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PubMed2003

Prenatal exposure of rats to Ginkgo biloba extract (EGb 761) increases neuronal survival/growth and alters gene expression in the developing fetal hippocampus.

Hippocampal neuron survival/growth and gene expression have been examined after prenatal (in utero) exposure of rats to EGb 761, a leaf extract of Ginkgo biloba. Oral administration of EGb 761 (100 or 300 mg/kg/day) to pregnant dams for 5 days increased the number of hippocampal neurons (maintained in culture) of their fetuses, indicating a neurotrophic effect of the extract. Using large-scale oligonucleotide microarrays containing over 8000 combined rat genes and expressed sequence tag clusters, it was shown that treatment of pregnant dams with EGb 761 (25, 50 or 100 mg/kg/day for 5 days) altered the expression of 187 genes in the hippocampi of male fetuses and 160 genes in those of female fetuses. Using gene-cluster analysis, these genes were grouped into 18 distinct clusters for males and 17 distinct clusters for females. Among these clusters, 35 genes shared a common expression pattern in male and female hippocampal development. Of these genes, the changes observed in insulin growth factor II, insulin growth factor binding protein 2, testosterone repressed prostate message-2, glutathione-dependent dehydroascorbate reductase, lipoprotein lipase, guanylate cyclase and DNA binding protein Brn-2 were confirmed by real-time quantitative polymerase chain reaction. These findings, which have provided the first genetic profile of the effects of EGb 761 on the developing rat hippocampus, increase our understanding of the molecular and genetic programs that are activated by the extract. These effects of EGb 761 may underlie its neuroprotective properties.

Animals↗

PubMed1999

The role of apoptosis in normal and accelerated lung development in fetal rabbits.

BACKGROUND/PURPOSE: During fetal development, the mammalian lung undergoes progressive parenchymal involution. Intrauterine tracheal occlusion induces accelerated architectural maturation of the fetal lungs associated with depletion of the surfactant-producing type II cells. This study investigates the spatiotemporal pattern of apoptosis during normal fetal lung development and its modulation in tracheal occlusion-induced accelerated fetal lung growth. METHODS: Fetal rabbit lungs were studied at 25 to 31 days' gestational age (DGA; term, 31 DGA), corresponding to late pseudoglandular through terminal air sac stages of fetal lung development. Intrauterine tracheal ligation (TL) was performed at 24 DGA. TL fetuses were monitored until 29 DGA, a time-point previously shown to coincide with significant type II cell depletion. Apoptotic cells were identified by light and electron microscopy, as well as terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end labeling (TUNEL). Epithelial (type I and II) cell apoptosis was studied by TUNEL labeling in conjunction with antisurfactant protein and anticytokeratin immunohistochemistry. DNA fragmentation was analyzed by gel electrophoresis. Sham-operated littermates served as controls. RESULTS: The number of apoptotic cells progressively increased with advancing lung growth and architectural maturation (apoptotic index [Al] 1.2 +/- 0.7 x 10(-3) at 25 DGA v 4.2 +/- 1.4 x 10(-3) at 31 DGA; P< .05, analysis of variance). In TL fetuses, the apoptotic rate was significantly higher than in non-TL fetuses from the third postligation day on, coinciding with the onset of significantly increased airspace distension (Al 4.9 +/- 1.3 x 10(-3) in TL v2.6 +/- 0.4 x 10(-3) in controls at 29 DGA; P< .05, Student's ttest). Apoptosis occurred in parenchymal cells and in isolated cells within the airspaces. The apoptotic activity of type II cells was significantly higher in TL fetuses than C fetuses at 29 DGA (type II Al 25.5 +/- 6.3 x 10(-3) in TL v2.3 +/- 0.8 x 10(-3) in C; P< .001). Electron microscopic studies confirmed the presence of apoptotic nuclei in interstitial macrophages and in degenerating intraluminal type II cells. DNA analysis showed nucleosomal bands. CONCLUSIONS: Normal fetal lung development is associated with a progressive increase of epithelial and interstitial apoptotic activity, a process enhanced by TL. Tracheal occlusion induces a significant increase of type II cell apoptosis, which likely contributes to the observed type II cell depletion after TL. We speculate that fetal type II cell apoptosis after TL may be induced by mechanical distension (stretch) of the airspaces.

Animals↗

PubMed1983

Effect of chlorine dioxide and its metabolites in drinking water on fetal development in rats.

The chlorination of surface waters is known to form trihalomethanes. Therefore, chlorine dioxide (C1O2) is being considered as an alternative disinfectant. This study was designed to determine the effect of chlorine dioxide and its metabolites, chlorite (C1O-2) and chlorate (C1O-3), on rat fetuses exposed in utero. Female rats were administered C1O2 at 0, 1, 10 and 100 mg 1(-1) and C1O-2 or C1O-3 at 1 and 10 mg 1(-1) daily in the drinking water for 2 1/2 months prior to the throughout gestation. Rats were killed on day 20 and fetuses examined for external, skeletal and visceral malformations. Slight decreases in weight gain during pregnancy were seen in the C1O2 administered groups. A significant dose-response relationship in the decreases of the numbers of implants and live fetuses were observed in the C1O2 groups. Although there were increased incidences of resorptions in the C1O-2 and C1O-3 groups, no statistically significant increase was found in the groups. Fetal weight was significantly increased in the 100 mg 1(-1) C1O2 group. Also, fetal length was increased in the 10 mg 1(-1) C1O-2 and C1O-3 treatment groups. Skeletal defects, such as incompletely ossified or missing sternebrae, rudimentary ribs and incompletely ossified skull bones were increased in all treatment groups, but none were significantly different from the control group. A few cases of hypoplastic kidney, hydronephrosis and dextrocardia were observed in the treatment groups.

Animals↗

PubMed1984

Appearance of chemotactic responsiveness to elastin peptides by developing fetal bovine ligament fibroblasts parallels the onset of elastin production.

We studied chemotaxis to elastin peptides by bovine ligamentum nuchae fibroblasts to determine whether there is a developmental association between chemotactic responsiveness to elastin and expression of the elastin phenotype. Undifferentiated ligament cells demonstrate chemotactic responsiveness to platelet-derived growth factor and fibronectin, known chemoattractants for fibroblasts, but do not show chemotaxis to elastin peptides. After matrix-induced differentiation, however, young cells display a positive chemotactic response to elastin that persists even after the cells are removed from the matrix substratum. Matrix-induced chemotaxis to elastin could be inhibited selectively by incorporation of bromodeoxyuridine into DNA of undifferentiated cells before (but not after) contact with inducing matrix. These results show that the appearance of chemotaxis to elastin peptides parallels the onset of elastin synthesis and suggests that the acquisition of chemotactic responsiveness to elastin and expression of the elastin phenotype are affected by the same inducing elements or processes and may be closely coupled in development.

Animals↗

PubMed2001

An investigation of the conus medullaris termination level during the period of fetal development to adulthood.

The spinal cord fills the length of the vertebral canal at the early period of intrauterine term. It is reported to extend to the level of the third lumbar vertebra at birth, because the vertebral column is growing more rapidly in the longitudinal direction than the spinal cord. The present investigation aimed to determine the changes in the termination level of conus medullaris (TLCM) from fetus to adulthood in a total of 285 individuals who had no defects in the central or peripheral nervous system, and were obtained from our Faculties of Medicine and Konya Maternity Hospital between 1992-1995. The age distribution was as follows: 36 fetuses, 20 prematures and 50 neonates, 51 children aged 1 to 7 years and 128 adults aged 15 to 68 years. In this study, for fetuses, prematures, neonates and children the TLCM was determined using ultrasonography. In addition, microdissection was used in fetuses to confirm the results obtained from the above technique. Also, magnetic resonance imaging was used in adults. During fetal life the end of the conus altered its levels from S5 to L3 vertebrae. The tip of the conus medullaris of the prematures and neonates ranged from L1 to L3 vertebrae. The tip of the conus medullaris in the children lay between the Th12 and L3 vertebrae, and in the adults it was between the Th12 and L2 vertebrae. There were slight differences between the prematures and neonates in terms of the TLCM. We concluded that there are differences in the TLCM between the age groups and therefore, especially in prematures and infants the determination of the tip of conus medullaris might be important for preventing postoperative neurological complications.

Adolescent↗

PubMed1986

[Cardiac weight in cattle (Bos taurus L.) during early fetal development].

68 bovine fetuses of both sexes (37 males, 31 females) from early developmental stage (80-990 gm) were studied. The coefficient of the absolute heart weights (42.4%) and the relative heart weight (0.76%) were described. Body weight (125.9 gm) were given when the heart of the fetus reach 1 gm. For the relation between body and heart weight were found following equation: logY = 0.958 logX--2.009 and plotted on double logarythmic paper. The results from bovine fetuses were compared with analogical data for water buffalo and camel (Berg, Taher, Moustafa).

Animals↗

PubMed1989

A transgenic mouse model that is useful for analyzing cellular and geographic differentiation of the intestine during fetal development.

Regional as well as cell-specific differences in gene expression are established and maintained in the perpetually regenerating intestinal epithelium. We have recently linked regions of the 5'-nontranscribed domain of the rat "liver" fatty acid binding protein (L-FABP) gene which is normally expressed in both liver and intestine, to a reporter, the human growth hormone (hGH) gene, and examined hGH expression in adult transgenic mice (Sweetser, D. A., Birkenmeier, E. H., Hoppe, P. C., McKeel, D. W., and Gordon, J. I. (1988) Genes Dev. 2, 1318-1332). Our results indicated that cis-acting elements, including an orientation-independent suppressor, could produce a pattern of cellular and geographic expression of hGH which mimics that of the intact, endogenous murine Fabpl gene in both organs. We now show that nucleotides -4000 to +21 of the rat L-FABP gene can direct "appropriate" cell-specific, regional, and temporal expression of the hGH reporter during a period of remarkable cellular expansion, cytodifferentiation, and morphologic transformation of the fetal gut epithelium. These studies also indicate that the polyclonal stem cell population located in the intervillous regions of the late fetal intestine exhibits a different pattern of transgene regulation than does the monoclonally derived crypt stem cell population in adult transgenic mice. Nucleotides -4000 to +21 are not sufficient to reproduce the normal temporal pattern of L-FABP gene activation in liver. Precocious expression of growth hormone in this pedigree of transgenic mice results in early induction of insulin-like growth factor I mRNA accumulation in liver but has no effect on insulin-like growth factor II mRNA levels. In contrast, local synthesis of growth hormone in the small intestine does not influence its insulin-like growth factor I or II mRNA levels.

Animals↗

PubMed1987

Effect of chlortetracycline supplementation during prebreeding and early gestation on age at puberty, ovulation rate, embryo survival and fetal development in gilts.

A total of 166 crossbred gilts weighing approximately 87 +/- 1 kg was limit-fed (2.5 kg/d) a corn-soybean meal gestation diet containing either 0 or 220 ppm of chlortetracycline (CTC) from 157 +/- 1 d of age until 15 d after breeding. These gilts were slaughtered at 31 +/- 1 or 71 d +/- 1 d of gestation for evaluation of reproductive performance. Age (190 +/- 3 d vs 195 +/- 3 d) and body weights (106 +/- 2 kg vs 106 +/- 2 kg) at puberty were similar for control and CTC-fed gilts, respectively. Although not significant (P > 0.05), ovulation rate was higher in CTC-fed than in control gilts as assessed at both 31 d (14.2 +/- 0.7 vs 12.9 +/- 0.9, P = 0.31) and 71 d (13.9 +/- 0.6 vs 12.4 +/- 0.5, P = 0.10) of gestation. There was an increase (P = 0.04) in the number of live embryos for CTC-fed gilts at 31 d (12.1 +/- 0.7 vs 9.7 +/- 0.7) but not at 71 d (10.0 +/- 1.1 vs 9.6 +/- 1.0) of gestation. The mean uterine length, placental length, placental weight, fetal length, fetal weight, and allantoic fluid volumes were similar between the control and CTC-fed gilts. Results indicated that feeding CTC during prebreeding and early gestation did not influence the proportion or age of gilts at puberty. However, CTC feeding may have influenced a trend to-ward an increased ovulation rate and increased number of live embryos in gilts.

Journal Article↗

PubMed1975

Moderate hypoxia exposure and fetal development.

Exposure of rabbits to 15.5% oxygen during pregnancy resulted in a 17% decrease of birth weight and a neonatal mortality of 19% as opposed to 1% in the control groups, just corresponding to the effects obtained previously by moderate exposure of pregnant rabbits to carbon monoxide. Since additive effects of hypoxia exposure and carbon monoxide exposure are supposed to occur, it is concluded that women living at a high altitude should be warned particularly about the risk of delivering small babies if they have been smoking during their pregnancy.

Animals↗

PubMed1983

[Twin pregnancies: incidence, fetal development and perinatal mortality].

The authors study 233 pairs of twins in a big maternity of Tunis, they analyse the frequency, the intra-uterine growth and the perinatal mortality. The frequency of twinning was 1.56%, the occurrence of preterm delivery was 45.92% and foetal hypotrophy was observed in 9.84% of the cases. The perinatal mortality rate was 143.77%: still born = 55.79% and neonatal deaths = 87.98%; the ratio of still born to neonatal deaths was 1.6. 29.3% of the neonatal twin deaths were due to hyaline membrane disease, 24.5% to immaturity, 14.6% to perinatal asphyxia and 12.4% to infection. The authors compare their findings to other studies on twin pregnancies.

Female↗

PubMed1977

Chronotropism and blood flow patterns following teratogenic doses of catecholamines in 5-day-old chick embryos.

In vivo heart rates of 5-day-old chick embryos were recorded from electrodes placed in close proximity to the heart. L-epinephrine (4X10(-10) mole), 1-norepinephrine (1X10(-9)mole) and 1-isoproterenol (1.6X10(-10)mole) in 5 microliter of isotonic saline transiently accerlerated the mean heart rate by almost 9 percent. L-phenylephrine (2X10(-9)mole/5microliter) and the experimental procedure produced no appreciable effect. The positive chronotropic effect of the catecholamines was found to be highly significant (P less than 0.0005) as computed by Student's t test. However, no direct relationship could be established between the chronotropic response and the aortic arch anomalies produced. A prolonged reduction of blood flow in the primitive heart tube and the sixth aortic arch after administration of epinephrine and isoproterenol is apparently related to the induction of hypoplastic right pulmonary artery with absent or hypoplastic right ductus arteriosus.

Abnormalities, Drug-Induced↗

PubMed2003

[Angiogenic proteins: possible markers of physiopathological processes during fetal development].

Pregnancy involves the coordinated formation of new vessels, a process known as angiogenesis. Several growth factors and specific receptors, e.g. vascular endothelial growth factor (VEGF), PlGF (placenta growth factor) and the soluble VEGF-1 receptor (VEGFR-1) play essential roles in the process. Pregnancy-related pathological conditions (preeclampsia and intrauterine growth restriction (IUGR)) are associated with aberrant expressions of these molecules, which can be measured in blood fractions from pregnant women. Using these as markers before a clinical diagnosis is evident, seems feasible. Pathological conditions, such as inflammation and cancer, also induce angiogenesis. Measurements of other endothelium-derived molecules may add to the specificity and sensitivity of angiogenic proteins as markers.

Angiogenesis Inducing Agents↗

PubMedDate not supplied

Effects of various exposure levels of 2-phenylethanol on fetal development and survival in Long-Evans rats.

Phenylethanol was given at different levels (432, 43, or 4.3 mg/kg) by gavage to pregnant Long-Evans rats during the "critical period" of organogenesis. Examination of offspring revealed adverse reproductive and teratogenic effects in a dose-related manner. Intrauterine growth retardation occurred at levels of 432 and 4.3 mg/kg. Embryolethality was 18% at 43 mg/kg and 10% at 4.3 mg/kg. Malformations occurred in the following sequence: 100% at 432 mg/kg; 93% at 43 mg/kg, and 50% at 4.3 mg/kg. Noteworthy dose-related teratogenic effects of phenylethanol in offspring manifested themselves in increased incidences of malformed eyes, neural-tube defects, hydronephrosis, and limb defects.

Animals↗

PubMed1976

[Growth and functional activiy of the adrenal cortex during fetal development during exposure to hypoxic and hyperoxic conditions].

A study was made of lipid, cholesterol, and ascorbic acid content in the adrenal cortex of rabbit fetuses developing under conditions of normal pregnancy and under the action of hypoxic and hyperoxic exposures during its third trimester. It appeared that in normal pregnancy the adrenal cortex was activated, this being associated with the adaptive motor reactions of the developing fetus. The action of moderate hypoxic exposures led to a greater activation of moderate hypoxic exposures led to a greater activation of the adrenal cortex, this being expressed in a marked fall of lipid, cholesterol and ascorbic acid content. The weight of the total muscle mass and of the fetuses increased as a whole. The adrenal cortex became disactivated under conditions of the hyperoxic exposures; this is expressed in a marked increase in the content of the mentioned formations. The weight of the total mass and of the fetuses decreases.

Adrenal Cortex↗

PubMed1984

[Pregnancy and fetal development in epileptic women].

Epilepsy affects almost 1% of all pregnant women. Epileptic women marry more often than epileptic men. Married epileptic women have a lower socio-economic status and are more severely ill than married male epileptics.--Several reasons are discussed--poor compliance being probably the most essential one--for an explanation of an occasional increase in the rate of attacks and a frequently observed tendency to a drop in plasma concentrations of anti-epileptics during pregnancy. Pregnancy and parturition are not more complicated in epileptic women than in non-epileptics women. Nevertheless, abortions are performed, and delivery by surgery is initiated, more often with epileptics, although there are no convincing arguments in favour of such procedures. For unknown reasons, perinatal lethality is up to twice as high than with controls.--Children of mothers treated with anti-epileptics have a tendency to intrauterine dystrophia, which is manifested mainly by a reduced size of the head which is not made up completely during the first few years of life, contrary to other body dimensions. We do not know as yet whether there are any links between dystrophia of the body, malformations and inhibited psychomotoric development.--Depending on the type of anti-epileptics given to the mothers who are breast-feeding their children, and on the concentration of these drugs in the plasma or in the mother's milk, breast-fed children may display signs of withdrawal or sedation. This must not be overlooked when considering the problem of breast-feeding.--The slightly enhanced risk of malformations appears to be less intimately connected, with intrauterine exposition of anti-epileptics than with the underlying disease itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

PubMed1976

Maternal thyroid function, iodine deficiency and fetal development.

In an area of New Guinea where there is dietary iodine deficiency, measurements of thyroid function have been made on women of child-bearing age, several of whom were pregnant at the time. The outcome of these pregnancies, and also of those occurring in the four preceding years, were examined in relation to indices of thyroid function. More stillbirths, infant deaths and endemic cretins occurred among the offspring of women who showed biochemical evidence of iodine deficiency, without clinical evidence of hypothyroidism. This situation differs from that of untreated myxoedema or congenital hypothyroidism in women, which is usually associated with altered menstrual function, infertility or repeated abortion. Mechanisms that may account for these differences and the possible implications are discussed.

Child, Preschool↗

PubMed1990

[Pregnancy-induced hypotonia. A prospective study of fetal development, labor and morbidity of newborn infants].

Maternal and foetal risk of hypotension in pregnancy were examined in a prospective study, comprising a total of 770 pregnant women i.e. 700 normotensives and 70 hypotensives. We conducted a minimum of 5 pressure controls beginning after the 20th week of gestation. All pressure controls were conducted by the same person and in each control 4 pressure values were taken (left and right arm, lying, standing). No difference was discovered in the statistical analysis of our data of pregnancy, delivery and foetal outcome. Our special interest was in the frequency of preterm delivery and foetal growth retardation. The rate was similar in the hypotensive group (6.7/3.1%) compared to the normotensive group (6.8/2.8%). From our results we conclude, that maternal hypotension is not a risk factor in pregnancy, and that no therapy is needed.

Acidosis↗

PubMed1977

Prostaglandin biosynthesis and catabolism in the developing fetal sheep lung.

The prostaglandin biosynthetic and catabolic capacity of homogenates of lungs from fetal sheep of various gestational ages was measured. Prostaglandin biosynthesis was assayed by the deuterium-isotope dilution technique making use of mass fragmentography whereas prostaglandin catabolism was measured by the radioisotope-dilution method described previous (Pace-Asciak, C.R. and Rangaraj, G. (1976) J. Biol. Chem. 251, 3381-3385). Homogenates of lungs from fetuses of all ages tested (40 days to term) formed both prostaglandins E2 and F2alpha; although prostaglandin F2alpha was formed to a greater extent than prostaglandin E2 by the 40 days lung, prostaglandin E2 increased with increasing age until at term the ratio of both prostaglandins approached unity. Total prostaglandin biosynthesis (E2 + F2alpha) rose gradually with age (approx. 3 fold increase between 40 days and term). Prostaglandin F2alpha catabolism occurred mainly by the prostaglandin 15-hydroxy dehydrogenase pathway; this activity was detectable even at 40 days and remained unchanged up to 80 days. Prostaglandin catabolic activity rose sharply at 90 days (approx. 3 fold) with a maximum around 110 days (approx. 4 fold) decreasing back to 40 day levels by term (143 days). The increasing prostaglandin catabolic activity around 90-100 days in this species is discussed in relation to the hemodynamic changes in the lungs starting around this age and the appearance of surfactant. Prostaglandin catabolism might play an important role in the developing organ controlling steady state concentrations of prostaglandins during certain periods of organogenesis.

Animals↗