanced deposition of glycogen was apparent in the liver of the growth-retarded fetus. The results indicate some of the ways in which nutritional deprivation of the fetuses leads to reprogramming of growth and maturation of selected fetal tissues to allow non-essential changes to await more favourable times.

Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation

PubMed Central

Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

2016-01-01

The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38–83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P < 0.05, R = 0.45), GH (P < 0.05, R = 0.47), IGF-1 (P < 0.05, R = 0.62) was significantly correlated in yaks colonies with lighter body weights. Trial 2, fifteen 1-year-old Qinghai high plateau yaks with growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P < 0.05). Both GHRP-2 and CS administration significantly enhanced the myofiber diameter and area of skeletal muscle (P<0.05). GHRP-2 significantly enhanced the serum GH and IGF-1 levels (P < 0.05), and up-regulated GHR, IGF-1 and IGF-1R mRNA expression in the liver and skeletal muscle (P < 0.05), enhanced the mRNA expression of PI3K, AKt and mTOR in the skeletal muscle (P<0.05). CS significantly reduced the serum SS levels and the hypothalamus SS mRNA expression (P < 0.05), and enhanced GHR and IGF-1 mRNA expression in the liver (P < 0.05), decreased the mRNA expression of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) mRNA (P < 0.05). Conclusions: Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks with growth retardation. GHRP-2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway. PMID:26894743

Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation.

PubMed

Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

2016-01-01

The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38-83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P < 0.05, R = 0.45), GH (P < 0.05, R = 0.47), IGF-1 (P < 0.05, R = 0.62) was significantly correlated in yaks colonies with lighter body weights. Trial 2, fifteen 1-year-old Qinghai high plateau yaks with growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P < 0.05). Both GHRP-2 and CS administration significantly enhanced the myofiber diameter and area of skeletal muscle (P<0.05). GHRP-2 significantly enhanced the serum GH and IGF-1 levels (P < 0.05), and up-regulated GHR, IGF-1 and IGF-1R mRNA expression in the liver and skeletal muscle (P < 0.05), enhanced the mRNA expression of PI3K, AKt and mTOR in the skeletal muscle (P<0.05). CS significantly reduced the serum SS levels and the hypothalamus SS mRNA expression (P < 0.05), and enhanced GHR and IGF-1 mRNA expression in the liver (P < 0.05), decreased the mRNA expression of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) mRNA (P < 0.05). Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks with growth retardation. GHRP-2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway.

Exposure to preeclampsia in utero affects growth from birth to late childhood dependent on child’s sex and severity of exposure: Follow-up of a nested case-control study

PubMed Central

Øymar, Knut; Eide, Geir Egil; Forman, Michele R.; Júlíusson, Pétur Benedikt

2017-01-01

Background and objective An adverse intrauterine environment may affect offspring growth and development. Our aim was to explore whether preeclampsia (PE) exposure in utero influences growth from birth to 13 years. Methods In a nested case-control study, 229 children were exposed to PE (mild/moderate: n = 164, severe: n = 54) and 385 were unexposed. Length/height and weight were abstracted from records at birth, 3 and 6 months, 1 and 4 years, and measured along with waist circumference and skinfolds at follow-up at 11/12 (girls/boys) and 13 years (both sexes). Associations between PE and z-scores for growth were analyzed by multiple linear and fractional polynomial regression with adjustment for potential confounders. Results In boys, exposure to mild/moderate PE was positively associated with linear growth after 0.5 years, but severe PE was negatively associated with linear growth in all ages. In girls, both exposure to mild/moderate and severe PE were negatively associated with linear growth. Exposure to PE was negatively associated with weight and body mass index (BMI) during infancy, but positively associated with weight and BMI thereafter, except that boys exposed to severe PE consistently had a lower weight and BMI compared to the unexposed. Exposure to severe PE only was positively associated with waist-to-height ratio at 11/12 (girls/boys) and 13 years (both sexes). Conclusions From birth to adolescence, linear growth, weight and BMI trajectories differed between the sexes by severity of exposure to PE. In general, PE exposure was negatively associated with linear growth, while in girls; positive associations with weight and BMI were observed. This underlines fetal life as a particularly sensitive period affecting subsequent growth and this may have implications for targeted approaches for healthy growth and development. PMID:28486480

Effects of polychlorinated biphenyl (PCB) on regulation of thyroid-, growth-, and neurochemically related developmental processes in young rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juarez de Ku, L.M.

1992-01-01

Neonatal exposure to the toxic chemical polychlorinated biphenyl (PCB) induces hypothyroidism and retarded growth. Neonatal rats made hypothyroid by chemical or surgical means experience retarded growth and subnormal activity of choline acetyltransferase (ChAT) This study compared thyroid-, growth-, and neurochemically-related processes altered by hypothyroidism induced by other means, with PCB-induced hypothyroidism: (1) titers of thyroid stimulating hormone (TSH); (2) titers of hormones that regulate growth [growth hormone (GH), insulin-growth like factor-I (IGF-1), growth hormone releasing hormone (GHRH) and somatostatin (SS)]; or (3) brain ChAT activity. Whether PCB-induced growth retardation and other alterations are secondary to accompanying hypothyroidism rather than ormore » in addition to a direct effect of PCB was also examined. Pregnant rats were fed chow containing 0 (controls), 62.5, 125, or 250 ppm PCB (entering offspring through placenta and milk) throughout pregnancy and lactation. Neonates exposed to PCB displayed many alterations similar to those made hypothyroid by other means: depression of overall and skeletal growth, circulating by other means: depression of overall and skeletal growth, circulating T[sub 4] levels and ChAT activity, and no change in hypothalamic GHRH and SS concentrations. Differences included a paradoxical increase in circulating GH levels, and no significant alteration of circulation IGF-1 and TSH levels and pituitary GH and TSH levels (although trends were in the expected direction). Thus, PCB-induced hypothyroidism may partially cause altered skeletal growth, circulating GH and TSH concentrations, and ChAT activity. Both T[sub 4] and T[sub 3] injections returned circulating TSH and GH levels and pituitary TSH content toward control levels; T[sub 3] restored skeletal, but not overall growth; and T[sub 4] elevated ChAT activity.« less

National Study of Public Spending for Mental Retardation and Developmental Disabilities.

ERIC Educational Resources Information Center

Braddock, David; And Others

1987-01-01

Results of a nationwide study of public mental retardation/developmental disabilities spending in the states during Fiscal Years 1977 through 1986 were analyzed and identified trends such as continuing growth in spending for community services, contraction of total spending for institutional operations, and predominance of support for intermediate…

ER stress-induced protein, VIGG, disturbs plant cation homeostasis, which is correlated with growth retardation and robustness to ER stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katoh, Hironori; Fujita, Keiko; Takuhara, Yuki

2011-02-18

Highlights: {yields} VIGG is an ER stress-induced protein in plant. {yields} We examine the characteristics of VIGG-overexpressing Arabidopsis plants. {yields} VIGG-overexpressing plants reveal growth retardation and robustness to ER stress. {yields} VIGG disturbs cation homeostasis in plant. -- Abstract: VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. Themore » overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation.« less

A health priority for developing countries: the prevention of chronic fetal malnutrition.

PubMed

Villar, J; Altobelli, L; Kestler, E; Beliźan, J

1986-01-01

A prospective study of 3557 consecutively born neonates from a lower middle class district in Guatemala City documented a 23.8% incidence of intrauterine growth retardation due to fetal malnutrition. Those infants whose weights are below the 10th percentile of a sex- and race-specific birthweight and gestational age distribution, based on a developed country population, were considered to manifest intrauterine growth retardation. Ponderal index values were then used to further classify this population as having chronic fetal malnutrition (above the 10th percentile of the standard distribution) or subacute fetal malnutrition (below the 10th percentile); the incidences of these conditions were 79.1% and 20.8%, respectively. The results of numerous studies carried out in various populations suggest that developing countries have a higher incidence of chronically malnourished infants within the intrauterine growth retardation population, while subacute fetal malnutrition is more prevalent in developed countries. Moreover, it has been shown that chronically malnourished infants do not recover from their intrauterine damage and score the lowest in mental development tests even up to school age. They remain lighter, shorter, and with a smaller head circumference until at least 3 years of age. Based on the incidence rates ascertained in this study, it can be estimated that at least 2 million infants born each year in Latin America are at risk of chronic intrauterine growth retardation. Screening programs are needed to identify at-risk mothers early in pregnancy so that medical and nutritional interventions can be implemented.

Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice

PubMed Central

Rozhdestvensky, Timofey S.; Robeck, Thomas; Galiveti, Chenna R.; Raabe, Carsten A.; Seeger, Birte; Wolters, Anna; Gubar, Leonid V.; Brosius, Jürgen; Skryabin, Boris V.

2016-01-01

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5′HPRT-LoxP-NeoR cassette (5′LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScrp−/m5′LoxP), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScrp−/m5′LoxP mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScrp−/m5′LoxP mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. PMID:26848093

Analysis of PFOA in Dosed CD-1 Mice Part 2: Disposition of PFOA in Tissues and fluids from pregnant and lactating mice and their pups

EPA Science Inventory

Previous studies in mice with multiple gestational exposures to perfluorooctanoic acid (PFOA) demonstrate numerous dose dependent growth and developmental effects which appeared to worsen if offspring exposed in utero nursed from PFOA-exposed dams. To evaluate the disposition of ...

Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development.

PubMed

Kozul-Horvath, Courtney D; Zandbergen, Fokko; Jackson, Brian P; Enelow, Richard I; Hamilton, Joshua W

2012-01-01

Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations.

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays.

PubMed

Windpassinger, Christian; Piard, Juliette; Bonnard, Carine; Alfadhel, Majid; Lim, Shuhui; Bisteau, Xavier; Blouin, Stéphane; Ali, Nur'Ain B; Ng, Alvin Yu Jin; Lu, Hao; Tohari, Sumanty; Talib, S Zakiah A; van Hul, Noémi; Caldez, Matias J; Van Maldergem, Lionel; Yigit, Gökhan; Kayserili, Hülya; Youssef, Sameh A; Coppola, Vincenzo; de Bruin, Alain; Tessarollo, Lino; Choi, Hyungwon; Rupp, Verena; Roetzer, Katharina; Roschger, Paul; Klaushofer, Klaus; Altmüller, Janine; Roy, Sudipto; Venkatesh, Byrappa; Ganger, Rudolf; Grill, Franz; Ben Chehida, Farid; Wollnik, Bernd; Altunoglu, Umut; Al Kaissi, Ali; Reversade, Bruno; Kaldis, Philipp

2017-09-07

In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development. Copyright © 2017 American Society of Human Genetics. All rights reserved.

Maternal environment and craniofacial growth: geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice.

PubMed

Kesterke, Matthew J; Judd, Margaret A; Mooney, Mark P; Siegel, Michael I; Elsalanty, Mohammed; Howie, R Nicole; Weinberg, Seth M; Cray, James J

2018-07-01

An estimated 3% of US pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1000 pregnancies being complicated by overactive maternal thyroid levels. Excess thyroid hormones are linked to neurological impairment and excessive craniofacial variation, affecting both endochondral and intramembranous bone. Using a geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Canonical variate analysis utilized 16 unilateral mandibular landmarks obtained from 3D micro-computed tomography to assess shape changes between unexposed controls (n = 63) and exposed mice (n = 178). By evaluating shape changes in the mandible among three age groups (15, 20 and 25 days postnatal) and different dosage levels (low, medium and high), this study found that excess maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners. Group differences in overall shape were significant (P < 0.001), and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter the cranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development, as well as the medical implications of craniofacial growth and development. © 2018 Anatomical Society.

SHOX haploinsufficiency presenting with isolated short long bones in the second and third trimester.

PubMed

Ramachandrappa, Shwetha; Kulkarni, Abhijit; Gandhi, Hina; Ellis, Cheryl; Hutt, Renata; Roberts, Lesley; Hamid, Rosol; Papageorghiou, Aris; Mansour, Sahar

2018-03-01

Haploinsufficiency of the transcription factor short stature homeobox (SHOX) manifests as a spectrum of clinical phenotypes, ranging from disproportionate short stature and Madelung deformity to isolated short stature. Here, we describe five infants with molecularly confirmed diagnoses of SHOX haploinsufficiency who presented in utero with short long bones during routine antenatal scanning from as early as 19 weeks gestation. Other foetal growth parameters were normal. The molecular basis of SHOX haploinsufficiency was distinct in each case. In four cases, SHOX haploinsufficiency was inherited from a previously undiagnosed parent. In our de novo case, SHOX haploinsufficiency reflected the formation of a derivative sex chromosome during paternal meiosis. Final adult height in the SHOX-deficient parents ranged from -1.9 to -1.2 SDS. All affected parents had disproportionately short limbs and two affected mothers had bilateral Madelung deformity. To our knowledge, SHOX haploinsufficiency has not previously been reported to present in utero. Our experience illustrates that SHOX deficiency should form part of the differential diagnosis of foetal short long bones and suggests a low threshold for genetic testing. This should be particularly targeted at, but not limited to, families with a history of features suggestive of SHOX deficiency. Data on the postnatal growth of our index cases is presented which demonstrates that antenatal presentation of SHOX haploinsufficiency is not indicative of severe postnatal growth restriction. Early identification of SHOX deficiency will enable accurate genetic counselling reflecting a good postnatal outcome and facilitate optimal initiation of growth hormone therapy.

Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

PubMed

Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

2011-09-01

Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Şanlıurfa, Turkey.

PubMed

Yentur Doni, Nebiye; Yildiz Zeyrek, Fadile; Simsek, Zeynep; Gurses, Gulcan; Sahin, İbrahim

2015-12-01

The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. This case-control study was performed in Şanlıurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children.

Suspected X-linked facial dysmorphia and growth retardation in related Labrador retriever puppies.

PubMed

Dierks, C; Hoffmann, H; Heinrich, F; Hellige, M; Hewicker-Trautwein, M; Distl, O

2017-02-01

Seven male Labrador retriever puppies from four different litters were identified with a brachycephalic-like face and skull, associated with low birth weight, severe growth retardation, and reduced abilities to crawl and suckle, which were not compatible with survival. Excessive doming of the cranium, brachygnathia superior and inferior, and an abnormally opened fontanelle were found in all affected puppies by computed tomography and at post-mortem examination. Pedigree analysis supported an X-linked recessive mode of inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early-Onset Endocrine Disruptor–Induced Prostatitis in the Rat

PubMed Central

Cowin, Prue A.; Foster, Paul; Pedersen, John; Hedwards, Shelley; McPherson, Stephen J.; Risbridger, Gail P.

2008-01-01

Background Androgens are critical for specifying prostate development, with the fetal prostate sensitive to altered hormone levels and endocrine-disrupting chemicals (EDCs) that exhibit estrogenic or antiandrogenic properties. Prostatic inflammation (prostatitis) affects 9% of men of all ages, and > 90% of cases are of unknown etiology. Objectives In this study we aimed to evaluate effects of in utero exposure to the antiandrogenic EDC vinclozolin, during the period of male reproductive tract development, on neonatal, prepubertal, and postpubertal prostate gland function of male offspring. Methods Fetal rats were exposed to vinclozolin (100 mg/kg body weight) or vehicle control (2.5 mL/kg body weight) in utero from gestational day 14 (GD14) to GD19 via oral administration to pregnant dams. Tissue analysis was carried out when male offspring were 0, 4, or 8 weeks of age. Results In utero exposure to vinclozolin was insufficient to perturb prostatic development and branching, although expression of androgen receptor and mesenchymal fibroblast growth factor-10 was down-regulated. Prostate histology remained normal until puberty, but 100% of animals displayed prostatitis postpubertally (56 days of age). Prostatic inflammation was associated with phosphorylation and nuclear translocation of nuclear factor-kappa B (NFκB) and postpubertal activation of proinflammatory NFκB-dependent genes, including the chemokine interleukin-8 and the cytokine transforming growth factor-β1. Significantly, inflammation arising from vinclozolin exposure was not associated with the emergence of premalignant lesions, such as prostatic intra-epithelial neoplasia or proliferative inflammatory atrophy, and hence mimics nonbacterial early-onset prostatitis that commonly occurs in young men. Conclusions These data are the first to unequivocally implicate EDCs as a causative factor and fill an important knowledge gap on the etiology of prostatitis. PMID:18629315

[Roberts-SC phocomelia syndrome].

PubMed

Musfeld, D A; Bühler, E M; Heinzl, S

2001-01-01

The Roberts-SC phocomelia syndrome is a rare autosomal recessive inherited disorder clinically manifested by tetraphocomelia, pre- and postnatal growth retardation, and craniofacial abnormalities (skull, eyes, lip, and palate), accompanied at times by centromer puffing and splitting, renal abnormalities, heart defect, clitoral or penile enlargement, and bilateral corneal opacities. Mental retardation is common in surviving patients.

Residential Programming for Mentally Retarded Persons. Volume II, A Developmental Model for Residential Services.

ERIC Educational Resources Information Center

National Association for Retarded Children, Arlington, TX. South Central Regional Office.

The second of a series of four booklets on residential programing for the mentally retarded (MR) presents a developmental model for residential services based on the premise that MR persons are capable of growth, development, and learning. Architectural factors, staff resistance and financial considerations are described as impediments to…

VARIATIONS IN LARVAL GROWTH AND METABOLISM OF AN ESTUARINE SHRIMP DURING TOXICOSIS BY AN INSECT GROWTH REGULATOR

EPA Science Inventory

Exposure of the estuarine shrimp, Ptiaemonetes pugio, to a juvenile hormone analogue (> 3 ug methoprene-1) throughout larval development inhibited successful completion of metamorphosis. Methoprene exposure retarded growth in early larval stages and postlarvae enhanced growth in ...

Flame retardants in UK furniture increase smoke toxicity more than they reduce fire growth rate.

PubMed

McKenna, Sean T; Birtles, Robert; Dickens, Kathryn; Walker, Richard G; Spearpoint, Michael J; Stec, Anna A; Hull, T Richard

2018-04-01

This paper uses fire statistics to show the importance of fire toxicity on fire deaths and injuries, and the importance of upholstered furniture and bedding on fatalities from unwanted fires. The aim was to compare the fire hazards (fire growth and smoke toxicity) using different upholstery materials. Four compositions of sofa-bed were compared: three meeting UK Furniture Flammability Regulations (FFR), and one using materials without flame retardants intended for the mainland European market. Two of the UK sofa-beds relied on chemical flame retardants to meet the FFR, the third used natural materials and a technical weave in order to pass the test. Each composition was tested in the bench-scale cone calorimeter (ISO 5660) and burnt as a whole sofa-bed in a sofa configuration in a 3.4 × 2.25 × 2.4 m 3 test room. All of the sofas were ignited with a No. 7 wood crib; the temperatures and yields of toxic products are reported. The sofa-beds containing flame retardants burnt somewhat more slowly than the non-flame retarded EU sofa-bed, but in doing so produced significantly greater quantities of the main fire toxicants, carbon monoxide and hydrogen cyanide. Assessment of the effluents' potential to incapacitate and kill is provided showing the two UK flame retardant sofa-beds to be the most dangerous, followed by the sofa-bed made with European materials. The UK sofa-bed made only from natural materials (Cottonsafe ® ) burnt very slowly and produced very low concentrations of toxic gases. Including fire toxicity in the FFR would reduce the chemical flame retardants and improve fire safety. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Substrate-mediated diffusion-induced growth of single-crystal nanowires.

PubMed

Mohammad, S Noor

2009-11-28

Theoretical investigations of the growth and growth rates of single-crystal nanowires (NWs) by vapor phase mechanisms have been carried out. Substrate-induced processes are assumed to dominate this growth. The modeling for growth takes adsorption, desorption, surface scattering, and diffusion into account. It takes into consideration also the retarding electric field arising from the scattering of the NW vapor species by both the substrate and the NW sidewalls. Growth characteristics under the influence of the retarding electric field have been studied. Competitive roles of adatom diffusivity and the electric field in the NW growth are elucidated. Influence of the growing NW length and the adatom impingement rate on the NW growth rate has been described. The effect of adatom collection area around each NW has been examined. The NW tapering and kinking have been explained. The fundamentals of the substrate induction and details of the growth parameters have been analyzed. The influence of foreign element catalytic agents in the vapor-liquid-solid mechanism has been presented. All these have led to the understanding and resolution of problems, controversies, and contradictions involving substrate-induced NW growths.

Growth profiles of 34 patients with Wolf-Hirschhorn syndrome

PubMed Central

Shimojima, Keiko; Yamamoto, Toshiyuki

2012-01-01

Wolf-Hirschhorn syndrome (WHS) encompasses multiple congenital anomalies and mental retardation and is caused by partial deletions in the short arm of chromosome 4. Prenatal-onset growth deficiency is one of the WHS characteristics. Assessing and recording growth profiles of patients with WHS were the aims of this study. Anonymous questionnaire surveys were conducted with cooperation of a WHS peer-support group in Japan, and data from 34 WHS patients (12 males and 22 females; age, 1–23 years) were retrospectively collected. Height, weight, and head circumference (occipitofrontal head circumference) were measured and plotted on the standard growth charts of healthy Japanese children. Results indicated that most WHS patients showed growth retardation under the 3rd percentile since the first year of life and extremely poor body-weight gain after pubertal age. These findings are characteristic of WHS patients. The assessed growth patterns in this study could help monitoring and documentation of growth of WHS patients. PMID:27625799

Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats.

PubMed

Yang, Yuxian; Fan, Xiaorong; Tao, Jianying; Xu, Ting; Zhang, Yingying; Zhang, Wenna; Li, Lingjun; Li, Xiang; Ding, Hongmei; Sun, Miao; Gao, Qinqin; Xu, Zhice

2018-03-07

Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling. The results indicated prenatal hypoxia not only delayed fetal skeletal growth, but also increased OVX-induced osteoporosis in the elder offspring probably through down-regulated IGF1 signaling and inhibition of ECM synthesis, providing important information of prenatal hypoxia on functional and molecular bone growth and metabolism in fetal and offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

In Vitro Conservation of Date Palm Shoot-Tip Explants and Callus Cultures Under Minimal Growth Conditions.

PubMed

El-Dawayati, Maiada M

2017-01-01

Date palm fruit production has great economic significance for many countries. There is a fundamental necessity to conserve valuable date palm germplasm, but there are various problems with in vivo and ex situ conservation. In vitro storage has several advantages over conventional germplasm conservation methods. The in vitro technique offers a developed method of slow-growth storage, which is considered as an alternate solution for short- and medium-term storage of date palm germplasm under controlled conditions. Minimal growth conditions for germplasm conservation are generally achieved by reducing growth rate through modification of environmental growing conditions and culture, by using low temperatures, and the addition of growth retardants and osmotic agents. This chapter describes a protocol for short-term in vitro conservation of date palm shoot-tip and callus cultures under slow-growth storage conditions, using sucrose as an osmotic agent and abscisic acid (ABA) as a growth retardant at 15 °C for 12 months.

[Diagnosis of a case with Williams-Beuren syndrome with nephrocalcinosis using chromosome microarray analysis].

PubMed

Jin, S J; Liu, M; Long, W J; Luo, X P

2016-12-02

Objective: To explore the clinical phenotypes and the genetic cause for a boy with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders. Method: Routine G-banding and chromosome microarray analysis were applied to a child with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders treated in the Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in September 2015 and his parents to conduct the chromosomal karyotype analysis and the whole genome scanning. Deleted genes were searched in the Decipher and NCBI databases, and their relationships with the clinical phenotypes were analyzed. Result: A six-month-old boy was refered to us because of unexplained growth retardation and feeding intolerance.The affected child presented with abnormal manifestation such as special face, umbilical hernia, growth retardation, hypothyroidism, congenital heart disease, right ear sensorineural deafness, hypercalcemia and nephrocalcinosis. The child's karyotype was 46, XY, 16qh + , and his parents' karyotypes were normal. Chromosome microarray analysis revealed a 1 436 kb deletion on the 7q11.23(72701098_74136633) region of the child. This region included 23 protein-coding genes, which were reported to be corresponding to Williams-Beuren syndrome and its certain clinical phenotypes. His parents' results of chromosome microarray analysis were normal. Conclusion: A boy with characteristic manifestation of Williams-Beuren syndrome and rare nephrocalcinosis was diagnosed using chromosome microarray analysis. The deletion on the 7q11.23 might be related to the clinical phenotypes of Williams-Beuren syndrome, yet further studies are needed.

The Underlying Ecological Processes of Gut Microbiota Among Cohabitating Retarded, Overgrown and Normal Shrimp.

PubMed

Xiong, Jinbo; Dai, Wenfang; Zhu, Jinyong; Liu, Keshao; Dong, Chunming; Qiu, Qiongfen

2017-05-01

Increasing evidence of tight links among the gut microbiota, obesity, and host health has emerged, but knowledge of the ecological processes that shape the variation in microbial assemblages across growth rates remains elusive. Moreover, inadequately control for differences in factors that profoundly affect the gut microbial community, hampers evaluation of the gut microbiota roles in regulating growth rates. To address this gap, we evaluated the composition and ecological processes of the gut bacterial community in cohabitating retarded, overgrown, and normal shrimps from identically managed ponds. Gut bacterial community structures were distinct (P = 0.0006) among the shrimp categories. Using a structural equation modeling (SEM), we found that changes in the gut bacterial community were positively related to digestive activities, which subsequently affected shrimp growth rate. This association was further supported by intensified interspecies interaction and enriched lineages with high nutrient intake efficiencies in overgrown shrimps. However, the less phylogenetic clustering of gut microbiota in overgrown and retarded subjects may offer empty niches for pathogens invasion, as evidenced by higher abundances of predicted functional pathways involved in disease infection. Given no differences in biotic and abiotic factors among the cohabitating shrimps, we speculated that the distinct gut community assembly could be attributed to random colonization in larval shrimp (e.g., priority effects) and that an altered microbiota could be a causative factor in overgrowth or retardation in shrimp. To our knowledge, this is the first study to provide an integrated overview of the direct roles of gut microbiota in shaping shrimp growth rate and the underlying ecological mechanisms.

Deletion of a 760 kb region at 4p16 determines the prenatal and postnatal growth retardation characteristic of Wolf-Hirschhorn syndrome.

PubMed

Concolino, Daniela; Rossi, Elena; Strisciuglio, Pietro; Iembo, Maria Antonietta; Giorda, Roberto; Ciccone, Roberto; Tenconi, Romano; Zuffardi, Orsetta

2007-10-01

Recently the genotype/phenotype map of Wolf-Hirschhorn syndrome (WHS) has been refined, using small 4p deletions covering or flanking the critical region in patients showing only some of the WHS malformations. Accordingly, prenatal-onset growth retardation and failure to thrive have been found to result from haploinsufficiency for a 4p gene located between 0.4 and 1.3 Mb, whereas microcephaly results from haploinsufficiency of at least two different 4p regions, one of 2.2-2.38 Mb and a second one of 1.9-1.28 Mb. We defined the deletion size of a ring chromosome (r(4)) in a girl with prenatal onset growth retardation, severe failure to thrive and true microcephaly but without the WHS facial gestalt and mental retardation. A high-resolution comparative genome hybridisation array revealed a 760 kb 4p terminal deletion. This case, together with a familial 4p deletion involving the distal 400 kb reported in normal women, may narrow the critical region for short stature on 4p to 360-760 kb. This region is also likely to contain a gene for microcephaly. "In silico" analysis of all genes within the critical region failed to reveal any strikingly suggestive expression pattern; all genes remain candidates for short stature and microcephaly.

Anthropometric characteristics and nutrition in a cohort of PAH-deficient patients.

PubMed

Aldámiz-Echevarría, Luis; Bueno, María A; Couce, María L; Lage, Sergio; Dalmau, Jaime; Vitoria, Isidro; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Peña-Quintana, Luis; Ruiz, María A; González, David; Sánchez-Valverde, Felix

2014-08-01

Treating phenylketonuria based upon strict vegetarian diets has occasionally been found to hamper physical development, some patients presenting with growth retardation and malnutrition. In addition, some researchers have reported an association between higher protein intakes and attaining better developmental outcomes, although it remains unclear which protein fraction (natural or synthetic) has the greatest influence on growth. The present study aimed to evaluate anthropometric characteristics and nutrition in a cohort of patients with phenylketonuria and mild-hyperphenylalaninaemia from birth to adulthood. We conducted a retrospective longitudinal study comparing anthropometric characteristics (weight, height, body mass index, and growth rate) in our patients and healthy subjects, with the measurements expressed as z-scores. Nutritional issues were also considered. Data were collected every 6 months from birth to 18 years of age. Growth impairment was observed in phenylketonuric patients. Specifically, there were two well-differentiated periods throughout which height fell well below z-score = 0: from birth to two years of age, and on reaching adulthood. We also found height and weight to be positively correlated with phenylalanine intake. No growth retardation was seen in the patients with mild-hyperphenylalaninaemia. Phenylketonuric patients showed growth impairment in the early stages, with higher phenylalanine intakes being associated with attaining better developmental outcomes in this period. Therefore, prescribing very stringent diets in the early years might predispose phenylketonuric patients to retarded growth later in life, with growth outcomes in adulthood being well below the 50th percentile for healthy subjects. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

PPARα, PPARβ, and PPARγ expression in prenatal and postnatal mouse tissues and an evaluation of the effects of perfluorooctanoic acid (PFOA) on peroxisome proliferator-activated receptor (PPAR) expression.

EPA Science Inventory

PFOA is developmentally toxic, reducing in utero and neonatal survival, and altering development and growth in mice. PFOA activates PPARα and studies in PPARα knockout mice showed that PPARα signaling is required to produce these effects. This study examines the expression of PPA...

Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

PubMed

Studholme, Colin

2011-08-15

The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

Data Mining of Determinants of Intrauterine Growth Retardation Revisited Using Novel Algorithms Generating Semantic Maps and Prototypical Discriminating Variable Profiles

PubMed Central

Buscema, Massimo; Grossi, Enzo; Montanini, Luisa; Street, Maria E.

2015-01-01

Objectives Intra-uterine growth retardation is often of unknown origin, and is of great interest as a “Fetal Origin of Adult Disease” has been now well recognized. We built a benchmark based upon a previously analysed data set related to Intrauterine Growth Retardation with 46 subjects described by 14 variables, related with the insulin-like growth factor system and pro-inflammatory cytokines, namely interleukin -6 and tumor necrosis factor -α. Design and Methods We used new algorithms for optimal information sorting based on the combination of two neural network algorithms: Auto-contractive Map and Activation and Competition System. Auto-Contractive Map spatializes the relationships among variables or records by constructing a suitable embedding space where ‘closeness’ among variables or records reflects accurately their associations. The Activation and Competition System algorithm instead works as a dynamic non linear associative memory on the weight matrices of other algorithms, and is able to produce a prototypical variable profile of a given target. Results Classical statistical analysis, proved to be unable to distinguish intrauterine growth retardation from appropriate-for-gestational age (AGA) subjects due to the high non-linearity of underlying functions. Auto-contractive map succeeded in clustering and differentiating completely the conditions under study, while Activation and Competition System allowed to develop the profile of variables which discriminated the two conditions under study better than any other previous form of attempt. In particular, Activation and Competition System showed that ppropriateness for gestational age was explained by IGF-2 relative gene expression, and by IGFBP-2 and TNF-α placental contents. IUGR instead was explained by IGF-I, IGFBP-1, IGFBP-2 and IL-6 gene expression in placenta. Conclusion This further analysis provided further insight into the placental key-players of fetal growth within the insulin-like growth factor and cytokine systems. Our previous published analysis could identify only which variables were predictive of fetal growth in general, and identified only some relationships. PMID:26158499

LEOPARD syndrome: what are café noir spots?

PubMed

Rodríguez-Bujaldón, Alfonso; Vazquez-Bayo, Carmen; Jimenez-Puya, Rafael; Galan-Gutierrez, Manuel; Moreno-Gimenez, José; Rodriguez-Garcia, Alfonso; Tercedor, Jesus; Velez-Garcia, Antonio

2008-01-01

Lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome (multiple lentigines syndrome) is most often characterized by multiple lentigines and cardiac conduction defects. Café noir spot is a term proposed, by analogy to café au lait spots, for the larger and darkly pigmented patches that are frequently observed in patients with this syndrome. Although presumed by some authors to represent lentigines, the histologic features of café noir spots have not been well documented in the literature. Only two previous cases have been reported in which a biopsy of the café noir spots than melanocytic nevi. We describe the histologic characteristics of seven café noir spots in six patients with lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome. Three lesions represented melanocytic nevi (one with dysplastic features), and four were compatible with lentigo simplex. These findings help our understanding of the histologic spectrum of pigmented lesions in lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome.

Cone calorimeter evaluation of wood products

Treesearch

Robert H. White; Mark A. Dietenberger

2004-01-01

The Forest Products Laboratory uses the cone calorimeter for the initial evaluation of the flammability of untreated and fire retardant treated wood products. The results of various studies are reviewed using a model presented at the 12th Annual BBC Conference on Flame Retardancy. The model uses data from the cone calorimeter to provide measures of fire growth...

Curriculum Guide: Educable Mentally Retarded, Senior High Program; Little Rock Public Schools.

ERIC Educational Resources Information Center

Arkansas State Dept. of Education, Little Rock. Special Education Section.

Emphasizing social and economic growth of the educable retarded secondary student, provision is made for lesson and unit plans which give information on vocational and educational opportunities and which develop habits, attitudes and skills necessary for the individual to hold a job. The basic skills to be taught, books and materials useful in…

[Trisomy 18 syndrome: A case report].

PubMed

Saldarriaga, Wilmar; Rengifo-Miranda, Heidy; Ramírez-Cheyne, Julián

2016-01-01

The trisomy 18 syndrome occurs due to the presence of an extra chromosome 18 in most cases. The prevalence in infants is estimated at 1:6000 to 1:8000. Those affected have a high mortality rate, only 4% may survive their first year of life. There are few reported cases exceeding five years of age. The aim of this paper is to report a case of trisomy 18 of long survival with oral cavity features not described in the literature, and to provide information to physicians and paediatricians about aetiology, phenotype, survival and genetic counselling. A 7 year-old female patient with 2 karyotypes performed by lymphocyte culture showing 47XX+18 in all metaphases. She presented with growth deficiency, dysmorphic facies, severe psychomotor retardation and cognitive disability, inability to feed, lack of verbal language, sensorineural hearing loss, ataxia, cerebellar hypoplasia, and genitals with hypoplastic labia majora and minora. In the oral cavity: dome shaped palate, macroglossia, absence of upper central incisors and first upper and lower molars in mouth. X-ray findings showed formation of missing teeth, with late eruption being concluded. In cases of trisomy 18 syndrome there is an increased risk of neonatal and infant mortality. The clinical characteristics in utero and in neonates have been well described. Since few cases exceeding five years of age have been reported, the phenotype is yet to be established. In the case being reported we describe oral cavity findings not documented in the literature. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Dubowitz syndrome: review of 141 cases including 36 previously unreported patients.

PubMed

Tsukahara, M; Opitz, J M

1996-05-03

We review clinical information on 141 individuals with Dubowitz syndrome, 105 reported since 1965, and 36 previously unreported. We define the Dubowitz syndrome phenotype on the basis of clinical descriptions. The facial appearance is characteristic and present in most patients with Dubowitz syndrome. The phenotypic spectrum is quite variable and ranges from normal growth and head circumference with mild psychomotor retardation and lack of eczema to a condition of severe growth retardation, mental retardation, microcephaly, and eczema. Overall, the condition may involve the cutaneous, ocular, dental, digestive, musculoskeletal, urogenital, cardiovascular, neurological, hematological, and immune systems. Characteristic behavior patterns which have not been cited previously are present in our cases; most patients are hyperactive, shy, hate crowds, and like music, rhythm, and vibrations from music speakers, tape recorders, or transmitted through floors. Dubowitz syndrome is an autosomal recessive disorder with possibly increased frequency of parental consanguinity. Heterogeneity cannot be excluded at this time.

Critical differences between two low protein diet protocols in the programming of hypertension in the rat.

PubMed

Langley-Evans, S C

2000-01-01

Maternal nutrition has been identified as a factor determining fetal growth and risk of adult disease. In rats, the feeding of a low protein diet during pregnancy retards fetal growth and induces hypertension in the resulting offspring. Rat models of low protein feeding have been extensively used to study the mechanisms that may link maternal nutrition with impaired fetal growth and later cardiovascular disease and diabetes. Low protein diets of differing composition used in different laboratories have yielded inconsistent data on the relationship between maternal protein intake and offsprings' blood pressure. Two separate low protein diet protocols were compared in terms of their ability to programme hypertension during fetal life. Pregnant rats were assigned to receive one of four diets. Two diets were obtained from a commercial supplier and provided casein at 22 or 9% by weight (H22, control; H9, low protein). The other two diets, manufactured in our own facility, provided 18% casein (S18, control) or 9% casein (S9, low protein) by weight. The diets differed principally in their overall fat content, fatty acid composition, methionine content and the source of carbohydrate. Feeding of the experimental diets commenced on the first day of pregnancy and continued until the rats delivered their litters. Following weaning all the offspring had blood pressure determined on a single occasion. Both low protein diets reduced maternal weight gain relative to their corresponding control diets. Despite this litter sizes were unaffected by the dietary protocols. Both low protein diets reduced birthweights of the pups. Systolic blood pressure was significantly elevated in the offspring of rats fed a low protein S9 diet relative to all other groups (P < 0.05). Animals exposed to H9 diet in utero had similar blood pressures to their H22 controls. It is concluded from this work that differing low protein diet manipulations in rat pregnancy elicit different programming effects upon the developing cardiovasculature. The balance of protein and other nutrients may be a critical determinant of the long-term health effects of maternal undernutrition in pregnancy.

A new familial intrauterine growth retardation syndrome the "3-M syndrome".

PubMed

Spranger, J; Opitz, J M; Nourmand, A

1976-09-01

Two pairs of siblings are described with proportionate dwarfism due to skeletal hypoplasia of prenatal onset. The head size was normal for age and disproportionately large for height. The patients had a characteristic face different from that seen in the Silver-Russell syndrome. The family data are in accordance with autosomal recessive inheritance. In spite of some similarities, the bulk of clinical and genetic evidence suggests that the described intrauterine growth retardation syndrome is different from the Silver-Russell syndrome and presents an apparently "new" entity which has been designated 3-M syndrome.

A Nerve Growth Factor Peptide Retards Seizure Development and Inhibits Neuronal Sprouting in a Rat Model of Epilepsy

NASA Astrophysics Data System (ADS)

Rashid, Kashif; van der Zee, Catharina E. E. M.; Ross, Gregory M.; Chapman, C. Andrew; Stanisz, Jolanta; Riopelle, Richard J.; Racine, Ronald J.; Fahnestock, Margaret

1995-10-01

Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization.

Head circumferences of children born to HIV-infected and HIV-uninfected mothers in Zimbabwe during the preantiretroviral therapy era

PubMed Central

Evans, Ceri; Chasekwa, Bernard; Ntozini, Robert; Humphrey, Jean H.; Prendergast, Andrew J.

2016-01-01

Objectives: To describe the head growth of children according to maternal and child HIV infection status. Design: Longitudinal analysis of head circumference data from 13 647 children followed from birth in the ZVITAMBO trial, undertaken in Harare, Zimbabwe, between 1997 and 2001, prior to availability of antiretroviral therapy (ART) or cotrimoxazole prophylaxis. Methods: Head circumference was measured at birth, then at regular intervals through 24 months of age. Mean head circumference-for-age Z-scores (HCZ) and prevalence of microcephaly (HCZ < −2) were compared between HIV-unexposed children, HIV-exposed uninfected (HEU) children and children infected with HIV in utero (IU), intrapartum (IP) and postnatally (PN). Results: Children infected with HIV in utero had head growth restriction at birth. Head circumference Z-scores remained low throughout follow-up in IP children, whereas they progressively declined in IU children. During the second year of life, HCZ in the PN group declined, reaching a similar mean as IP-infected children by 21 months of age. Microcephaly was more common among IU and IP children than HIV-uninfected children through 24 months. HEU children had significantly lower head circumferences than HIV-unexposed children through 12 months. Conclusion: HIV-infected children had lower head circumferences and more microcephaly than HIV-uninfected children. Timing of HIV acquisition; influenced HCZ, with those infected before birth having particularly poor head growth. HEU children had poorer head growth until 12 months of age. Correlations between head growth and neurodevelopment in the context of maternal/infant HIV infection, and further studies from the current ART era, will help determine the predictive value of routine head circumference measurement. PMID:27428746

Insulin-like growth factor I gene deletion causing intrauterine growth retardation and severe short stature.

PubMed

Woods, K A; Camacho-Hübner, C; Barter, D; Clark, A J; Savage, M O

1997-11-01

The first human case of a homozygous molecular defect in the gene encoding insulin-like growth factor I (IGF-I) is described. The patient was a 15-year-old boy from a consanguineous pedigree who presented with severe intrauterine growth failure, sensorineural deafness and mild mental retardation. Endocrine evaluation of the growth hormone (GH)--IGF-I axis revealed elevated GH secretion, undetectable serum IGF-I and normal serum IGF-binding protein-3, acid-labile subunit, and GH-binding activity. Analysis of the IGF-I gene revealed a homozygous partial IGF-I gene deletion involving exons 4 and 5, which encodes a severely truncated mature IGF-I peptide. This patient demonstrates that complete disruption of the IGF-I gene in man is compatible with life, and indicates a major role for IGF-I in human fetal growth. In addition, his neurological abnormalities suggest that IGF-I may be involved in central nervous system development.

Growth Hormone Studies in Growth Retardation—Therapeutic Response to Administration of Androgen

PubMed Central

Deller, John J.; Plunket, Daniel C.; Forsham, Peter H.

1966-01-01

Growth hormone assays were performed before and after androgen administration in a 12-year-old boy with unexplained growth retardation. A subnormal growth hormone secretion in response to a standard hypoglycemic stimulus was demonstrated, and it was corrected by androgen pretreatment. After that, a normal serum growth hormone level and a temporary growth spurt were demonstrated. ImagesFigure 1. PMID:5942009

Effects of environmental factors on perinatal outcome: neurological development in cases of intrauterine growth retardation and school performance of children perinatally exposed to ionizing radiation.

PubMed Central

Ikenoue, T; Ikeda, T; Ibara, S; Otake, M; Schull, W J

1993-01-01

We performed two studies to investigate environmental factors in relation to neurological development in infants. The first, a field study, examined the elementary school performance of 929 children who were born from mothers exposed to the atomic bombing of Hiroshima, Japan, August 6, 1945. The most severe mental retardation was observed in the group exposed between 8 and 15 weeks following fertilization, and the second most severely damaged group was exposed between 16 and 25 weeks. The second, a clinical investigation, examined infants in the perinatal center who survived intrauterine growth retardation (IUGR). Those who survived with abnormal neurological development had a mean growth arrest corresponding to a uterine height of 27 weeks of gestation. This was at an earlier stage than those who survived with normal neurological development and had a mean growth arrest corresponding to 29-30 weeks of gestation. A smaller head circumference at birth was closely correlated with abnormal neurological sequelae. These results indicate that the brain development of the fetuses may have been affected by neurotoxic events similar to ionizing radiation. We emphasize the importance of avoiding neurotoxic stress to pregnant women when the fetus is in the critical period of neuronal development, before 27 weeks of gestational age. PMID:8243407

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

PubMed Central

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

2014-01-01

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

PubMed

Bleker, O P; Buimer, M; van der Post, J A M; van der Veen, F

2006-01-01

In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

Children of Deprivation, Changing the Course of Familial Retardation.

ERIC Educational Resources Information Center

Kugel, Robert B.; Parsons, Mabel H.

The growth of preschool familial retarded children was recorded, and attempts were made to alter the course of their development. Of lower socioeconomic class, the 16 subjects aged from 3 to 6, had IQ scores from 50 to 84 and no neurological deficits. One or both of their parents and at least one sibling were mentally subnormal. The subjects and…

THE EFFECTS OF A PRESCHOOL PROGRAM UPON YOUNG EDUCABLE MENTALLY RETARDED CHILDREN--VOLUME 1, THE EXPERIMENTAL PRESCHOOL CURRICULUM.

ERIC Educational Resources Information Center

FOURACRE, MAURICE H.; AND OTHERS

THIS CURRICULUM REPORT DESCRIBES A SPECIAL EDUCATION PROGRAM FOR EDUCABLE PRESCHOOL RETARDATES TOGETHER WITH AN ACCOUNT OF ITS DEVELOPMENT IN EXPERIMENTAL CLASSES OF NEW YORK CITY. THE SETTING AND PROCESS OF THE DEVELOPMENTAL CURRICULUM, THE CURRICULUM GUIDE AND ITS IMPLEMENTATION, AND THE OBSERVED BEHAVIOR AND GROWTH OF THE PARTICIPATING CHILDREN…

Proximal dup(10q): Case report and literature review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barritt, J.A.; Teague, K.E.; Bodurtha, J.N.

We report a case of a proximal dir dup(10q) in a female with multiple congenital anomalies. During infancy she was noted to gave growth retardation, microcephaly, microphthalmia, coloboma, a long, beaked nose, posteriorly rotated ears with simple helices, full bowed lips, widely-spaced nipples, broad first toes, hypermobile and proximally placed thumbs, a heart murmur, PDA, and coarctation of the aorta. Additional findings at age 13 included a full columella, short philtrum, thin limbs, bilateral blindness, and mental retardation, as well as continued growth retardation. Her medical history included precocious puberty at age 8 and a diagnosis of hyperactivity. Using FISHmore » with multiple probes combined with GTG-banding, the aberrant chromosome was determined to be a dir dup(10)(q21{r_arrow}q22). Parental chromosomes were normal and the family history was unremarkable. The parental origin of the dir dup(10) is being assessed using DNA markers. Five similar cases of proximal dup(10q) have been reported previously. Consistent characteristics include low birth weight, developmental and psychomotor delay, growth retardation, and microcephaly. Also found in most cases were short prominent philtrum, bowed mouth, PDA, thin limbs, coloboma, micropthalmia, deep set eyes, and other ocular anomalies. Our case is unique in that she has a long, beaked nose, precocious puberty, and hyperactivity. Future studies such as this, using molecular cytogenetic techniques to better define the chromatin involved in proximal dup(10q), may lead to its recognition as a distinct clinical phenotype.« less

Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

ERIC Educational Resources Information Center

Pueschel, Seigfried M.

1993-01-01

This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

Sex differences in the malnourished status of Chinese children due to schistosomiasis infections and inadequate dietary intake.

PubMed

Zhou, Huan; He, Yongkang; Ohtsuka, Ryutaro

2005-01-01

Based on nutritional and parasitological examinations of 389 children aged 10-13 years in five primary schools in the schistosomiasis endemic Dongting Lake region of China, the causal factors of their retarded growth, represented by height, weight, mid-upper arm circumference and body mass index, were investigated. Among the four parasites, schistosomiasis infection due to Schistosoma japonicum played a significant role, with higher rates in girls than in boys. Praziquantel treatment of schistosomiasis decreased the infection rate and improved the children's growth. For dietary intake factors, the contribution of protein to total energy intake, which was lower in girls than in boys, had the greatest effect on the growth patterns. The sex difference in growth retardation is judged to be attributable to the traditional norms, such as girls spending more time in infested environments and gender discrimination in food distribution.

[Study on malnutrition status among Wa ethnicity children and adolescents in Lingcang prefecture, Yunnan province].

PubMed

Yang, Yunjuan; Chang, Litao; Chen, Lu; Wei, Xijing

2015-12-01

To analyze the malnutrition status among children and adolescents of Wa ethnicity in Lincang prefecture, Yunnan province from 2005 to 2014, and to provide evidence for the improvement of the situation. From 2005 to 2014, children and adolescents aged 7 to 18, from 19 primary and secondary schools in Cangyuan county of Lincang prefecture, Yunnan province, were chosen, using the multistage-stratified-random cluster sampling method, to receive physic examination. WHO-2006 standard was used. Situation related to the rate of growth retardation and malnutrition among students was analyzed, from 2005 to 2014. Data was from the National Student Physical Health Research Project. From 2000 to 2014, trends on nutrition development among these students were also studied. The rates related to growth retardation among 7-18 years-old Wa boys in 2005, 2010 and 2014 were 45.61%, 52.36% and 35.85%, with the rates of thinness as 1.44%, 0.76% and 1.36% , respectively. Rates on malnutrition were 52.35% , 56.01% and 41.13% , respectively. Rates related to growth retardation among 7-18 years-old Wa girls were 42.03%, 47.41% and 33.06%, respectively, with rates of thinness as 0.91%, 0.68% and 0.83%, respectively. The rates on malnutrition were 46.13%, 49.77% and 35.56%, respectively. From year 2005 to 2014, spurt on height growth of boys and girls were among the 13-14 years-old and 9-10 years-old, respectively. Girls were 4 years earlier, entering the sudden increase in the peak age than boys. Sex difference on height among the 18 years-old Wa youngsters were 11.99, 9.34 and 11.38 cm in 2005, 2010 and 2014, respectively. Malnutrition status of retardation on growth among Wa children and adolescents remained quite serious.

The effects of soil moisture, texture, and nutrient levels on the growth of black walnut.

Treesearch

Richard E. Dickson

1971-01-01

Black walnut seedlings grown in a clay loam and sandy soil were subjected to two soil moisture regimes and three fertility levels. Fertilization increased growth only under most conditions. Under draught, fertilization retarded growth in the sand. Nitrogen was the element primarily responsible for the greater growth under moist conditions.

Developmental programming: the role of growth hormone.

PubMed

Oberbauer, Anita M

2015-01-01

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

Anesthesia for cleft lip surgery in a child with Seckel syndrome--a case report.

PubMed

Rajamani, Arvind; Kamat, Vijaylakshmi; Murthy, Jyotsna; Hussain, Syed Altaf

2005-04-01

We describe the anesthetic management of a 5-year-old girl diagnosed with Seckel syndrome, for cleft lip surgery. The syndrome is characterized by severe intrauterine and postnatal growth retardation with proportional dwarfism, typical beak-like triangular nose, and mental retardation, accounting for its various synonyms such as bird-headed dwarfism, microcephalic primordial dwarfism, nanocephalic dwarfism and Seckel-type dwarfism.

Evaluation of a biocidal turbine-fuel additive.

DOT National Transportation Integrated Search

1967-08-01

Growth of microorganisms in water-contaminated, kerosene-type fuels is a widespread problem in aviation. One approach to the solution of this problem is the introduction into fuel of a chemical additive which could stop or retard growth of microbes. ...

Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

PubMed

Wang, Yan-Ping; Chen, Xu; Zhang, Zhi-Kun; Cui, Hong-Yan; Wang, Peng; Wang, Yue

2015-12-01

Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods. © The Author(s) 2014.

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

PubMed

Matsumoto, Tadashi; Miyakoshi, Kei; Saisho, Yoshifumi; Ishii, Tomohiro; Ikenoue, Satoru; Kasuga, Yoshifumi; Kadohira, Ikuko; Sato, Seiji; Momotani, Naoko; Minegishi, Kazuhiro; Yoshimura, Yasunori

2013-01-01

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Hypoxia and fetal heart development.

PubMed

Patterson, A J; Zhang, L

2010-10-01

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

PubMed Central

Serra, Andreas L; Kistler, Andreas D; Poster, Diane; Struker, Marian; Wüthrich, Rudolf P; Weishaupt, Dominik; Tschirch, Frank

2007-01-01

Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune®) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918 PMID:17868472

Alimentary tract innervation deficits and dysfunction in mice lacking GDNF family receptor alpha2.

PubMed

Rossi, Jari; Herzig, Karl-Heinz; Võikar, Vootele; Hiltunen, Païvi H; Segerstråle, Mikael; Airaksinen, Matti S

2003-09-01

Subsets of parasympathetic and enteric neurons require neurturin signaling via glial cell line-derived neurotrophic factor family receptor alpha2 (GFRalpha2) for development and target innervation. Why GFRalpha2-deficient (Gfra2-/-) mice grow poorly has remained unclear. Here, we analyzed several factors that could contribute to the growth retardation. Neurturin mRNA was localized in the gut circular muscle. GFRalpha2 protein was expressed in most substance P-containing myenteric neurons, in most intrapancreatic neurons, and in surrounding glial cells. In the Gfra2-/- mice, density of substance P-containing myenteric ganglion cells and nerve bundles in the myenteric ganglion cell layer was significantly reduced, and transit of test material through small intestine was 25% slower compared to wild-type mice. Importantly, the knockout mice had approximately 80% fewer intrapancreatic neurons, severely impaired cholinergic innervation of the exocrine but not the endocrine pancreas, and increased fecal fat content. Vagally mediated stimulation of pancreatic secretion by 2-deoxy-glucose in vivo was virtually abolished. Retarded growth of the Gfra2-/- mice was accompanied by reduced fat mass and elevated basal metabolic rate. Moreover, the knockout mice drank more water than wild-type controls, and wet-mash feeding resulted in partial growth rescue. Taken together, the results suggest that the growth retardation in mice lacking GFRalpha2 is largely due to impaired salivary and pancreatic secretion and intestinal dysmotility.

Medicaid-financed residential care for persons with mental retardation.

PubMed

Lakin, K C; Hall, M J

1990-12-01

Two sources of Medicaid support for persons with mental retardation and related conditions (MR/RC) are examined, the intermediate care facility for the mentally retarded (ICF/MR) program and the home and community-based services (HCBS) waiver. Results indicate that Medicaid support through the ICF/MR program has shown little recent growth in terms of number of persons served, although expenditures continue to increase. Medicaid's HCBS waiver is being used increasingly by States to support residential placement because of its greater flexibility and more individualized approach relative to ICF/MR care. Use of Medicaid to finance care for persons with MR/RC varies considerably across States.

Medicaid-financed residential care for persons with mental retardation

PubMed Central

Lakin, K. Charlie; Hall, Margaret Jean

1990-01-01

Two sources of Medicaid support for persons with mental retardation and related conditions (MRIRC) are examined, the intermediate care facility for the mentally retarded (ICF/MR) program and the home and community-based services (HCBS) waiver. Results indicate that Medicaid support through the ICF/MR program has shown little recent growth in terms of number of persons served, although expenditures continue to increase. Medicaid's HCBS waiver is being used increasingly by States to support residential placement because of its greater flexibility and more individualized approach relative to ICF/MR care. Use of Medicaid to finance care for persons with MR/RC varies considerably across States. PMID:10113489

Historical (1749-1899) vs. present-day sugar maple and beech diameter growth in the northeast

Treesearch

William B. Leak

2011-01-01

Possible environmental impacts in the Northeast from climate change, acid deposition, nutrient depletion, and other factors could retard tree growth and development in the northeastern United States. To gain insight into growth trends before the 20th century, approximately 150 years of radial growth records taken in 1899 on sugar maple and beech were examined and...

Effect of lauricidin and ethylenediaminetetraacetic acid on growth of nine hymenomycetous fungi.

Treesearch

C. Y. Li; Paul E. Aho

1984-01-01

Growth of nine wood-decaying basidiomycetes was measured on media containing 10, 100, and 1,000 parts per million (p/m) Lauricidin with or without 0.1 percent ethylenediaminetetraacetic acid (EDTA). EDTA alone significantly reduced the growth of all fungi tested. Lauricidin at 1,000 p/m significantly retarded the growth of all fungi except two: Ganoderma...

Influence of Aphelenchus avenae on Vesicular-arbuscular Endomycorrhizal Growth Response in Cotton.

PubMed

Hussey, R S; Roncadori, R W

1981-01-01

The influence of Aphelenchus avenae on the relationship between cotton (Gossypium hirsutum 'Stoneville 213') and Gigaspora margarita or Glomus etunicatus was assessed by its effect on the mycorrhizal stimulation of plant growth and microorganism reproduction. The mycophagous nematode usually did not suppress stimulation of shoot growth resulting from mycorrhizae (G. margarita) at inoculum levels of 3,000 or 6,000 nematodes per pot, but retarded root growth at 6,000 per pot. When the nematode inoculum was increased to 10, 40, or 80 thousand, G. margarita stimulation of shoot or root growth was retarded at the two higher rates. Shoot growth enhancement by G. etunicatus was suppressed by 10 thousand A. avenae but not by 40 or 80 thousand. A. avenae reproduced better when the nematode was added 3 wk after G. margarita than with simultaneous inoculations. Sporulation of both fungi was affected little by the mycophagous nematode. The high numbers of A. avenae required for an antagonistic effect probably precludes the occurrence of any significant interaction between these two organisms under field conditions.

Validation of In utero Tractography of Human Fetal Commissural and Internal Capsule Fibers with Histological Structure Tensor Analysis

PubMed Central

Mitter, Christian; Jakab, András; Brugger, Peter C.; Ricken, Gerda; Gruber, Gerlinde M.; Bettelheim, Dieter; Scharrer, Anke; Langs, Georg; Hainfellner, Johannes A.; Prayer, Daniela; Kasprian, Gregor

2015-01-01

Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic characterization of axon guidance disorders at prenatal stages of human brain development. PMID:26732460

A Social Attitude Approach to Sex Education for the Educable Mentally Retarded. In-Service Training Materials for Teachers of the Educable Mentally Retarded, Session III.

ERIC Educational Resources Information Center

Meyen, Edward L.; Carr, Donald L.

Designed for educable mentally handicapped children, these lessons on social attitudes stress sex education and also present broader coverage of information relevant to the development of social skills. The pre-primary unit, for ages 4 to 7, includes lessons on healthy body image, proper toilet habits, male and female roles, sequence of growth,…

Perinatal transport: problems in neonatal intensive care capacity.

PubMed

Gill, A B; Bottomley, L; Chatfield, S; Wood, C

2004-05-01

To assess the quantity and nature of transfers within the Yorkshire perinatal service, with the aim of identifying suitable outcome measures for the assessment of future service improvements. Collection of data on perinatal transfers from all neonatal and maternity units located in the Yorkshire region of the United Kingdom from May to November 2000. Expectant mothers (in utero transfers) and neonates (ex utero transfers). None Quantification of in utero and ex utero transfers; the reasons for and resources required to support transfers; the nature of each transfer (acute, specialist, non-acute, into or out of region). In the period studied, there were 800 transfers (337 in utero; 463 ex utero); 306 transfers were "acute" (80% of transfers in utero), 214 because of specialist need, and 280 "non-acute". Some 37% of capacity transfers occurred from the two level 3 units in the region. Of 254 transfers out of the 14 neonatal units for intensive care, 44 (17.3%) were transferred to hospitals outside the normal neonatal commissioning boundaries. The study highlights a continuing apparent lack of capacity within the neonatal service in the Yorkshire region, resulting in considerable numbers of neonatal and maternal transfers.

Maternal exposure to ambient air pollution and fetal growth in North-East Scotland: A population-based study using routine ultrasound scans.

PubMed

Clemens, Tom; Turner, Steve; Dibben, Chris

2017-10-01

Maternal ambient air pollution exposure is associated with reduced birthweight. Few studies have examined the effect on growth in utero and none have examined the effect of exposure to particulates less than 2.5µm (PM 2.5 ) and possible effect modification by smoking status. Examine the effect of maternal exposure to ambient concentrations of PM 10 , PM 2.5 and nitrogen dioxide (NO 2 ) for in utero fetal growth, size at birth and effect modification by smoking status. Administratively acquired second and third trimester fetal measurements (bi-parietal diameter, femur length and abdominal circumference), birth outcomes (weight, crown heel length and occipito-frontal circumference) and maternal details were obtained from routine fetal ultrasound scans and maternity records (period 1994-2009). These were modelled against residential annual pollution concentrations (calendar year mean) adjusting for covariates and stratifying by smoking status. In the whole sample (n=13,775 pregnancies), exposure to PM 10 , PM 2.5 and NO 2 was associated with reductions in measurements at birth and biparietal diameter from late second trimester onwards. Among mothers who did not smoke at all during pregnancy (n=11,075), associations between biparietal diameter and pollution exposure remained significant but were insignificant among those who did smoke (n=2700). Femur length and abdominal circumference were not significantly associated with pollution exposure. Fetal growth is strongly associated with particulates exposure from later in second trimester onwards but the effect appears to be subsumed by smoking. Typical ambient exposures in this study were relatively low compared to other studies and given these results, it may be necessary to consider reducing recommended "safe" ambient air exposures. Copyright © 2017. Published by Elsevier Ltd.

Influence of primiparity on size at birth, growth, the somatotrophic axis and fertility in dairy heifers.

PubMed

Swali, A; Wathes, D C

2007-11-01

Epidemiological studies in humans suggest that small size at birth is a predictor of some adult diseases. Nutritional constraint experienced in utero may result in fetal adaptations, which alter subsequent body structure and physiology. Size at birth is influenced by maternal age and parity. Most dairy cows are bred for the first time at about 60% of their mature body weight and therefore carry their first pregnancy whilst still growing. We hypothesized that this might alter the nutritional environment in utero and thus influence the development of the calf. This study compared birth size, growth rates and fertility in consecutively born heifer offspring of 45 primiparous (PP) and 71 multiparous (MP) dairy cows on one farm. Measures of the somatotrophic axis (GH, insulin, IGF-I and glucose) were compared in blood samples collected at the start of the first lactation. Offspring of PP cows were significantly smaller at birth (weight, length, height, girth, P<0.01) than those born to MP dams. The ponderal index (weight/height(3)) was similar, showing that growth restriction was proportional. These differences were no longer apparent at 3 months, indicative of early catch up growth. The PP offspring conceived more rapidly during their first service period as nulliparous heifers (P<0.02). They experienced a greater weight loss postpartum (P<0.002) and had lower concentrations of IGF-I and insulin following their first calving (P<0.05). Fertility in the first lactation was, however, similar between the two groups. We conclude that having a primiparous dam resulted in a smaller size at birth and influenced the somatotrophic axis around calving. Fertility was generally better in offspring of PP than MP dams.

Altered glucose transport to utero-embryonic unit in relation to delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

PubMed

Arnab, Banerjee; Amitabh, Krishna

2011-02-10

The aim of this study was to compare the changes in concentration of glucose and glucose transporters (GLUTs) in the utero-embryonic unit, consisting of decidua, trophoblast and embryo, during delayed and non-delayed periods to understand the possible cause of delayed embryonic development in Cynopterus sphinx. The results showed a significantly decreased concentration of glucose in the utero-embryonic unit due to decline in the expression of insulin receptor (IR) and GLUT 3, 4 and 8 proteins in the utero-embryonic unit during delayed period. The in vitro study showed suppressive effect of insulin on expression of GLUTs 4 and 8 in the utero-embryonic unit and a significant positive correlation between the decreased amount of glucose consumed by the utero-embryonic unit and decreased expression of GLUTs 4 (r=0.99; p<0.05) and 8 (r=0.98; p<0.05). The in vivo study showed expression of IR and GLUT 4 proteins in adipose tissue during November suggesting increased transport of glucose to adipose tissue for adipogenesis. This study showed increased expression of HSL and OCTN2 and increased availability of l-carnitine to utero-embryonic unit suggesting increased transport of fatty acid to utero-embryonic unit during the period of delayed embryonic development. Hence it appears that due to increased transport of glucose for adipogenesis prior to winter, glucose utilization by utero-embryonic unit declines and this may be responsible for delayed embryonic development in C. sphinx. Increased supply of fatty acid to the delayed embryo may be responsible for its survival under low glucose condition but unable to promote embryonic development in C. sphinx. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

In utero heat stress increases postnatal core body temperature in pigs

USDA-ARS?s Scientific Manuscript database

In utero heat stress (IUHS) negatively impacts postnatal development, but how it alters future body temperature parameters and energetic metabolism is not well-understood. Objectives were to characterize future temperature indices and bioenergetic markers in pigs originating from differing in utero...

A comprehensive tool for image-based generation of fetus and pregnant women mesh models for numerical dosimetry studies

NASA Astrophysics Data System (ADS)

Dahdouh, S.; Varsier, N.; Serrurier, A.; De la Plata, J.-P.; Anquez, J.; Angelini, E. D.; Wiart, J.; Bloch, I.

2014-08-01

Fetal dosimetry studies require the development of accurate numerical 3D models of the pregnant woman and the fetus. This paper proposes a 3D articulated fetal growth model covering the main phases of pregnancy and a pregnant woman model combining the utero-fetal structures and a deformable non-pregnant woman body envelope. The structures of interest were automatically or semi-automatically (depending on the stage of pregnancy) segmented from a database of images and surface meshes were generated. By interpolating linearly between fetal structures, each one can be generated at any age and in any position. A method is also described to insert the utero-fetal structures in the maternal body. A validation of the fetal models is proposed, comparing a set of biometric measurements to medical reference charts. The usability of the pregnant woman model in dosimetry studies is also investigated, with respect to the influence of the abdominal fat layer.

Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

PubMed

Miner, Jonathan J; Cao, Bin; Govero, Jennifer; Smith, Amber M; Fernandez, Estefania; Cabrera, Omar H; Garber, Charise; Noll, Michelle; Klein, Robyn S; Noguchi, Kevin K; Mysorekar, Indira U; Diamond, Michael S

2016-05-19

Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations. Copyright © 2016 Elsevier Inc. All rights reserved.

Zika virus infection during pregnancy in mice causes placental damage and fetal demise

PubMed Central

Miner, Jonathan J.; Cao, Bin; Govero, Jennifer; Smith, Amber M.; Fernandez, Estefania; Cabrera, Omar H.; Garber, Charise; Noll, Michelle; Klein, Robyn S.; Noguchi, Kevin K.; Mysorekar, Indira U.; Diamond, Michael S.

2016-01-01

SUMMARY Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1−/−) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations. PMID:27180225

Effect of an ozone injury-retardant chemical on isozyme profiles from alfalfa callus in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rier, J.P.; Sood, V.K.; Whitaker, A.

1983-01-01

Plant ozone injury retardant (EDU or ethylenediurea) at 1.0 ppm inhibited growth of callus of alfalfa cultivars Williamsburg (ozone-sensitive) and MSB-CW5An2(ozone-insensitive) germplasm of Medicago sative. The presence of EDU(0.1 ppm) in growth medium increased the number of protein and peroxidase isozyme bands in alfalfa cultivar stem callus and ozone modified their intensities. Protein profiles of MSB stem callus from media containing EDU or exposed to ozone were unchanged. Marked differences were observed between the peroxidase profiles of ozonated and control ozone-insensitive stem callus from media containing EDU. Protein profiles of ozonated ozone-insensitive leaf callus differed slightly from controls.

Williams-Beuren syndrome associated with single kidney and nephrocalcinosis: a case report.

PubMed

Abidi, Kamel; Jellouli, Manel; Ben Rabeh, Rania; Hammi, Yousra; Gargah, Tahar

2015-01-01

Williams-Beuren syndrome is a rare neurodevelopmental disorder, characterized by congenital heart defects, abnormal facial features, mental retardation with specific cognitive and behavioral profile, growth hormone deficiency, renal and skeletal anomalies, inguinal hernia, infantile hypercalcaemia. We report a case with Williams-Beuren syndrome associated with a single kidney and nephrocalcinosis complicated by hypercalcaemia. A male infant, aged 20 months presented growth retardation associated with a psychomotor impairment, dysmorphic features and nephrocalcinosis. He had also hypercalciuria and hypercalcemia. Echocardiography was normal. DMSA renal scintigraphy showed a single functioning kidney. The FISH generated one ELN signal in 20 metaphases read and found the presence of ELN deletion, with compatible Williams-Beuren syndrome.

[Associated factors in newborns with intrauterine growth retardation].

PubMed

Thompson-Chagoyán, Oscar C; Vega-Franco, Leopoldo

2008-01-01

To identify the risk factors implicated in the intrauterine growth retardation (IUGR) of neonates born in a social security institution. Case controls design study in 376 neonates: 188 with IUGR (weight < 10 percentile) and 188 without IUGR. When they born, information about 30 variables of risk for IUGR were obtained from mothers. Risk analysis and logistical regression (stepwise) were used. Odds ratios were significant for 12 of the variables. The model obtains by stepwise regression included: weight gain at pregnancy, prenatal care attendance, toxemia, chocolate ingestion, father's weight, and the environmental house. Must of the variables included in the model are related to socioeconomic disadvantages related to the risk of RCIU in the population.

A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes.

PubMed

Thiffault, Isabelle; Saunders, Carol; Jenkins, Janda; Raje, Nikita; Canty, Kristi; Sharma, Mukta; Grote, Lauren; Welsh, Holly I; Farrow, Emily; Twist, Greyson; Miller, Neil; Zwick, David; Zellmer, Lee; Kingsmore, Stephen F; Safina, Nicole P

2015-05-07

Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage, often leading to immunodeficiency, growth retardation and increased risk of malignancy. We performed exome sequencing on a girl with a suspected chromosome instability syndrome that manifested as growth retardation, microcephaly, developmental delay, dysmorphic features, poikiloderma, immune deficiency with pancytopenia, and myelodysplasia. She was homozygous for a previously reported splice variant, c.4444 + 3A > G in the POLE1 gene, which encodes the catalytic subunit of DNA polymerase E. This is the second family with POLE1-deficency, with the affected individual demonstrating a more severe phenotype than previously described.

Late radiation responses in man: Current evaluation from results from Hiroshima and Nagasaki

NASA Astrophysics Data System (ADS)

Schull, William J.

Among the late effects of exposure to the atomic bombings of Hiroshima and Nagasaki, none looms larger than radiation related malignancies. Indeed, the late effects of A-bomb radiation on mortality appear to be limited to an increase in malignant tumors. At present, it can be shown that cancers of the breast, colon, esophagus, lungs, stomach, thyroid, and urinary tract as well as leukemia and multiple myeloma increase in frequency with an increase in exposure. No significant relationship to radiation can as yet be established for malignant lymphoma, nor cancers of the rectum, pancreas or uterus. Radiation induced malignancies other than leukemia seem to develop proportionally to the natural cancer rate for the attained age. For specific age-at-death intervals, both relative and absolute risks tend to be higher for those of younger age at the time of bombing. Other late effects include radiation-related lenticular opacities, disturbances of growth among those survivors still growing at the time of exposure, and mental retardation and small head sizes among the in utero exposed. Chromosomal abnormalities too are more frequently encountered in the peripheral leucocytes of survivors, and this increase is functionally related to their exposure. Some uncertainty continues to surround both the quantity and quality of the radiation released by these two nuclear devices, particularly the Hiroshima bomb. A recent reassessment suggests that the gamma radiation estimates which have been used in the past may be too low at some distances and the neutron radiation estimates too high at all distances; moreover, the energies of the neutrons released now appear ``softer'' than previously conjectured. These uncertainties not sufficiently large, however, to compromise the reality of the increased frequency of malignancy, but make estimates of the dose response, particularly in terms of gamma and neutron exposures, tentative.

Predicting autism at birth.

PubMed

Steinman, Gary

2013-07-01

The amounts of at least three biochemical factors are more often abnormal in autistic people than neurologically normal ones. They include insulin-like growth factor, anti-myelin basic protein, and serotonin. This may explain why processes initiated in utero which hinder normal neurogenesis, especially myelination, continue after delivery. Quantitation of these parameters may make possible the calculation of an autism index, anticipating at birth which children will ultimately develop overt autism. Copyright © 2013 Elsevier Ltd. All rights reserved.

In Utero DDT and DDE Exposure and Obesity Status of 7-Year-Old Mexican-American Children in the CHAMACOS Cohort

PubMed Central

Schall, Raul Aguilar; Harley, Kim G.; Bradman, Asa; Barr, Dana; Eskenazi, Brenda

2013-01-01

Background: In utero exposure to endocrine disrupting compounds including dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) has been hypothesized to increase risk of obesity later in life. Objectives: The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study is a longitudinal birth cohort of low-income Latinas living in a California agricultural community. We examined the relation of in utero DDT and DDE exposure to child obesity at 7 years of age. We also examined the trend with age (2, 3.5, 5, and 7 years) in the exposure–obesity relation. Methods: We included 270 children with o,p´-DDT, p,p´-DDT, and p,p´-DDE concentrations measured in maternal serum during pregnancy (nanograms per gram lipid) and complete 7-year follow-up data including weight (kilograms) and height (centimeters). Body mass index (BMI; kilograms per meter squared) was calculated and obesity was defined as ≥ 95th percentile on the sex-specific BMI-for-age Centers for Disease Control and Prevention 2000 growth charts. Results: At 7 years, 96 (35.6%) children were obese. A 10-fold increase in o,p´-DDT, p,p´-DDT, or p,p´-DDE, was nonsignificantly associated with increased odds (OR) of obesity [o,p´-DDT adjusted (adj-) OR = 1.17, 95% CI: 0.75, 1.82; p,p´-DDT adj-OR = 1.19, 95% CI: 0.81, 1.74; p,p´-DDE adj-OR = 1.22, 95% CI: 0.72, 2.06]. With increasing age at follow-up, we observed a significant trend toward a positive association between DDT and DDE exposure and odds of obesity. Conclusion: We did not find a significant positive relation between in utero DDT and DDE exposure and obesity status of 7-year-old children. However, given the observed trend with age, continued follow-up will be informative. PMID:23512307

Intelligence of very preterm or very low birthweight infants in young adulthood.

PubMed

Weisglas-Kuperus, N; Hille, E T M; Duivenvoorden, H J; Finken, M J J; Wit, J M; van Buuren, S; van Goudoever, J B; Verloove-Vanhorick, S P

2009-05-01

To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era. A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin. The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (<25 years) had a 2.7-point lower IQ, and men had a 2.1-point higher IQ than women. The effect on intelligence after early (symmetric) intrauterine growth retardation was more pronounced than after later (asymmetric) intrauterine or neonatal growth retardation. These differences in mean IQ remained when participants with overt handicaps were excluded. Prematurity as well as the timing of growth retardation are important for later intelligence. Parental education, however, best predicted later intelligence in very preterm or very low birthweight infants.

Fontanelles - excessively large

MedlinePlus

... Hydrocephalus Intrauterine growth retardation (IUGR) Premature birth Rarer causes: Achondroplasia Apert syndrome Cleidocranial dysostosis Congenital rubella Neonatal hypothyroidism Osteogenesis imperfecta Rickets When to Contact a Medical ...

Fundamental Investigation of Fatigue Crack Growth Retardation in Aluminum Alloys

DTIC Science & Technology

1976-09-01

Fatigue Crack Propagation in 2024 -T3 Aluminum Alloy , " ASTM STP 536, p. 115, 1973. 9. J. Schijve, " Effect of Load Sequences...Hertzberg, " Effect of Multiple Over- loads on Fatigue Crack Propagation in 2024 -T3 Aluminum Alloy , " ASTM STP-536, p. 115, 1973. 9. J. Schijve... Effect of Thickness on Retardation Behavior of 7075 and 2024 Aluminum Alloys .......... 185 vi LIST OF ILLUSTRATIONS FIGURE PAGE 1 SEN

X-linked mental retardation syndrome: Three brothers with the Brooks-Wisniewski-Brown syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morava, E.; Storcz, J.; Kosztolanyi, G.

1996-07-12

We report on 3 brothers with growth and mental retardation, bifrontal narrowness, short palpebral fissures, deeply set eyes with entropion, wide bulbous nose, small mouth, myopia, and spastic diplegia. The patients were born to normal and non-consanguineous parents. The similarity of our cases with those recently reported by Brooks et al. supports their suggestion that these patients are representative of a distinct entity. 8 refs., 3 figs., 1 tab.

Mechanism of gibberellin-dependent stem elongation in peas

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.; Sovonick-Dunford, S. A.

1989-01-01

Stem elongation in peas (Pisum sativum L.) is under partial control by gibberellins, yet the mechanism of such control is uncertain. In this study, we examined the cellular and physical properties that govern stem elongation, to determine how gibberellins influence pea stem growth. Stem elongation of etiolated seedlings was retarded with uniconozol, a gibberellin synthesis inhibitor, and the growth retardation was reversed by exogenous gibberellin. Using the pressure probe and vapor pressure osmometry, we found little effect of uniconozol and gibberellin on cell turgor pressure or osmotic pressure. In contrast, these treatments had major effects on in vivo stress relaxation, measured by turgor relaxation and pressure-block techniques. Uniconozol-treated plants exhibited reduced wall relaxation (both initial rate and total amount). The results show that growth retardation is effected via a reduction in the wall yield coefficient and an increase in the yield threshold. These effects were largely reversed by exogenous gibberellin. When we measured the mechanical characteristics of the wall by stress/strain (Instron) analysis, we found only minor effects of uniconozol and gibberellin on the plastic compliance. This observation indicates that these agents did not alter wall expansion through effects on the mechanical (viscoelastic) properties of the wall. Our results suggest that wall expansion in peas is better viewed as a chemorheological, rather than a viscoelastic, process.

Arch fingerprints, hypotonia, and areflexia associated with X linked mental retardation.

PubMed Central

Stevenson, R E; Häne, B; Arena, J F; May, M; Lawrence, L; Lubs, H A; Schwartz, C E

1997-01-01

A syndrome with distinctive facies, poor muscle tone, absent deep tendon reflexes, tapered fingers, excessive fingerprint arches, genu valgum and mild-moderate mental retardation has occurred in four males in two generations of a white family of European ancestry. The facies are characterised by square configuration, tented upper lip, and thickening of the helices, upper eyelids, and alae nasi. At birth and at maturity, growth (head circumference, height, weight) of affected males is comparable to or greater than unaffected male sibs. Moderate impairment of cognitive function was documented (IQ scores between 40-51). Carriers show no heterozygote manifestations. This X linked condition appears to be different from other syndromes with mental retardation, although there are certain similarities with the alpha thalassaemia-mental retardation syndrome (ATR-X). Linkage analysis found tight linkage to DXS1166 and DXS995 in Xq13 and Xq21 respectively. Images PMID:9192265

Arch fingerprints, hypotonia, and areflexia associated with X linked mental retardation.

PubMed

Stevenson, R E; Häne, B; Arena, J F; May, M; Lawrence, L; Lubs, H A; Schwartz, C E

1997-06-01

A syndrome with distinctive facies, poor muscle tone, absent deep tendon reflexes, tapered fingers, excessive fingerprint arches, genu valgum and mild-moderate mental retardation has occurred in four males in two generations of a white family of European ancestry. The facies are characterised by square configuration, tented upper lip, and thickening of the helices, upper eyelids, and alae nasi. At birth and at maturity, growth (head circumference, height, weight) of affected males is comparable to or greater than unaffected male sibs. Moderate impairment of cognitive function was documented (IQ scores between 40-51). Carriers show no heterozygote manifestations. This X linked condition appears to be different from other syndromes with mental retardation, although there are certain similarities with the alpha thalassaemia-mental retardation syndrome (ATR-X). Linkage analysis found tight linkage to DXS1166 and DXS995 in Xq13 and Xq21 respectively.

Macroenvironment effects on oocytes and embryos in swine.

PubMed

Foxcroft, G R; Vinsky, M D; Paradis, F; Tse, W-Y; Town, S C; Putman, C T; Dyck, M K; Dixon, W T

2007-09-01

As in other domestic mammals, the interaction between genotype and environment in swine has profound effects on the ultimate phenotype of the individual born. Interactions within the litter in utero add an additional level of complexity in a litter-bearing species like the pig. Nutritional manipulations during the preovulatory period affect the maturity of the follicle and enclosed oocyte, and the metabolic and endocrine mechanisms potentially mediating these effects have been described. Extensive research on lactational catabolism in the first parity sow has established an association between the development of immature follicles and oocytes, and the reduced fertility of these sows when bred at the first postweaning estrus. This negative impact of lactational catabolism appears to be exaggerated in contemporary dam-lines by a minimal delay between weaning and first estrus, further limiting the maturity of the follicle and oocyte at the time of ovulation. Metabolic programming may induce gender-specific loss of embryos by Day 30 and affects embryonic development directly, without significant effects on placental size. In contrast, inadvertent crowding of embryos in utero, particularly evident in a sub-population of mature sows with high ovulation rates and moderate to high embryonic survival to Day 30, significantly limits placental development of crowded litters. However, even at Day 30, moderate crowding in utero also appears to affect myogenesis in the embryo in a gender-specific manner. In the absence of compensatory placental growth after Day 30, classic measures of IUGR are evident in surviving fetuses at Day 90 and at term.

Renal development: a complex process dependent on inductive interaction.

PubMed

Upadhyay, Kiran K; Silverstein, Douglas M

2014-01-01

Renal development begins in-utero and continues throughout childhood. Almost one-third of all developmental anomalies include structural or functional abnormalities of the urinary tract. There are three main phases of in-utero renal development: Pronephros, Mesonephros and Metanephros. Within three weeks of gestation, paired pronephri appear. A series of tubules called nephrotomes fuse with the pronephric duct. The pronephros elongates and induces the nearby mesoderm, forming the mesonephric (Woffian) duct. The metanephros is the precursor of the mature kidney that originates from the ureteric bud and the metanephric mesoderm (blastema) by 5 weeks of gestation. The interaction between these two components is a reciprocal process, resulting in the formation of a mature kidney. The ureteric bud forms the major and minor calyces, and the collecting tubules while the metanephrogenic blastema develops into the renal tubules and glomeruli. In humans, all of the nephrons are formed by 32 to 36 weeks of gestation. Simultaneously, the lower urinary tract develops from the vesico urethral canal, ureteric bud and mesonephric duct. In utero, ureters deliver urine from the kidney to the bladder, thereby creating amniotic fluid. Transcription factors, extracellular matrix glycoproteins, signaling molecules and receptors are the key players in normal renal development. Many medications (e.g., aminoglycosides, cyclooxygenase inhibitors, substances that affect the renin-angiotensin aldosterone system) also impact renal development by altering the expression of growth factors, matrix regulators or receptors. Thus, tight regulation and coordinated processes are crucial for normal renal development.

Evidence for altered placental blood flow and vascularity in compromised pregnancies

PubMed Central

Reynolds, Lawrence P; Caton, Joel S; Redmer, Dale A; Grazul-Bilska, Anna T; Vonnahme, Kimberly A; Borowicz, Pawel P; Luther, Justin S; Wallace, Jacqueline M; Wu, Guoyao; Spencer, Thomas E

2006-01-01

The placenta is the organ that transports nutrients, respiratory gases, and wastes between the maternal and fetal systems. Consequently, placental blood flow and vascular development are essential components of normal placental function and are critical to fetal growth and development. Normal fetal growth and development are important to ensure optimum health of offspring throughout their subsequent life course. In numerous sheep models of compromised pregnancy, in which fetal or placental growth, or both, are impaired, utero-placental blood flows are reduced. In the models that have been evaluated, placental vascular development also is altered. Recent studies found that treatments designed to increase placental blood flow can ‘rescue’ fetal growth that was reduced due to low maternal dietary intake. Placental blood flow and vascular development are thus potential therapeutic targets in compromised pregnancies. PMID:16469783

Successful Growth Hormone Therapy in Cornelia de Lange Syndrome.

PubMed

de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Willem Redeker, Egbert Johan; Eduard Santen, Gijs Willem; Henriëtta Verkerk, Annemieke Johanna Maria; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

2017-12-15

Cornelia de Lange syndrome (CdLS) is a both clinically and genetically heterogeneous syndrome. In its classical form, it is characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay, and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge, there are no reports on the effect of recombinant human GH treatment in CdLS patients. We present a patient born small for gestational age with persistent severe growth retardation [height -3.4 standard deviation score (SDS)] and mild dysmorphic features, who was treated with GH from 4.3 years of age onward and was diagnosed 6 years later with CdLS using whole-exome sequencing. Treatment led to a height gain of 1.6 SDS over 8 years. Treatment was interrupted shortly due to high serum insulin-like growth factor-1 serum values. In conclusion, GH therapy may be effective and safe for short children with CdLS.

The gut eukaryotic microbiota influences the growth performance among cohabitating shrimp.

PubMed

Dai, Wenfang; Yu, Weina; Zhang, Jinjie; Zhu, Jinyong; Tao, Zhen; Xiong, Jinbo

2017-08-01

Increasing evidence has revealed a close interplay between the gut bacterial communities and host growth performance. However, until recently, studies generally ignored the contribution of eukaryotes, endobiotic organisms. To fill this gap, we used Illumina sequencing technology on eukaryotic 18S rRNA gene to compare the structures of gut eukaryotic communities among cohabitating retarded, overgrown, and normal shrimp obtained from identically managed ponds. Results showed that a significant difference between gut eukaryotic communities differed significantly between water and intestine and among three shrimp categories. Structural equation modeling revealed that changes in the gut eukaryotic community were positively related to digestive enzyme activities, which in turn influenced shrimp growth performance (λ = 0.97, P < 0.001). Overgrown shrimp exhibited a more complex and cooperative gut eukaryotic interspecies interaction than retarded and normal shrimp, which may facilitate their nutrient acquisition efficiency. Notably, the distribution of dominant eukaryotic genera and shifts in keystone species were closely concordant with shrimp growth performance. In summary, this study provides an integrated overview on direct roles of gut eukaryotic communities in shrimp growth performance instead of well-studied bacterial assembly.

Successful Growth Hormone Therapy in Cornelia de Lange Syndrome

PubMed Central

de Graaf, Michael; Kant, Sarina G; Wit, Jan Maarten; Redeker, Egbert Johan Willem; Santen, Gijs Willem Eduard; Verkerk, Annemieke Johanna Maria Henriëtta; Uitterlinden, André Gerardus; Losekoot, Monique; Oostdijk, Wilma

2017-01-01

Cornelia de Lange syndrome (CdLS) is a both clinically and genetically heterogeneous syndrome. In its classical form, it is characterised by distinctive facial features, intra-uterine growth retardation, short stature, developmental delay, and anomalies in multiple organ systems. NIPBL, SMC1A, SMC3, RAD21 and HDAC8, all involved in the cohesin pathway, have been identified to cause CdLS. Growth hormone (GH) secretion has been reported as normal, and to our knowledge, there are no reports on the effect of recombinant human GH treatment in CdLS patients. We present a patient born small for gestational age with persistent severe growth retardation [height -3.4 standard deviation score (SDS)] and mild dysmorphic features, who was treated with GH from 4.3 years of age onward and was diagnosed 6 years later with CdLS using whole-exome sequencing. Treatment led to a height gain of 1.6 SDS over 8 years. Treatment was interrupted shortly due to high serum insulin-like growth factor-1 serum values. In conclusion, GH therapy may be effective and safe for short children with CdLS. PMID:28588001

Prenatal lead exposure and bone growth. Doctoral thesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, J.D.; O'Flaherty, E.J.

1990-07-24

An experimental system of lead (7439921) related prenatal and postnatal growth retardation in rats was developed. Sprague-Dawley-rats and Long-Evans-rats were used in these studies. Rats were exposed to lead in their drinking water at up to 1000 parts per million. A significant effect on fetal bone mineralization could not be excluded and there was a definite effect on fetal body weight following maternal lead exposure. Reduced food intake during the first week of lead exposure was the primary determinant of reduced body and skeletal growth in the lead exposed weanling female rats. When maternal lead exposure was continued during lactationmore » a greater degree of lead related growth retardation in rat offspring occurred than when maternal lead exposure was terminated at parturition. Combined prenatal and postnatal lead exposure impaired bone resorption and increased growth plate widths. In studies using matrix induced endochondral bone plaques, locally applied lead enhanced plaque mineralization through comineralization of lead with calcium. When lead was administered in drinking water, plaque mineralization was also enhanced through the comineralization of lead with calcium.« less

The Essential Role of Mbd5 in the Regulation of Somatic Growth and Glucose Homeostasis in Mice

PubMed Central

Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

2012-01-01

Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis. PMID:23077600

The essential role of Mbd5 in the regulation of somatic growth and glucose homeostasis in mice.

PubMed

Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

2012-01-01

Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis.

Mild Wolf-Hirschhorn phenotype and partial GH deficiency in a patient with a 4p terminal deletion.

PubMed

Titomanlio, L; Romano, A; Conti, A; Genesio, R; Salerno, M; De Brasi, D; Nitsch, L; Del Giudice, E

2004-06-01

Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients. Copyright 2004 Wiley-Liss, Inc.

A newly recognized syndrome of severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features.

PubMed

Vinkler, Chana; Leshinsky-Silver, Esther; Michelson, Marina; Haas, Dorothea; Lerman-Sagie, Tally; Lev, Dorit

2014-01-01

Genetic syndromes with proportionate severe short stature are rare. We describe two sisters born to nonconsanguineous parents with severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and severe intellectual disability. During infancy and early childhood, the girls had transient hepatosplenomegaly and low blood cholesterol levels that normalized later. A thorough evaluation including metabolic studies, radiological, and genetic investigations were all normal. Cholesterol metabolism and transport were studied and no definitive abnormality was found. No clinical deterioration was observed and no metabolic crises were reported. After due consideration of other known hereditary causes of post-natal severe linear growth retardation, microcephaly, and intellectual disability, we propose that this condition represents a newly recognized autosomal recessive multiple congenital anomaly-intellectual disability syndrome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Role of ST-analysis of fetal ECG in intrapartal fetus monitoring with presumed growth retardation].

PubMed

Hruban, L; Janků, P; Zahradnícková, J; Kurecová, B; Roztocil, A; Kachlík, P; Kucera, M; Jelenek, G

2006-07-01

Evaluation of the role of ST analysis of fetus ECG for early detection of developing acute hypoxia in the course of delivery of fetuses with presumed growth retardation. A comparison with present way of intrapartal fetus monitoring. Impact on the number of surgical births for indications of threatening fetus hypoxia. Influence of the method on perinatal results and postnatal adaptation of the newborns. A prospective study. Gynecology-Obstetrics Clinic, Masaryk University and Teaching Hospital Brno. Forty seven women with a growth retardation of the fetus diagnosed before delivery who gave birth in the Teaching Hospital in Brno during 2003-2005 and intrapartal ST analysis of fetus ECG was subsequently used, were enrolled into this prospective study (group A). The control group consisted of 87 deliveries taking place in the same period of time and concerning women with fetuses suffering from growth retardation and monitored by standard methods (group B). The standard methods included cardiotocography (CTG), supplemented with pulse oximetry (IFPO) if needed. The diagnosis of intrauterine fetus growth retardation was established on the basis of the results of repeated prepartal ultrasound fetus biometry with estimation of the mass, which corresponded to a group below 10 percentile for the given gestational age. The numbers of vaginal deliveries and surgically treated delivery due to threatening fetus hypoxia (Cesarean section, forceps delivery) were recorded. The authors evaluated postpartal pH from umbilical artery, independently for the group of values of pH < 7.00, the group of pH 7.00-0.10 and pH 7.10 or more. The values of Apgar score were evaluated for the first, fifth and tenth minute, respectively. The neonatologist followed the duration of stay of the newborn at the Newborn Intensive Care Unit, the Intermediate Care Unit, total duration of hospitalization, the occurrence of sepsis in the early newbotn period, the occurrence of hyperbilirubinemia, and the conclusion of neurological examination. All the results were evaluated statistically by the chi2 test, Kruskal-Wallis test or the Anova method. There was no statistically significantly difference in the number of delivery ended by surgery for threatening fetus hypoxia (p = 0.856) or the detection rate of intrapartal hypoxia according to pH values of umbilical blood divided into the three groups (p = 0.657, p = 0.958, p = 0.730, respectively). The values of Apgar score differed in favor of the group A significantly only in the first minute at the level of 5% opf significance (p = 0.018). The values of Apgar score in the fifth and tenth minute did not show any significant difference (P = 0301 and p = 0313, respectively). There was no statistically significant difference in neonatological results between the group A and B. The use of ST analysis of fetal ECG in the course of delivery of fetuses with presumed intrauterine growth retardation did not show any significant difference from the presently used methods (CTG supplemented with IFPO if needed). In using the method there was not any effect on the number of surgically treated deliveries for indications of threatening acute fetus hypoxia or perinatal results and postnatal adaptation of the newborns.

Developmental Toxicology##

EPA Science Inventory

Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

PubMed

Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

2014-08-01

The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

Increased nutritional quality of plants for long-duration spaceflight missions through choice of plant variety and manipulation of growth conditions

NASA Astrophysics Data System (ADS)

Cohu, Christopher M.; Lombardi, Elizabeth; Adams, William W.; Demmig-Adams, Barbara

2014-02-01

Low levels of radiation during spaceflight increase the incidence of eye damage and consumption of certain carotenoids (especially zeaxanthin), via a whole-food-based diet (rather than from supplements), is recommended to protect human vision against radiation damage. Availability of fresh leafy produce has, furthermore, been identified as desirable for morale during long spaceflight missions. We report that only trace amounts of zeaxanthin are retained post-harvest in leaves grown under conditions conducive to rapid plant growth. We show that growth of plants under cool temperatures and very high light can trigger a greater retention of zeaxanthin, while, however, simultaneously retarding plant growth. We here introduce a novel growth condition—low growth light supplemented with several short daily light pulses of higher intensity—that also triggers zeaxanthin retention, but without causing any growth retardation. Moreover, two plant varieties with different hardiness exhibited a different propensity for zeaxanthin retention. These findings demonstrate that growth light environment and plant variety can be exploited to simultaneously optimize nutritional quality (with respect to zeaxanthin and two other carotenoids important for human vision, lutein and β-carotene) as well as biomass production of leafy greens suitable as bioregenerative systems for long-duration manned spaceflight missions.

Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity.

PubMed

Naganos, Shintaro; Ueno, Kohei; Horiuchi, Junjiro; Saitoe, Minoru

2016-04-06

Reduced insulin/insulin-like growth factor signaling (IIS) is a major cause of symmetrical intrauterine growth retardation (IUGR), an impairment in cell proliferation during prenatal development that results in global growth defects and mental retardation. In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative learning. However, the physiological and molecular bases of learning defects caused by chico mutations, and by symmetrical IUGR, are not clear. In this study, we found that chico mutations impair memory-associated synaptic plasticity in the mushroom bodies (MBs), neural centers for olfactory learning. Mutations in chico reduce expression of the rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the MBs. Expressing a rut (+) transgene in the MBs restores memory-associated plasticity and olfactory associative learning in chico mutants, without affecting growth. Thus chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in the MBs. Our results suggest that some cognitive defects associated with reduced IIS may occur, independently of developmental defects, from acute reductions in cAMP signaling.

Assessing the Magnitude of Polycyclic Aromatic Hydrocarbon Loading from Road Surfaces and Its Effect on Algal Productivity

DOT National Transportation Integrated Search

2010-06-01

The hypotheses of the study were that PAHs washing off roads would retard the growth of aquatic life-supporting algae and promote the growth of harmful, toxin-producing algae in estuaries, such as the Chesapeake Bay. Runoff from various road surfaces...

In utero methanesulfonyl fluoride differentially affects learning and maze performance in the absence of long-lasting cholinergic changes in the adult rat.

PubMed

Carcoba, Luis M; Santiago, Miguel; Moss, Donald E; Cabeza, Rafael

2008-02-01

There is increasing evidence that acetylcholinesterase (AChE) may have various specific developmental roles in brain development. Nevertheless, specific effects of AChE inhibition during early brain development have not been adequately described. Therefore, methanesulfonyl fluoride (MSF), an irreversible AChE inhibitor that shows high selectivity for the CNS was used to produce AChE inhibition in utero to study subsequent adult behaviors, sleep, and cholinergic markers. Rats exposed to MSF in utero showed a deficit in spatial learning tasks using appetitive motivation but, surprisingly, they performed equally well or better than controls when aversive motivation was used. One hypothesis was that MSF treatment in utero affected the response to stress. Tests of anxiety however showed no differences in basal levels of anxiety. Studies of sleep behavior, however, indicated a higher level of REM sleep which is only seen during the light phase of male rats exposed to MSF in utero as compared to controls. No differences in cholinergic markers in the brains of adults were found except that females exposed to MSF in utero had a higher level of ChAT activity in the synaptosomal fraction of the hippocampus. Even so, whether cholinergic alterations accompany the in utero MSF exposure remains to be determined. The failure to find widespread changes in cholinergic markers in the adult brains suggests changes in behaviors should be further investigated by testing the participation of postsynaptic mechanisms, measuring of cholinergic markers during earlier development periods and the possible participation of other neurotransmitter systems to clearly reveal the role of the cholinergic system following in utero MSF exposure.

In utero methanesulfonyl fluoride differentially affects learning and maze performance in the absence of long-lasting cholinergic changes in the adult rat

PubMed Central

Carcoba, Luis M .; Santiago, Miguel; Moss, Donald E.; Cabeza, Rafael

2008-01-01

There is increasing evidence that acetylcholinesterase (AChE) may have various specific developmental roles in brain development. Nevertheless, specific effects of AChE inhibition during early brain development have not been adequately described. Therefore, methanesulfonyl fluoride (MSF), an irreversible AChE inhibitor that shows high selectivity for the CNS was used to produce AChE inhibition in utero to study subsequent adult behaviors, sleep, and cholinergic markers. Rats exposed to MSF in utero showed a deficit in spatial learning tasks using appetitive motivation but, surprisingly, they performed equally well or better than controls when aversive motivation was used. One hypothesis was that MSF treatment in utero affected the response to stress. Tests of anxiety however showed no differences in basal levels of anxiety. Studies of sleep behavior, however, indicated a higher level of REM sleep which is only seen during the light phase of male rats exposed to MSF in utero as compared to controls. No differences in cholinergic markers in the brains of adults were found except that females exposed to MSF in utero had a higher level of ChAT activity in the synaptosomal fraction of the hippocampus. Even so, whether cholinergic alterations accompany the in utero MSF exposure remains to be determined. The failure to find widespread changes in cholinergic markers in the adult brains suggests changes in behaviors should be further investigated by testing the participation of postsynaptic mechanisms, measuring of cholinergic markers during earlier development periods and the possible participation of other neurotransmitter systems to clearly reveal the role of the cholinergic system following in utero MSF exposure. PMID:17920111

Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency.

PubMed

Jamsheer, Aleksander; Olech, Ewelina M; Kozłowski, Kazimierz; Niedziela, Marek; Sowińska-Seidler, Anna; Obara-Moszyńska, Monika; Latos-Bieleńska, Anna; Karczewski, Marek; Zemojtel, Tomasz

2016-07-01

Desbuquois dysplasia type 2 (DBQD2) is a rare recessively inherited skeletal genetic disorder characterized by severe prenatal and postnatal growth retardation, generalized joint laxity with dislocation of large joints and facial dysmorphism. The condition was recently described to result from autosomal recessive mutations in XYLT1, encoding the enzyme xylosyltransferase-1. In this paper, we report on a Polish patient with DBQD2 who presented with severe short stature of prenatal onset, joint laxity, psychomotor retardation and multiple radiological abnormalities including short metacarpals, advanced bone age and exaggerated trochanters. Endocrinological examinations revealed that sleep-induced growth hormone (GH) release and GH peak in clonidine- and glucagon-induced provocative tests as well as insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 levels were all markedly decreased, confirming deficiency of GH secretion. Bone age, unlikely to GH deficiency, was significantly advanced. To establish the diagnosis at a molecular level, we performed whole-exome sequencing and bioinformatic analysis in the index patient, which revealed compound heterozygous XYLT1 mutations: c.595C>T(p.Gln199*) and c.1651C>T(p.Arg551Cys), both of which are novel. Sanger sequencing showed that the former mutation was inherited from the healthy mother, whereas the latter one most probably occurred de novo. Our study describes the first case of DBQD2 resulting from compound heterozygous XYLT1 mutation, expands the mutational spectrum of the disease and provides evidence that the severe growth retardation and microsomia observed in DBQD2 patients may result not only from the skeletal dysplasia itself but also from GH and IGF-1 deficiency.

Direct writing of birefringent elements by ultrafast laser nanostructuring in multicomponent glass

NASA Astrophysics Data System (ADS)

Fedotov, S. S.; Drevinskas, R.; Lotarev, S. V.; Lipatiev, A. S.; Beresna, M.; ČerkauskaitÄ--, A.; Sigaev, V. N.; Kazansky, P. G.

2016-02-01

Self-assembled nanostructures created by femtosecond laser irradiation are demonstrated in alkali-free aluminoborosilicate glass. The growth of the induced retardance associated with the nanograting formation is three orders of magnitude slower than in silica glass and is observed only within a narrow range of pulse energies. However, the strength of retardance asymptotically approaches the value typically measured in pure silica glass, which is attractive for practical applications. A similar intensity threshold for nanograting formation of about 1 TW/cm2 is observed for all glasses studied. The radially polarized vortex beam micro-converter designed as a space-variant quarter-wave retarder for the near-infrared spectral range is imprinted in commercial Schott AF32 glass.

Polyploidization delay in rat hepatocytes under liver growth inhibition by hypokinesia

NASA Technical Reports Server (NTRS)

Faktor, V. M.; Malyutin, V. F.; Li, S. Y.; Brodskiy, V. Y.

1981-01-01

A study of young rats, weighing 55 to 59 g, after being for 10 days in conditions of limited mobility, shows a retardation of body growth as well as that of liver growth. The decrease in the rate of growth is accompanied by a reduction of cell proliferation and by delay polyploidization of hepatocytes in the liver of experimental rats. The materials, methods, and results of research are discussed.

Low melatonin production by suppression of either serotonin N-acetyltransferase or N-acetylserotonin methyltransferase in rice causes seedling growth retardation with yield penalty, abiotic stress susceptibility, and enhanced coleoptile growth under anoxic conditions.

PubMed

Byeon, Yeong; Back, Kyoungwhan

2016-04-01

Serotonin N-acetyltransferase (SNAT) and N-acetylserotonin methyltransferase (ASMT) are the last two key enzymes for melatonin biosynthesis in living organisms. In this study, we demonstrated that transgenic rice (Oryza sativa L.) plants, in which expression of either endogenous SNAT or ASMT was suppressed, had reduced melatonin synthesis, confirming that both SNAT and ASMT are functionally involved in melatonin synthesis. The melatonin-deficient SNAT rice had retarded seedling growth, which was partially restored by exogenous melatonin application, suggesting melatonin's role in seedling growth. In addition, the plants were more sensitive to various abiotic stresses, including salt and cold, compared with the wild type. Melatonin-deficient SNAT rice had increased coleoptile growth under anoxic conditions, indicating that melatonin also inversely regulates plant growth under anaerobic conditions with the concomitant high expression of alcohol dehydrogenase genes. Similarly, the melatonin-deficient ASMT rice exhibited accelerated senescence in detached flag leaves, as well as significantly reduced yield. These loss-of-function studies on the melatonin biosynthetic genes confirmed most previous pharmacological reports that melatonin not only promotes plant growth but also mitigates various abiotic stresses. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of electromagnetic signal of antibiotics excited by low-frequency pulsed electromagnetic fields on growth of Escherichia coli.

PubMed

Ke, Yin-Lung; Chang, Fu-Yu; Chen, Ming-Kun; Li, Shun-Lai; Jang, Ling-Sheng

2013-01-01

Energy medicine (EM) provides a new medical choice for patients, and its advantages are the noninvasive detection and nondrug treatment. An electromagnetic signal, a kind of EM, induced from antibiotic coupling with weak, extremely low-frequency pulsed electromagnetic fields (PEMFs) is utilized for investigating the growth speed of Escherichia coli (E. coli). PEMFs are produced by solenoidal coils for coupling the electromagnetic signal of antibiotics (penicillin). The growth retardation rate (GRR) of E. coli is used to investigate the efficacy of the electromagnetic signal of antibiotics. The E. coli is cultivated in the exposure of PEMFs coupling with the electromagnetic signal of antibiotics. The maximum GRR of PEMFs with and without the electromagnetic signal of antibiotics on the growth of E. coli cells in the logarithmic is 17.4 and 9.08%, respectively. The electromagnetic signal of antibiotics is successfully coupled by the electromagnetic signal coupling instrument to affect the growth of E. coli. In addition, the retardation effect on E. coli growth can be improved of by changing the carrier frequency of PEMFs coupling with the electromagnetic signal of antibiotics. GRR caused by the electromagnetic signal of antibiotics can be fixed by a different carrier frequency in a different phase of E. coli growth.

Hyperthyroidism during pregnancy

PubMed Central

Inoue, Miho; Arata, Naoko; Koren, Gideon; Ito, Shinya

2009-01-01

ABSTRACT QUESTION I have a 33-year-old patient with hyperthyroidism who is 6 weeks pregnant. Her thyroid function is well controlled with a 5-mg dose of methimazole 3 times daily. She was initially treated with propylthiouracil but was switched to methimazole owing to urticaria. I have heard about birth defects in infants whose mothers used methimazole during pregnancy. How safe is it? ANSWER In North America, propylthiouracil has been the drug of choice for hyperthyroidism during pregnancy. Methimazole is widely used in Europe, South America, and Asia, and is an alternative for patients who cannot tolerate propylthiouracil. Some case reports raised concern about fetal toxicity from methimazole, which is reportedly characterized by aplasia cutis, esophageal atresia, choanal atresia, facial abnormalities, and mental retardation. However, causality is unclear and the overall risk of congenital abnormalities in infants exposed to methimazole in utero was not higher than in those exposed to nonteratogenic drugs in cohort studies. It is important for a pregnant woman to continue methimazole, if necessary, because uncontrolled hyperthyroidism increases the risk of complications such as preterm labour and low birth weight. PMID:19602653

Early-life chemical exposures and risk of metabolic syndrome.

PubMed

De Long, Nicole E; Holloway, Alison C

2017-01-01

The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity.

National study of public spending for mental retardation and developmental disabilities.

PubMed

Braddock, D; Hemp, R; Fujiura, G

1987-09-01

Results of a nationwide study of public mental retardation/developmental disabilities (MR/DD) spending in the states during Fiscal Years 1977 through 1986 were summarized. Trends identified included: (a) continuing growth in spending for community services, (b) contraction of total spending for institutional operations, and (c) predominance of ICF/MR support in large (16+ beds) congregate care settings. Periodic replication of the study was recommended as was additional research to identify the political and economic determinants of state MR/DD spending.

The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis

DTIC Science & Technology

2007-03-01

study display dwarfism and the retardation of mammary gland growth [9]. At the 4-month time point, I similarly observed an overall decrease in mammary...Coactivator A1B1 in Growth Factor- Mediated Mammary Tumorigenesis PRINCIPAL INVESTIGATOR: Mark P Fereshteh (BS) CONTRACTING ORGANIZATION...U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION

Metabolomic analysis of the longissimus from underperforming piglets suggests impaired carbohydrate metabolism, increased lipid utilization and higher protein breakdown in comparison to piglets with normal preweaning growth

USDA-ARS?s Scientific Manuscript database

The present study was designed to determine if normal birth weight pigs that grow poorly during the pre-weaning period have altered skeletal muscle metabolism, as previously reported for intrauterine growth retarded pigs relative to littermates with normal growth rates. Eight pairs of average birth...

Biological Roles of Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11B1), HSD11B2, and Glucocorticoid Receptor (NR3C1) in Sheep Conceptus Elongation.

PubMed

Brooks, Kelsey; Burns, Gregory; Spencer, Thomas E

2015-08-01

In sheep, the elongating conceptus synthesizes and secretes interferon tau (IFNT) as well as prostaglandins (PGs) and cortisol. The enzymes, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) and HSD11B2 interconvert cortisone and cortisol. In sheep, HSD11B1 is expressed and active in the conceptus trophectoderm as well as in the endometrial luminal epithelia; in contrast, HSD11B2 expression is most abundant in conceptus trophectoderm. Cortisol is a biologically active glucocorticoid and ligand for the glucocorticoid receptor (NR3C1 or GR) and mineralocorticoid receptor (NR3C2 or MR). Expression of MR is not detectable in either the ovine endometrium or conceptus during early pregnancy. In tissues that do not express MR, HSD11B2 protects cells from the growth-inhibiting and/or proapoptotic effects of cortisol, particularly during embryonic development. In study one, an in utero loss-of-function analysis of HSD11B1 and HSD11B2 was conducted in the conceptus trophectoderm using morpholino antisense oligonucleotides (MAOs) that inhibit mRNA translation. Elongating, filamentous conceptuses were recovered on Day 14 from ewes infused with control morpholino or HSD11B2 MAO. In contrast, HSD11B1 MAO resulted in severely growth-retarded conceptuses or conceptus fragments with apoptotic trophectoderm. In study two, clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing was used to determine the role of GR in conceptus elongation and development. Elongating, filamentous-type conceptuses (12-14 cm in length) were recovered from ewes gestating control embryos (n = 7/7) and gestating GR-edited embryos (n = 6/7). These results support the idea that the effects of HSD11B1-derived cortisol on conceptus elongation are indirectly mediated by the endometrium and are not directly mediated through GR in the trophectoderm. © 2015 by the Society for the Study of Reproduction, Inc.

Amelioration of improper differentiation of somatostatin-positive interneurons by triiodothyronine in a growth-retarded hypothyroid mouse strain.

PubMed

Uchida, Katsuya; Taguchi, Yusuke; Sato, Chika; Miyazaki, Hidetaka; Kobayashi, Kenichi; Kobayashi, Tetsuya; Itoi, Keiichi

2014-01-24

Thyroid hormone (TH) plays an important role in brain development, and TH deficiency during pregnancy or early postnatal periods leads to neurological disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to examine whether somatostatin (Sst)-positive interneurons that are generated from the same pool of neural progenitor cells as PV-positive cells are also altered by TH deficiency. The number of PV-positive interneurons was significantly decreased in the neocortex and hippocampus of grt mice as compared with normal control mice. In contrast to the decrease in the number of PV neurons, the number of Sst-positive interneurons in grt mice was increased in the stratum oriens of the hippocampus and the hilus of the dentate gyrus, although their number was unchanged in the neocortex. These changes were reversed by triiodothyronine administration from postnatal day (PD) 0 to 20. TH supplementation that was initiated after PD21 did not, however, affect the number of PV- or Sst-positive cells. These results suggest that during the first three postnatal weeks, TH may be critical for the generation of subpopulations of interneurons. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus

PubMed Central

Zawaski, Janice A.; Sahnoune, Iman

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT. PMID:27242931

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.

PubMed

Rodgers, Shaefali P; Zawaski, Janice A; Sahnoune, Iman; Leasure, J Leigh; Gaber, M Waleed

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.

Cerebral metabolic intermediate response following severe canine intrauterine growth retardation.

PubMed

Kliegman, R M

1986-07-01

The effect of intrauterine growth retardation and neonatal hypoglycemia on cerebral metabolic intermediates were determined in newborn dogs subjected to 5 days of maternal canine starvation (MCS) before birth. Birth weight was reduced 23% (232 +/- 6 versus 300 +/- 10 g). Circulating blood glucose was reduced after 3 h of neonatal fasting in MCS pups (2.7 +/- 0.4 +/- versus 5.7 +/- 1.1 mM). Cerebral cortical levels of glucose were also reduced at this time. Cerebral glucose-6-phosphate was not altered; nonetheless fructose-6-phosphate was lower in MCS pups at 6 and 9 h, while fructose 1,6-diphosphate appeared elevated at 3 h. These data suggest that cerebral glycolytic activity may be increased by increased activity of phosphofructokinase. Cerebral glutamine appeared reduced in fasting MCS pups at 3, 6, and 8 h of age. A considerable disturbance of the adenine nucleotide pool was noted between 3-9 h in MCS pups; while the cerebral energy reserve was diminished in MCS pups between 3-24 h. The data of reduced cerebral energy status and reserve suggest that cerebral energy production was diminished. Although glucose levels were low at 3 h, subsequent recovery was not immediate as adenine-nucleotides remained low beyond the period of hypoglycemia. The combined effects of intrauterine growth retardation and transient neonatal hypoglycemia appear to result in reduced cerebral oxidative metabolism; this occurs despite an apparent enhanced utilization of alternate fuels.

In utero exposure to pets is associated with asthma and wheezing in Mexican American children.

PubMed

Eldeirawi, Kamal; Kunzweiler, Colin; Combs, Angela M T; Persky, Victoria W

2016-01-01

To examine the associations of in utero and early life exposure to cats/dogs and birds with the risk of lifetime doctor-diagnosed asthma and other respiratory conditions in a sample of Mexican American (MA) children 4-18 years of age. This study is a population-based cross-sectional investigation of 1816 MA children. We conducted multiple logistic models examining the relationship of asthma and wheezing with exposures to cats/dogs and birds in utero, infancy and at the time of the survey adjusted for country of birth, family history of asthma/allergies, antibiotics use in infancy and other covariates. In adjusted analyses, in utero exposure to cats/dogs and birds jointly was associated with increased odds of asthma (adjusted odds ratio (aOR): 2.89; 95% confidence interval (CI): 1.34-6.23), ever wheezing (aOR: 1.96; 95% CI: 1.11-3.46) and current exercise-induced wheezing (aOR: 3.16; 95% CI: 1.27-7.85) compared to children not exposed to these pets in utero. Children who were exposed to both cats/dogs and birds in utero had an elevated, albeit statistically non-significant, odds of current wheezing. Exposures in infancy and at the time of the survey to cats/dogs and birds were not associated with asthma or wheezing. In utero exposure to pets might be associated with an increased risk of asthma and respiratory conditions in a sample of non-affluent MA children.

Use of diuretics during pregnancy

PubMed Central

Al-Balas, Mosa’b; Bozzo, Pina; Einarson, Adrienne

2009-01-01

ABSTRACT QUESTION Several of my pregnant patients use diuretics for hypertension. I have heard that diuretics cannot be used in pregnancy because of the reduction of plasma volume and the potential for decreasing placental perfusion, as well as a possible diabetogenic effect. ANSWER Many studies—including a meta-analysis of almost 7000 neonates exposed to diuretics during pregnancy—did not find an increased risk of adverse effects, such as birth defects, fetal growth restriction, thrombocytopenia, or diabetes, among neonates exposed to diuretics in utero. PMID:19155365

Social networking between cells of the foetal skeleton: the importance of thyroid hormones.

PubMed

Farquharson, Colin

2011-08-01

In this issue of Journal of Endocrinology, Lanham et al. investigated the effects of hypothyroidism on the developing skeleton of the ovine foetus in utero. Their analyses indicated that, following thyroidectomy, bone growth, structure and mechanical properties were all altered at late gestation or at term. Adrenalectomy, whilst preventing the prepartum rise in triiodothyronine, did not modify skeletal development. The hypothyroid-mediated skeletal defects of the developing foetus described in this study may have clinical implications for bone health in later life.

Birth Weight, Intrauterine Growth Retardation and Fetal Susceptibility to Porcine Reproductive and Respiratory Syndrome Virus

PubMed Central

Ladinig, Andrea; Foxcroft, George; Ashley, Carolyn; Lunney, Joan K.; Plastow, Graham; Harding, John C. S.

2014-01-01

The severity of porcine reproductive and respiratory syndrome was compared in pregnant gilts originating from high and low birth weight litters. One-hundred and eleven pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus on gestation day 85 (±1) were necropsied along with their fetuses 21 days later. Ovulation rates and litter size did not differ between groups, but fetuses from low birth weight gilts were shorter, lighter and demonstrated evidence of asymmetric growth with large brain:organ weight ratios (i.e. brain sparing). The number of intrauterine growth retarded fetuses, defined by brain:organ weight ratios greater than 1 standard deviation from the mean, was significantly greater in low, compared to high, birth weight gilts. Although γδ T cells significantly decreased over time in high compared to low birth weight gilts, viral load in serum and tissues, gilt serum cytokine levels, and litter outcome, including the percent dead fetuses per litter, did not differ by birth weight group. Thus, this study provided no substantive evidence that the severity of porcine reproductive and respiratory syndrome is affected by dam birth weight. However, intrauterine growth retarded fetuses had lower viral loads in both fetal thymus and in endometrium adjacent to the umbilical stump. Crown rump length did not significantly differ between fetuses that survived and those that died at least one week prior to termination. Taken together, this study clearly demonstrates that birth weight is a transgenerational trait in pigs, and provides evidence that larger fetuses are more susceptible to transplacental PRRSv infection. PMID:25275491

Rate of Physical Growth and Its Affect on Head Start Children's Motor and Cognitive Development.

ERIC Educational Resources Information Center

Marcon, Rebecca A.

In the United States, growth retardation is higher among low-income children, with adverse cognitive effects of undernutrition more prevalent when combined with poverty. This study examined anthropometric indicators of physical development and their relationship to motor and cognitive development in Head Start children. Motor integration and…

Infant Nutrition and 12 and 18 Months Secure Base Behavior: An Exploratory Study

ERIC Educational Resources Information Center

Wachs, Theodore D.; Posada, German; Carbonell, Olga A.; Creed-Kanashiro, Hillary; Gurkas, Pinar

2011-01-01

A notable omission in studies of developmental links to early nutritional deficiencies is infant attachment. In those few studies investigating associations between infant nutrition and attachment, nutrition was defined solely by physical growth, and infants had moderate-severe growth retardation. In this study, we utilized multiple markers of…

Effect of polyglycerol esters additive on palm oil crystallization using focused beam reflectance measurement and differential scanning calorimetry.

PubMed

Saw, M H; Hishamuddin, E; Chong, C L; Yeoh, C B; Lim, W H

2017-01-01

The effect of 0.1-0.7% (w/w) of polyglycerol esters (PGEmix-8) on palm oil crystallization was studied using focused beam reflectance measurement (FBRM) to analyze the in-line changes of crystal size distribution during the crystallization. FBRM results show that 0.1-0.5% (w/w) of PGEmix-8 did not significantly affect nucleation but slightly retarded crystal growth. The use of 0.7% (w/w) additive showed greater heterogeneous nucleation compared to those with lower dosages of additive. Crystal growth was also greatly reduced when using 0.7% (w/w) dosage. The morphological study indicated that the palm oil crystals were smaller and more even in size than when more additive was added. Isothermal crystallization studies using differential scanning calorimetry (DSC) showed increased inhibitory effects on palm oil crystal growth with increasing concentration of PGEmix-8. These results imply that PGEmix-8 is a nucleation enhancing and crystal growth retarding additive in palm oil crystallization at 0.7% (w/w) dosage. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Congenital telangiectatic atrophic patch on a healthy child.

PubMed

Teresa Garcia-Romero, Maria; Ching, Joyce C Y; Ho, Nhung

2014-01-01

Rapidly involuting congenital hemangiomas (RICHs) are rare vascular tumors that have a proliferative phase in utero, present fully grown at birth, and have a fast involution phase after birth. Even rarer cases have completed involution in utero and present at birth as an atrophic plaque with redundant skin. We present one case of a RICH that underwent involution in utero and revise the diagnostic and management implications.

Corticosteroid-induced mandibular growth retardation and palatal malformation in the ICR mouse fetus.

PubMed Central

Silbermann, M; Levitan, S

1979-01-01

Pregnant ICR mice were treated with triamcinolone hexacetonide at various stages of gestation. The mandibular ramus and its condylar cartilage were studied histologically in both viable and non-viable offspring. In addition, measurements were made of the overall height of the posterior vertical dimension of the mandible and of condylar height and width. Significant changes were noted in these parameters. Concomitantly, marked changes were observed in the various zones of the condylar cartilage. A very high incidence of cleft palate was noted in newborn and stillborn mice previously treated with triamcinolone. A possible correlation between mandibular growth retardation and palatal clefting is discussed. Images Fig. 4 Fig. 5 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:489465

657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family.

PubMed

Tekin, Mustafa; Doğu, F; Taçyíldiz, N; Akar, E; Ikincioğullari, A; Oğur, G; Yavuz, G; Babacan, E; Akar, N

2002-07-01

We report on a consanguineous Turkish family whose first son died of anal atresia and whose second son presented with severe pre- and post-natal growth retardation as well as striking microcephaly, immunodeficiency, congenital heart disease, chromosomal instability and rhabdomyosarcoma in the anal region. The proband was found to carry the homozygous 657del5 mutation in the NBS1 gene, which is responsible for Nijmegen breakage syndrome (NBS) in most of the Slav populations. Our family, the first diagnosed with NBS in the Turkish population, represents one of the most severely affected examples of the syndrome, with profound pre- and post-natal growth retardation associated with structural abnormalities, and expands the clinical spectrum of this rare disorder.

Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults.

PubMed

Van de Pette, Mathew; Abbas, Allifia; Feytout, Amelie; McNamara, Gráinne; Bruno, Ludovica; To, Wilson K; Dimond, Andrew; Sardini, Alessandro; Webster, Zoe; McGinty, James; Paul, Eleanor J; Ungless, Mark A; French, Paul M W; Withers, Dominic J; Uren, Anthony; Ferguson-Smith, Anne C; Merkenschlager, Matthias; John, Rosalind M; Fisher, Amanda G

2017-01-31

Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent) Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The grass isn't always greener: The effects of cannabis on embryological development.

PubMed

Friedrich, Joseph; Khatib, Dara; Parsa, Keon; Santopietro, Ariana; Gallicano, G Ian

2016-09-29

With the increasing publicity of marijuana due to recent legislation, it is pertinent that the effects of fetal exposure to the drug are assessed. While in utero cannabis exposure has been associated with early pregnancy failure, birth defects and developmental delay, the mechanisms of such outcomes are largely unexplained. Furthermore, the use of cannabinoids in cancer treatment via growth inhibition and apoptosis may indicate how cannabis exposure likely harms a growing fetus. Cannabinoid signaling is required for proper pre-implantation development, embryo transport to the uterus, and uterine receptivity during implantation. In post-implantation development, cannabinoid signaling functions in a multitude of pathways, including, but not limited to, folic acid, VEGF, PCNA, MAPK/ERK, and BDNF. Disrupting the normal activity of these pathways can significantly alter many vital in utero processes, including angiogenesis, cellular replication, tissue differentiation, and neural cognitive development. This paper aims to demonstrate the effects of cannabis exposure on a developing embryo in order to provide a molecular explanation for the adverse outcomes associated with cannabis use during pregnancy.

Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

PubMed

Kartal, Ömer; Aydınöz, Seçil; Kartal, Ayşe Tuğba; Kelestemur, Taha; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Karademir, Ferhan; Süleymanoğlu, Selami; Kul, Mustafa; Yulug, Burak; Kilic, Ertugrul

2016-08-01

Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.

Does intrauterine crowding affect locomotor development? A comparative study of motor performance, neuromotor maturation and gait variability among piglets that differ in birth weight and vitality

PubMed Central

Aerts, Peter; Prims, Sara; Ayuso, Miriam; Van Cruchten, Steven; Van Ginneken, Chris

2018-01-01

In polytocous species, such as pigs, the growth of an individual fetus is affected by competition from its littermates and the sow. This intrauterine competition greatly influences postnatal traits such as birth weight and vitality (physical strength). A lowered vitality is most often observed among low birth weight piglets. Since it has been argued that locomotion might be key to unraveling vitality-related differences, we compared gait development in piglets with a low birth weight and low vitality (L piglets) with piglets with a normal birth weight and normal vitality (N piglets) by means of spatio-temporal gait analysis during locomotion at self-selected speed. Video recordings of L and N piglets walking along a corridor at ten time points (between birth and 96 h after birth) were made and the footfalls were digitized. Hence, self-selected speed, spatio-temporal characteristics and gait symmetry were analyzed to compare motor performance, neuromotor maturation (motor task, interlimb and intralimb coordination) and gait variability for L and N piglets. The analysis included both absolute and normalized data (according to the dynamic similarity concept), to distinguish neuromotor maturation from effects caused by growth. Results indicate that intrauterine crowding affects locomotion, mainly by impairing growth in utero, with a lowered motor performance during the first 96 h of age as a consequence. A difference in neuromotor skills was also visible, though only for swing and stance duration, implying a difference in neuromotor development in utero. However, further maturation during the first days after birth does not seem to be affected by intrauterine crowding. We can therefore conclude that L piglets might be considered a smaller and fictitious younger version of N piglets. PMID:29689084

New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wittwer, B.; Kircheisen, R.; Leutelt, J.

1996-07-12

X-linked mental retardation (XLMR) is genetically heterogeneous and clinically variable. We describe a new XLMR syndrome of severe mental retardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons. In 2 cases, oligohydramnios and intrauterine growth retardation were noted. Common anomalies included a square-shaped face, high and broad forehead, frontal bossing, downward slant of palpebral fissures, hypertelorism, epicanthic folds, long philtrum, thin upper lip, and apparently low-set ears. One boy has bilateral microphthalmos and sclerocornea, and his cousin has atrophy of the optic nerve. All 3 patients are blind and have profound statomotor andmore » mental retardation, seizures, and a grossly abnormal electroencephalographic pattern. Additional findings are short stature, delayed bone matuation, hydronephrosis, vesicorenal reflux, cryptorchidism, clinodactyly of the 5th fingers, and transverse palmar creases. The karyotype is normal (46,XY). Segregation analysis showed perfect coinheritance between the clinical phenotype and alleles at several loci in Xp22.3, whereas recombinants were identified with marker loci from Xp22.2-qter. Analysis of multiple informative meioses suggests that the disease locus maps in Xp22.3 distal to DXS16. 9 refs., 5 figs., 2 tabs.« less

Fréquence et facteurs de risque maternels de la mort fœtale in utero à Kamina, République Démocratique du Congo

PubMed Central

Kangulu, Ignace Bwana; A'Nkoy, Albert Mwembo Tambwe; Lumbule, John Ngoy; Umba, Elie Kilolo Ngoy; Nzaji, Michel Kabamba; Kayamba, Prosper Kalenga Muenze

2016-01-01

Introduction La mort fœtale in utero constitue un problème fréquent dans la pratique obstétricale. Les objectifs de cette étude étaient de déterminer la fréquence et d'identifier les facteurs de risque de la mort fœtale in utero à l'Hôpital Général de Référence de Kamina. Méthodes L’étude était effectuée en deux temps. En premier lieu, une étude descriptive transversale sur 379 accouchements qui avait permis de déterminer la fréquence de la mort fœtale in utero. La détermination des facteurs de risque était faite à l'aide d'une étude cas-témoins dans laquelle les caractéristiques de 53 morts in utero ont été comparées à 106 témoins constitués des naissances vivantes et à terme. Résultats La fréquence de la mort fœtale in utero à l'Hôpital Général de Référence de Kamina était de 13,9%. Après ajustement, l’âge maternel de plus de 35 ans (OR = 6,23; IC= (1,30-29,80)), l'antécédent de mort fœtale in utero (OR = 3,13; IC= (1,06-9,27)) et la maladie au cours de la grossesse (OR = 31,6, IC= (7,66-130,71)) ont été retenus comme facteurs significativement associés à l'augmentation de la survenue de la mort fœtale. L'instruction élevée de la mère (OR = 0,11; IC= IC= [0,03-0,42]) et la résidence à Kamina (OR = 0,23; IC= (0,08-0,62)) diminuaient ce risque. Conclusion La fréquence de la mort fœtale in utero était de 13,9%. L’âge maternel avancé l'antécédent de mort in utero et la maladie au cours de la grossesse étaient associés à la mort fœtale in utero mais par contre, l'instruction élevée de la femme et la résidence à Kamina diminuaient le risque. La surveillance des gestantes à risque, le dépistage et la prise en charge des maladies pendant la grossesse s'avèrent nécessaires dans la perspective de réduire la fréquence de la mort fœtale in utero dans notre milieu. PMID:27279941

The effects of in utero bisphenol A exposure on the ovaries in multiple generations of mice

PubMed Central

Berger, Amelia; Ziv-Gal, Ayelet; Cudiamat, Jonathan; Wang, Wei; Zhou, Changqing; Flaws, Jodi A.

2016-01-01

Bisphenol A is used in polycarbonate plastics and epoxy resins. Previous studies show that in utero BPA exposure inhibits germ cell nest breakdown in the F1 generation of mice, but its effects on germ cell nest breakdown and on the ovary in the F2–F3 generations were unknown. Thus, we tested the hypothesis that BPA has transgenerational effects on the ovary. Mice were exposed to BPA in utero (BPA 0.5, 20, or 50 µg/kg/day), and ovaries were collected at postnatal days (PND) 4 and 21 from the F1–F3 generations and subjected to histological evaluation and gene expression analyses. In utero BPA exposure did not have transgenerational effects on germ cell nest breakdown and gene expression on PND 4, but it caused transgenerational changes in expression in multiple genes on PND 21. Collectively, these data indicate that in utero BPA exposure has some transgenerational effects in mice. PMID:26746108

Hypoparathyroidism-retardation-Dysmorphism (HRD) syndrome--a review.

PubMed

Hershkovitz, Eli; Parvari, Ruti; Diaz, George A; Gorodischer, Rafael

2004-12-01

Hypoparathyroidism, retardation, and dysmorphism (HRD) is a newly recognized genetic syndrome, described in patients of Arab origin. The syndrome consists of permanent congenital hypoparathyroidism, severe prenatal and postnatal growth retardation, and profound global developmental delay. The patients are susceptible to severe infections including life-threatening pneumococcal infections especially during infancy. The main dysmorphic features are microcephaly, deep-set eyes or microphthalmia, ear abnormalities, depressed nasal bridge, thin upper lip, hooked small nose, micrognathia, and small hands and feet. A single 12-bp deletion (del52-55) in the second coding exon of the tubulin cofactor E (TCFE) gene, located on the long arm of chromosome 1, is the cause of HRD among Arab patients. Early recognition and therapy of hypocalcemia is important as is daily antibiotic prophylaxis against pneumococcal infections.

Effect of an ozone injury retardant chemical on isozyme profiles from alfalfa callus in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rier, J.P. Jr.; Sood, V.K.; Whitaker, A.

1983-01-01

Plant ozone injury retardant N-(2-(2-oxo-1-imidazolidinyl)-ethyl)-N'-phenylurea (EDU or ethylenediurea) at 1.0 ppm inhibited growth of callus of alfalfa cultivars Williamsburg (ozone-sensitive) and MSB-CW5An2 (ozone-insensitive) germplasm of Medicago sativa. The presence of EDU (0.1 ppm)in the growth medium increased the number of protein and peroxidase isozyme bands in alfalfa cultivar Williamsburg stem callus and ozone modified their intensities. Protein profiles of MSB stem callus from media containing EDU or exposed to ozone were unchanged. Marked differences were observed between the peroxidase profiles of ozonated and control ozone-insensitive stem callus from media containing EDU. Protein profiles of ozonated ozone-sensitive leaf callus differed slightlymore » from controls. The peroxidase profile of ozonated ozone-sensitive leaf callus was not altered when its growth medium contained EDU, but when it was absent, changes were observed in these profiles.« less

Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.

PubMed

Barraza-García, Jimena; Iván Rivera-Pedroza, Carlos; Salamanca, Luis; Belinchón, Alberta; López-González, Vanesa; Sentchordi-Montané, Lucía; del Pozo, Ángela; Santos-Simarro, Fernando; Campos-Barros, Ángel; Lapunzina, Pablo; Guillén-Navarro, Encarna; González-Casado, Isabel; García-Miñaur, Sixto; Heath, Karen E

2016-01-01

Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges. © 2015 Wiley Periodicals, Inc.

Multiple Hereditary Osteochondromatosis: A Case Report

PubMed Central

Küçükesmen, Çiḡdem; Özen, Buḡra; Akçam, Mustafa

2007-01-01

Objectives Common carious lesions owing to vomiting are not widespread in children. In this case, we aimed to report an 11-years-old male patient with common carious lesions due to repeated vomitings, chewing and eating difficulty and retarded growth with Multiple Hereditary Osteochondromatosis (MHO). Case Report An 11-years-old boy was referred to Department of Pediatric Dentistry in Faculty of Dentistry because of eating difficulty owing to common carious lesions. It was seen that the patient growth was generally retarded in extra-oral examination. Some exostoses were also present on the extremities. It was learned that he was previously diagnosed as MHO in Faculty of Medicine. Nausea and vomiting have been commonly occurring after taking of Didronat. Chewing and eating difficulty and inadequate nutrition were present because of bad oral hygiene, carious lesions and remained roots. Growth was negatively affected by malnutrition and MHO. Results Diet recommendations were given and oral hygiene behaviors were rearranged. Preventive, surgical, restorative and prosthetical dental applications were applied for dental treatments. PMID:19212564

Fish oil improves lipid profile in juvenile rats with intrauterine growth retardation by altering the transcriptional expression of lipid-related hepatic genes.

PubMed

Chen, Lian-Hui; Liang, Li; Fang, Yan-Lan; Wang, Ying-Min; Zhu, Wei-Fen

2016-10-01

To determine whether maternal intrauterine undernutrition and post-weaning fish oil intake influence lipid profile in juvenile offspring, and explore the possible mechanisms at transcriptional levels. After weaning, 32 control offspring and 24 intrauterine growth retardation (IUGR) offspring were randomly allocated to standard chow or fish oil diet. At 10 weeks, fasting plasma glucose, triglycerides, total cholesterol and expressions of related hepatic genes were examined. IUGR offspring without catch-up growth tended to develop hyperglycemia, dyslipidemia and hepatic steatosis. Down-regulation of CPT-1 and LDLR at transcriptional levels were found in IUGR offspring. Early short-term fish oil intervention reversed these unfavorable changes in juvenile rats with IUGR. The mechanisms might be mediated by decreased expression of ACC-1, increased expression of CPT-1, LDLR and ABCG5. These data suggest that IUGR offspring already present lipid abnormality in juvenile stage, and early short-term fish oil consumption is beneficial to prevent these unfavorable changes.

Molecular mechanisms of intrauterine growth restriction.

PubMed

Gurugubelli Krishna, Rao; Vishnu Bhat, B

2017-07-10

Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFβ causes the placental apoptosis and altered expression of TGFβ due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez–Arguelles, D.B.; Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4; McIntosh, M.

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressuremore » in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.« less

Perfluorooctanoate (PFOA) and Neuropsychological Outcomes in Children

PubMed Central

Stein, Cheryl R.; Savitz, David A.; Bellinger, David C.

2014-01-01

BACKGROUND In animal studies, perfluorinated compounds affect fetal growth, development, viability, and postnatal growth. The limited epidemiologic findings on child neurobehavioral development are mixed. METHODS We recruited and evaluated 320 children who participated in the C8 Health Project, a 2005–2006 survey in a mid-Ohio-Valley community highly exposed to perfluorooctanoate (PFOA) through contaminated drinking water. We examined associations between estimated in utero PFOA exposure, measured childhood PFOA serum concentration, and subsequent performance on neuropsychological tests 3–4 years later at ages 6–12 years. We assessed IQ reading and math skills, language, memory and learning, visual-spatial processing, and attention. All multivariable linear-regression models were adjusted for age, sex, home environment, test examiner, and maternal IQ. Models with measured childhood PFOA were additionally adjusted for child body mass index. RESULTS Children in the highest as compared to lowest quartile of estimated in utero PFOA had increases in full scale IQ (β 4.6, 95% CI 0.7, 8.5) and decreases in characteristics of attention deficit/hyperactivity disorder as measured by the Clinical Confidence Index of Connors' Continuous Performance Test-II (β −8.5, 95% CI −16.1, −0.8). There were negligible associations between PFOA and reading or math skills or neuropsychological functioning. CONCLUSION These results do not suggest an adverse association between the levels of PFOA exposure experienced by children in this cohort and their performance on neuropsychological tests. PMID:23680941

Preclinical Validation of Anti-Nuclear Factor Kappa B Therapy Against Vestibular Schwannoma and Neurofibromatosis Type II

DTIC Science & Technology

2016-06-01

therapies that simply reduce tumor volume and retard growth can be life- saving. The most successful drug used today to treat NF2, bevacizumab, works...in only about 50% of patients in halting tumor growth or causing tumor shrinkage. Bevacizumab is known to inhibit vascular endothelial growth factor...of TNF (and hence of NFkB) may prevent both VS growth and the associated hearing loss. Using human volumetric VS measurements in a retrospective

A variant microcephalic osteodysplastic slender-bone disorder with growth hormone deficiency and a pigmentary retinopathy.

PubMed

Maclean, K; Ambler, G; Flaherty, M; Kozlowski, K; Adès, L C

2002-10-01

We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.

COMPARISONS OF THE EFFECTS OF TCDD AND HYDROCORTISONE (HC) ON GROWTH FACTOR EXPRESSION PROVIDE INSIGHT INTO THE SYNERGISTIC INTERACTION OCCURRING IN EMBRYONIC PALATES

EPA Science Inventory

Cleft palate (CP) can be Induced In embryonic mice by a Wide range of compounds, including glucocorticoids and 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD). ydrocortisone (HC), a glucocorticoid, retards embryonic growth producing small palatal shelves, while TCDD exposure blocks t...

Haemopoiesis in the Beagle Foetus after in utero Irradiation

DTIC Science & Technology

1983-01-01

i-4 I - Haemopoiesis in the beagle foetus after in utero irradiation S. R. Weinberg Q T. J. MacVittie R- A. C. Bakarich M. P. McGarry ’:’--""Cf E...Z All2 4. TITLE (and Subtitle) 5. TYPE OF REPORT & PERIOD COVERED HAEMOPOJESIS IN THE BEAGLE FOETUS AFTER IN UTERO IRRADIATION ___________ 6...York - .20. ABSTRACT (cortinued) Differences in haemopoietic progenitor cell activity between irradiated and normal foetuses were observed. In

In utero gratification behaviour in male fetus.

PubMed

Rodríguez Fernández, Vanesa; López Ramón Y Cajal, Carlos

2016-10-01

Fetal masturbation has been described previously once in utero but only as a description of an action. Masturbation is well described in infancy and early childhood when they discover that this practice can give them pleasure. Our letter proves that it could begin in utero as a 'gratification behaviour'. We have shown this pattern clearly by using a volumetric rendering mode study. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. Belgian and French Pediatric Clinics and Sanofi-Choay (France).

PubMed

Chatelain, P; Job, J C; Blanchard, J; Ducret, J P; Oliver, M; Sagnard, L; Vanderschueren-Lodeweyckx, M

1994-06-01

This study reports the results of a 2-yr clinical trial with GH in 95 short prepubertal children with non-GH-deficient intrauterine growth retardation. This randomized, double blind, controlled study compared the effects of placebo (restricted to the first 6 months) and two doses of GH (0.4 and 1.2 IU/kg.week) given sc 6 days/week for 2 yr. A significant GH dose-dependent growth acceleration was observed. Mean height gain (SDS/CA) was 0.66 +/- 0.07 in group I (low dose, 0.4 IU/kg.week) compared to 1.25 +/- 0.07 in group II (high dose, 1.2 IU/kg.week). Mean bone maturation progression (expressed in months) was 26.2 +/- 1.7 and 30.2 +/- 1.5 over 24 months in groups I and II, respectively. Onset of puberty was observed in some patients of both groups. Whether chronic use of a high GH dose will advance the onset of puberty remains to be established. A great variability of growth acceleration was seen among GH dose groups, suggesting that factors in addition to GH dose might modulate individual responses to treatment. In conclusion, it is suggested that in these patients, dose-dependent catch-up growth could be induced by GH treatment.

Concurrent primaries of vaginal clear cell adenocarcinoma and endometrial adenocarcinoma in a 39-year old woman with in utero diethylstilbestrol exposure.

PubMed

Keller, C; Nanda, R; Shannon, R L; Amit, A; Kaplan, A L

2001-01-01

Diethylstilbestrol (DES) was used widely in the late 1940s in an attempt to prevent adverse pregnancy outcomes. In 1971 the US Food and Drug Administration proscribed its use for pregnancy support secondary to its association with clear cell adenocarcinoma of the vagina. Several studies in animal models demonstrated an association with endometrial cancer among offspring following in utero DES exposure. To date, there is only one case report of endometrial cancer in women exposed to DES in utero. We present the first case, to our knowledge, of a woman exposed to DES in utero who presented with double primaries of clear cell cancer of the vagina concomitant with endometrial cancer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacquet, P.; Gerber, G.B.; Maes, J.

Lead exposure of women can cause abortion and delay prenatal and postnatal growth (Weller, 1915). Earlier (Jacquet et al., 1975, 1976) we have observed that 0.125% to 0.5% of lead in the diet given after mating reduces the incidence of pregnancies, retards early divisions, diminishes embryonic weight and can cause death during the late stages of gestation. In order to elucidate the mechanism of embryonic retardation and death, we have now studied in embryos at the 16, 17 and 18th day of pregnancy several biochemical parameters thought to be related to the action of lead.

Williams syndrome starts making sense

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashkenas, J.

1996-10-01

1996 may be marked as a transitional year in the study of Williams syndrome (WS), when the causes of this complex condition and a practical way to investigate began to come into focus. WS presents a remarkable collection of symptoms that affect blood vessels, growth, intelligence, and behavior. WS commonly leads to infantile hypercalcemia, retardation of growth, prematurely wrinkled skin, supraventricular aortic stenosis (SVAS), and sensitivity to loud noise. Children with this condition are often mentally retarded, with distinctive {open_quotes}elfin{close_quotes} facial features, a hoarse voice, and an {open_quotes}engaging{close_quotes} personality. Their cognitive deficits may be minimal or profound but typically involvemore » a specific pattern of strengths and weaknesses, with better-than-average face recognition but little ability to recognize how parts of patterns that they see fit into a whole. 36 refs.« less

Skeletal manifestations of stress in child victims of the Great Irish Famine (1845-1852): prevalence of enamel hypoplasia, Harris lines, and growth retardation.

PubMed

Geber, Jonny

2014-09-01

The Great Irish Famine of 1845-1852 is among the worst food crises in human history. While numerous aspects of this period have been studied by generations of scholars, relatively little attention has so far been given to the physiological impact it is likely to have had on the people who suffered and succumbed to it. This study examines the prevalence of enamel hypoplasia, Harris lines, and growth retardation in the nonadult proportion of a skeletal population comprising victims of the Famine who died in the workhouse in the city of Kilkenny between 1847 and 1851. The frequency of enamel hypoplasia in these children does not appear to have increased as a consequence of famine, although this fact is likely to be a reflection of the osteological paradox. Harris lines and growth retardation; however, were very prevalent, and the manifestation and age-specific distribution of these may be indicators of the Famine experience. While there was no clear correlation in the occurrence of the assessed markers, the presence of cribra orbitalia displayed a significant relationship to enamel hypoplasia in 1- to 5-year-old children. While starvation, metabolic disorders and infectious diseases are likely to have greatly contributed to the manifestation of the markers, the psychosocial stress relating to institutionalization in the workhouse should not be underestimated as a substantial causative factor for skeletal stress in this population. Copyright © 2014 Wiley Periodicals, Inc.

[Study of 178 ante partum deaths in 2001-2004 in the southern part of Reunion Island].

PubMed

Randrianaivo, H; Robillard, P-Y; Barau, G; Gérardin, P; Heisert, M; Kauffmann, E; Laffite, A; Fourmaintraux, A

2006-11-01

The perinatal mortality rate is 18.5 in the southern part of the Reunion Island (Indian Ocean), of which 2/3 are due to antepartum fetal deaths (APFD). During a 4-year period (2001-2004) all APFD from 22 weeks gestation were recorded and analyzed with placental histology, bacteriological samples and autopsies in 27% of cases. The Australasian and New-Zealand classification PSANZ-PDC (2000) was used. Risk factors of fetal death with monofetal pregnancies are determined in comparison with live births. Out of 21.495 total births, 178 APFD were recorded. The main obstetrical risk factors were primiparity (OR 1.6, p = 0.002), maternal age over 34 years (OR 1.6, p = 0.01), hypertensive disorders of pregnancy (OR 3.0, p < .001) and multiple births (OR 2.5, p < 0.001). The great majority of APFD (76%) involved preterm fetuses, of which 61% of very preterm (<33 weeks), and 25% of fetuses were growth retarded (OR 3.9, p < 0.001). Only 8% of cases were considered unexplained. The main etiologies were infectious causes in 26% of cases, vascular fetal growth restriction (18%), specific perinatal conditions (14%) of which one-third were due to cord anomalies, preeclampsia (10%), maternal conditions (8%), congenital anomalies (8%) and ante-partum hemorrhage (7%). We discuss the interests and the limitations of using the Australian and New-Zealand classification PSANZ 2000. Intra-uterine growth retardation is one of the principal risk factors of fetal death. Besides well-known obstetrical risk factors such as diabetes, hypertension, multiple pregnancies, all screening of intra-uterine growth retardation in the second trimester of pregnancy should include a special survey in order to minimize the incidence of APFDs.

Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy.

PubMed

Mickiewicz, M; Zabielski, R; Grenier, B; Le Normand, L; Savary, G; Holst, J J; Oswald, I P; Metges, C C; Guilloteau, P

2012-06-01

Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets from sows fed a control (C, 12.1% protein), a high protein (HP, 30% protein), or a low protein (LP, 6.5% protein) diet during pregnancy. Newborns were classified as IUGR (birth weight ≤1.18 kg) and non-IUGR (birth weight >1.18 kg). The piglets were euthanized on postnatal day (PD)1, PD28 and PD188. The LP diet in non-IUGR neonates resulted in decreased body weight on PD1. The LP and HP diets resulted in both decreased body weight and delayed catch-up growth in the IUGR piglets. The HP and LP-diets increased the length of villi on PD1 in non-IUGRs but not in IUGRs. At birth, the expressions of Ki67 and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes.

Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

PubMed Central

Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

2013-01-01

Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

In Utero Exposure to Exosomal and B-Cell Alloantigens Lessens Alloreactivity of Recipients' Lymphocytes Rather than Confers Allograft Tolerance.

PubMed

Chen, Jeng-Chang; Ou, Liang-Shiou; Chan, Cheng-Chi; Kuo, Ming-Ling; Tseng, Li-Yun; Chang, Hsueh-Ling

2018-01-01

According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients' lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients' lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.

In Utero Exposure to Low-Dose Alcohol Induces Reprogramming of Mammary Development and Tumor Risk in MMTV-erbB-2 Transgenic Mice

PubMed Central

Ma, Zhikun; Blackwelder, Amanda J.; Lee, Harry; Zhao, Ming; Yang, Xiaohe

2015-01-01

There is increasing evidence that prenatal exposure to environmental factors may modify breast cancer risk later in life. This study aimed to investigate the effects of in utero exposure to low-dose alcohol on mammary development and tumor risk. Pregnant MMTV-erbB-2 mice were exposed to alcohol (6 g/kg/day) between day 13 and day 19 of gestation, and the female offspring were examined for tumor risk. Whole mount analysis indicated that in utero exposure to low-dose alcohol induced significant increases in ductal extension at 10 weeks of age. Molecular analysis showed that in utero alcohol exposure induced upregulation of ERα signaling and activation of Akt and Erk1/2 in pubertal mammary glands. However, enhanced signaling in the EGFR/erbB-2 pathway appeared to be more prominent in 10-week-old glands than did signaling in the other pathways. Interestingly, tumor development in mice with in utero exposure to low-dose alcohol was slightly delayed compared to control mice, but tumor multiplicity was increased. The results indicate that in utero exposure to low-dose alcohol induces the reprogramming of mammary development by mechanisms that include altered signaling in the estrogen receptor (ER) and erbB-2 pathways. The intriguing tumor development pattern might be related to alcohol dose and exposure conditions, and warrants further investigation. PMID:25853264

The Intrauterine and Nursing Period Is a Window of Susceptibility for Development of Obesity and Intestinal Tumorigenesis by a High Fat Diet in Min/+ Mice as Adults

PubMed Central

Ngo, Ha Thi; Hetland, Ragna Bogen; Steffensen, Inger-Lise

2015-01-01

We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development. PMID:25874125

Effects of In Utero Exposure to Bisphenol A or Diethylstilbestrol on the Adult Male Reproductive System

PubMed Central

LaRocca, Jessica; Boyajian, Alanna; Brown, Caitlin; Smith, Stuart Duncan; Hixon, Mary

2011-01-01

The objective of this study was to determine if in utero exposure to Bisphenol A (BPA) induced reproductive tract abnormalities in the adult male testis. Using the C57/Bl6 mouse, we examined sex-organ weights, anogenital distance (AGD), and testis histopathology in adult males exposed in utero via oral gavage to sesame oil, 50 μg/kg BPA, 1,000 μg/kg BPA, or 2 μg/kg diethylstilbestrol (DES) as a positive control from gestational days 10–16. No changes in sperm production or germ cell apoptosis were observed in adult testes following exposure to either chemical. Adult mRNA levels of genes associated with sexual maturation and differentiation, GATA4 and ID2, were significantly lower only in DES-exposed testes. In summary, the data indicate no gross alterations in spermatogenesis following in utero exposure to BPA or DES. At the molecular level, in utero exposure to DES, but not BPA, leads to decreased mRNA expression of genes associated with Sertoli cell differentiation. PMID:21922642

Assessing the impact of in-utero exposures: potential effects of paracetamol on male reproductive development.

PubMed

Kilcoyne, Karen R; Mitchell, Rod T

2017-12-01

Human male reproductive disorders (cryptorchidism, hypospadias, testicular cancer and low sperm counts) are common and some may be increasing in incidence worldwide. These associated disorders can arise from subnormal testosterone production during fetal life. This has resulted in a focus on in-utero environmental influences that may result in reproductive effects on the offspring in later life. Over recent years, there has been a dramatic increase in the scientific literature describing associations between in-utero environmental exposures (eg, industrial chemicals and pharmaceuticals) and subsequent reproductive outcomes in male offspring. This includes studies investigating a potential role for in-utero analgesic exposure(s) on the fetal testis; however, providing definitive evidence of such effects presents numerous challenges. In this review, we describe an approach to assessing the potential clinical relevance of in-utero (and postnatal) environmental exposures on subsequent male reproductive function using exposure to the analgesic paracetamol as an example. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

PubMed Central

Almeida-Porada, Graça; Atala, Anthony; Porada, Christopher D

2016-01-01

Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

Equivalence relations in individuals with language limitations and mental retardation.

PubMed Central

O'Donnell, Jennifer; Saunders, Kathryn J

2003-01-01

The study of equivalence relations exhibited by individuals with mental retardation and language limitations holds the promise of providing information of both theoretical and practical significance. We reviewed the equivalence literature with this population, defined in terms of subjects having moderate, severe, or profound mental retardation. The literature includes 55 such individuals, most of whom showed positive outcomes on equivalence tests. The results to date suggest that naming skills are not necessary for positive equivalence test outcomes. Thus far, however, relatively few subjects with minimal language have been studied. Moreover, we suggest that the scientific contributions of studies in this area would be enhanced with better documentation of language skills and other subject characteristics. With recent advances in laboratory procedures for establishing the baseline performances necessary for equivalence tests, this research area is poised for rapid growth. PMID:13677612

Physical growth and development of the malnourished child: contributions from 50 years of research at INCAP.

PubMed

Martorell, Reynaldo

2010-03-01

This paper reviews the main findings and policy implications of 50 years (1949-1999) of research conducted by INCAP on growth and development. Topical areas reviewed include a) maternal size and birthweight and the causes of intrauterine growth retardation (IUGR), b) patterns and causes of postnatal growth retardation, c) the relative importance of genetics and the environment in explaining differences in growth among populations, d) the implications of being small, for both children and adults, e) bone growth and maturation and dental development, f) menarche, and g) methodological contributions such as anthropometric reference data, quality control of data collection, development of risk indicators and use of anthropometry in nutrition surveillance systems. Key contributions to knowledge by INCAP include a) characterization of growth failure and maturational delays as mainly occurring during the intrauterine period and the first 3 years of life b) clarification of the role of small maternal size and of inadequate dietary intakes during pregnancy as major causes of intrauterine growth failure, c) evidence that diarrheal diseases and poor dietary intakes are the principal causes of growth failure in early childhood, d) demonstration that environmental factors related to poverty, and not genetic or racial ancestry, account for most of the differences in growth between populations, e) evidence that growth failure predicts functional impairment in the child as well as in the adult andf) demonstration that nutrition interventions are effective in preventing growth failure and its consequences, if targeted to needy women and young children. INCAP's work has contributed knowledge that has informed and improved policies and programs aimed at overcoming maternal and child undernutrition and promoting optimal growth and development.

Bioaccumulation and toxicity of the flame retardant TBPH or ...

EPA Pesticide Factsheets

The use of polybrominated diphenyl ethers as flame retardants in consumer products has been scrutinized increasingly due to their environmental persistence and potential toxicity; however, alternative replacement flame retardants may have similar drawbacks. The alternative brominated flame retardant bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is a component of several commercial flame retardants, including Firemaster® 550, Firemaster® BZ-54 and DP-45. Here we investigate the bioaccumulation, bioenergetics and other adverse outcomes pathways (AOPs) predicted for dietary exposure to a carrier control, two levels of TBPH, or 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153, a well-studied compound acting as a positive control for some aspects of the study). The TBPH concentrations chosen were at or well above the environmental concentrations documented in the literature, but similar to those causing toxicity in a previous study. Our experimental model is a small estuarine fish, the mummichog (Fundulus heteroclitus), exposed as individually tagged fish held in small groups (2 male, 2 female) in replicate tanks and fed contaminated food from day 0-28, followed by uncontaminated food from day 29-42. Throughout the experiment, individual growth was measured weekly, and at various time points, fish from replicate tanks were sacrificed, measured and dissected. To support putative AOPs, samples were obtained for analysis of hormone levels and transcriptomic responses

The Roberts syndrome/SC phocomelia spectrum--a case report of an adult with review of the literature.

PubMed

Goh, Elaine Suk-Ying; Li, Chumei; Horsburgh, Sheri; Kasai, Yumi; Kolomietz, Elena; Morel, Chantal France

2010-02-01

Roberts syndrome (RBS) (OMIM #268300) is a rare autosomal recessive disorder characterized by tetraphocomelia (symmetrical limb reduction), craniofacial anomalies, growth retardation, mental retardation, cardiac and renal abnormalities. The syndrome is caused by mutations in the ESCO2 (establishment of cohesion 1 homolog 2) (Entrez 609353) gene, which is located at 8p21.1, and encodes a protein essential in establishing sister chromatid cohesion during S phase. SC phocomelia (SC) (OMIM #269000), has less severe symmetric limb reduction, flexion contractures of various joints, minor facial anomalies, growth retardation and occasionally, mental retardation. These two syndromes can be considered part of a spectrum, with RBS at the most severe range in which severely affected infants may be stillborn or die in the post-natal period, while individuals with SC phocomelia represent the milder end of the spectrum and typically survive to adulthood. In both presentations, karyotype investigations characteristically reveal premature centromere separation (PCS), otherwise known as heterochromatin repulsion or puffing. There is little literature about the follow-up of adults with the spectrum of RBS/SC phocomelia or their recommended management. We report on an adult presentation of RBS/SC phocomelia spectrum disorder with a history of major cardiac malformation in childhood, normal limbs on physical examination, mild facial anomalies, mild learning difficulties, and PCS. Molecular studies of ESCO2 have confirmed the diagnosis. A literature review, focussing on adult manifestations of this condition and a discussion of follow-up guidelines are presented. Copyright 2010 Wiley-Liss, Inc.

Studies on the effects on growth and antioxidant responses of two marine microalgal species to uniconazole

NASA Astrophysics Data System (ADS)

Mei, Xueqiao; Zheng, Kang; Wang, Lingdong; Li, Yantuan

2014-10-01

Uniconazole, as a plant growth retardant, can enhance stress tolerance in plants, possibly because of improved antioxidation defense mechanisms with higher activities of superoxide dismutase (SOD) and peroxidase (POD) enzymes that retard lipid peroxidation and membrane deterioration. These years much attention has been focused on the responses of antioxidant system in plants to uniconazole stress, but such studies on aquatic organism are very few. Moreover, no information is available on growth and antioxidant response in marine microalgae to uniconazole. In this paper, the growth and antioxidant responses of two marine microalgal species, Platymonas helgolandica and Pavlova viridis, at six uniconazole concentrations (0-15 mg L-1) were investigated. The results demonstrated that 3 mg L-1 uniconazole could increase significantly chlorophyll a and carbohydrate contents of P. helgolandica ( P < 0.05). Higher concentrations (≥12 mg L-1) of uniconazole could inhibit significantly the growth, dry weight, chlorophyll-a and carbohydrate contents of P. helgolandica and P. viridis ( P < 0.05). Uniconazole caused a significant increase in lipid peroxidation production (MDA) at higher concentrations (≥ 9 mg L-1). The activities of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were enhanced remarkably at low concentrations of uniconazole. However, significant reduction of SOD and CAT activities was observed at higher concentrations of uniconazole.

Safety of MR Imaging at 1.5 T in Fetuses: A Retrospective Case-Control Study of Birth Weights and the Effects of Acoustic Noise.

PubMed

Strizek, Brigitte; Jani, Jacques C; Mucyo, Eugène; De Keyzer, Frederik; Pauwels, Inge; Ziane, Samir; Mansbach, Anne-Laure; Deltenre, Paul; Cos, Teresa; Cannie, Mieke M

2015-05-01

To evaluate the effects of exposure to routine magnetic resonance (MR) imaging at 1.5 T during pregnancy on fetal growth and neonatal hearing function in relation to the dose and timing of in utero exposure in a group of newborns at low risk for congenital hearing impairment or deafness. This retrospective case-control study was approved by the local ethics committee, and written informed consent was waived. Between January 2008 and December 2012, a group of 751 neonates exposed to MR imaging in utero and a group of control subjects comprising 10 042 nonexposed neonates, both groups with no risk factors for hearing impairment at birth, were included. Neonatal hearing screening was performed by means of otoacoustic emission testing and auditory brain stem response according to national guidelines, and the prevalence of hearing impairment in the two groups was compared by using a noninferiority test with Wilson score confidence intervals. The effect of MR exposure on birth weight percentile was examined between the singleton neonates in the exposed group and a randomly chosen subset of 1805 singleton newborns of the nonexposed group by performing an analysis of variance. The rate of hearing impairment or deafness was found to be 0% (0 of 751) in the neonates in the exposed group and was not inferior to that in the nonexposed group (34 of 10 042 [0.34%], P < .05). There was no between-group difference in birth weight percentiles (50.6% for exposed vs 48.4% for nonexposed; P = .22). This study showed no adverse effects of exposure to 1.5-T MR imaging in utero on neonatal hearing function or birth weight percentiles. (©) RSNA, 2015.

Developmental Effects of Prenatal Exposure to Bisphenol A on the Uterus of Rat Offspring1

PubMed Central

Schönfelder, Gilbert; Friedrich, Karin; Paul, Martin; Chahoud, Ibrahim

2004-01-01

Abstract Exposure to estrogenic compounds during critical periods of fetal development could result in adverse effects on the development of reproductive organs that are not apparent until later in life. Bisphenol A (BPA), which is employed in the manufacture of a wide range of consumer products, is a prime candidate for endocrine disruption. We examined BPA to address the question of whether in utero exposure affects the uterus of the offspring and studied the expression and distribution of the estrogen receptors alpha (ERα) and beta (ERβ), because estrogens influence the development, growth, and function of the uterus through both receptors. Gravid Sprague-Dawley dams were administered by gavage either 0.1 or 50 mg/kg per day BPA or 0.2 mg/kg per day 17α-ethinyl estradiol (EE2) as reference dose on gestation days 6 through 21. Female offspring were killed in estrus. Uterine morphologic changes as well as ERα and ERβ distribution and expression were measured by immunohistochemistry and Western blot analysis. Striking morphologic changes were observed in the uterine epithelium of postpubertal offspring during estrus of the in utero BPA-treated animals (the thickness of the total epithelium was significantly reduced). ERα expression was increased in the 50-mg BPA and EE2-treated group. In contrast, we observed significantly decreased ERβ expression in all BPA- and EE2-treated animals when compared with the control. In summary, these results clearly indicate that in utero exposure of rats to BPA promotes uterine disruption in offspring. We hypothesize that the uterine disruption could possibly be provoked by a dysregulation of Erα and ERβ. PMID:15548368

Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure.

PubMed

Liu, Jie; Xie, Yaxiong; Ducharme, Danica M K; Shen, Jun; Diwan, Bhalchandra A; Merrick, B Alex; Grissom, Sherry F; Tucker, Charles J; Paules, Richard S; Tennant, Raymond; Waalkes, Michael P

2006-03-01

Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed > 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.

Regulation of Baboon Fetal Ovarian Development by Placental Estrogen: Onset of Puberty Is Delayed in Offspring Deprived of Estrogen In Utero1

PubMed Central

Pepe, Gerald J.; Lynch, Terrie J.; Albrecht, Eugene D.

2013-01-01

ABSTRACT Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen. PMID:24132960

Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero.

PubMed

Pepe, Gerald J; Lynch, Terrie J; Albrecht, Eugene D

2013-12-01

Using the baboon as a model for studies of human reproductive biology, we previously showed that placental estrogen regulates fetal ovarian follicle development. In this study, offspring of baboons untreated or treated in utero with the aromatase inhibitor letrozole (estradiol reduced >95%) or letrozole and estradiol were reared to adulthood to determine whether estrogen programming of the fetal ovary impacted puberty and reproduction in adulthood. All offspring exhibited normal growth and blood pressure/chemistries. Puberty onset in untreated baboons (43.2 ± 1.4 mo) was delayed (P < 0.01) in animals of letrozole-treated mothers (49.0 ± 1.2 mo) and normal in offspring of mothers treated with letrozole and estradiol (42.7 ± 0.8 mo). During the first 2 yr postmenarche, menstrual cycles in estrogen-suppressed animals (43.2 ± 1.3 days) were longer (P < 0.05) than in untreated baboons (38.3 ± 0.5 days) or those treated with letrozole and estrogen (39.6 ± 0.8 days). Moreover, in estrogen-suppressed offspring, serum levels of estradiol were lower and follicle-stimulating hormone greater (P < 0.05) in the follicular and luteal phases, and the elevation in luteal-phase progesterone extended (P < 0.02). Thus, puberty onset was delayed and menstrual cycles prolonged and associated with altered serum hormone levels in baboon offspring that developed in an intrauterine environment in which estradiol levels were suppressed. Because puberty and follicle development, as shown previously, were normal in baboons treated in utero with letrozole and estradiol, we propose that fetal ovarian development and timely onset of puberty in the primate is programmed by fetal exposure to placental estrogen.

In utero exposure to venlafaxine, a serotonin-norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat.

PubMed

Laurent, Laetitia; Huang, Chunwei; Ernest, Sheila R; Berard, Anick; Vaillancourt, Cathy; Hales, Barbara F

2016-12-01

Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT 2B /Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044-1055, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

PubMed

Comish, Paul B; Drumond, Ana Luiza; Kinnell, Hazel L; Anderson, Richard A; Matin, Angabin; Meistrich, Marvin L; Shetty, Gunapala

2014-01-01

Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

Fetal Cyclophosphamide Exposure Induces Testicular Cancer and Reduced Spermatogenesis and Ovarian Follicle Numbers in Mice

PubMed Central

Comish, Paul B.; Drumond, Ana Luiza; Kinnell, Hazel L.; Anderson, Richard A.; Matin, Angabin; Meistrich, Marvin L.; Shetty, Gunapala

2014-01-01

Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼70% of control and induced atrophic seminiferous tubules in ∼30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan. PMID:24691397

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

PubMed Central

Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth

2016-01-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466

Alcohol-Induced Developmental Origins of Adult-Onset Diseases.

PubMed

Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth

2016-07-01

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by the Research Society on Alcoholism.

Computational Modeling and Simulation of Developmental Toxicity (EuroTox 2016)

EPA Science Inventory

Standard practice for assessing developmental toxicity is the observation of apical endpoints (intrauterine death, fetal growth retardation, structural malformations) in pregnant rats/rabbits following exposure during organogenesis. EPA’s computational toxicology research program...

Genetics Home Reference: abdominal wall defect

MedlinePlus

... are two main types of abdominal wall defects: omphalocele and gastroschisis . Omphalocele is an opening in the center of the ... covering the exposed organs in gastroschisis. Fetuses with omphalocele may grow slowly before birth (intrauterine growth retardation) ...

Nutritional status and growth in Korean children with Crohn's disease: a single-center study.

PubMed

Song, Seung Min; Kim, Young; Oh, Seak Hee; Kim, Kyung Mo

2014-09-01

Malnutrition and growth retardation are important issues in treating pediatric Crohn's disease (CD). Thus, we aimed to investigate the prevalence of various nutritional and growth parameters at the time of diagnosis in Korean children with CD. Seventy-one children (<18 years) were enrolled. We analyzed the Z-scores of height-for-age (HAZ), weight-for-height (WHZ), body mass index for age (BMIZ), bone mineral density for age (BMDZ), and the biochemical markers measured at the time of diagnosis. At diagnosis, HAZ <-2 was observed in three patients (4%), WHZ <-2 in 20 patients (28%), BMIZ <-2 in 19 patients (27%), and BMDZ <-2 in 11 patients (18%). The HAZ was significantly lower in females and patients with extraintestinal manifestations, and the WHZ and BMIZ were significantly lower in patients with stricturing and penetrating disease. Subnormal serum levels were highly prevalent for hemoglobin, albumin, iron, ferritin, calcium, magnesium, folate, vitamin B12, and zinc. There was a significant correlation between nutritional status, growth retardation, and disease activity. Abnormal nutritional status was highly prevalent in Korean children with CD at the time of diagnosis and was associated with the extent, behavior, and activity of the disease.

Neural Compensations After Lesion of the Cerebral Cortex

PubMed Central

Kolb, Bryan; Brown, Russell; Witt-Lajeunesse, Alane; Gibb, Robbin

2001-01-01

Functional improvement after cortical injury can be stimulated by various factors including experience, psychomotor stimulants, gonadal hormones, and neurotrophic factors. The, timing of the administration of these factors may be critical, however. For example, factors such as gonadal hormones, nerve growth factor, or psychomotor stimulants may act to either enhance or retard recovery, depending upon the timing of administration. Nicotine, for instance, stimulates recovery if given after an injury but is without neuroprotective effect and may actually retard recovery if it is given only preinjury. A related timing problem concerns the interaction of different treatments. For example, behavioral therapies may act, in part, via their action in stimulating the endogenous production of trophic factors. Thus, combining behavioral therapies with pharmacological administration of compounds to increase the availability of trophic factors enhances functional outcome. Finally, anatomical evidence suggests that the mechanism of action of many treatments is through changes in dendritic arborization, which presumably reflects changes in synaptic organization. Factors that enhance dendritic change stimulate functional compensation, whereas factors that retard or block dendritic change block or retard compensation. PMID:11530881

Dyslipidemia is not associated with cardiovascular disease risk in an animal model of mild chronic suboptimal nutrition.

PubMed

Lifshitz, Fima; Pintos, Patricia M; Lezón, Christian E; Macri, Elisa V; Friedman, Silvia M; Boyer, Patricia M

2012-01-01

Previous studies performed in an experimental model of nutritional growth retardation (NGR) have observed metabolic adaptation. We hypothesized that changes in lipid-lipoprotein profile, glucose, and insulin levels occur, whereas overall body growth is reduced.The aim of this study was to assess serum lipid-lipoprotein profile, hepatogram, insulinemia and glycemia, and CVD risk markers in rats fed a suboptimal diet. Weanling male rats were assigned either to control (C) or NGR group. In this 4-week study, C rats were fed ad libitum a standard diet, and NGR rats received 80% of the amount of food consumed by C. Zoometric parameters, body fat content, serum lipid-lipoprotein profile, hepatogram, insulinemia, and glycemia were determined, and the cardiovascular disease (CVD) risk markers homeostasis model assessment-insulin resistance and homeostasis model assessment and β-cell function were calculated. Suboptimal food intake induced a significant decrease in body weight and length, which were accompanied by a reduction of 50% in body fat mass. Serum lipoproteins were significantly higher in NGR rats, with the exception of high-density lipoprotein cholesterol, which remained unchanged. Nutritional growth retardation rats had decreased triglycerides compared with C rats. No significant differences were detected in liver function parameters. The CVD risk markers homeostasis model assessment (HOMA)-insulin resistance and homeostasis model assessment and β-cell function were significantly lower in NGR rats. Mild chronic suboptimal nutrition in weanling male rats led to growth retardation and changes in the lipid-lipoprotein profile, glucose, and insulin levels while preserving the integrity of liver function. These data suggest a metabolic adaptation during suboptimal food intake, which ensures substrates flux to tissues that require constant energy-in detriment to body growth. The CVD risk markers suggested that mild chronic food restriction of approximately 20% could provide protection against this degenerative disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Exposure to Ergot Alkaloids During Gestation Reduces Fetal Growth in Sheep

NASA Astrophysics Data System (ADS)

Duckett, Susan; Pratt, Scott; Andrae, John

2014-08-01

Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: 1) endophyte-infected (Neotyphodium coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and 2) endophyte-free tall fescue seed (E-; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E-. Organ and muscle weights were also lighter for E+ than E-. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development.

Iron in tubewell water and linear growth in rural Bangladesh.

PubMed Central

Briend, A; Hoque, B A; Aziz, K M

1990-01-01

The growth of 694 children from rural Bangladesh was studied. Children drinking water containing greater than 1 mg iron/l (n = 628) were significantly taller than those drinking less than 1 mg iron/l (n = 66): their mean (SD) height for age Z score was -2.10 (1.34) compared with -2.45 (1.24), p less than 0.05. This suggests that iron deficiency may contribute to growth retardation in poor communities. PMID:2317069

PROSTATE REGULATION: MODELING ENDOGENOUS ...

EPA Pesticide Factsheets

ALTERATIONS IN PROSTATE WEIGHT AND HISTOPATHOLOGY ARE OBSERVED FOLLOWING IN UTERO, PUBERTAL AND ADULT EXPOSURES TO ANTIANDROGENS. ALTERATIONS IN PROSTATE WEIGHT AND HISTOPATHOLOGY ARE OBSERVED FOLLOWING IN UTERO, PUBERTAL AND ADULT EXPOSURES TO ANTIANDROGENS.

Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

PubMed

Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

2014-05-05

Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei, E-mail: weiwang2@illinois.edu; Hafner, Katlyn S., E-mail: katlynhafner@gmail.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestationalmore » day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in female mouse offspring.« less

The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ziv-Gal, Ayelet, E-mail: zivgal1@illinois.edu; Wang, Wei, E-mail: weiwang2@illinois.edu; Zhou, Changqing, E-mail: czhou27@illinois.edu

In utero bisphenol A (BPA) exposure affects reproductive function in the first generation (F1) of mice; however, not many studies have examined the reproductive effects of BPA exposure on subsequent generations. In this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50 μg/kg/day) or diethylstilbestrol (DES; 0.05 μg/kg/day) daily from gestation day 11 until birth. F1 females were used to generate the F2 generation, and F2 females were used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9 months were conducted to evaluate reproductive capacity over time. Further, studiesmore » were conducted to evaluate pubertal onset, litter size, and percentage of dead pups; and to calculate pregnancy rate, and mating, fertility, and gestational indices. The results indicate that BPA exposure (0.5 and 50 μg/kg/day) significantly delayed the age at vaginal opening in the F3 generation compared to vehicle control. Both DES (0.05 μg/kg/day) and BPA (50 μg/kg/day) significantly delayed the age at first estrus in the F3 generation compared to vehicle control. BPA exposure reduced gestational index in the F1 and F2 generations compared to control. Further, BPA exposure (0.5 μg/kg/day) compromised the fertility index in the F3 generation compared to control. Finally, in utero BPA exposure reduced the ability of female mice to maintain pregnancies as they aged. Collectively, these data suggest that BPA exposure affects reproductive function in female mice and that some effects may be transgenerational in nature. - Highlights: • In utero BPA delayed vaginal opening in the F3 generation compared to control. • In utero BPA delayed estrus in the F3 generation compared to control. • In utero BPA reduced the ability of F1 and F2 female mice to maintain pregnancies. • In utero BPA compromised the ability of F3 female mice to become pregnant. • Some effects of in utero BPA may be transgenerational in nature.« less

Intrauterine Growth Restriction: Hungry for an Answer

PubMed Central

Chu, Alison

2016-01-01

Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID:26889018

Experimental hyperphenylalaninemia in the pregnant guinea pig: possible phenylalanine teratogenesis and p-chlorophenylalanine embryotoxicity.

PubMed

Kronick, J B; Whelan, D T; McCallion, D J

1987-10-01

Maternal hyperphenylalaninemia (HPH) due to deficient phenylalanine (Phe) hydroxylation is a recognized human teratogen associated with an increased incidence of intrauterine growth retardation, microcephaly, congenital heart disease, and mental retardation. There are no previous reports of experimental HPH during organogenesis. Sustained HPH was produced in pregnant guinea pigs by adding 3.5% Phe and 1.0% parachlorophenylalanine (pCPA), an inhibitor of Phe hydroxylase, to standard guinea pig chow. Animals consumed the supplemented test diets from gestation day 1 until killed on gestation day 17. Examination of day 17 embryos revealed that embryonic mortality was associated only with maternal pCPA administration and was independent of the degree of maternal HPH. Embryonic malformation was associated with maternal HPH as well as maternal pCPA administration. Both maternal HPH and pCPA administration were associated with embryonic growth retardation. There was no association between maternal food intake or plasma tyrosine levels and embryonic abnormality or mortality. Both Phe and tyrosine were found to be concentrated in gestation day 17 yolk sac fluid when compared to maternal plasma Phe and tyrosine. The association of embryonic malformation and maternal HPH is consistent with human data. The embryotoxicity of pCPA requires further study and highlights the necessity of appropriate controls in models of experimental HPH.

Predictive modeling of developmental toxicity using EPA’s Virtual Embryo

EPA Science Inventory

Standard practice in prenatal developmental toxicology involves testing chemicals in pregnant laboratory animals of two species, typically rats and rabbits, exposed during organogenesis and evaluating for fetal growth retardation, structural malformations, and prenatal death just...

Fatigue Crack Growth in Peened Friction Stir Welds

NASA Technical Reports Server (NTRS)

Forth, Scott C.; Hatamleh, Omar

2008-01-01

Friction stir welding induces residual stresses that accelerates fatigue crack growth in the weld nugget. Shot peening over the weld had little effect on growth rate. Laser peening over the weld retarded the growth rate: Final crack growth rate was comparable to the base, un-welded material. Crack tunneling evident from residual compressive stresses. 2195-T8 fracture surfaces were highly textured. Texturing makes comparisons difficult as the material system is affecting the data as much as the processing. Material usage becoming more common in space applications requiring additional work to develop useful datasets for damage tolerance analyses.

Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-12-01

The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

Child development following in utero exposure

PubMed Central

Shallcross, R.; Bromley, R.L.; Irwin, B.; Bonnett, L.J.; Morrow, J.

2011-01-01

Objective: Children born to women with epilepsy (WWE), exposed in utero to levetiracetam (LEV, n = 51), were assessed for early cognitive development and compared to children exposed to sodium valproate in utero (VPA, n = 44) and a group of children representative of the general population (n = 97). Methods: Children were recruited prospectively from 2 cohorts in the United Kingdom and assessed using the Griffiths Mental Development Scale (1996), aged <24 months. Information regarding maternal demographics were collected and controlled for. This is an observational study with researchers not involved in the clinical management of the WWE. Results: On overall developmental ability, children exposed to LEV obtained higher developmental scores when compared to children exposed to VPA (p < 0.001). When compared, children exposed to LEV did not differ from control children (p = 0.62) on overall development. Eight percent of children exposed to LEV in utero fell within the below average range (DQ score of <84), compared with 40% of children exposed to VPA. After controlling for maternal epilepsy and demographic factors using linear regression analysis, exposure to LEV in utero was not associated with outcome (p = 0.67). Conversely, when compared with VPA exposure, LEV exposure was associated with higher scores for the overall developmental quotient (p < 0.001). Conclusion: Children exposed to LEV in utero are not at an increased risk of delayed early cognitive development under the age of 24 months. LEV may therefore be a preferable drug choice, where appropriate, for WWE prior to and of childbearing age. PMID:21263139

Effects of growth retardants and fumigations with ozone and sulfur dioxide on growth and flowering of Euphorbia pulcherrima Willd

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cathey, H.M.; Heggestad, H.E.

1973-01-01

Eight cultivars of poinsettia, Euphorbia pulcherrima Willd., were evaluated for sensitivity to ..cap alpha..-cyclopropyl-..cap alpha.. (4-methoxyphenyl)-5-pyrimidine methanol (ancymidol) and protection from ozone and sulfur dioxide injury afforded by applications of ancymidol and (2-chloroethyl) trimethyl ammonium chloride (chlormequat). Foliar sprays of ancymidol were at least 80 to 500 times and the soil drench 1000 times more active than chlormequat in retarding stem elongation. The diam of the bracts was reduced, but branching increased more on plants treated with ancymidol than on untreated plants. The cv. Annette Hegg (AH) was more sensitive to ozone fumigations than was Eckespoint C-1' (C-1). Sulfur dioxidemore » also caused more injury to AH than to C-1. Ancymidol and chlormequat reduced visible injury induced by ozone and sulfur dioxide.« less

Double talon cusps on supernumerary tooth fused to maxillary central incisor: Review of literature and report of case

PubMed Central

2014-01-01

Human tooth development is a continuous process begin at the sixth weeks in utero and extends to about sixth months after birth for the primary dentition and from sixteenth week in utero to late adolescence for permanent dentition. There is no other organ of the human body which takes so long to attain its ultimate morphology as dentition. Several physiologic growth processes participate in the progressive development of the teeth including: initiation, proliferation, histodifferentiation, morphodifferentiation, apposition, calcification, and eruption. Aberrations in different stages of tooth development can result in unique manifestations both in primary and permanent dentitions. The fact that premaxilla is the predilection site for the occurrence of supernumerary teeth, talon cusp, dens invaginatus, and geminated teeth may suggest that the embryological development of premaxilla differ from other sites of the jaws. The dental abnormalities presented in this review are of great concern to dentist and parents because they create clinical, pathological and esthetic problems. Dental practitioner should be aware of the clinical sign, associated problems and treatment options for a given case. Key words:Double talon cusps, fusion, supernumerary, case report. PMID:25593664

A nuclear-encoded chloroplast protein harboring a single CRM domain plays an important role in the Arabidopsis growth and stress response.

PubMed

Lee, Kwanuk; Lee, Hwa Jung; Kim, Dong Hyun; Jeon, Young; Pai, Hyun-Sook; Kang, Hunseung

2014-04-16

Although several chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins have been characterized for intron splicing and rRNA processing during chloroplast gene expression, the functional role of a majority of CRM domain proteins in plant growth and development as well as chloroplast RNA metabolism remains largely unknown. Here, we characterized the developmental and stress response roles of a nuclear-encoded chloroplast protein harboring a single CRM domain (At4g39040), designated CFM4, in Arabidopsis thaliana. Analysis of CFM4-GFP fusion proteins revealed that CFM4 is localized to chloroplasts. The loss-of-function T-DNA insertion mutants for CFM4 (cfm4) displayed retarded growth and delayed senescence, suggesting that CFM4 plays a role in growth and development of plants under normal growth conditions. In addition, cfm4 mutants showed retarded seed germination and seedling growth under stress conditions. No alteration in the splicing patterns of intron-containing chloroplast genes was observed in the mutant plants, but the processing of 16S and 4.5S rRNAs was abnormal in the mutant plants. Importantly, CFM4 was determined to possess RNA chaperone activity. These results suggest that the chloroplast-targeted CFM4, one of two Arabidopsis genes encoding a single CRM domain-containing protein, harbors RNA chaperone activity and plays a role in the Arabidopsis growth and stress response by affecting rRNA processing in chloroplasts.

A nuclear-encoded chloroplast protein harboring a single CRM domain plays an important role in the Arabidopsis growth and stress response

PubMed Central

2014-01-01

Background Although several chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins have been characterized for intron splicing and rRNA processing during chloroplast gene expression, the functional role of a majority of CRM domain proteins in plant growth and development as well as chloroplast RNA metabolism remains largely unknown. Here, we characterized the developmental and stress response roles of a nuclear-encoded chloroplast protein harboring a single CRM domain (At4g39040), designated CFM4, in Arabidopsis thaliana. Results Analysis of CFM4-GFP fusion proteins revealed that CFM4 is localized to chloroplasts. The loss-of-function T-DNA insertion mutants for CFM4 (cfm4) displayed retarded growth and delayed senescence, suggesting that CFM4 plays a role in growth and development of plants under normal growth conditions. In addition, cfm4 mutants showed retarded seed germination and seedling growth under stress conditions. No alteration in the splicing patterns of intron-containing chloroplast genes was observed in the mutant plants, but the processing of 16S and 4.5S rRNAs was abnormal in the mutant plants. Importantly, CFM4 was determined to possess RNA chaperone activity. Conclusions These results suggest that the chloroplast-targeted CFM4, one of two Arabidopsis genes encoding a single CRM domain-containing protein, harbors RNA chaperone activity and plays a role in the Arabidopsis growth and stress response by affecting rRNA processing in chloroplasts. PMID:24739417

Computer-assisted image analysis of plant growth, thigmomorphogenesis and gravitropism

NASA Technical Reports Server (NTRS)

Jaffe, M. J.; Wakefield, A. H.; Telewski, F.; Gulley, E.; Biro, R.

1985-01-01

A nonintrusive auxonometric system, based on the DARWIN image processor (Telewski et al. 1983 Plant Physiol 72: 177-181), is described and demonstrated in the analysis of gravitropism and thigmomorphogenesis in corn seedlings (Zea mays). Using this system, growth and bending of regularly shaped plants or organs can be quickly and accurately measured without, in any way, interfering with the plant. Furthermore, the growth and bending curves are automatically plotted. Thigmomorphogenesis in the aerial part of corn seedlings involves growth promotion at a low force load and growth retardation at higher force loads. The time courses of the two kinds of response are somewhat different, with retardation occurring immediately after mechanical perturbation and growth promotion taking somewhat longer to begin. Gravitropic experiments show that when dark-grown corn seedlings are placed on their side in the light, the resulting curvature is due to two consecutive morphological mechanisms. In the first instance, lasting for about 15 minutes, the elongation of the bottom edge of the plant accelerates, while the elongation of the top edge remains constant. After that, for the next 1.75 hours, the elongation of the top edge decelerates and stops while that of the bottom edge remains constant at the increased rate for most of the period. The measurements taken from both experiments at relatively high resolution (0.08-0.1 millimeter) show that the growth curves are not smooth but show many small irregularities which may or may not involve micronutations.

Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease

PubMed Central

Sureshbabu, Angara; Doty, Steve B.; Zhu, Yuan-Shan; Patino, Edwin; Cunningham-Rundles, Susanna; Choi, Mary E.; Boskey, Adele; Rivella, Stefano

2016-01-01

Growth delay is common in children with chronic kidney disease (CKD), often associated with poor quality of life. The role of anemia in uremic growth delay is poorly understood. Here we describe an induction of uremic growth retardation by a 0.2% adenine diet in wild-type (WT) and hepcidin gene (Hamp) knockout (KO) mice, compared with their respective littermates fed a regular diet. Experiments were started at weaning (3 wk). After 8 wk, blood was collected and mice were euthanized. Adenine-fed WT mice developed CKD (blood urea nitrogen 82.8 ± 11.6 mg/dl and creatinine 0.57 ± 0.07 mg/dl) and were 2.1 cm shorter compared with WT controls. WT adenine-fed mice were anemic and had low serum iron, elevated Hamp, and elevated IL6 and TNF-α. WT adenine-fed mice had advanced mineral bone disease (serum phosphorus 16.9 ± 3.1 mg/dl and FGF23 204.0 ± 115.0 ng/ml) with loss of cortical and trabecular bone volume seen on microcomputed tomography. Hamp disruption rescued the anemia phenotype resulting in improved growth rate in mice with CKD, thus providing direct experimental evidence of the relationship between Hamp pathway and growth impairment in CKD. Hamp disruption ameliorated CKD-induced growth hormone-insulin-like growth factor 1 axis derangements and growth plate alterations. Disruption of Hamp did not mitigate the development of uremia, inflammation, and mineral and bone disease in this model. Taken together, these results indicate that an adenine diet can be successfully used to study growth in mice with CKD. Hepcidin appears to be related to pathways of growth retardation in CKD suggesting that investigation of hepcidin-lowering therapies in juvenile CKD is warranted. PMID:27440777

The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome.

PubMed

Laron, Z

1999-12-01

Fifty patients with primary GH resistance (Laron syndrome) due to molecular defects of the GH receptor or post-receptor pathways were followed from infancy through adulthood. This condition leading to long-term insulin-like growth factor-I (IGF-I) deprivation caused marked growth retardation (-4 to 8 height SD), acromicia, organomicria, retarded development of the skeletal and muscular systems, a small cranium, slow motor development, and impairment of intellectual development in some of the patients. In addition, there was progressive obesity, insulin resistance, a tendency for hypoglycemia, followed later in life by hypercholesterolemia and by glucose intolerance and even diabetes. IGF-I treatment of children with Laron syndrome, by our and other groups (150-240 microg/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abnormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primary IGF-I deprivation induces severe auxological, biochemical, and hormonal changes, the only treatment being biosynthetic IGF-I administration.

Mitochondrial deficiency impairs hypoxic induction of HIF-1 transcriptional activity and retards tumor growth

PubMed Central

Koido, Masaru; Haga, Naomi; Furuno, Aki; Tsukahara, Satomi; Sakurai, Junko; Tani, Yuri; Sato, Shigeo; Tomida, Akihiro

2017-01-01

Mitochondria can be involved in regulating cellular stress response to hypoxia and tumor growth, but little is known about that mechanistic relationship. Here, we show that mitochondrial deficiency severely retards tumor xenograft growth with impairing hypoxic induction of HIF-1 transcriptional activity. Using mtDNA-deficient ρ0 cells, we found that HIF-1 pathway activation was comparable in slow-growing ρ0 xenografts and rapid-growing parental xenografts. Interestingly, we found that ex vivo ρ0 cells derived from ρ0 xenografts exhibited slightly increased HIF-1α expression and modest HIF-1 pathway activation regardless of oxygen concentration. Surprisingly, ρ0 cells, as well as parental cells treated with oxidative phosphorylation inhibitors, were unable to boost HIF-1 transcriptional activity during hypoxia, although HIF-1α protein levels were ordinarily increased in these cells under hypoxic conditions. These findings indicate that mitochondrial deficiency causes loss of hypoxia-induced HIF-1 transcriptional activity and thereby might lead to a constitutive HIF-1 pathway activation as a cellular adaptation mechanism in tumor microenvironment. PMID:28060746

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

PubMed

Nose, Osamu; Tatsumi, Keita; Nakano, Yukiko; Amino, Nobuyuki

2006-04-01

Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank.

PubMed

Bassiouny, M R; El-Chennawi, F; Mansour, A K; Yahia, S; Darwish, A

2015-06-01

Umbilical cord blood (UCB) contains stem cells and can be used as an alternative to bone marrow transplantation. Engraftment is dependent on the total nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study was designed to evaluate the effect of the method of collection of the UCB on the yield of the cord blood units. Informed consent was obtained from 100 eligible mothers for donation of cord blood. Both in utero and ex utero methods were used for collection. The cord blood volume was measured. The TNC and the CD34+ cell counts were enumerated. We have found that in utero collection gave significantly larger volumes of cord blood and higher TNC counts than ex utero collection. There was no significant difference between both methods regarding the CD34+ cell counts. This study revealed a significant correlation between the volume of the collected cord blood and both TNC and CD34+ cell counts. It is better to collect cord blood in utero before placental delivery to optimize the quality of the cord blood unit. © 2015 AABB.

Crack Growth Behavior of Alloy in-100 under Sustained Load at 732 C (1350 F).

DTIC Science & Technology

1981-04-01

were not taken into account in this investigation. pi 63 63 AFWAL-TR-80-4131 REFERENCES 1. D. E. Macha , "Fatigue Crack Growth Retardation Behavior of...IN-1O0 at Elevated Temperature," Eng. Fract. Mech, Vol. 12, pp. 1-11, 1979. 2. D. E. Macha , A. F. Grandt, and B. J. Wicks, "Effects of Gas Turbine

RETARDED GROWTH OF BONES OF THE FOREARM IN A GIRL FOLLOWING RADIUM THERAPY OF SKIN HEMANGIOMA (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirimova, T.D.

1960-07-01

A 9-month-old girl was subjected to radium therapy of skin hemangioma in the region of the forearm. Thirteen years afterwards there was revealed a considerable impairment in the growth and development of long bones that were within the field of the irradiation, resulting in the formation of a deformed shortened hand with restricted functions. (auth)

Growth retardation, intellectual disability, facial anomalies, cataract, thoracic hypoplasia and skeletal abnormalities: a novel phenotype

PubMed Central

Shah, Hitesh; Bens, Susanne; Caliebe, Almuth; Graham, John M.; Girisha, Katta Mohan

2012-01-01

We report a fourteen year old adolescent girl with growth deficiency, microcephaly, intellectual disability, distinctive dysmorphic features (bulbous nose with wide nasal base, hypotelorism, deeply set eyes, protruding cupped ears and thick lips), cataract, pigmentary retinopathy, hypoplastic thorax, kyphoscoliosis and unusual skeletal changes but without chromosomal imbalances detected by array-CGH who probably represents a novel phenotype. PMID:22987502

Long-Term Effects of Food Supplementation and Psychosocial Intervention on the Physical Growth of Colombian Infants at Risk of Malnutrition.

ERIC Educational Resources Information Center

Super, Charles M.; And Others

1990-01-01

At 3 years of age, children who had received food supplementation were an average of 2.6 cm and 642 grams larger than controls. Home visiting and supplementation combined reduced the number of children with severe growth retardation. Participants were 280 infants and their families from poor neighborhoods in Bogota, Colombia. (RH)

Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi; Medical Research Center, Oulu University Hospital, Oulu; Alhonen, Leena

Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism andmore » uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this stage is so vulnerable to the development of neural tube defect, and growth restriction, the findings previously observed in fetal alcohol syndrome.« less

Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay.

PubMed

Daoud, Hussein; Zhang, Dong; McMurray, Fiona; Yu, Andrea; Luco, Stephanie M; Vanstone, Jason; Jarinova, Olga; Carson, Nancy; Wickens, James; Shishodia, Shifali; Choi, Hwanho; McDonough, Michael A; Schofield, Christopher J; Harper, Mary-Ellen; Dyment, David A; Armour, Christine M

2016-03-01

A homozygous loss-of-function mutation p.(Arg316Gln) in the fat mass and obesity-associated (FTO) gene, which encodes for an iron and 2-oxoglutarate-dependent oxygenase, was previously identified in a large family in which nine affected individuals present with a lethal syndrome characterised by growth retardation and multiple malformations. To date, no other pathogenic mutation in FTO has been identified as a cause of multiple congenital malformations. We investigated a 21-month-old girl who presented distinctive facial features, failure to thrive, global developmental delay, left ventricular cardiac hypertrophy, reduced vision and bilateral hearing loss. We performed targeted next-generation sequencing of 4813 clinically relevant genes in the patient and her parents. We identified a novel FTO homozygous missense mutation (c.956C>T; p.(Ser319Phe)) in the affected individual. This mutation affects a highly conserved residue located in the same functional domain as the previously characterised mutation p.(Arg316Gln). Biochemical studies reveal that p.(Ser319Phe) FTO has reduced 2-oxoglutarate turnover and N-methyl-nucleoside demethylase activity. Our findings are consistent with previous reports that homozygous mutations in FTO can lead to rare growth retardation and developmental delay syndrome, and further support the proposal that FTO plays an important role in early development of human central nervous and cardiovascular systems. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

PubMed

Golub, M S; Macintosh, M S; Baumrind, N

1998-01-01

Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

International Conference on Crystal Growth (10th) Held in San Diego, California, on 16-21 August 1992

DTIC Science & Technology

1993-07-14

precipitation. This additive appeared to retard growth be different for the nuclei formed on additive molecules and and to stimulate nucleation of BaSO4...dispersion is described by some of different crystals of the same material grow at different rates. the mentioned distributions. Aiming at that, the...of crystals that grow with different a from the histo- grams of distributions of crystal growth rates [2,3], and it is 1. U.K. Burton et al., Phil

Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: a characterization of the BPH/5 mouse in postnatal life

PubMed Central

Sutton, Elizabeth F.; Lob, Heinrich E.; Song, Jiunn; Xia, YunWei; Butler, Scott; Liu, Chin-Chi; Redman, Leanne M.

2017-01-01

Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes. PMID:28122721

A Mouse Model of Transplacental Cocaine Exposure: Clinical Implications for Exposed Infants and Childrena.

PubMed

Kosofsky, Barry E; Wilkins, Aaron S

1998-06-01

To characterize the effects of cocaine on developing brain we have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food ad libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting α-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dams. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

A mouse model of transplacental cocaine exposure. Clinical implications for exposed infants and children.

PubMed

Kosofsky, B E; Wilkins, A S

1998-06-21

To characterize the effects of cocaine on developing brain we have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food ad libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting alpha-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dams. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Hanwen; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071; Deng, Zixin

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats.more » F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced reproductive and developmental toxicities in F1 have hereditary effect. • Caffeine-induced programming of HPA axis in F2 has gender and parental differences.« less

ATENOLOL: PHARMACOKINETIC/DYNAMIC ASPECTS OF COMPARATIVE DEVELOPMENTAL TOXICITY: A REVIEW

EPA Science Inventory

Atenolol is a cardioselective B-adrenoreceptor blocking agent, used for treatment of hypertension, including hypertension in pregnancy. Beta-adrenoreceptor antagonists have been impacted in the production of intrauterine growth retardation and considerable range of neonatal probl...

Impacts of Maternal Nutrition on Vascularity of Nutrient Transferring Tissues during Gestation and Lactation

PubMed Central

Vonnahme, Kimberly A.; Lemley, Caleb O.; Caton, Joel S.; Meyer, Allison M.

2015-01-01

As the demand for food increases with exponential growth in the world population, it is imperative that we understand how to make livestock production as efficient as possible in the face of decreasing available natural resources. Moreover, it is important that livestock are able to meet their metabolic demands and supply adequate nutrition to developing offspring both during pregnancy and lactation. Specific nutrient supplementation programs that are designed to offset deficiencies, enhance efficiency, and improve nutrient supply during pregnancy can alter tissue vascular responses, fetal growth, and postnatal offspring outcomes. This review outlines how vascularity in nutrient transferring tissues, namely the maternal gastrointestinal tract, the utero-placental tissue, and the mammary gland, respond to differing nutritional planes and other specific nutrient supplementation regimes. PMID:25984740

In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism.

PubMed

Radford, Elizabeth J; Ito, Mitsuteru; Shi, Hui; Corish, Jennifer A; Yamazawa, Kazuki; Isganaitis, Elvira; Seisenberger, Stefanie; Hore, Timothy A; Reik, Wolf; Erkek, Serap; Peters, Antoine H F M; Patti, Mary-Elizabeth; Ferguson-Smith, Anne C

2014-08-15

Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, which may have an impact on F2 development. Differential methylation is not maintained in F2 tissues, yet locus-specific expression is perturbed. Thus, in utero nutritional exposures during critical windows of germ cell development can impact the male germline methylome, associated with metabolic disease in offspring. Copyright © 2014, American Association for the Advancement of Science.

Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response

PubMed Central

Bromer, Jason G.; Zhou, Yuping; Taylor, Melissa B.; Doherty, Leo; Taylor, Hugh S.

2010-01-01

Bisphenol-A (BPA) is a nonsteroidal estrogen that is ubiquitous in the environment. The homeobox gene Hoxa10 controls uterine organogenesis, and its expression is affected by in utero BPA exposure. We hypothesized that an epigenetic mechanism underlies BPA-mediated alterations in Hoxa10 expression. We analyzed the expression pattern and methylation profile of Hoxa10 after in utero BPA exposure. Pregnant CD-1 mice were treated with BPA (5 mg/kg IP) or vehicle control on d 9–16 of pregnancy. Hoxa10 mRNA and protein expression were increased by 25% in the reproductive tract of mice exposed in utero. Bisulfite sequencing revealed that cytosine-guanine dinucleotide methylation was decreased from 67 to 14% in the promoter and from 71 to 3% in the intron of Hoxa10 after in utero BPA exposure. Decreased DNA methylation led to an increase in binding of ER-α to the Hoxa10 ERE both in vitro as and in vivo as determined by EMSA and chromatin immunoprecipitation, respectively. Diminished methylation of the ERE-containing promoter sequence resulted in an increase in ERE-driven gene expression in reporter assays. We identify altered methylation as a novel mechanism of BPA-induced altered developmental programming. Permanent epigenetic alteration of ERE sensitivity to estrogen may be a general mechanism through which endocrine disruptors exert their action.—Bromer, J. G., Zhou, Y., Taylor, M. B., Doherty, L., Taylor, H. S.. Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. PMID:20181937

DDT Exposure in Utero and Breast Cancer.

PubMed

Cohn, Barbara A; La Merrill, Michele; Krigbaum, Nickilou Y; Yeh, Gregory; Park, June-Soo; Zimmermann, Lauren; Cirillo, Piera M

2015-08-01

Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation. In utero exposure to DDT is associated with an increased risk of breast cancer. This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year). Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study. Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured. Maternal o,p'-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings. This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.

Detection of polybrominated biphenyl ethers (PBDEs) in pediatric hair as a tool for determining in utero exposure.

PubMed

Aleksa, Katarina; Carnevale, Amanda; Goodyer, Cynthia; Koren, Gideon

2012-05-10

Cryptorchidism, or undescended/maldescended testis, is the most common birth defect of male genitalia. Its prevalence has been increasing over the past few decades. This may be due to an increase in the prevalence of anti-androgenic chemicals such as polychlorinated biphenyls, organochloride pesticides, plasticizers and fungicides. A newer group of chemicals, brominated flame retardants (BFRs), are being implicated as endocrine-disrupting chemicals. These chemicals are used worldwide in polymers that are incorporated into a variety of consumer products (e.g., textile, computers and televisions, insulating foam, electrical equipment and kitchen appliances). In order to quantify BFRs we introduce the use of hair levels of polybrominated diphenyl esters (PBDEs) as biomarkers of systemic exposure. This approach will allow for the estimation of in utero BFR exposure, in the process of evaluating the potential link between the incidence of cryptorchidism in newborn males and level of exposure of the pregnant mother to environmentally relevant BFRs. For that end we have developed a GC/MS assay in which children's hair is analyzed for the presence of polybrominated biphenyl ethers (PBDEs). In this pilot, 10-40mg of hair from 24 children (12 newborn and 12 from children 1 to 15 years) was extracted overnight at 40°C with 4N HCl and hexane (4:1). The samples were eluted from 2g NaSO(4):2g Florisil SPE columns with 8mL hexane. Dried samples are reconstituted with anhydrous isooctane and injected onto a GC/MS and analyzed for BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183 and BDE-209. PBDEs were detected in all of the newborn and child hair. The ΣPBDE ranged from 0.038 to 1.01pg/mg newborn hair and from 0.208 to 2.695ng/mg child hair. The most abundant PBDE in newborn hair was BDE-153 while in child hair the variable PBDEs were BDE-47 and BDE-99. The highest molecular weight congener BDE-209 was detected in 10/24 pediatric hair samples. The LOQ is 0.0625pg/mg (BDE-209 0.625pg/mg) and the efficiency of extraction was between 70 and 90%. This GC/MS method is sufficiently sensitive to detect the presence of all 8 PBDE congeners tested in as little as 10mg of pediatric hair. The results show that PBDEs are present in newborn hair, making this matrix useful in examining in utero exposure to PBDEs and linking it to cryptorchidism. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire

PubMed Central

Gilbert-Diamond, Diane; Emond, Jennifer A.; Baker, Emily R.; Korrick, Susan A.; Karagas, Margaret R.

2016-01-01

Background: Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. Objective: We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Methods: Among 706 mother–infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Results: Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7–6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: –0.19, –0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: –0.82, –0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: –111.6, –14.2) in birth weight, though the association was null in the other strata. Conclusions: Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Citation: Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299–1307; http://dx.doi.org/10.1289/ehp.1510065 PMID:26955061

Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire.

PubMed

Gilbert-Diamond, Diane; Emond, Jennifer A; Baker, Emily R; Korrick, Susan A; Karagas, Margaret R

2016-08-01

Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Among 706 mother-infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7-6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: -0.19, -0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: -0.82, -0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: -111.6, -14.2) in birth weight, though the association was null in the other strata. Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299-1307; http://dx.doi.org/10.1289/ehp.1510065.

Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele

PubMed Central

Brown, Erin G.; Lankford, Lee; Keller, Benjamin A.; Pivetti, Christopher D.; Sitkin, Nicole A.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Farmer, Diana L.

2015-01-01

Myelomeningocele (MMC)—commonly known as spina bifida—is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients. Significance This study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC. PMID:25911465

Cyclin A2 promotes DNA repair in the brain during both development and aging.

PubMed

Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

2016-07-01

Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.

Elevated levels of insulin-like growth factor (IGF)-I in serum rescue the severe growth retardation of IGF-I null mice.

PubMed

Wu, Yingjie; Sun, Hui; Yakar, Shoshana; LeRoith, Derek

2009-09-01

IGF-I plays a vital role in growth and development and acts in an endocrine and an autocrine/paracrine fashion. The purpose of the current study was to clarify whether elevated levels of IGF-I in serum can rescue the severe growth retardation and organ development and function of igf-I null mice. To address that, we overexpressed a rat igf-I transgene specifically in the liver of igf-I null mice. We found that in the total absence of tissue IGF-I, elevated levels of IGF-I in serum can support normal body size at puberty and after puberty but are insufficient to fully support the female reproductive system (evident by irregular estrous cycle, impaired development of ovarian corpus luteum, reduced number of uterine glands and endometrial hypoplasia, all leading to decreased number of pregnancies and litter size). We conclude that most autocrine/paracrine actions of IGF-I that determine organ growth and function can be compensated by elevated levels of endocrine IGF-I. However, in mice, full compensatory responses are evident later in development, suggesting that autocrine/paracrine IGF-I is critical for neonatal development. Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I.

Neurodevelopmental Consequences of Low-Level Thyroid Hormone Disruption Induced by Environmental Contaminants

EPA Science Inventory

Inadequate levels of thyroid hormone during critical developmental periods lead to stunted growth, mental retardation, and neurological 'cretinism'. Animal models of developmental thyroid hormone deficiency mirror well the impact of severe insults to the thyroid system. However, ...

The inhibition of tetrahydrofuran clathrate-hydrate formation with antifreeze protein

NASA Astrophysics Data System (ADS)

Zeng, H.; Wilson, L. D.; Walker, V. K.; Ripmeester, J. A.

2003-01-01

The effect of Type I fish antifreeze protein (AFP) from the winter flounder, Pleuronectes americanus (Walbaum), (WfAFP) on the formation of tetrahydrofuran (THF) clathrate hydrate was studied by observing changes in THF crystal morphology and determining the induction time for nucleation. AFP retarded THF clathrate-hydrate growth at the tested temperatures and modified the THF clathrate-hydrate crystal morphology from octahedral to plate-like. AFP appears to be even more effective than the kinetic inhibitor, polyvinylpyrrolidone (PVP). Recombinant AFP from an insect, a spruce budworm, Choristoneura fumiferana (Clem.), moth, (Cf) was also tested for inhibition activity by observation of the THF-hydrate-crystal-growth habit. Like WfAFP, CfAFP appeared to show adsorption on multiple THF-hydrate-crystal faces. A protein with no antifreeze activity, cytochrome C, was used as a control and it neither changed the morphology of the THF clathrate-hydrate crystals, nor retarded the formation of the hydrate. Preliminary experiments on the inhibition activity of WfAFP on a natural gas hydrate assessed induction time and the amount of propane gas consumed. Similar to the observations for THF, the data indicated that WfAFP inhibited propane-hydrate growth. Taken together, these results support our hypothesis that AFPs can inhibit clathrate-hydrate growth and as well, offer promise for the understanding of the inhibition mechanism.

Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review.

PubMed

Frank, D A; Augustyn, M; Knight, W G; Pell, T; Zuckerman, B

2001-03-28

Despite recent studies that failed to show catastrophic effects of prenatal cocaine exposure, popular attitudes and public policies still reflect the belief that cocaine is a uniquely dangerous teratogen. To critically review outcomes in early childhood after prenatal cocaine exposure in 5 domains: physical growth; cognition; language skills; motor skills; and behavior, attention, affect, and neurophysiology. Search of MEDLINE and Psychological Abstracts from 1984 to October 2000. Studies selected for detailed review (1) were published in a peer-reviewed English-language journal; (2) included a comparison group; (3) recruited samples prospectively in the perinatal period; (4) used masked assessment; and (5) did not include a substantial proportion of subjects exposed in utero to opiates, amphetamines, phencyclidine, or maternal human immunodeficiency virus infection. Thirty-six of 74 articles met criteria and were reviewed by 3 authors. Disagreements were resolved by consensus. After controlling for confounders, there was no consistent negative association between prenatal cocaine exposure and physical growth, developmental test scores, or receptive or expressive language. Less optimal motor scores have been found up to age 7 months but not thereafter, and may reflect heavy tobacco exposure. No independent cocaine effects have been shown on standardized parent and teacher reports of child behavior scored by accepted criteria. Experimental paradigms and novel statistical manipulations of standard instruments suggest an association between prenatal cocaine exposure and decreased attentiveness and emotional expressivity, as well as differences on neurophysiologic and attentional/affective findings. Among children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure is associated with developmental toxic effects that are different in severity, scope, or kind from the sequelae of multiple other risk factors. Many findings once thought to be specific effects of in utero cocaine exposure are correlated with other factors, including prenatal exposure to tobacco, marijuana, or alcohol, and the quality of the child's environment. Further replication is required of preliminary neurologic findings.

Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure

PubMed Central

Frank, Deborah A.; Augustyn, Marilyn; Knight, Wanda Grant; Pell, Tripler; Zuckerman, Barry

2008-01-01

Context Despite recent studies that failed to show catastrophic effects of prenatal cocaine exposure, popular attitudes and public policies still reflect the belief that cocaine is a uniquely dangerous teratogen. Objective To critically review outcomes in early childhood after prenatal cocaine exposure in 5 domains: physical growth; cognition; language skills; motor skills; and behavior, attention, affect, and neurophysiology. Data Sources Search of MEDLINE and Psychological Abstracts from 1984 to October 2000. Study Selection Studies selected for detailed review (1) were published in a peerreviewed English-language journal; (2) included a comparison group; (3) recruited samples prospectively in the perinatal period; (4) used masked assessment; and (5) did not include a substantial proportion of subjects exposed in utero to opiates, amphetamines, phencyclidine, or maternal human immunodeficiency virus infection. Data Extraction Thirty-six of 74 articles met criteria and were reviewed by 3 authors. Disagreements were resolved by consensus. Data Synthesis After controlling for confounders, there was no consistent negative association between prenatal cocaine exposure and physical growth, developmental test scores, or receptive or expressive language. Less optimal motor scores have been found up to age 7 months but not thereafter, and may reflect heavy tobacco exposure. No independent cocaine effects have been shown on standardized parent and teacher reports of child behavior scored by accepted criteria. Experimental paradigms and novel statistical manipulations of standard instruments suggest an association between prenatal cocaine exposure and decreased attentiveness and emotional expressivity, as well as differences on neurophysiologic and attentional/affective findings. Conclusions Among children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure is associated with developmental toxic effects that are different in severity, scope, or kind from the sequelae of multiple other risk factors. Many findings once thought to be specific effects of in utero cocaine exposure are correlated with other factors, including prenatal exposure to tobacco, marijuana, or alcohol, and the quality of the child’s environment. Further replication is required of preliminary neurologic findings. PMID:11268270

Placental alterations in structure and function in intra-uterine growth-retarded horses.

PubMed

Robles, M; Peugnet, P M; Valentino, S A; Dubois, C; Dahirel, M; Aubrière, M-C; Reigner, F; Serteyn, D; Wimel, L; Couturier-Tarrade, A; Chavatte-Palmer, P

2018-05-01

Following embryo transfer (ET), the size and breed of the recipient mare can affect fetal development and subsequent post natal growth rate and insulin sensitivity in foals. To investigate placental adaptation in pregnancies where increased or restricted fetal growth was induced through ET between Pony, Saddlebred and Draught horses. In vivo experiment. Control Pony (P, n = 21) and Saddlebred (S, n = 28) pregnancies were obtained by artificial insemination. Increased pregnancies were obtained by transferring Pony (P-D, n = 6) and Saddlebred (S-D, n = 8) embryos into Draught mares. Restricted pregnancies were obtained by transferring Saddlebred embryos into Pony mares (S-P, n = 6). Placental weight and surface were recorded and samples collected for stereology and analysis of expression of genes involved in placental growth, vascularisation and nutrient transport. Data were analysed by linear model. S-P foals were growth retarded when compared with controls despite increased gestational length. Placental weight was reduced but placental surface density and volume fraction were increased. Placental expression of genes involved in growth and development and nutrient transfer was strongly reduced. In contrast, placental size and weight were increased in enhanced growth P-D and S-D foals. The trophoblastic surface density and the allantoic vessels surface density were decreased in P-D and S-D, respectively, both with very few modifications in gene expression. Control embryos were produced by artificial insemination whereas experimental embryos were produced by ET. Placental structure and gene expression are modified after ET into a smaller or larger breed than that of the embryo. These adaptations contribute to the observed phenotype of foal growth restriction or enhanced growth at birth. © 2017 EVJ Ltd.

A Case With Short Stature, Growth Hormone Deficiency and 46, XX, Xq27-qter Deletion.

PubMed

Yıldırım, Şule; Topaloğlu, Naci; Tekin, Mustafa; Sılan, Fatma

2017-10-01

We report a case of 11-year-old girl with growth retardation and 46, XX, Xq27-qter deletion. The endocrinologic evaluation revealed growth hormone deficiency. In karyotype analysis  46, XX, Xq27-qter deletion was determined. The deletion of terminal region of chromosome 27 is most commonly being detected during the evaluation of infertility, premature ovarian insufficiency or in screening for fragile X carrier status. To our knowledge, this is the first reported case with 46, XX, Xq27-qter deletion and growth hormone deficiency. Furthermore, this case might facilitate future search for candidate genes involved in growth hormone deficiency.

Growth hormone investigation in patients with mental dysfunction.

PubMed

Pozsonyi, J; Friesen, H

1971-01-09

Seventy-three children with disorders of physical growth and mental development were stimulated by insulin hypoglycemia and arginine infusion and their human growth hormone (HGH) responses were determined. Only four patients exhibited absent or impaired pituitary hormone secretion and one of them presented a unique syndrome of panhypopituitarism associated with intrauterine growth retardation, long eyelashes and eyebrows, sparse hair and degeneration of the retina. Statistical analysis indicated no significant HGH peak concentrations in groups of either tall males or stunted females who possessed various sex chromosome abnormalities, nor did these groups differ in a variety of clinical parameters including age, physical growth, birth weight and intelligence.

Growth Hormone Investigation in Patients with Mental Dysfunction

PubMed Central

Pozsonyi, J.; Friesen, H.

1971-01-01

Seventy-three children with disorders of physical growth and mental development were stimulated by insulin hypoglycemia and arginine infusion and their human growth hormone (HGH) responses were determined. Only four patients exhibited absent or impaired pituitary hormone secretion and one of them presented a unique syndrome of panhypopituitarism associated with intrauterine growth retardation, long eyelashes and eyebrows, sparse hair and degeneration of the retina. Statistical analysis indicated no significant HGH peak concentrations in groups of either tall males or stunted females who possessed various sex chromosome abnormalities, nor did these groups differ in a variety of clinical parameters including age, physical growth, birth weight and intelligence. PMID:4250364

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

PubMed

Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

2016-07-01

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

Strategies for optimizing maternal nutrition to promote infant development.

PubMed

Hambidge, K Michael; Krebs, Nancy F

2018-06-22

The growing appreciation of the multi-faceted importance of optimal maternal nutrition to the health and development of the infant and young child is tempered by incompletely resolved strategies for combatting challenges. To review the importance of maternal nutrition and strategies being employed to optimize outcomes. Selected data from recent literature with special focus on rationale for and currently published results of maternal nutrition supplements, including lipid based nutrition supplements. 1) An impelling rationale for improving the maternal and in utero environment of low resource populations has emerged to achieve improved fetal and post-natal growth and development. 2) Based partly on population increases in adult height over one-two generations, much can be achieved by reducing poverty. 3) Maternal, newborn and infant characteristics associated with low resource environments include evidence of undernutrition, manifested by underweight and impaired linear growth. 4) Apart from broad public health and educational initiatives, to date, most specific efforts to improve fetal growth and development have included maternal nutrition interventions during gestation. 5) The relatively limited but real benefits of both iron/folic acid (IFA) and multiple micronutrient (MMN) maternal supplements during gestation have now been reasonably defined. 6) Recent investigations of a maternal lipid-based primarily micronutrient supplement (LNS) have not demonstrated a consistent benefit beyond MMN alone. 7) However, effects of both MMN and LNS appear to be enhanced by commencing early in gestation. Poor maternal nutritional status is one of a very few specific factors in the human that not only contributes to impaired fetal and early post-natal growth but for which maternal interventions have demonstrated improved in utero development, documented primarily by both improvements in low birth weights and by partial corrections of impaired birth length. A clearer definition of the benefits achievable by interventions specifically focused on correcting maternal nutrition deficits should not be limited to improvements in the quality of maternal nutrition supplements, but on the cumulative quantity and timing of interventions (also recognizing the heterogeneity between populations). Finally, in an ideal world these steps are only a prelude to improvements in the total environment in which optimal nutrition and other health determinants can be achieved.

Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction

PubMed Central

Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.

2012-01-01

The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434

Computer-Assisted Image Analysis of Plant Growth, Thigmomorphogenesis, and Gravitropism 1

PubMed Central

Jaffe, Mordecai J.; Wakefield, Andrew H.; Telewski, Frank; Gulley, Edward; Biro, Ronald

1985-01-01

A nonintrusive auxonometric system, based on the DARWIN image processor (Telewski et al. 1983 Plant Physiol 72: 177-181), is described and demonstrated in the analysis of gravitropism and thigmomorphogenesis in corn seedlings (Zea mays). Using this system, growth and bending of regularly shaped plants or organs can be quickly and accurately measured without, in any way, interfering with the plant. Furthermore, the growth and bending curves are automatically plotted. Thigmomorphogenesis in the aerial part of corn seedlings involves growth promotion at a low force load and growth retardation at higher force loads. The time courses of the two kinds of response are somewhat different, with retardation occurring immeditely after mechanical perturbation and growth promotion taking somewhat longer to begin. Gravitropic experiments show that when dark-grown corn seedlings are placed on their side in the light, the resulting curvature is due to two consecutive morphological mechanisms. In the first instance, lasting for about 15 minutes, the elongation of the bottom edge of the plant accelerates, while the elongation of the top edge remains constant. After that, for the next 1.75 hours, the elongation of the top edge decelerates and stops while that of the bottom edge remains constant at the increased rate for most of the period. The measurements taken from both experiments at relatively high resolution (0.08-0.1 millimeter) show that the growth curves are not smooth but show many small irregularities which may or may not involve micronutations. Images Fig. 1 Fig. 2 Fig. 3 PMID:11539042

Overexpression of the AtSHI Gene in Poinsettia, Euphorbia pulcherrima, Results in Compact Plants

PubMed Central

Islam, M. Ashraful; Lütken, Henrik; Haugslien, Sissel; Blystad, Dag-Ragnar; Torre, Sissel; Rolcik, Jakub; Rasmussen, Søren K.; Olsen, Jorunn E.; Clarke, Jihong Liu

2013-01-01

Euphorbia pulcherrima, poinsettia, is a non-food and non-feed vegetatively propagated ornamental plant. Appropriate plant height is one of the most important traits in poinsettia production and is commonly achieved by application of chemical growth retardants. To produce compact poinsettia plants with desirable height and reduce the utilization of growth retardants, the Arabidopsis SHORT INTERNODE (AtSHI) gene controlled by the cauliflower mosaic virus 35S promoter was introduced into poinsettia by Agrobacterium-mediated transformation. Three independent transgenic lines were produced and stable integration of transgene was verified by PCR and Southern blot analysis. Reduced plant height (21–52%) and internode lengths (31–49%) were obtained in the transgenic lines compared to control plants. This correlates positively with the AtSHI transcript levels, with the highest levels in the most dwarfed transgenic line (TL1). The indole-3-acetic acid (IAA) content appeared lower (11–31% reduction) in the transgenic lines compared to the wild type (WT) controls, with the lowest level (31% reduction) in TL1. Total internode numbers, bract numbers and bract area were significantly reduced in all transgenic lines in comparison with the WT controls. Only TL1 showed significantly lower plant diameter, total leaf area and total dry weight, whereas none of the AtSHI expressing lines showed altered timing of flower initiation, cyathia abscission or bract necrosis. This study demonstrated that introduction of the AtSHI gene into poinsettia by genetic engineering can be an effective approach in controlling plant height without negatively affecting flowering time. This can help to reduce or avoid the use of toxic growth retardants of environmental and human health concern. This is the first report that AtSHI gene was overexpressed in poinsettia and transgenic poinsettia plants with compact growth were produced. PMID:23308204

Nutrition and Learning in Preschool Children.

ERIC Educational Resources Information Center

Thomas, Susan B.

This paper describes the behavior of nutritionally deprived children, and findings indicate retarded physical and mental growth. Based on the extensive bibliography entitled, "Malnutrition, Cognitive Development and Learning," which contains 187 citations with abstracts, a concern is whether malnutrition effects are reversible or permanent. Since…

The CHARGE Association: Implications for Teachers.

ERIC Educational Resources Information Center

Jones, Thomas W.; Dunne, Michele T.

1988-01-01

CHARGE association is described as a diagnostic label for a group of congenital malformations, including coloboma, heart defects, atresia choanae, retarded postnatal growth/central nervous system defects, genital hypoplasia, and ear deformities. Etiology and characteristics of the CHARGE association are discussed, along with implications for…

Bioplasmic Forces: A New Concept of Readiness

ERIC Educational Resources Information Center

Ogletree, Earl J.

1973-01-01

Discusses the concept of bioplasmic forces--the foundation of human growth, regeneration of cells, and life energy--and the relationship between physical and mental development of the child, focusing on the theory that premature or forced learning may cause intellectual or academic retardation. (TO)

Evaluating the performance of guardrail posts installed by driving through asphalt layers.

DOT National Transportation Integrated Search

2015-12-01

The preferred procedure for guardrail installation in the State of Georgia includes a layer of asphalt (usually : referred to as a mow strip) placed to retard vegetation growth around the guardrail. The objective of this multi-phase : research ...

Interactions between microbial agents and gypsy moth parasites

Treesearch

Ronald M. Weseloh

1985-01-01

The parasite Cotesia melanoscelus attacks small gypsy moth larvae more successfully than large ones, and Bacillus thuringiensis retards the growth of caterpillars it does not kill. Together, both factors lead to higher parasitism by C. melanoscelus in areas sprayed with B. thuringiensis than...

System analysis of metabolism and the transcriptome in Arabidopsis thaliana roots reveals differential co-regulation upon iron, sulfur and potassium deficiency.

PubMed

Forieri, Ilaria; Sticht, Carsten; Reichelt, Michael; Gretz, Norbert; Hawkesford, Malcolm J; Malagoli, Mario; Wirtz, Markus; Hell, Ruediger

2017-01-01

Deprivation of mineral nutrients causes significant retardation of plant growth. This retardation is associated with nutrient-specific and general stress-induced transcriptional responses. In this study, we adjusted the external supply of iron, potassium and sulfur to cause the same retardation of shoot growth. Nevertheless, limitation by individual nutrients resulted in specific morphological adaptations and distinct shifts within the root metabolite fingerprint. The metabolic shifts affected key metabolites of primary metabolism and the stress-related phytohormones, jasmonic, salicylic and abscisic acid. These phytohormone signatures contributed to specific nutrient deficiency-induced transcriptional regulation. Limitation by the micronutrient iron caused the strongest regulation and affected 18% of the root transcriptome. Only 130 genes were regulated by all nutrients. Specific co-regulation between the iron and sulfur metabolic routes upon iron or sulfur deficiency was observed. Interestingly, iron deficiency caused regulation of a different set of genes of the sulfur assimilation pathway compared with sulfur deficiency itself, which demonstrates the presence of specific signal-transduction systems for the cross-regulation of the pathways. Combined iron and sulfur starvation experiments demonstrated that a requirement for a specific nutrient can overrule this cross-regulation. The comparative metabolomics and transcriptomics approach used dissected general stress from nutrient-specific regulation in roots of Arabidopsis. © 2016 John Wiley & Sons Ltd.

Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

PubMed Central

Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K.; Foster, Paul M. D.; Scott, Hamish S.; Risbridger, Gail P.

2010-01-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, −3A, −3B, and −3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-κB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression. PMID:20056826

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

PubMed

Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

PAH Particles Perturb Prenatal Processes and Phenotypes: Protection from Deficits in Object Discrimination Afforded by Dampening of Brain Oxidoreductase Following In Utero Exposure to Inhaled Benzo(a)pyrene

PubMed Central

Chadalapaka, Gayathri; Ramesh, Aramandla; Khoshbouei, Habibeh; Maguire, Mark; Safe, Stephen; Rhoades, Raina E.; Clark, Ryan; Jules, George; McCallister, Monique; Aschner, Michael; Hood, Darryl B.

2012-01-01

The wild-type (WT) Cprlox/lox (cytochrome P450 oxidoreductase, Cpr) mouse is an ideal model to assess the contribution of P450 enzymes to the metabolic activation and disposition of environmental xenobiotics. In the present study, we examined the effect of in utero exposure to benzo(a)pyrene [B(a)P] aerosol on Sp4 and N-methyl-D-aspartate (NMDA)–dependent systems as well as a resulting behavioral phenotype (object discrimination) in Cpr offspring. Results from in utero exposure of WT Cprlox/lox mice were compared with in utero exposed brain-Cpr-null offspring mice. Null mice were used as they do not express brain cytochrome P4501B1–associated NADPH oxidoreductase (CYP1B1-associated NADPH oxidoreductase), thus reducing their capacity to produce neural B(a)P metabolites. Subsequent to in utero (E14–E17) exposure to B(a)P (100 μg/m3), Cprlox/lox offspring exhibited: (1) elevated B(a)P metabolite and F2-isoprostane neocortical tissue burdens, (2) elevated concentrations of cortical glutamate, (3) premature developmental expression of Sp4, (4) decreased subunit ratios of NR2B:NR2A, and (5) deficits in a novelty discrimination phenotype monitored to in utero exposed brain-Cpr-null offspring. Collectively, these findings suggest that in situ generation of metabolites by CYP1B1-associated NADPH oxidoreductase promotes negative effects on NMDA-mediated signaling processes during the period when synapses are first forming as well as effects on a subsequent behavioral phenotype. PMID:21987461

DDT Exposure in Utero and Breast Cancer

PubMed Central

La Merrill, Michele; Krigbaum, Nickilou Y.; Yeh, Gregory; Park, June-Soo; Zimmermann, Lauren; Cirillo, Piera M.

2015-01-01

Context: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation. Hypothesis: In utero exposure to DDT is associated with an increased risk of breast cancer. Design: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year). Setting and Participants: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study. Main Outcome Measure: Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured. Results: Maternal o,p′-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5–9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings. Conclusions: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk. PMID:26079774

In utero and intra-partum HIV-1 transmission and acute HIV-1 infection during pregnancy: using the BED capture enzyme-immunoassay as a surrogate marker for acute infection.

PubMed

Marinda, Edmore T; Moulton, Lawrence H; Humphrey, Jean H; Hargrove, John W; Ntozini, Robert; Mutasa, Kuda; Levin, Jonathan

2011-08-01

The BED assay was developed to estimate the proportion of recent HIV infections in a population. We used the BED assay as a proxy for acute infection to quantify the associated risk of mother-to-child-transmission (MTCT) during pregnancy and delivery. Design A total of 3773 HIV-1 sero-positive women were tested within 96 h of delivery using the BED assay, and CD4 cell count measurements were taken. Mothers were classified according to their likelihood of having recently seroconverted. The risk of MTCT in utero and intra-partum was assessed comparing different groups defined by BED and CD4 cell count, adjusting for background factors using multinomial logistic models. Compared with women with BED ≥ 0.8/CD4 ≥ 350 (typical of HIV-1 chronic patients) there was insufficient evidence to conclude that women presenting with BED < 0.8/CD4 ≥ 350 (typical of recent infections) were more likely to transmit in utero [adjusted odds ratio (aOR) = 1.37, 96% confidence interval (CI) 0.90-2.08, P = 0.14], whereas women with BED < 0.8/CD4 200-349 (possibly recently infected patients) had a 2.57 (95% CI 1.39-4.77, P-value < 0.01) odds of transmitting in utero. Women who had BED < 0.8/CD4 < 200 were most likely to transmit in utero (aOR 3.73, 95% CI 1.27-10.96, P = 0.02). BED and CD4 cell count were not predictive of intra-partum infections. These data provide evidence that in utero transmission of HIV might be higher among women who seroconvert during pregnancy.

CDKN1C mutation affecting the PCNA-binding domain as a cause of familial Russell Silver syndrome.

PubMed

Brioude, F; Oliver-Petit, I; Blaise, A; Praz, F; Rossignol, S; Le Jule, M; Thibaud, N; Faussat, A-M; Tauber, M; Le Bouc, Y; Netchine, I

2013-12-01

Russell Silver syndrome (RSS) leads to prenatal and postnatal growth retardation. About 55% of RSS patients present a loss-of-methylation of the paternal ICR1 domain on chromosome 11p15. CDKN1C is a cell proliferation inhibitor encoded by an imprinted gene in the 11p15 ICR2 domain. CDKN1C mutations lead to Beckwith Wiedemann syndrome (BWS, overgrowth syndrome) and in IMAGe syndrome which associates growth retardation and adrenal insufficiency. We searched for CDKN1C mutations in a cohort of clinically diagnosed RSS patients with no molecular anomaly. The coding sequence and intron-exon boundaries of CDKN1C were analysed in 97 RSS patients. The impact of CDKN1C variants on the cell cycle in vitro were determined by flow cytometry. Stability of CDKN1C was studied by western immunoblotting after inhibition of translation with cycloheximide. We identified the novel c.836G>[G;T] (p.Arg279Leu) mutation in a familial case of intrauterine growth retardation (IUGR) with RSS phenotype and no evidence of IMAGe. All the RSS patients inherited this mutation from their mothers (consistent with monoallelic expression from the maternal allele of the gene). A mutation of this amino acid (p.Arg279Pro) has been reported in cases of IMAGe. Functional analysis showed that Arg279Leu (RSS) did not affect the cell cycle, whereas the Arg279Pro mutation (IMAGe) led to a gain of function. Arg279Leu (RSS) led to an increased stability which could explain an increased activity of CDKN1C. CDKN1C mutations cause dominant maternally transmitted RSS, completing the molecular mirror with BWS. CDKN1C should be investigated in cases with family history of RSS.

Mechanical mandible competence in rats with nutritional growth retardation.

PubMed

Lezón, Christian Esteban; Pintos, Patricia Mabel; Bozzini, Clarisa; Romero, Alan Agüero; Casavalle, Patricia; Friedman, Silvia María; Boyer, Patricia Mónica

2017-08-01

In order to provide a better understanding of the sympathetic nervous system as a negative regulator of bone status, the aim of the study was to establish the biomechanical mandible response to different doses of a β-adrenergic antagonist such as propranolol (P) in a stress-induced food restriction model of growth retardation. Rats were assigned to eight groups: Control (C), C+P3.5 (CP3.5), C+P7 (CP7), C+P14 (CP14), NGR, NGR+P3.5 (NGRP3.5), NGR+P7 (NGRP7) and NGR+P14 (NGRP14). C, CP3.5, CP7 and CP14 rats were freely fed with the standard diet. NGR, NGRP3.5, NGRP7 and NGRP14 rats received, for 4 weeks (W4), 80% of the amount of controls food consumed. Propranolol 3.5, 7 and 14mg/kg/day was injected ip 5days per week in CP3.5 and NGRP3.5, CP7 and NGRP7, CP14 and NGRP14, respectively. At W4, zoometry, mandible morphometry, static histomorphometric and biomechanical competence were performed. A dose of Propranolol 7mg/kg/day induced interradicular bone volume accretion reaching a mandible stiffness according to chronological age. These findings evidenced that sympathetic nervous system activity is a negative regulator of mandible mechanical competence in the nutritional growth retardation model. Propranolol 7mg/kg/day, under the regimen usage, seems to be appropriate to blockade SNS activity on mandible mechanical performance in NGR rats, probably associated to an effect on bone mechanostat system ability to detect disuse mode as an error. Copyright © 2017 Elsevier Ltd. All rights reserved.

Local Control of Lung Derived Tumors by Diffusing Alpha-Emitting Atoms Released From Intratumoral Wires Loaded With Radium-224

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cooks, Tomer; Schmidt, Michael; Bittan, Hadas

2009-07-01

Purpose: Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520). Methods and Materials: An in vitro setup tested the dose-dependent killing of tumor cells exposed to alpha particles. In in vivo studies, radioactive wires (0.3 mm diameter, 5 mm long) with {sup 224}Ra activities in the range of 21-38 kBq were inserted into LL/2 tumors in C57BL/6 mice and into human-derived A427 or NCI-H520 tumors inmore » athymic mice. The efficacy of the short-lived daughters of {sup 224}Ra to produce tumor growth retardation and prolong life was assessed, and the spread of radioisotopes inside tumors was measured using autoradiography. Results: The insertion of a single DART wire into the center of 6- to 7-mm tumors had a pronounced retardation effect on tumor growth, leading to a significant inhibition of 49% (LL2) and 93% (A427) in tumor development and prolongations of 48% (LL2) in life expectancy. In the human model, more than 80% of the treated tumors disappeared or shrunk. Autoradiographic analysis of the treated sectioned tissue revealed the intratumoral distribution of the radioisotopes, and histological analysis showed corresponding areas of necrosis. In vitro experiments demonstrated a dose-dependent killing of tumors cells exposed to alpha particles. Conclusions: Short-lived diffusing alpha-emitters produced tumor growth retardation and increased survival in mice bearing lung tumor implants. These results justify further investigations with improved dose distributions.« less

Magnetic effect on oxide-scale growth of Fe-5Cr alloy

NASA Astrophysics Data System (ADS)

Zhou, C. H.; Li, X. W.; Wang, S. H.; Ma, H. T.

2018-01-01

The oxidation behaviour of Fe-5Cr alloy was investigated at 650°C in the presence of magnetic field. Results indicated that the oxide scales were both consisted of an outer Fe-oxide scale and an inner mixed-oxide scale in the presence or absence of magnetic field. The oxide-scale growth of Fe-5Cr alloy, gained by measuring the oxide-scale thickness, was verified to follow parabolic lawyer. And the oxidation kinetics showed that the applied magnetic field retarded the oxide-scale growth of Fe-5Cr alloy.

In utero Undernutrition Programs Skeletal and Cardiac Muscle Metabolism.

PubMed

Beauchamp, Brittany; Harper, Mary-Ellen

2015-01-01

In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease.

In utero Undernutrition Programs Skeletal and Cardiac Muscle Metabolism

PubMed Central

Beauchamp, Brittany; Harper, Mary-Ellen

2016-01-01

In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease. PMID:26779032

Social behavior impairment in offspring exposed to maternal seizures in utero.

PubMed

Novaes, Gisane Faria; Amado, Debora; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

2012-06-01

Human and animal models have demonstrated that maternal seizures in utero could be deleterious to the development of the offspring. This study focused on the social behavior of offspring exposed to seizures in utero. A pilocarpine model of temporal lobe epilepsy was induced in female Wistar rats that were mated after the first spontaneous seizure. Early after birth, pups from an epileptic mother were reared by a control mother. To evaluate the influence of the adoption process, two other groups were added: rat pups from control mothers cross-fostered with other control mothers, and rat pups reared by their birth mother. Animals exposed to seizures in utero showed impaired social behavior with no signs of anxiety-like behavior. This study demonstrated that epileptic seizures during pregnancy could be harmful to brain development and may increase the risk of developing neurodevelopmental disorders. The mechanisms underlying the abnormalities of social behavior are not well understood, and further studies in this field are warranted.

In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27Kip1

PubMed Central

Mitsuhashi, Takayuki; Yonemoto, Junzo; Sone, Hideko; Kosuge, Yasuhiro; Kosaki, Kenjiro; Takahashi, Takao

2010-01-01

Dioxins have been reported to exert various adverse effects, including cell-cycle dysregulation in vitro and impairment of spatial learning and memory after in utero exposure in rodents. Furthermore, children born to mothers who are exposed to dioxin analogs polychlorinated dibenzofurans or polychlorinated biphenyls have developmental impairments in cognitive functions. Here, we show that in utero exposure to dioxins in mice alters differentiation patterns of neural progenitors and leads to decreased numbers of non-GABAergic neurons and thinner deep neocortical layers. This reduction in number of non-GABAergic neurons is assumed to be caused by accumulation of cyclin-dependent kinase inhibitor p27Kip1 in nuclei of neural progenitors. Lending support to this presumption, mice lacking p27Kip1 are not susceptible to in utero dioxin exposure. These results show that environmental pollutants may affect neocortical histogenesis through alterations of functions of specific gene(s)/protein(s) (in our case, dioxins), exerting adverse effects by altering functions of p27Kip1. PMID:20805476

The hopes and fears of in utero gene therapy for genetic disease--a review.

PubMed

Coutelle, C; Themis, M; Waddington, S; Gregory, L; Nivsarkar, M; Buckley, S; Cook, T; Rodeck, C; Peebles, D; David, A

2003-10-01

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease. It is based on the concept that application of gene therapy vectors to the fetus in utero may prevent the development of early disease related tissue damage, may allow targeting of otherwise inaccessible organs, tissues and still expanding stem cell populations and may also provide postnatal tolerance against the therapeutic transgenic protein. This review outlines the hypothesis and scientific background of in utero gene therapy and addresses some of the frequently expressed concerns raised by this still experimental, potentially preventive gene therapy approach. We describe and discuss the choice of vectors, of animal models and routes of administration to the fetus. We address potential risk factors of prenatal gene therapy such as vector toxicity, inadvertent germ line modification, developmental aberration and oncogenesis as well as specific risks of this procedure for the fetus and mother and discuss their ethical implications.

Infant growth patterns in the slums of Dhaka in relation to birth weight, intrauterine growth retardation, and prematurity.

PubMed

Arifeen, S E; Black, R E; Caulfield, L E; Antelman, G; Baqui, A H; Nahar, Q; Alamgir, S; Mahmud, H

2000-10-01

Relations between size and maturity at birth and infant growth have been studied inadequately in Bangladesh, where the incidence of low birth weight is high and most infants are breast-fed. This study was conducted to describe infant growth patterns and their relations to birth weight, intrauterine growth retardation, and prematurity. A total of 1654 infants born in selected low-socioeconomic areas of Dhaka, Bangladesh, were enrolled at birth. Weight and length were measured at birth and at 1, 3, 6, 9, and 12 mo of age. The infants' mean birth weight was 2516 g, with 46.4% weighing <2500 g; 70% were small for gestational age (SGA) and 17% were premature. Among the SGA infants, 63% had adequate ponderal indexes. The mean weight of the study infants closely tracked the -2 SD curve of the World Health Organization pooled breast-fed sample. Weight differences by birth weight, SGA, or preterm categories were retained throughout infancy. Mean z scores based on the pooled breast-fed sample were -2.38, -1. 72, and -2.34 at birth, 3 mo, and 12 mo. Correlation analysis showed greater plasticity of growth in the first 3 mo of life than later in the first year. Infant growth rates were similar to those observed among breast-fed infants in developed countries. Most study infants experienced chronic intrauterine undernourishment. Catch-up growth was limited and weight at 12 mo was largely a function of weight at birth. Improvement of birth weight is likely to lead to significant gains in infant nutritional status in this population, although interventions in the first 3 mo are also likely to be beneficial.

Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats.

PubMed

Ferrando, Susana; Rodríguez, Julián; Santos, Fernando; Weruaga, Ana; Fernández, Marta; Carbajo, Eduardo; García, Enrique

2002-09-01

A decreased ability of pituitary cells to secrete growth hormone (GH) in response to growth hormone releasing hormone (GHRH) stimulation has been shown in young uremic rats. The aim of the current study was to examine the effect of uremia and GH treatment on pituitary GHRH receptor expression. Pituitary GHRH receptor mRNA levels were analyzed by RNase protection assay in young female rats made uremic by subtotal nephrectomy, either untreated (UREM) or treated with 10 IU/kg/day of GH (UREM-GH), and normal renal function animals fed ad libitum (SAL) or pair-fed with the UREM group (SPF). Rats were sacrificed 14 days after the second stage nephrectomy. Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1). UREM rats became growth retarded as shown by a daily longitudinal tibia growth rate below (P < 0.05) that observed in SAL animals (156 +/- 3 vs. 220 +/- 5 microm/day). GH treatment resulted in significant growth rate acceleration (213 +/- 6 microm/day). GHRH receptor mRNA levels were no different among the SAL (0.43 +/- 0.03), SPF (0.43 +/- 0.08) and UREM (0.44 +/- 0.04) groups, whereas UREM-GH rats had significantly higher values (0.72 +/- 0.07). The status of pituitary GHRH receptor is not modified by nutritional deficit or by severe uremia causing growth retardation. By contrast, the growth promoting effect of GH administration is associated with stimulated GHRH receptor gene expression.

Maxillary growth after maxillary protraction: Appliance in conjunction with presurgical orthopedics, gingivoperiosteoplasty, and Furlow palatoplasty for complete bilateral cleft lip and palate patients with protruded premaxilla.

PubMed

Kobayashi, Shinji; Hirakawa, Takashi; Fukawa, Toshihiko; Maegawa, Jiro

2015-06-01

In bilateral cleft lip and palate (BCLP) with premaxillary protrusion, a good outcome with adequate maxillary development is difficult to achieve. The purpose of this article is to evaluate the maxillary growth after using presurgical orthopedics (PSO), gingivoperiosteoplasty (GPP), Furlow palatoplasty, and maxillary protraction appliance (MPA) for BCLP with premaxillary protrusion. Seven patients with complete BCLP with premaxillary protrusion were treated by PSO, cheiloplasty, GPP, and Furlow palatoplasty. MPA was used as part of the protocol for 6 months to 1 year for postoperative retardation of maxillary growth cases. Maxillary growth was evaluated by cephalometric analysis at 4 and 10 years of age, and bone formation at the alveolar cleft was evaluated by computed tomography (CT) imaging at 5 years of age. At 4 years of age, three of seven patients had apparent retardation of maxillary growth. The maxillary growth at 10 years of age was equivalent to the average value of normal Japanese after using MPA in three cases. At 5 years of age, only two of seven patients showed sufficient bone formation at the alveolar cleft to avoid alveolar bone grafting (ABG). Subsequently, ABG was performed in five patients. Although three of seven patients had apparent crossbite at 4 years of age, the maxillary growth of all patients at 10 years of age was approximately equivalent to the average value of normal Japanese after using MPA. A treatment protocol based on PSO, GPP, Furlow palatoplasty, and MPA may be an option, but long-term growth is unknown. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Analysis of Flame Retardancy in Polymer Blends by Synchrotron X-ray K-edge Tomography and Interferometric Phase Contrast Movies.

PubMed

Olatinwo, Mutairu B; Ham, Kyungmin; McCarney, Jonathan; Marathe, Shashidhara; Ge, Jinghua; Knapp, Gerry; Butler, Leslie G

2016-03-10

Underwriters Laboratories 94 test bars have been imaged with X-ray K-edge tomography between 12 and 32 keV to assess the bromine and antimony concentration gradient across char layers of partially burnt samples. Phase contrast tomography on partially burnt samples showed gas bubbles and dark-field scattering ascribed to residual blend inhomogeneity. In addition, single-shot grating interferometry was used to record X-ray movies of test samples during heating (IR and flame) intended to mimic the UL 94 plastics flammability test. The UL 94 test bars were formulated with varying concentrations of a brominated flame retardant, Saytex 8010, and a synergist, Sb2O3, blended into high-impact polystyrene (HIPS). Depending on the sample composition, samples will pass or fail the UL 94 plastics flammability test. Tomography and interferometry imaging show differences that correlate with UL 94 performance. Key features such as char layer, gas bubble formation, microcracks, and dissolution of the flame retardant in the char layer regions are used in understanding the efficiency of the flame retardant and synergist. The samples that pass the UL 94 test have a thick, highly visible char layer as well as an interior rich in gas bubbles. Growth of gas bubbles from flame-retardant thermal decomposition is noted in the X-ray phase contrast movies. Also noteworthy is an absence of bubbles near the burning surface of the polymer; dark-field images after burning suggest a microcrack structure between interior bubbles and the surface. The accepted mechanism for flame retardant activity includes free radical quenching in the flame by bromine and antimony species. The imaging supports this as well as provides a fast inspection of other parameters, such as viscosity and surface tension.

Cephalometric study of facial growth in children after combined pushback and pharyngeal flap operations.

PubMed

Pearl, R M; Kaplan, E N

1976-04-01

Linear and angular cephalometric measurements of children who had had combined palatal pushbacks and superiorly-based pharyngeal flaps do not show later growth retardation of the face. There was an inherent tendency for children with overt clefts of the secondary palate, classic submucous clefts, or occult submucous clefts to demonstrate pre-operatively a narrow SNA and SNB--but the difference between these angles (ANB) was normal.

Ontogeny of Daucus carota Infected with Meloidogyne hapla

PubMed Central

Slinger, L. A.; Bird, G. W.

1978-01-01

The ontogeny of carrots (Daucus carota cv. 'Spartan Premium') grown under greenhouse conditions in pots of organic soil infected with Meloidogyne hapla was influenced detrimentally as early as 4 days after seeding, as determined through analysis of plant surface area, dry weight, fresh weight, net assimilation rate, relative growth rate, and leaf-area ratio. Only 58% of the diseased carrots were suitable for fresh market, compared with 97% of those grown in nematode-free soil. Growth and development of the shoot system (height, surface area, dry weight, and fresh weight) were retarded by M. hapla as early as 12 days after seeding. During the first 12 days after seeding, root dry weight was greater for diseased plants than for controls. Root growth and development (surface area, dry weight, and fresh weight) associated with this nematode, however, were retarded as early as 16 days after seeding. M. hapla caused a delay in the occurrence of 2nd-, 4th-, and 5th-order roots, and an increase in the occurrence of 6th-order roots in infected plants. Parasitized plants had 44% fewer roots (primary through 6th-order) and 50% less total root length. PMID:19305837

High- and low-temperature manipulation during late incubation: effects on embryonic development, the hatching process, and metabolism in broilers.

PubMed

Willemsen, H; Kamers, B; Dahlke, F; Han, H; Song, Z; Ansari Pirsaraei, Z; Tona, K; Decuypere, E; Everaert, N

2010-12-01

Temperatures continuously higher and lower than the standard incubation temperature by 3°C from embryonic d 16 until embryonic d 18.5 result in differential effects on embryonic development, the hatching process, and embryonic metabolism. Embryos in the high-temperature group were forced into a state of malnutrition by the temperature treatment, as reflected by reduced embryo growth and yolk consumption, resulting in a significantly lower chick weight at hatch. In addition, altered air cell and blood gases as well as a retarded hatching process further indicated reduced growth of embryos exposed to higher incubation temperatures during the latter part of incubation. In addition, hatchability was significantly reduced by the high-temperature treatment due to higher embryonic mortality during the treatment period and the hatching process. Levels of blood glucose, lactate, liver glycogen, plasma triglycerides, and nonesterified fatty acids indicated an altered carbohydrate and lipid metabolism for the high-temperature group. Although the hatching process of embryos exposed to lower incubation temperatures was also significantly retarded, their embryonic development and growth were strikingly similar to those of the control group.

Impact of phthalate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males.

PubMed

Watkins, Deborah J; Sánchez, Brisa N; Téllez-Rojo, Martha Maria; Lee, Joyce M; Mercado-García, Adriana; Blank-Goldenberg, Clara; Peterson, Karen E; Meeker, John D

2017-06-21

Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort. We measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. We measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively. In sensitivity analyses we evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes. Exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings. Associations between in utero phthalate and BPA exposure and peripubertal measures of male reproductive development are dependent on the timing of that exposure during gestation. These findings suggest that future epidemiological studies relating in utero EDC exposure to pubertal outcomes should consider windows of susceptibility.

Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice

PubMed Central

Rodriguez, Karina F.; Ungewitter, Erica K.; Crespo-Mejias, Yasmin; Liu, Chang; Nicol, Barbara; Kissling, Grace E.; Yao, Humphrey Hung-Chang

2015-01-01

Background Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear. Objectives We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood. Methods Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood. Results Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance. Conclusion Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice. Citation Rodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. 2016. Effects of in utero exposure to arsenic during the second half of gestation on reproductive end points and metabolic parameters in female CD-1 mice. Environ Health Perspect 124:336–343; http://dx.doi.org/10.1289/ehp.1509703 PMID:26295903

[Perinatal regional hotline organisation and rate of perinatal transfer. Results from 2003 and 2004 in the French Rhône-Alpes area: A two year study of 4079 transfers].

PubMed

Dupuis, O; Gaucherand, P; Mellier, G

2006-11-01

This study aims to describe the organization that was implemented at the Rhône-Alpes perinatal hotline, as well as to describe in utero transfer and neonate transport from an epidemiological point of view. A cohort study was performed between January 2003 and December 2004. Every in utero transfer and neonate transport was included. Transfers performed in 2003 were compared to transfers performed in 2004. Three endpoints were defined: the rate of in utero transfer (number of in utero transfers/number of in utero transfers + number of neonatal transfers), the rate of transfer toward level II units (number of transfers from level I to level II/number of transfers from level I to level II + number of transfers from level I to level III) as well as the rate of intra network transfer (number of intra network transfers/number of intra network transfers + number of extra network transfers). In 2003, 865 in utero transfers (IUT) and 1297 neonate transports (NT) were performed, in 2004 848 IUT and 1069 NT were performed. The rate of in utero transfer significantly increased from 40 to 44.2% in 2004 (865/2162 versus 848/1917, p = 0.007). The rate of transfer toward level II units increased for the mothers from 31.8% to 36.9% (177/557 versus 174/471, p = 0.09) and significantly increased for the neonates from 43.2 to 51.6% in 2004 (335/775 versus 327/633, p = 0.002). Finally the rate of intra network transfer has not significantly changed: for the IUT it decreased from 87 to 86% (755/865 versus 732/848, p = 0.59) and for the NT from 91% to 90% (1179/1297 versus 963/1069, p = 0.45). The organization that was implemented allows not only a safe 24 hour on call management of maternal transfers as well as neonate transport, but also a precise knowledge of epidemiologic indications relative to perinatal transfer.

Enteric disease in broiler chickens following experimental infection with chicken parvovirus

USDA-ARS?s Scientific Manuscript database

Day-old broiler chickens were inoculated orally with the chicken parvovirus strain, chicken parvovirus-P1. In four independent experiments, characteristic clinical signs of enteric disease including watery, mustard color diarrhea and growth retardation were observed following infection. The virus wa...

UNDERNUTRITION IN EARLY LIFE DOES NOT IMPAIR LEARNING IN YOUNG OR AGING RATS.

EPA Science Inventory

Prenatal undernutrition is associated with increased incidence of obesity, heart disease, diabetes. Effects of pre- and post-natal undernutrition on nervous system function in middle-aged and aging male SD rats were examined. Intrauterine growth retardation (IUGR) was induced by ...

22.5 MB DELETION OF 13q31.1-q34 ASSOCIATED WITH HPE, DWM, AND HSCR: A CASE REPORT AND REDEFINING THE SMALLEST DELETED REGIONS.

PubMed

Alp, M Y; Çebi, A H; Seyhan, S; Cansu, A; Aydin, H; Ikbal, M

2016-01-01

Partial deletion of the long arm of the chromosome 13, 13q deletion syndrome is a rare chromosomal disorder characterized by severe growth and mental retardation, microcephaly, facial dysmorphism, brain malformations (holoprosencephaly, Dandy-Walker malformation), distal limb defects, eye anomalies, genitourinary and gastrointestinal tract malformations (Hirschsprung's disease). Approximately 1.2 Mb region in 13q32 was suggested as minimal critical region which is responsible for severe mental and growth retardation and brain anomalies. Here we described a male patient with de novo interstitial deletion of 13q31.1-q34 associated with short stature, microcephaly, facial dysmorphism, clinodactyly, cryptorchidism, micropenis, epilepsy, HPE, DWM, and HSCR. According to the literature review, present case indicated that smallest deleted region associated with DWM and HPE might be located at the 13q32.3, limb defects 13q34, anogenital malformations 13q33.3-34, and HSCR 13q31.1-32.1.

Palladium silicide formation under the influence of nitrogen and oxygen impurities

NASA Technical Reports Server (NTRS)

Ho, K. T.; Lien, C.-D.; Nicolet, M.-A.

1985-01-01

The effect of impurities on the growth of the Pd2Si layer upon thermal annealing of a Pd film on 100 line-type and amorphous Si substrates is investigated. Nitrogen and oxygen impurities are introduced into either Pd or Si which are subsequently annealed to form Pd2Si. The complementary techniques of Rutherford backscattering spectrometry, and N-15(p, alpha)C-12 or O-18(p, alpha)N-15 nuclear reaction, are used to investigate the behavior of nitrogen or oxygen and the alterations each creates during silicide formation. Both nitrogen and oxygen retard the silicide growth rate if initially present in Si. When they are initially in Pd, there is no significant retardation; instead, an interesting snow-plowing effect of N or O by the reaction interface of Pd2Si is observed. By using N implanted into Si as a marker, Pd and Si appear to trade roles as the moving species when the silicide front reaches the nitrogen-rich region.

Violence, selection and infant mortality in Congo.

PubMed

Dagnelie, Olivier; Luca, Giacomo Davide De; Maystadt, Jean-François

2018-05-01

This paper documents the effects of the recent civil war in the Democratic Republic of Congo on mortality both in utero and during the first year of life. It instruments for conflict intensity using a mineral price index, which exploits the exogenous variation in the potential value of mineral resources generated by changes in world mineral prices to predict the geographic distribution of the conflict. Using estimates of civil war exposure on mortality across male and female newborn to assess their relative health, it provides evidence of culling effect (in utero selection) as a consequence of in utero shocks. Copyright © 2018 Elsevier B.V. All rights reserved.

In utero phthalate effects in the female rat: a model for MRKH syndrome##

EPA Science Inventory

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phen...

In Utero Phthalate Effects in the Female Rat: A Model for MRKH Syndrome

EPA Science Inventory

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly define etiology. Reproductive toxicity of phthlate esters (PEs) occurs in rat offspring exposed in utero. a phenome...

Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: a characterization of the BPH/5 mouse in postnatal life.

PubMed

Sutton, Elizabeth F; Lob, Heinrich E; Song, Jiunn; Xia, YunWei; Butler, Scott; Liu, Chin-Chi; Redman, Leanne M; Sones, Jenny L

2017-04-01

Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes. Copyright © 2017 the American Physiological Society.

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

PubMed Central

Brown, Traci A.; Holian, Andrij; Pinkerton, Kent E.; Lee, Joong Won; Cho, Yoon Hee

2016-01-01

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

Varying Susceptibility of the Female Mammary Gland to In Utero Windows of BPA Exposure.

PubMed

Hindman, Andrea R; Mo, Xiaokui Molly; Helber, Hannah L; Kovalchin, Claire E; Ravichandran, Nanditha; Murphy, Alina R; Fagan, Abigail M; St John, Pamela M; Burd, Craig J

2017-10-01

In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes. Copyright © 2017 Endocrine Society.

In utero exposure to radiation and haematological malignancies: pooled analysis of Southern Urals cohorts

PubMed Central

Schüz, Joachim; Deltour, Isabelle; Krestinina, Lyudmila Y; Tsareva, Yulia V; Tolstykh, Evgenia I; Sokolnikov, Mikhail E; Akleyev, Alexander V

2017-01-01

Background: It is scientifically uncertain whether in utero exposure to low-dose ionising radiation increases the lifetime risk of haematological malignancies. Methods: We pooled two cohorts from the Southern Urals comprising offspring of female workers of a large nuclear facility (the Mayak Production Association) and of women living in areas along the Techa River contaminated by nuclear accidents/waste from the same facility, with detailed dosimetry. Results: The combined cohort totalled 19 536 subjects with 700 504 person-years at risk over the period of incidence follow-up, and slightly more over the period of mortality follow-up, yielding 58 incident cases and 36 deaths up to age 61 years. Risk was increased in subjects who received in utero doses of ⩾80 mGy (excess relative risk (ERR): 1.27; 95% confidence interval (CI): −0.20 to 4.71), and the risk increased consistently per 100 mGy of continuous exposure in utero (ERR: 0.77; CI: 0.02 to 2.56). No association was apparent in mortality-based analyses. Results for leukaemia and lymphoma were similar. A very weak positive association was observed between incidence and postnatal exposure. Conclusions: In summary, the results suggest a positive association between in utero exposure to ionising radiation and risk of haematological malignancies, but the small number of outcomes and inconsistent incidence and mortality findings preclude firm conclusions. PMID:27855443

Role of Gab1 in Heart, Placenta, and Skin Development and Growth Factor- and Cytokine-Induced Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Activation

PubMed Central

Itoh, Motoyuki; Yoshida, Yuichi; Nishida, Keigo; Narimatsu, Masahiro; Hibi, Masahiko; Hirano, Toshio

2000-01-01

Gab1 is a member of the Gab/DOS (Daughter of Sevenless) family of adapter molecules, which contain a pleckstrin homology (PH) domain and potential binding sites for SH2 and SH3 domains. Gab1 is tyrosine phosphorylated upon stimulation of various cytokines, growth factors, and antigen receptors in cell lines and interacts with signaling molecules, such as SHP-2 and phosphatidylinositol 3-kinase, although its biological roles have not yet been established. To reveal the functions of Gab1 in vivo, we generated mice lacking Gab1 by gene targeting. Gab1-deficient embryos died in utero and displayed developmental defects in the heart, placenta, and skin, which were similar to phenotypes observed in mice lacking signals of the hepatocyte growth factor/scatter factor, platelet-derived growth factor, and epidermal growth factor pathways. Consistent with these observations, extracellular signal-regulated kinase mitogen-activated protein (ERK MAP) kinases were activated at much lower levels in cells from Gab1-deficient embryos in response to these growth factors or to stimulation of the cytokine receptor gp130. These results indicate that Gab1 is a common player in a broad range of growth factor and cytokine signaling pathways linking ERK MAP kinase activation. PMID:10779359

Maternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta

PubMed Central

Brett, Kendra Elizabeth; Ferraro, Zachary Michael; Yockell-Lelievre, Julien; Gruslin, Andrée; Adamo, Kristi Bree

2014-01-01

Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth. PMID:25222554

Effects of induced placental and fetal growth restriction, size at birth and early neonatal growth on behavioural and brain structural lateralization in sheep.

PubMed

Hunter, Damien Seth; Hazel, Susan J; Kind, Karen L; Liu, Hong; Marini, Danila; Giles, Lynne C; De Blasio, Miles J; Owens, Julie A; Pitcher, Julia B; Gatford, Kathryn L

2017-09-01

Poor perinatal growth in humans results in asymmetrical grey matter loss in fetuses and infants and increased functional and behavioural asymmetry, but specific contributions of pre- and postnatal growth are unclear. We therefore compared strength and direction of lateralization in obstacle avoidance and maze exit preference tasks in offspring of placentally restricted (PR: 10M, 13F) and control (CON: 23M, 17F) sheep pregnancies at 18 and 40 weeks of age, and examined gross brain structure of the prefrontal cortex at 52 weeks of age (PR: 14M, 18F; CON: 23M, 25F). PR did not affect lateralization direction, but 40-week-old PR females had greater lateralization strength than CON (P = .021). Behavioural lateralization measures were not correlated with perinatal growth. PR did not alter brain morphology. In males, cross-sectional areas of the prefrontal cortex and left hemisphere correlated positively with skull width at birth, and white matter area correlated positively with neonatal growth rate of the skull (all P < .05). These studies reinforce the need to include progeny of both sexes in future studies of neurodevelopmental programming, and suggest that restricting in utero growth has relatively mild effects on gross brain structural or behavioural lateralization in sheep.

Control of Abscission in Agricultural Crops and Its Physiological Basis 1

PubMed Central

Cooper, W. C.; Rasmussen, G. K.; Rogers, B. J.; Reece, P. C.; Henry, W. H.

1968-01-01

Some naphthalene and phenoxy compounds prevent preharvest drop of apples, pears, and citrus fruits. These studies have been complicated by an unrecognized high level of ethylene produced by leaves and fruit on trees sprayed with these growth regulators. An apparent contradiction is the effectiveness of both 2,4-dichlorophenoxyacetic acid and n-dimethylaminosuccinamic acid (a growth retardant which retards biosynthesis of auxin) in preventing abscission of apples. Thus, in the presence of low auxin concentrations in the tissue, this growth retardant prevents fruit abscission even more effectively than 2,4-dichlorophenoxyacetic acid at high auxin concentrations in the tissue. This anomaly is clarified on the basis that n-dimethylaminosuccinamic acid, in the presence of a known low ethylene biosynthesis, delays maturity of the fruit and thus prevents fruit abscission. On the other hand, 2,4-dichlorophenoxyacetic acid prevents abscission by direct growth hormone action, in spite of the side effects of ethylene production which speeds ripening of the fruit. With the promotion of abscission of leaves and fruit of agricultural crops, attention is given to the use of chemicals which induce ethylene production when applied to the plant, but which have no growth promotion effect to retard abscission. We can distinguish 5 kinds of such chemicals. One group includes gibberellic and abscisic acids that induce treated leaves to produce ethylene and abscise (under certain circumstances). However, they do not induce ethylene production by fruit and do not promote fruit abscission. A second group includes ascorbic acid, which, when used at relatively high levels, induces fruit to produce enough ethylene to promote abscission. Ascorbic acid-treated leaves also produce ethylene but not enough to cause much defoliation. A third group includes protein-synthesis inhibitors, such as cycloheximide. When low concentrations (about 30 μmoles/l) are sprayed on the fruit, the rapid effect of the freely moving ethylene (produced by the treated fruit) appears to mask temporarily any potential effect of the slowly moving inhibitor. A fourth group includes 2-chloroethylphosphonic and cupric ethylenediaminetetracetic acids, which induce ethylene production of fruit and leaves; production by leaves is substantially greater than by fruit and substantial defoliation results. A fifth group includes the cotton defoliation chemicals which clearly produce ethylene primarily as a result of chemical injury to the leaf blade. Another group of compounds, represented by beta-hydroxyethylhydrazine, produces ethylene by a chemical reaction with formaldehyde and water, and the presence of leaves or fruit is not required. At this time we are unaware of how chemicals in groups one to four act to promote ethylene evolution in leaves and fruit, but possible biological and chemical paths of ethylene production are discussed. Images PMID:16657019

Control Design Strategies to Enhance Long-Term Aircraft Structural Integrity

NASA Technical Reports Server (NTRS)

Newman, Brett A.

1999-01-01

Over the operational lifetime of both military and civil aircraft, structural components are exposed to hundreds of thousands of low-stress repetitive load cycles and less frequent but higher-stress transient loads originating from maneuvering flight and atmospheric gusts. Micro-material imperfections in the structure, such as cracks and debonded laminates, expand and grow in this environment, reducing the structural integrity and shortening the life of the airframe. Extreme costs associated with refurbishment of critical load-bearing structural components in a large fleet, or altogether reinventoring the fleet with newer models, indicate alternative solutions for life extension of the airframe structure are highly desirable. Increased levels of operational safety and reliability are also important factors influencing the desirability of such solutions. One area having significant potential for impacting crack growth/fatigue damage reduction and structural life extension is flight control. To modify the airframe response dynamics arising from command inputs and gust disturbances, feedback loops are routinely applied to vehicles. A dexterous flight control system architecture senses key vehicle motions and generates critical forces/moments at multiple points distributed throughout the airframe to elicit the desired motion characteristics. In principle, these same control loops can be utilized to influence the level of exposure to harmful loads during flight on structural components. Project objectives are to investigate and/or assess the leverage control has on reducing fatigue damage and enhancing long-term structural integrity, without degrading attitude control and trajectory guidance performance levels. In particular, efforts have focused on the effects inner loop control parameters and architectures have on fatigue damage rate. To complete this research, an actively controlled flexible aircraft model and a new state space modeling procedure for crack growth have been utilized. Analysis of the analytical state space model for crack growth revealed the critical mathematical factors, and hence the physical mechanism they represent, that influenced high rates of airframe crack growth. The crack model was then exercised with simple load inputs to uncover and expose key crack growth behavior. To characterize crack growth behavior, both "short-term" laboratory specimen test type inputs and "long-term" operational flight type inputs were considered. Harmonic loading with a single overload revealed typical exponential crack growth behavior until the overload application, after which time the crack growth was retarded for a period of time depending on the overload strength. An optimum overload strength was identified which leads to maximum retardation of crack growth. Harmonic loading with a repeated overload of varying strength and frequency again revealed an optimum overload trait for maximizing growth retardation. The optimum overload strength ratio lies near the range of 2 to 3 with dependency on frequency. Experimental data was found to correlate well with the analytical predictions.

Targeted Deletion of Autophagy Genes Atg5 or Atg7 in the Chondrocytes Promotes Caspase-Dependent Cell Death and Leads to Mild Growth Retardation.

PubMed

Vuppalapati, Karuna K; Bouderlique, Thibault; Newton, Phillip T; Kaminskyy, Vitaliy O; Wehtje, Henrik; Ohlsson, Claes; Zhivotovsky, Boris; Chagin, Andrei S

2015-12-01

Longitudinal bone growth takes place in epiphyseal growth plates located in the ends of long bones. The growth plate consists of chondrocytes traversing from the undifferentiated (resting zone) to the terminally differentiated (hypertrophic zone) stage. Autophagy is an intracellular catabolic process of lysosome-dependent recycling of intracellular organelles and protein complexes. Autophagy is activated during nutritionally depleted or hypoxic conditions in order to facilitate cell survival. Chondrocytes in the middle of the growth plate are hypoxic and nutritionally depleted owing to the avascular nature of the growth plate. Accordingly, autophagy may facilitate their survival. To explore the role of autophagy in chondrocyte survival and constitutional bone growth, we generated mice with cartilage-specific ablation of either Atg5 (Atg5cKO) or Atg7 (Atg7cKO) by crossing Atg5 or Atg7 floxed mice with cartilage-specific collagen type 2 promoter-driven Cre. Both Atg5cKO and Atg7cKO mice showed growth retardation associated with enhanced chondrocyte cell death and decreased cell proliferation. Similarly, inhibition of autophagy by Bafilomycin A1 (Baf) or 3-methyladenine (3MA) promoted cell death in cultured slices of human growth plate tissue. To delineate the underlying mechanisms we employed ex vivo cultures of mouse metatarsal bones and RCJ3.IC5.18 rat chondrogenic cell line. Baf or 3MA impaired metatarsal bone growth associated with processing of caspase-3 and massive cell death. Similarly, treatment of RCJ3.IC5.18 chondrogenic cells by Baf also showed massive cell death and caspase-3 cleavage. This was associated with activation of caspase-9 and cytochrome C release. Altogether, our data suggest that autophagy is important for chondrocyte survival, and inhibition of this process leads to stunted growth and caspase-dependent death of chondrocytes. © 2015 American Society for Bone and Mineral Research.

Dose related shifts in the developmental progress of chick embryos exposed to mobile phone induced electromagnetic fields.

PubMed

Zareen, Nusrat; Khan, Muhammad Yunus; Minhas, Liaqat Ali

2009-01-01

The possible adverse effects of Electromagnetic Fields (EMFs) emitted from mobile phones present a major public concern today. Some studies indicate EMFs effects on genes, free radical production, immunological and carcinogenic effects. On the other hand there are studies which do not support the hypothesis of any biological impacts of EMFs. This study was designed to observe the effects of mobile phone induced EMFs on survival and general growth and development of chick embryo, investigating dose-response relationship if any. This was an experimental study in which developing chick embryos were exposed to different doses of mobile phone induced EMFs. For this purpose a mobile phone was placed in the incubator in the centre of fertilised eggs in silent ringing mode and was 'rung' upon from any other line or cell phone. After incubation for 10 or 15 days the eggs were opened and the developmental mile-stones of the surviving embryos were compared with the non exposed subgroup. EMFs exposure significantly decreased the survivability of the chick embryos. The lower doses of EMFs caused growth retardation. However, this effect of growth retardation reallocated to partial growth enhancement on increasing the dose of EMFs and shifted over to definite growth enhancement on further raising the dose. There is an adverse effect of EMFs exposure on embryo survivability. Chick embryos developmental process is influenced by EMFs. However, these effects are variable depending upon the dose of EMFs exposure.

A putative APSES transcription factor is necessary for normal growth and development of Aspergillus nidulans.

PubMed

Lee, Ji-Yeon; Kim, Lee-Han; Kim, Ha-Eun; Park, Jae-Sin; Han, Kap-Hoon; Han, Dong-Min

2013-12-01

The nsdD gene encoding a GATA type transcription factor positively controls sexual development in Aspergillus nidulans. According to microarray data, 20 genes that were upregulated by deleting nsdD during various life cycle stages were randomly selected and deleted for functional analysis. None of the mutants showed apparent changes in growth or development compared with those of the wild-type except the AN3154 gene that encodes a putative APSES transcription factor and is an ortholog of Saccharomyces cerevisiae swi4. Deleting AN3154 resulted in retarded growth and development, and the gene was named rgdA (retared growth and development). The rgdA deletion mutant developed a reduced number of conidia even under favorable conditions for asexual development. The retarded growth and development was partially suppressed by the veA1 mutation. The conidial heads of the mutant aborted, showing reduced and irregular shaped phialides. Fruiting body development was delayed compared with that in the wild-type. The mutant did not respond to various nutritional or environmental factors that affected the development patterns. The rgdA gene was expressed at low levels throughout the life cycle and was not significantly affected by several regulators of sexual and asexual development such as nsdD, veA, stuA, or brlA. However, the rgdA gene affected brlA and abaA expression, which function as key regulators of asexual sporulation, suggesting that rgdA functions upstream of those genes.

The herbicide linuron reduces testosterone production from the fetal rat testis both in utero and in vitro

EPA Science Inventory

In utero exposure to linuron, an urea-based herbicide, results in a pattern of malformations of androgen-dependent tissues in adult male rat offspring resembling that produced by some phthalate esters which are known to decrease fetal testosterone production. This study investiga...

LONG-TERM EFFECTS OF ADVERSE ENVIRONMENTS DURING DEVELOPMENT: EFFECTS ON ADULTHOOD IN RATS EXPOSED TO TOXICANTS OR UNDERNUTRITION IN UTERO.

EPA Science Inventory

Studies have shown correlations between in utero and early life environments and diseases later in life, including hypertension, coronary heart disease, diabetes, obesity, schizophrenia, early onset chronic renal failure, cancer and compromised repro-duction. Current development...

THE HERBICIDE LINURON REDUCES FETAL TESTOSTERONE PRODUCTION DURING BOTH IN UTERO AND IN VITRO EXPOSURES

EPA Science Inventory

Linuron, a urea-based herbicide, is a weak antagonist for the androgen receptor. Previous studies in our lab have shown that in utero exposureresults in malformations of androgen dependent tissues in adult male offspring. The pattern of malformations, however, differs somewha...

Disruption of insulin-like growth factor-II imprinting during embryonic development rescues the dwarf phenotype of mice null for pregnancy-associated plasma protein-A.

PubMed

Bale, Laurie K; Conover, Cheryl A

2005-08-01

Pregnancy-associated plasma protein-A (PAPP-A), an insulin-like growth factor-binding protein (IGFBP) protease, increases insulin-like growth factor (IGF) activity through cleavage of inhibitory IGFBP-4 and the consequent release of IGF peptide for receptor activation. Mice homozygous for targeted disruption of the PAPP-A gene are born as proportional dwarfs and exhibit retarded bone ossification during fetal development. Phenotype and in vitro data support a model in which decreased IGF-II bioavailability during embryogenesis results in growth retardation and reduction in overall body size. To test the hypothesis that an increase in IGF-II during embryogenesis would overcome the growth deficiencies, PAPP-A-null mice were crossed with DeltaH19 mutant mice, which have increased IGF-II expression and fetal overgrowth due to disruption of IgfII imprinting. DeltaH19 mutant mice were 126% and PAPP-A-null mice were 74% the size of controls at birth. These size differences were evident at embryonic day 16.5. Importantly, double mutants were indistinguishable from controls both in terms of size and skeletal development. Body size programmed during embryo development persisted post-natally. Thus, disruption of IgfII imprinting and consequent elevation in IGF-II during fetal development was associated with rescue of the dwarf phenotype and ossification defects of PAPP-A-null mice. These data provide strong genetic evidence that PAPP-A plays an essential role in determining IGF-II bioavailability for optimal fetal growth and development.

A scheme for reducing deceleration-phase Rayleigh-Taylor growth in inertial confinement fusion implosions

NASA Astrophysics Data System (ADS)

Wang, L. F.; Ye, W. H.; Wu, J. F.; Liu, Jie; Zhang, W. Y.; He, X. T.

2016-05-01

It is demonstrated that the growth of acceleration-phase instabilities in inertial confinement fusion implosions can be controlled, especially in the high-foot implosions [O. A. Hurricane et al., Phys. Plasmas 21, 056314 (2014)] on the National Ignition Facility. However, the excessive growth of the deceleration-phase instabilities can still destroy the hot spot ignition. A scheme is proposed to retard the deceleration-phase Rayleigh-Taylor instability growth by shock collision near the waist of the inner shell surface. Two-dimensional radiation hydrodynamic simulations confirm the improved deceleration-phase hot spot stability properties without sacrificing the fuel compression.

Influence of stress in GaN crystals grown by HVPE on MOCVD-GaN/6H-SiC substrate

PubMed Central

Zhang, Lei; Yu, Jiaoxian; Hao, Xiaopeng; Wu, Yongzhong; Dai, Yuanbin; Shao, Yongliang; Zhang, Haodong; Tian, Yuan

2014-01-01

GaN crystals without cracks were successfully grown on a MOCVD-GaN/6H-SiC (MGS) substrate with a low V/III ratio of 20 at initial growth. With a high V/III ratio of 80 at initial growth, opaque GaN polycrystals were obtained. The structural analysis and optical characterization reveal that stress has a great influence on the growth of the epitaxial films. An atomic level model is used to explain these phenomena during crystal growth. It is found that atomic mobility is retarded by compressive stress and enhanced by tensile stress. PMID:24569601

A scheme for reducing deceleration-phase Rayleigh–Taylor growth in inertial confinement fusion implosions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, L. F., E-mail: wang-lifeng@iapcm.ac.cn; Ye, W. H.; Liu, Jie

It is demonstrated that the growth of acceleration-phase instabilities in inertial confinement fusion implosions can be controlled, especially in the high-foot implosions [O. A. Hurricane et al., Phys. Plasmas 21, 056314 (2014)] on the National Ignition Facility. However, the excessive growth of the deceleration-phase instabilities can still destroy the hot spot ignition. A scheme is proposed to retard the deceleration-phase Rayleigh–Taylor instability growth by shock collision near the waist of the inner shell surface. Two-dimensional radiation hydrodynamic simulations confirm the improved deceleration-phase hot spot stability properties without sacrificing the fuel compression.

Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort.

PubMed

Gossai, Anala; Lesseur, Corina; Farzan, Shohreh; Marsit, Carmen; Karagas, Margaret R; Gilbert-Diamond, Diane

2015-01-01

Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs+MMA+DMA) was associated with a 10.3% (95% CI: 0.8-20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: -1.0-18.6%) and 10.3% (95% CI: 1.2-20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: -3.4-17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Three-dimensional measurements of fatigue crack closure

NASA Technical Reports Server (NTRS)

Ray, S. K.; Grandt, A. F., Jr.

1984-01-01

Fatigue crack growth and retardation experiments conducted in polycarbonate test specimen are described. The transparent test material allows optical interferometry measurements of the fatigue crack opening (and closing) profiles. Crack surface displacements are obtained through the specimen thickness and three dimensional aspects of fatigue crack closure are discussed.

Fetal Alcohol Syndrome in Adolescents and Adults.

ERIC Educational Resources Information Center

Bert, Cynthia R. Greene; Bert, Minnie

Persons with fetal alcohol syndrome (FAS) may be diagnosed at birth based on specific symptoms and anomalies. These are history of prenatal alcohol exposure, mental retardation, central nervous system dysfunctions, growth deficiency, particular physical anomalies, and speech and language anomalies. With aging, cranial and skeletal anomalies become…

Spotted knapweed, Centaurea stoebe, control options

USDA-ARS?s Scientific Manuscript database

Spotted knapweed is a non native perennial forb that is spreading rapidly in the Western United States. This plant species produces a compound that retards the growth of many native plants, giving it a competitive advantage. Spotted knapweed has been identified in several areas of Alaska. A descript...

The Cognitive and Behavioural Phenotype of Roifman Syndrome

ERIC Educational Resources Information Center

de Vries, P. J.; McCartney, D. L.; McCartney, E.; Woolf, D.; Wozencroft, D.

2006-01-01

Background: Roifman syndrome (OMIM 300258) is a multi-system disorder with a physical phenotype that includes B-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and characteristic facial dysmorphism. So far, six cases, all boys, have been reported in the literature. Roifman…

The Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Umbreit, John; Ostrow, Lisa S.

1980-01-01

Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

Trends in antimicrobial food packaging systems: Emitting sachets and absorbent pads

USDA-ARS?s Scientific Manuscript database

Active antimicrobial packaging interacts with packaged food and headspace to reduce, retard, or even inhibit the growth of spoilage and pathogenic microorganisms. Sachets and pads are one of the most successful applications of active food packaging. This review discusses recent developments of antim...

Genetic and Environmental Influences on Fetal Growth Vary during Sensitive Periods in Pregnancy.

PubMed

Workalemahu, Tsegaselassie; Grantz, Katherine L; Grewal, Jagteshwar; Zhang, Cuilin; Louis, Germaine M Buck; Tekola-Ayele, Fasil

2018-05-08

Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34-1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.

PPARD is an Inhibitor of Cartilage Growth in External Ears.

PubMed

Zhang, Zhen; Duan, Yanyu; Wu, Zhongping; Zhang, Hui; Ren, Jun; Huang, Lusheng

2017-01-01

Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle. At the transcription level, PPARD upregulates a set of genes that are associated with CSPCs apoptosis and chondrogenic differentiation, chondroblast differentiation and extracellular matrix degradation. ChIP-seq identified direct target genes of PPARD, including a well-documented gene for cartilage development: PPARG . We further show that compared to wild-type PPARD, the G32E mutant up-regulates the expression of PPARG and subsequently leads to the downregulation of critical genes that inhibit cartilage growth. These findings allow us to conclude that PPARD is an inhibitor of auricular cartilage growth in pigs. The causative mutation (G32E) in the PPARD gene attenuates the PPARD-mediated retardation of cartilage growth in the auricle, contributing to enlarged ears in pigs. The findings advance our understanding of the mechanisms underlying auricular development in mammals, and shed insight into the studies of innate pinna disorders and cartilage regeneration medicine in humans.

Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda

2002-04-15

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNELmore » staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.« less

Growth Retardation Of Chick Embryo Exposed To A Low Dose Of Electromagnetic Waves.

PubMed

Siddiqi, Najam; John C, Muthusami; Norrish, Mark; Heming, Thomas

2016-01-01

The objectives of this study were to explore the effects of low dose of the nonionizing (REW) emitted by a mobile phone on the development of chick embryo. one hundred and twenty chick fertilized eggs were equally divided into a control and an exposed group. Sixty fertilized eggs were placed in an egg incubator with a mobile phone (SAR US: 1.10W/kg (head) 0.47 W/kg body) in silent mode having vibration disable mode. Mobile was called for a total of 20 minutes in 24 hours. Twenty embryos each were sacrificed at day 5, 10 and 15, mortality, wet body weight, head to rump length, eye diameter and morphological changes were noted. The control group, 60 eggs were incubated in the same conditions, having removed the phone. No mortality was noted. The experimental group exposed to REW showed subcutaneous haemorrhagic areas and significant growth retardation at day 10 as evidence by smaller eye diameter, wet weight and CR length than the control group. There were no significant growth differences at either day 5 or at day 15. Electromagnetic waves emitted from mobile phones even though for a very short duration of 20 minutes per day have affected the growth of the chick embryo at day 10 of incubation, Hence exposure of these waves are not 100% safe.

Dietary L-arginine supplementation improves the intestinal development through increasing mucosal Akt and mammalian target of rapamycin signals in intra-uterine growth retarded piglets.

PubMed

Wang, Yuanxiao; Zhang, Lili; Zhou, Genlai; Liao, Zhiyong; Ahmad, Hussain; Liu, Wenbin; Wang, Tian

2012-10-28

Intra-uterine growth retardation (IUGR) impairs postnatal growth and development of the small intestine (SI) in neonatal pigs and infants. L-Arginine (Arg), a critical amino acid involved in promoting growth and metabolism in young mammals, is more deficient in IUGR fetuses. However, little is known whether dietary Arg supplementation would accelerate the impaired development of the SI induced by IUGR in piglets. In the present study, a total of six litters of newborn piglets were used. In each litter, one normal and two IUGR littermates were obtained. Piglets were fed milk-based diets supplemented with 0 (Normal), 0 (IUGR) and 0·60% Arg (IUGR+Arg) from 7 to 14 d of age, respectively. Compared with Normal piglets at 14 d of age, IUGR decreased (P < 0·05) the growth performance, entire SI weight, and villus height in the jejunum and ileum. IUGR piglets had lower (P < 0·05) mucosal concentrations of Arg, insulin, insulin growth factor 1, as well as phosphorylated Akt, mammalian target of rapamycin (mTOR) and p70 S6 kinase but higher (P < 0·05) enterocyte apoptosis index (AI). After Arg treatment in IUGR piglets, the growth performance, weight of entire SI and mucosa, and villus height in the jejunum and ileum were increased (P < 0·05). Diet supplemented with Arg also increased (P < 0·05) the levels of Arg, insulin, phosphorylated Akt and mTOR in SI mucosa of IUGR piglets, and decreased (P < 0·05) the AI and caspase-3 activity. In conclusion, Arg has a beneficiary effect in improving the impaired SI development in IUGR piglets via regulating cell apoptosis and activating Akt and mTOR signals in SI mucosa.

D-Tagatose inhibits the growth and biofilm formation of Streptococcus mutans

PubMed Central

Hasibul, Khaleque; Nakayama-Imaohji, Haruyuki; Hashimoto, Masahito; Yamasaki, Hisashi; Ogawa, Takaaki; Waki, Junpei; Tada, Ayano; Yoneda, Saori; Tokuda, Masaaki; Miyake, Minoru; Kuwahara, Tomomi

2018-01-01

Dental caries is an important global health concern and Streptococcus mutans has been established as a major cariogenic bacterial species. Reports indicate that a rare sugar, D-tagatose, is not easily catabolized by pathogenic bacteria. In the present study, the inhibitory effects of D-tagatose on the growth and biofilm formation of S. mutans GS-5 were examined. Monitoring S. mutans growth over a 24 h period revealed that D-tagatose prolonged the lag phase without interfering with the final cell yield. This growth retardation was also observed in the presence of 1% sucrose, although it was abolished by the addition of D-fructose. S. mutans biofilm formation was significantly inhibited by growth in sucrose media supplemented with 1 and 4% D-tagatose compared with that in a culture containing sucrose alone, while S. mutans formed granular biofilms in the presence of this rare sugar. The inhibitory effect of D-tagatose on S. mutans biofilm formation was significantly more evident than that of xylitol. Growth in sucrose media supplemented with D-tagatose significantly decreased the expression of glucosyltransferase, exo-β-fructosidase and D-fructose-specific phosphotransferase genes but not the expression of fructosyltransferase compared with the culture containing sucrose only. The activity of cell-associated glucosyltransferase in S. mutans was inhibited by 4% D-tagatose. These results indicate that D-tagatose reduces water-insoluble glucan production from sucrose by inhibiting glucosyltransferase activities, which limits access to the free D-fructose released during this process and retards the growth of S. mutans. Therefore, foods and oral care products containing D-tagatose are anticipated to reduce the risk of caries by inhibiting S. mutans biofilm formation. PMID:29115611

ROLE OF CENTRAL NERVOUS SYSTEM INSULIN RESISTANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

PubMed Central

de la Monte, Suzanne M; Wands, Jack R

2011-01-01

Fetal alcohol spectrum disorder (FASD) is the most common preventable cause of mental retardation in the USA. Ethanol impairs neuronal survival and function by two major mechanisms: 1) it inhibits insulin signaling required for viability, metabolism, synapse formation, and acetylcholine production; and 2) it functions as a neurotoxicant, causing oxidative stress, DNA damage and mitochondrial dysfunction. Ethanol inhibition of insulin signaling is mediated at the insulin receptor (IR) level and caused by both impaired receptor binding and increased activation of phosphatases that reverse IR tyrosine kinase activity. As a result, insulin activation of PI3K-Akt, which mediates neuronal survival, motility, energy metabolism, and plasticity, is impaired. The neurotoxicant effects of ethanol promote DNA damage, which could contribute to mitochondrial dysfunction and oxidative stress. Therefore, chronic in utero ethanol exposure produces a dual state of CNS insulin resistance and oxidative stress, which we postulate plays a major role in ethanol neurobehavioral teratogenesis. We propose that many of the prominent adverse effects of chronic prenatal exposure to ethanol on CNS development and function may be prevented or reduced by treatment with peroxisome-proliferated activated receptor (PPAR) agonists which enhance insulin sensitivity by increasing expression and function of insulin-responsive genes, and reducing cellular oxidative stress. PMID:21063035

[Relationship between phthalates and testicular dysgenesis syndrome].

PubMed

Chen, Guo-Rong; Dong, Lei; Ge, Ren-Shan; Hardy, Matthew P

2007-03-01

Recent epidemiological evidence demonstrates that boys born to women exposed to phthalates during pregnancy have an increased incidence of cryptorchidism, hypospadias, testicular cancer and spermatogenic dysfunction, which are collectively referred to as testicular dysgenesis syndrome (TDS). TDS may be attributed to the dysfunction of Leydig cells and Sertoli cells during their differentiation after exposure to phthalates in utero. Fox example, Leydig cell functions are significantly affected by phthalates, leading to the decrease of two Leydig cell products--insulin-like growth factor 3 (INSL3) and testosterone, which are critical factors for testis descent. The disorientation of Leydig cells and Sertoli cells in the adult testis may be the cause of spermatogenic dysfunction.

[Adult twins].

PubMed

Charlemaine, Christiane

2006-12-31

This paper explores the deep roots of closeness that twins share in their youngest age and their effect on their destiny at the adult age. Psychologists believe the bond between twins begins in utero and develops throughout the twins' lives. The four patterns of twinship described show that the twin bond is determined by the quality of parenting that twins receive in their infancy and early childhood. Common problems of adult twins bring about difficulties to adapt in a non-twin world. The nature versus nurture controversy has taken on new life focusing on inter-twin differences and the importance of parent-child interaction as fundamental to the growth and development of personality.

Prescribed burning does not reduce yield from oak-pine stands of southern New Jersey

Treesearch

H. A. Somes; G. R. Moorhead

1950-01-01

When fire is prescribed as a silvicultural treatment, questions usually arise about the amount of damage the fire does by killing or wounding trees or by retarding growth. Some answers to these questions are now available for the oak-pine stands of southern New Jersey.

Spatial and Temporal Trends of Persistent Organic Chemicals with Emphasis on Brominated Flame Retardants

EPA Science Inventory

Rapid growth in chemical and agrochemical industries during the past century have resulted in the release of large numbers of persistent organic chemicals (POCs) into the environment. Since POCs are prevalent in air, water, soil and tissue of organisms throughout the world and r...

Eugregarines reduce susceptibility of the hide beetle, Dermestes maculatus, to apicomplexan pathogens and retard larval development

USDA-ARS?s Scientific Manuscript database

Eugregarines are abundant in a great diversity of invertebrates, and yet their relationships with their hosts are subject to controversy and confusion. We tested the effect of the eugregarine, Pyxinia crystalligera, on growth, development, and susceptibility to two Apicomplexa pathogens of the hide ...

Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Zerrer, Peggy

The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

Soviet Cinema and State Control: Lenin's Nationalization Decree Reconsidered.

ERIC Educational Resources Information Center

Kepley, Vance, Jr.

1990-01-01

Proposes a revisionist account of the immediate conditions and consequences of the 1919 Soviet cinema nationalization decree. Argues that nationalization was the least successful of a set of stop-gap measures; that it dispersed and diluted control; and that it actually retarded the growth of the film industry. (KEH)

Smith-Lemli-Opitz syndrome: review and report of two affected siblings.

PubMed

Johnson, V P

1975-01-01

This paper reports two siblings with the Smith-Lemli-Opitz syndrome and reviews the literature on the subject. SLOS is a syndrome of multiple congenital anomalies with mental and growth retardation, unusual facies, genito-urinary and hand and foot abnormalities inherited as an autosomal recessive trait.

21 CFR 573.685 - Natamycin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... composed of calcium carbonate, natamycin, and lactose) is used for retarding the growth of Aspergillus... g of lactose. The premix shall be mixed into broiler chicken feed at the rate of 1 pound (0.454... consisting of calcium carbonate, the additive, and lactose and their proportions in the premix as prescribed...

21 CFR 573.685 - Natamycin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... composed of calcium carbonate, natamycin, and lactose) is used for retarding the growth of Aspergillus... g of lactose. The premix shall be mixed into broiler chicken feed at the rate of 1 pound (0.454... consisting of calcium carbonate, the additive, and lactose and their proportions in the premix as prescribed...

Curriculum Guide in Sex Education for the TMR.

ERIC Educational Resources Information Center

Steward, Kathy L.

Presented is a sex education curriculum guide for teachers of trainable retarded students ages 12 to 21 years. The guide is divided into six units: body parts, gender identification, and restroom signs; living things; reproduction; growth; adolescence, menstruation, and street language; and maturity (including sexual feelings and birth control).…

EFFECTS OF DIBUTYL PHTHALATE IN MALE RABBITS FOLLOWING IN UTERO, ADOLESCENT OR POST-PUBERTAL EXPOSURE

EPA Science Inventory

Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or post-pubertal exposure
Ty T. Higuchi1, Jennifer S. Palmer1, L. Earl Gray Jr2., and D. N. Rao Veeramachaneni1
1Animal Reproduction and Biotechnology Laboratory, Colorado State University, Fort

The effect of diesel (DE) exposure in utero on reproductive and developmental immunotoxicity

EPA Science Inventory

Epidemiology studies are beginning to show that in utero exposure to traffic related pollutants might increase the incidence of immune mediated lung diseases. Time pregnant BALB/c mice were exposed to air or two concentrations of diesel exhaust (0.5 and 2 mg/m³...

POTENTIAL MEDIA FOR MONITORING IN UTERO EXPOSURE TO 2,2’,4,4’-TETRABROMODIPHENYL ETHER

EPA Science Inventory

There is evidence that many diseases are linked to environmental exposures early in life. Little is known about in utero exposures to most environmental chemicals. Polybrominated diphenyl ethers (PBDEs) are widespread in the environment as a result of many years of usage ...

HEPATIC GENE EXPRESSION PROFILES OF RATS EXPOSED TO PERFLUOROOCTANE SULFONATE (PFOS) IN UTERO

EPA Science Inventory

Hepatic Gene Expression Profiles of Rats Exposed to Perfluorooctanesulfonate (PFOS) in utero.
J.A. Bjork1, J.M. Berthiaume1, C. Lau2, J. L. Butenhoff3, and K.B. Wallace1

1Department of Biochemistry & Molecular Biology, University of Minnesota School of Medicine, Dulut...

PERIODS OF VERTEBRAL COLUMN SENSITIVITY TO BORIC ACID TREATMENT IN CD-1 MICE IN UTERO

EPA Science Inventory

Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.

Cherrington JW, Chernoff N.

Department of Toxicology, North Carolina State University, Raleigh, NC 27695, USA. jana_cherrington@hotmail.com

Boric acid (BA) has many uses as...

ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO

EPA Science Inventory

ATRAZINE INCREASES DIMETHYLBENZ[A]ANTHRACENE-INDUCED MAMMARY TUMOR INCIDENCE IN LONG EVANS OFFSPRING EXPOSED IN UTERO.

SE Fenton and CC Davis

Reproductive Toxicology Division, NHEERL, ORD, USEPA, Durham, NC, USA

Recently, we found that ATR exposure during ma...

The effects of in utero bisphenol A exposure on ovarian follicle numbers and steroidogenesis in the F1 and F2 generations of mice.

PubMed

Mahalingam, Sharada; Ther, Laura; Gao, Liying; Wang, Wei; Ziv-Gal, Ayelet; Flaws, Jodi A

2017-12-01

Bisphenol A (BPA) is a commonly used plasticizer. Previous studies show that in utero exposure to BPA affects reproductive outcomes in the F1-F3 generations of mice. However, its multigenerational effects on ovarian histology and steroidogenesis over the reproductive lifespan are unknown. Thus, we tested the hypothesis that BPA has multigenerational effects on follicle numbers and steroidogenesis. Mice were exposed in utero to vehicle control or BPA (0.5, 20, and 50μg/kg/day). Ovaries were collected for histological and gene expression analyses and sera were collected for hormone assays. In utero BPA exposure decreased preantral follicle numbers, cytochrome P450 aromatase mRNA levels, and estradiol levels in the F1 generation, whereas it decreased testosterone levels and altered steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage, 3β-hydroxysteroid dehydrogenase 1, and cytochrome P450 aromatase mRNA levels in the F2 generation. These data suggest that BPA has multigenerational effects on the ovary in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Genotype- phenotype correlation in trisomy X: a retrospective study of a selected group of 36 patients and review of literature.

PubMed

Butnariu, Lăcrămioara; Rusu, Cristina; Caba, Lavinia; Pânzaru, Monica; Braha, Elena; Grămescu, Mihaela; Popescu, Roxana; Bujoranu, C; Gorduza, E V

2013-01-01

Trisomy X (47,XXX) is a gonosomal aneuploidy characterized by the presence of an extra X chromosome in a female person. Usually the diagnosis is established made postnatally by chromosome analysis in patients with suggestive clinical signs. Clinical signs vary by age. In prepubertal patients have a growth retardation associated with uncharacteristic facial dysmorphism, mild mental retardation with behavioral disorders, plus clinical signs of ovarian dysgenesis, postpubertal. We analyzed retrospectively the genotype - phenotype correlations for a selected group of 36 patients diagnosed with trisomy X (homogeneous or mosaic) by cytogenetic methods (X chromatin and karyotype). Analysis of the clinical data of 36 patients diagnosed with trisomy X and correlation with the results of X chromatin and karyotype. Clinical signs detected in patients with homogeneous trisomy X 47,XXX (22.22%), mosaic 46,XX/47,XXX (16.66%) or 47,XXX/48,XXXX (5.55%) were prepubertal, growth retardation associated with dysmorphic facial (upslanted palpebral fissure, epichantus, thin lips) and postpubertal, signs of ovarian dysgenesis (secondary amenorrhea, early menopause). The phenotype of patients with different gonosomal mosaic corresponding to Turner syndrome, incorporating a cell line with trisomy X (55.55%) was variable, correlated with the type of chromosomal abnormalities detected. The results of our study are similar to those obtained in other studies and emphasizes that phenotypic variability of patients with trisomy X feature makes it difficult to genotype - phenotype correlations.

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.

PubMed

So, Joyce; Müller, Ines; Kunath, Melanie; Herrmann, Susanne; Ullmann, Reinhard; Schweiger, Susann

2008-01-01

Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS. (c) 2007 Wiley-Liss, Inc.

Two familial cases with a lethal gracile bone dysplasia and intrauterine growth retardation.

PubMed

Korniszewski, Lech; Arbuckle, Susan; Kozlowski, Kazimierz

2003-05-01

A number of more or less distinct entities with low birth weight and abnormal radiographic appearances have been identified. We studied two sisters who were unusual because of severe intrauterine growth restriction, absence of growth after birth, decrease of pre- and postnatal spontaneous mobility, and early fatal outcome. The chondro-osseous morphology documented a distinctive osteochondrodysplasia. The radiographic examination was superficially similar to gracile bone dysplasias but was inconsistent with any known types of this group. These two patients appear to have a unique gracile bone dysplasia. Copyright 2003 Wiley-Liss, Inc.

Fatigue crack growth under variable amplitude loading

NASA Astrophysics Data System (ADS)

Sidawi, Jihad A.

1994-09-01

Fatigue crack growth tests were conducted on an Fe 510 E C-Mn steel and a submerged arc welded joint from the same material under constant, variable, and random loading amplitudes. Paris-Erdogan's crack growth rate law was tested for the evaluation of m and C using the stress intensity factor K, the J-integral, the effective stress intensity factor K(sub eff), and the root mean square stress intensity factor K(sub rms) fracture mechanics concepts. The effect of retardation and residual stresses resulting from welding was also considered. It was found that all concepts gave good life predictions in all cases.

In utero exposure to levetiracetam vs valproate: development and language at 3 years of age.

PubMed

Shallcross, R; Bromley, R L; Cheyne, C P; García-Fiñana, M; Irwin, B; Morrow, J; Baker, G A

2014-01-21

To compare the cognitive and language development of children born to women with epilepsy (WWE) exposed in utero to levetiracetam (LEV) or sodium valproate (VPA) and control children born to women without epilepsy not taking medication during pregnancy. The children, aged between 36 and 54 months, were recruited from the United Kingdom and assessed using the Griffiths Mental Development Scales and the Reynell Language Development Scale. Maternal demographic and epilepsy information was also collected for use in statistical regression. This is an observational study with researchers not involved in the clinical management of the mothers enrolled. After controlling for confounding variables, children exposed to LEV in utero (n = 53) did not differ from unexposed control children (n = 131) on any scale administered. Children exposed to VPA (n = 44) in utero scored, on average, 15.8 points below children exposed to LEV on measures of gross motor skills (95% confidence interval [CI] -24.5 to -7.1, p < 0.001), 6.4 points below on comprehension language abilities (95% CI -11.0 to -1.8, p = 0.005), and 9.5 points below on expressive language abilities (95% CI -14.7 to -4.4, p < 0.001). The current study indicates that children exposed to LEV in utero were superior in their language and motor development in comparison to children exposed to VPA. This information should be used collaboratively between health care professionals and WWE when deciding on women's preferred choice of antiepileptic drug.

Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure

PubMed Central

Jorgensen, Elisa M.; Alderman, Myles H.; Taylor, Hugh S.

2016-01-01

Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)–binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERα. Gene–environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.—Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure. PMID:27312807

Rapid and simple method for in vivo ex utero development of mouse embryo explants.

PubMed

Gonçalves, André B; Thorsteinsdóttir, Sólveig; Deries, Marianne

2016-01-01

The in utero development of mammals drastically reduces the accessibility of the mammalian embryo and therefore limits the range of experimental manipulation that can be done to study functions of genes or signaling pathways during embryo development. Over the past decades, tissue and organ-like culture methods have been developed with the intention of reproducing in vivo situations. Developing accessible and simple techniques to study and manipulate embryos is an everlasting challenge. Herein, we describe a reliable and quick technique to culture mid-gestation explanted mouse embryos on top of a floating membrane filter in a defined medium. Viability of the cultured tissues was assessed by apoptosis and proliferation analysis showing that cell proliferation is normal and there is only a slight increase in apoptosis after 12h of culture compared to embryos developing in utero. Moreover, differentiation and morphogenesis proceed normally as assessed by 3D imaging of the transformation of the myotome into deep back muscles. Not only does muscle cell differentiation occur as expected, but so do extracellular matrix organization and the characteristic splitting of the myotome into the three epaxial muscle groups. Our culture method allows for the culture and manipulation of mammalian embryo explants in a very efficient way, and it permits the manipulation of in vivo developmental events in a controlled environment. Explants grown under these ex utero conditions simulate real developmental events that occur in utero. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Height reduction among prenatally exposed atomic-bomb survivors: A longitudinal study of growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakashima, Eiji; Funamoto, Sachiyo; Carter, R.L.

Using a random coefficient regression model, sex-specific longitudinal analyses of height were made on 801 (392 male and 409 female) atomic-bomb survivors exposed in utero to detect dose effects on standing height. The data set resulted from repeated measurements of standing height of adolescents (age 10-18 y). The dose effect, if any, was assumed to be linear. Gestational ages at the time of radiation exposure were divided into trimesters. Since an earlier longitudinal data analysis has demonstrated radiation effects on height, the emphasis in this paper is on the interaction between dose and gestational age at exposure and radiation effectsmore » on the age of occurrence of the adolescent growth spurt. For males, a cubic polynomial growth-curve model applied to the data was affected significantly by radiation. The dose by trimester interaction effect was not significant. The onset of adolescent growth spurt was estimated at about 13 y at 0 Gy. There was no effect of radiation on the adolescent growth spurt For females, a quadratic polynomial growth-curve model was fitted to the data. The dose effect was significant, while the dose by trimester interaction was again not significant. 27 refs., 3 figs., 4 tabs.« less

Fetal programming of blood pressure in a transgenic mouse model of altered intrauterine environment.

PubMed

Chiossi, Giuseppe; Costantine, Maged M; Tamayo, Esther; Hankins, Gary D V; Saade, George R; Longo, Monica

2016-12-01

Nitric oxide is essential in the vascular adaptation to pregnancy, as knockout mice lacking nitric oxide synthase (NOS3) have abnormal utero-placental perfusion, hypertension and growth restriction. We previously showed with ex vivo studies on transgenic animals lacking NOS3 that adverse intrauterine environment alters fetal programming of vascular reactivity in adult offspring. The current research shows that altered vascular reactivity correlates with higher blood pressure in vivo. Our data suggest that higher blood pressure depends on both genetic background (NOS3 deficiency) and uterine environment, becomes more evident with age (> 7 postnatal weeks), activity and stress, is gender specific (preponderant among males), and can be affected by the sleep-awake cycle. In utero or early postnatal life (< 7 weeks), before onset of hypertension, may represent a potential window for intervention to prevent future cardiovascular disorders. Nitric oxide is involved in the vascular adaptation to pregnancy. Using transgenic animals, we previously showed that adverse intrauterine environment alters vascular reactivity in adult offspring. The aim of our study was to determine if altered vascular programming is associated with abnormal blood pressure (BP) profiles in vivo. Mice lacking a functional endothelial nitric oxide synthase (KO, NOS3 -/- ) and wild-type mice (WT, NOS3 +/+ ) were crossbred to generate homozygous NOS3 -/- (KO), maternally derived heterozygous NOS3 +/- (KOM: mother with adverse intrauterine environment from NOS3 deficiency), paternally derived heterozygous NOS3 +/- (KOP: mother with normal in utero milieu) and NOS3 +/+ (WT) litters. BP was measured in vivo at 7, 14 and 21 weeks of age. After univariate analysis, multivariate population-averaged linear regression models were used to identify factors affecting BP. When compared to WT offspring, systolic (SBP), diastolic (DBP) and mean (MAP) BP progressively increased from KOP, to KOM, and peaked among KO (P < 0.001), although significance was not reached for KOP. Higher BP was also associated with male gender, older age (> 7 postnatal weeks), higher locomotor activity, daytime recordings, and recent blood pressure transducer insertion (P < 0.001). Post hoc analysis showed that KOM had higher SBP than KOP (P < 0.05). Our study indicates that adverse intrauterine environment contributes, along with multiple other factors, to account for hypertension; moreover, in utero or early postnatal life may represent a possible therapeutic window for prevention of cardiovascular disease later in life. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.