Experimental Intrauterine Growth Retardation Research Articles

Morphology of the parotid gland of rats under conditions of experimental intrauterine growth retardation.

Background . Child’s dental caries is one of the most topical problems in practical dentistry. In case of neglecting of prevention and treatment it can lead not only to local complications, but also to systemic processes. Many studies have shown the dependence of tooth tissue destruction on changing the properties of oral fluid. Therefore the problem of salivary glands pathomorphology and function are regarded as promising directions for further fundamental research. Objective . According to this, the aim of the study was an experimental investigation of the effect of intrauterine growth retardation on the structural remodeling of the parotid salivary gland. Methods . Parotid glands of 65 newborn rats, including 35 animals with signs of IUGR and 30 controls born after physiological pregnancy were the material of the study. Tissue samples of parotid glands were studied microscopically. The differences were analyzed by methods of mathematical statistics; data were compared with controls by Student’s t-test. Results revealed the reduction of the number and size of the parotid gland’s lobules with a concomitant stromal connective tissue proliferation. The vessels were hyperemic. There were also perivascular foci of stromal edema. Glandular acini had some features of the degenerative changes of epitheliocytes – sign of hydropic dystrophy. Morphometric study of the structural organization of the parotid glands of the newborn rat in case of IUGR defined the reduction in parenchymal VF to 25,00 ± 6,96% and increases VF of the stroma to 35,67 ± 4,29% (in controls - 51,72 ± 7,04 and 23,70 ± 3,25%, P <0.05, respectively). Conclusion . Results of the research are considered in terms of structural basis of functional deficiency of the parotid gland and the possible impact of developmental retardation on oral fluid properties.

Quantitative Immunohistochemical Analysis of Nitric Oxide Synthases and Apoptosis Regulator Proteins in the Fetal Rat Brain Following Maternal Uterine Artery Ligation

The purpose of this study was to determine the relation between nitric oxide synthases (calcium-independent iNOS and calcium-dependent eNOS) and apoptosis regulator proteins (anti-apoptotic Bcl-2, pro-apoptotic p53) of fetal rat brain in experimental intrauterine growth retardation (IUGR) model via quantitative immunohistochemistry. Cortical zone of parietal cerebral cortex and ventricular zone of third ventricle were studied following bilateral uterine artery ligation on gestational day 18. Significant increase in iNOS immunoreactivity was determined in parietal cerebral cortex and ventricular zones as eNOS immunoreactivity increased in ventricular zone of IUGR group. Bcl-2 expression was significantly decreased in ventricular zone; whereas cortical zone of IUGR group expressed p53 immunoreactivity.

Experimental Intrauterine Growth Retardation in the Rat Causes a Reduction of Pancreatic B-Cell Mass, Which Persists into Adulthood

Background and Objectives: The aim of this study was to investigate the possibility that intrauterine growth retardation (IUGR) causes alterations of glucose tolerance, insulin secretory response to glucose, and pancreatic B-cell growth, and if such changes may persist into adulthood. Methods: Pregnant rats were operated on day 16 of pregnancy ad modum Wigglesworth to induce IUGR. Operated rats gave birth to viable offspring but litter size was reduced. The mothers nursed their pups, which were subsequently weaned and reared to an age of 3 months in apparent good health. Results: At 1 day of age, IUGR pups were 10% lighter than control newborns whose mothers had been subjected to a sham operation. Pancreatic B-cell mass and insulin content were reduced by 35–40% in newborn IUGR offspring. Postnatal growth did not differ between IUGR and control animals of either sex and the difference in body weight at birth was not apparent from 1 week of age and onwards. Tests performed at 3 months of age could not demonstrate differences in glucose tolerance between IUGR and control animals. In females, but not in males, the peak insulin secretory response to glucose was lower in IUGR animals compared to controls. In the 3-month-old rats, B-cell mass was reduced by 40% in male and by 45% in female IUGR rats compared to controls, a reduction corresponding to a similar decrease in pancreatic insulin content (male reduction 48%, female reduction 45%). Conclusions: In the rat, IUGR causes a diminution of pancreatic B-cell mass which persists into adulthood. Normal glucose tolerance could be maintained but it is conceivable that increasing demands on insulin secretion may not be met by the reduced B-cell mass and that impaired glucose tolerance and even diabetes would hence develop.

Experimental intrauterine growth retardation alters renal development.

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation (IUGR), resulting in small-for-gestational-age, asymmetric newborns. IUGR neonates experience higher morbidity and mortality rates, as well as a possible contribution towards late sequelae, such as hypertension, and cardiovascular disease in adulthood. To simulate vascular placental insufficiency, an experimental rabbit IUGR model was used. Intrauterine growth retardation was achieved by ligation of 25-30% uteroplacental vessels of half of the fetuses during the last third of gestation. Ischemic fetuses were significantly small, asymmetric, and had a disproportionately small body with a relatively large head. The kidneys from all groups were analyzed for relative estimated glomeruli number (REGN) using an unbiased blind design. The glomeruli number was significantly reduced in the asymmetric IUGR rabbit fetuses, probably due to decreased renal vascular supply. Our results support the concept that the reduced number of glomeruli may contribute to impaired renal function, thus predisposing to neonatal renal dysfunction and late sequelae, such as adult hypertension. This study emphasizes the clinical importance of early IUGR diagnosis and prevention.

Neonatal sympathoadrenal response to acute hypoxia: impairment after experimental intrauterine growth retardation.

Sympathoadrenal system function may be altered following intrauterine growth retardation (IUGR). We tested the hypothesis that the growth-retarded newborn rat pup has increased basal sympathoadrenal activity under normoxic conditions and a blunted sympathoadrenal response to acute hypoxia. IUGR was established by uterine artery ligation on d 18 of gestation in Sprague-Dawley rats. Growth-retarded pups were chosen as those whose birth wt was more than 2 x SD below the mean birth wt of control pups delivered to sham-operated dams. At 24 +/- 12 h of age cardiac sympathetic neuronal activity (CSNA) was determined by 3H-norepinephrine tracer and alpha-methyltyrosine techniques. Adrenal medullary catecholamine synthesis (CAT SYN) was measured by 14C-tyrosine precursor methods, and adrenal catecholamine release (CAT REL) was determined using alpha-methyl-tyrosine. IUGR and control pups were studied over a 120-min period of normoxia or hypoxia (FiO2 = 0.09). Under normoxic conditions, the IUGR pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to controls. Adrenal CAT REL in normoxic IUGR pups was selective for epinephrine. In response to acute hypoxia, control pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to normoxic controls, with the proportion of norepinephrine and epinephrine released mimicking the ratio of the two amines in the adrenal. In contrast, in hypoxic IUGR pups CSNA and adrenal CAT SYN did not increase, and norepinephrine alone was released from the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth and Fatty Acid Metabolism in Experimental Intrauterine Growth Retardation: Effect of Postnatal Nutrition in Rat

Rats, 3½ to 4 d of age, were used to study weight gain and fatty acid (FA) metabolism as a function of degree of intrauterine growth retardation (IUGR) and of postnatal nutrition. The IUGR, quantified postnatally as mild and severe, was produced by uterine artery ligation on d 17 of gestation, and controls were sham-operated. Food intake was manipulated by varying the litter size; i.e., pup number per dam was 4 or 5 for overfeeding, 8–10 for normal feeding and 13–15 for underfeeding. Fatty acid synthesis rate (FASR) (determined by tritiated water incorporation in FA) and contents were determined in selected organs at 84 to 96 h of age. The initial weights (grams) at 2 to 12 h of age were: 5.88 ± 0.74 (mean ± SD) for controls, 5.18 ± 0.11 for mild IUGR and 4.18 ± 0.24 for severe IUGR. During the first 96 h of life, weight gain was less in underfed control pups while overfeeding resulted in the same weight gain as in normally fed pups. Pups with mild IUGR showed the same effect of under- or overfeeding as control pups. In the severe IUGR groups, weight gains were similar in all three feeding groups. In the carcass, the fatty acid content was reduced as a result of both prenatal and postnatal undernutrition. Although the underfed control group had a high FASR, underfeeding had no effect on the FASR of groups with IUGR. In the liver, the FA content was also lower in the underfed controls and in IUGR groups, without any difference in FASR. Feeding did not influence the FASR of liver. In the brain, the FA synthesis rate of normally fed IUGR pups was significantly greater and was almost twice as high in underfed IUGR pups as in normally fed IUGR pups. This was accompanied by significantly lower FA contents in both normally fed and underfed IUGR pups. It is concluded that in the rat, during the first few days of life, 1) a generous food supply does not augment weight gain, 2) a restricted food supply reduces weight gain in normal and mild IUGR but not in severe IUGR and 3) the reduction fatty acid content in prenatal and postnatal under-nutrition is consistent with the reduction in weight gain.

Effect of respiratory acidosis on glucose homeostasis in experimental intrauterine growth retardation in rats

Hypoglycemia and asphyxia account for a significant proportion of morbidity in the infant with intrauterine growth retardation (IUGR). The purpose of this study was to evaluate changes in glucose homeostasis in IUGR rats during acute respiratory acidosis. IUGR was produced by bilateral uterine artery ligation at 17 days of gestation in 14 pregnant rats with 23 successfully delivered pups. The normal pups ( n = 31) were those whose mothers were sham operated at the same gestational period. The IUGR and normal pups were studied at 2 days of age. One group of pups was studied under room air while another was subjected to 20 min of exposure to a gas mixture of 10% O 2/15% CO 2, balanced with N 2. Gluconeogenesis in the liver and carcass, as well as plasma glucose and catecholamines were determined before and after the exposure to the gas mixture. The results showed that the 2-day-old IUGR rats have lower body weight (P < 0.001), liver weight (P < 0.001), plasma glucose (P < 0.001), and rate of gluconeogenesis (P < 0.01) when compared with the normally grown rats. During respiratory acidosis, the normally grown rats showed an increase in plasma epinephrine (P < 0.005) without significant change in plasma glucose and rate of gluconeogenesis. The IUGR rats on the other hand, demonstrated a decrease in rate of gluconeogenesis (P < 0.02), an increase in plasma glucose (P < 0.001) while the plasma epinephrine level remained unchanged. We speculate that respiratory acidosis blunted cellular metabolism in the IUGR rat resulting in decreased peripheral glucose utilization.

Regional distribution of cerebral blood flow in experimental intrauterine growth retardation

The regional distribution of cerebral blood flow was assessed in eight control and eight morphometrically growth-retarded fetal lambs to determine whether perfusion patterns within the cerebral circulation are altered in this model of intrauterine growth retardation. Growth retardation was induced by repetitive embolization of the uterine circulation, and flow distribution was assessed by use of microspheres. Distribution to 22 separate areas, expressed as a flow/weight ratio, was virtually identical in the two groups. Cortical gray matter received 56% of total cerebral flow, and cortical white matter received 7%. However, flow · gm−1 in cortical white matter was 85% of that in cortical gray matter. We conclude that perfusion patterns within the cerebral circulation are not altered in this model of intrauterine growth retardation and that, compared to gray matter, cortical white matter has a high flow · gm−1 in fetal life.

Experimental intrauterine growth retardation in the rat. Evaluation of the Wigglesworth model

The validity of the Wigglesworth experimental model to produce newborn rats that are small for gestational age by ligation of one of both uterine vessels was confirmed. Newborn rats from the opposite horns are used as controls in the classical model. It is concluded from this study that newborns from sham-operated dams are more satisfactory controls for newborn rats that are small for gestational age from ligated horns.

OBSERVATION ON EXPERIMENTAL INTRAUTERINE GROWTH RETARDATION IN SHEEP

BJOG: An International Journal of Obstetrics & GynaecologyVolume 84, Issue 7 p. 555-555 OBSERVATION ON EXPERIMENTAL INTRAUTERINE GROWTH RETARDATION IN SHEEP J. S. Robinson, J. S. Robinson The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this authorI. Hart, I. Hart The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this authorC. T. Jones, C. T. Jones The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this authorG. D. Thorburn, G. D. Thorburn The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this author J. S. Robinson, J. S. Robinson The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this authorI. Hart, I. Hart The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this authorC. T. Jones, C. T. Jones The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this authorG. D. Thorburn, G. D. Thorburn The Nuffield Institute for Medical Research and the Nuffield Department of Obstetrics and Gynaecology University of Oxford, Headington Oxford and the National Institute for Research in Dairying, Shinfield, ReadingSearch for more papers by this author First published: July 1977 https://doi.org/10.1111/j.1471-0528.1977.tb12647.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume84, Issue7July 1977Pages 555-555 RelatedInformation

CEREBRAL OXIDATIVE METABOLISM IN INTRA-UTERINE GROWTH RETARDATION

Ligation of the uterine arteries during late gestation leads to retarded somatic growth and compromised cerebral development in experimental animals (Wigglesworth, 1964). The pathogenesis of the altered brain growth may stem from chronic tissue hypoxia and/or substrate deficiency. Pregnant rata of 17 days gestation were subjected to laparotomy, following which the uterine artery supplying one uterine horn was ligated. The opposite horn and its blood supply were left undisturbed, its fetuses serving as controls. Dams were sacrificed at term by decapitation & fetuses delivered by C-section. Fetal brains were removed & analyzed. Animals from the ligated horn exhibited decreased body (-25%) & brain (-10%) weights compared to controls. Brain dry weight was also lower (-7.4%), but lipid content was not different. Oxidative metabolites & high-energy reserves (mM/kg w.w.) were:The absence of significant differences in brain metabolites between control & experimental groups reflects adequate oxygenation of, & glucose delivery to, the brains of the growth retarded fetuses. Thus, a deficiency of substrates other than glucose appears to be the critical factor in the cerebral under development of experimental intra-uterine growth retardation.

Metabolic Response to Fasting in Experimental Intrauterine Growth Retardation Induced by Surgical and Nonsurgical Maternal Stress

Experimental intrauterine growth retardation was produced by two groups of neonatal rats by maternal sham surgery or by maternal obligatory exercise during the last 5 days of gestation (forced swim). Both experimental groups of neonates had lower plasma glucose and higher plasma insulin levels than controls after a 4-hour fast. Fetal stunting may be produced by a variety of maternal stresses in the rat and may be associated with alterations in the hormonal and glycemic response to fasting. Studies of the metabolic effects of experimental intrauterine growth retardation must be interpreted with caution if control animals have been subjected to intrauterine stress.

128: Observations on experimental intrauterine growth retardation in sheep

Low birthweight in sheep is associated with increased perinatal mortality. The sheep uterus contains folds of endometrium (caruncles) which form the maternal cotyledon in pregnancy. Alexander (1964) removed caruncles & in a subsequent pregnancy observed a reduction of placental & fetal weight, increased incidence of premature labour & stillbirths. 4 small fetuses have been produced using this technique. Catheters were implanted into the ewe & the fetus between 105 & 110 d. Serial measurements of blood gases, pH, metabolites, cortisol & ACTH were made. The mean fetal carotid PaO2 & haematocrit were 15.9 ± 1.3 mm Hg & 37.4 ± 2.2% compared to 21.6 ± 1.0 mm Hg & 30.3 ± 0.6% in 7 control fetuses (P < 0.01). There were no significant changes in PaCO2 or pH. Plasma glucose (0.66 ± 0.03 μmol/ml), lactate (0.9 ± 0.02 μmol/ml) and a amino nitrogen (aNH2, 6.11 ± 0.25 μmol/ml) were lower than in control fetuses (glucose 1.19 ± 0.02 μmol/ml, lactate 1.47 ± 0.02 μmol/ml and a NH2 7.64 ± 0.02 μmol/ml)suggesting a limitation of placental transfer. We have previously observed increased ACTH with hypoxaemia or hypoglycaemia. However, the concentration of ACTH (69.2 ± 29.7 pg/ml) and cortisol (21 ± 8.2 ng/ml) in the small fetuses was not significantly different from controls.

Metabolic Response to Fasting in Experimental Intrauterine Growth Retardation

Experimental intrauterine growth retardation was produced in two groups of neonatal rats by maternal dietary restriction (DR) or by bilateral ligation of the uterine vessels (UVL). Both experimental groups of neonates had lower plasma glucose levels than controls at delivery. Newborns of DR animals showed appropriate suppression of insulin release and rapid recovery from hypoglycemia during an 8-hour fast. In contrast, neonates in the UVL group displayed persistently lower plasma glucose levels and inappropriate hyperinsulinemia. The metabolic effects of these two models of intrauterine growth retardation reflect the nature of the fetal insult and are not uniform.

Experimental intrauterine growth retardation.

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.

Hepatic gluconeogenesis and lipogenesis in experimental intrauterine growth retardation in the rat

Intrauterine growth retardation in the rat was induced by ligating the artery supplying one uterine horn on the seventeenth day of gestation. The artery of the opposite uterine horn was left untouched, permitting normal development of fetuses in this side. The latter served as experimental controls. In vitro studies with liver slices 3 hours after a spontaneous delivery have shown impaired glucose production from labeled alanine in the dysmature newborn rats. It is suggested that the delay in postnatal development of hepatic gluconeogenesis may be a contributory factor to the susceptibility to neonatal hypoglycemia known to exist in this situation. Hepatic phospholipogenesis was also less active in the intrauterine growth-retarded fetuses. This observation might reflect developmental immaturity of membranous systems, which play an important role in the control and integration of hepatic metabolism.

Carbohydrate metabolism in experimental intrauterine growth retardation in rats

Intrauterine growth retardation was induced in 34 pregnant rats by ligating the uterine artery supplying one uterine horn of a bicornate uterus at 17 days of gestation. The opposite uterine horn was left untouched and served as the control. The fetuses were delivered at 21 days of gestation. One hundred and fifty-eight control and 141 intrauterine growth-retarded fetuses were used in a series of three experiments. The body weight, placenta, liver, heart, and kidney weights were smaller in the intrauterine growth-retarded fetuses. The blood glucose of intrauterine growth-retarded fetuses at birth was lower than in the controls. The liver glycogen contents were lower in the intrauterine growth-retarded fetuses during the last 2 days of pregnancy. Intravenous glucose infusion to the mother 2 hours prior to delivery of the fetuses effectively raised the fetal blood glucose to a hyperglycemic range and repletes the previously observed lower hepatic glycogen in the intrauterine growth retardation.

Fatty acid synthesis in vivo in maternal and fetal tissues in the rat

Fatty acid synthesis in vivo in maternal and fetal tissues in the rat