Transport of steroids between fetuses via amniotic fluid in relation to the intrauterine position phenomenon in rats.

In litter-bearing mammals, the course of development of male and female fetuses is affected by the presence of other fetuses of the same or opposite sex located nearby within the uterus. The transport of testosterone between rat fetuses was examined by implanting a Silastic capsule containing [3H]testosterone into the amniotic sac of a fetus at either the ovarian or cervical end of a uterine horn on days 19 and 20 of pregnancy. The amount of testosterone that was recovered from the amniotic fluid of other fetuses 12 h later was determined. The amniotic fluid surrounding the adjacent fetus on the cervical side of the implanted fetus contained three times as much [3H]testosterone as did the adjacent fetus on the ovarian side, regardless of where in the uterus the implant was made. The movement of dye injected into the uterine lumen was towards the cervix. Intraluminal fluid movement may thus mediate the greater transport of [3H]testosterone towards the cervix than towards the ovary. Our findings support the hypothesis that transport of testosterone between fetuses occurs across the fetal membranes via diffusion, such that any fetus (male or female) located between male fetuses receives the greatest supplement of testosterone.     

The fatty acid composition of placenta in intrauterine growth retardation

To examine the impact of intrauterine growth retardation (IUGR) on essential fatty acids in human placenta, fatty acid composition in total acylglycerol and in the major phosphoglycerides phosphatidylcholine (PC) and phosphatidylethanolamine (PE), of 15 placentas from small for gestational age (SGA) births was compared with that of 7 control placentas. The acylglycerol fatty acid content was similar between the two groups, but the proportion of fatty acids of the linoleic acid series, including arachidonic acid, was significantly lower in SGA placentas. When the fatty acid composition in PC was studied, the reduction in fatty acids of the linoleic acid series was even more striking, and fatty acids of the linolenic acid series was also significantly less in the SGA group. These fatty acid changes in placenta membrane phospholipids can affect the transport of important nutrients to the fetal compartment. The decreased level of arachidonic acid and docosahexanoic acid might also lead to a disturbed formation of fetal thromboxane and prostacyclin. However, cord plasma PC fatty acid patterns were nearly identical in the two groups suggesting that in IUGR, the essential fatty acids will be transported to the fetus at the expense of the placenta.     

Over-expression and secretion of angiogenin in intrauterine growth retardation placenta

Human angiogenin is a potent inducer of neovascularization. There is a strong evidence to suggest that it might be involved in morphological and angiogenic changes in the placenta, that are necessary for a successful fetal outcome during pregnancy. However, its precise role in the pathogenesis of abnormal pregnancies is yet unknown. Intrauterine growth retardation (IUGR), an abnormal pregnancy is not a specific disease entity per se, but rather a manifestation of many possible fetal and maternal disorders. In this study, we demonstrated, for the first time, that placental explants in vitro secrete significantly elevated levels of angiogenin in placental tissues from patients with IUGR. We also observed enhanced mRNA expression in placenta from these patients. In addition, using the immunohistochemical methods, we observed identical staining of angiogenin to villous syncytiotrophobalst and fetal endothelial cells in both IUGR and normal placenta. Functionally active placental explants were used to detect immunoreactive angiogenin in conditioned media of all the samples from IUGR placenta and normal term group. The mean levels of angiogenin secreted by IUGR placenta were 1.4-, 1.6-, and 1.3-fold higher (P < 0.01) than normal term samples at 24, 48, and 72 hr of culture, respectively. Expression profiles of angiogenin from term and IUGR cases are in agreement with its mRNA levels and immunoblot analysis. In conclusion, the significant elevated levels of angiogenin in IUGR placenta may provide a molecular mechanism for the abnormal placental development.     

Unusual increase in amniotic fluid alpha fetoprotein and trisomy 13

From 10 observations of trisomy 13, 3 presented an elevated amniotic fluid alpha-fetoprotein level considered as unusual in 2 cases, superior to cut-off level in the other case. Macroscopic examination of the three fetus could not reveal a cause of AFP elevation, neural tube defect or abdominal wall defect. The authors discuss the role of an undetected abnormality such as minor scalp defect with very thin membrane and for one case false-negative result of Kleihauer test.     

Determinants of intrauterine growth retardation: evidence against maternal depletion

This analysis examines the relationship between length of preceding birth interval and risk of intrauterine growth retardation using data on Swedish infants from the 1973 World Health Organization study of perinatal mortality. Results of a multivariate logit analysis demonstrate that the lower than average mean birth weight of infants born after short birth intervals cannot be completely attributed to their shorter mean gestation length. Infants born after birth intervals of 12 months or less are 30% more likely to be small for gestational age (SGA) than infants born 18-59 months after the previous birth, even when the effects of maternal age and parity are controlled. The results obtained here do not support maternal depletion as an explanation for the association between short birth intervals and elevated risk of SGA, since there is no evidence of an attenuation of the risk of SGA with increasing length of interval in the under 18 month birth interval range.     

Antenatal screening for intrauterine growth retardation with umbilical artery Doppler ultrasonography.

To assess the usefulness of continuous wave Doppler ultrasonography as an antenatal screening tool for the detection of intrauterine growth retardation and fetal compromise 2097 singleton pregnancies were studied. Umbilical artery velocity waveforms were obtained at 28, 34, and 38 weeks of gestation, from which the pulsatility index, A/B ratio, and resistance parameter were calculated. No abnormal features or indices of neonatal outcome were adequately predicted. The most sensitive index for being delivered of a growth retarded infant (less than 5th centile birth weight for gestation) was an A/B ratio at 34 weeks (sensitivity 40%, specificity 84%). Other measures that show poor neonatal nutritional state (ponderal index, skinfold thickness, and ratio of mid-arm circumference to head circumference) were even less well predicted. Acute and chronic hypoxia as determined by Apgar score, pH in blood from the cord artery, and packed cell volume correlated poorly with umbilical artery waveform indices, and there was no obvious difference between the indices of those who subsequently required operative or instrumental delivery for fetal distress and those requiring no intervention. There were three unexplained stillbirths in the series, in each of which the fetus had shown waveform patterns that suggested increased peripheral resistance, though the technique did not appear to be useful for predicting the time of subsequent death. Screening for small for dates babies in a three stage programme was of no value regardless of the threshold or index chosen. Obstetricians should resist the temptation to introduce screening with Doppler ultrasonography until its proper role has been determined.     

Radioimmunological assay of alpha-fetoprotein in maternal serum and intrauterine fetal growth retardation

Maternal plasma alpha-fetoprotein (AFP) was measured in fifteen women during first-mid-third-trimester of pregnancy. In three of these pregnacies by means ultrasound was relevable a condition of intrauterine growth retardation (IUGR). AFP was assayed by a double-antibody radioimmunoassay and values were compared with the median value of the normal range for the particular week of pregnancy. Plasma AFP levels were significantly higher in one subject with IUGR than in other patients.     

Nerve growth factor in human amniotic and cerebrospinal fluid

Nerve growth factor (NGF) is a polypeptide hormone involved in development of the sympathetic and central nervous systems. The detection and measurement of NGF in clinical samples would be useful in evaluating its role in various disease states. In this report, NGF activity and protein levels have been investigated in human amniotic fluid and cerebrospinal fluid samples. In amniotic fluid, NGF activity was found at levels ranging from less than 10 pM to nanomolar. The activity in all samples was blocked by polyclonal and monoclonal antibodies to mouse NGF. The finding of NGF in clinically obtainable samples raises the possibility of correlating NGF levels with a variety of disorders in which changes in NGF levels or activity have been implicated.     

Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat

Background

Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.

Methods

An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.

Results

Maternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.

Conclusions

These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.     

Generalized microdontia probably associated with intrauterine growth retardation in a medieval skeleton

True generalized microdontia in a subadult skeleton is described. The bones, dating from the Middle Ages, were excavated at Alborg, Denmark. True generalized microdontia is an extremely rare condition characterized by well-formed teeth with crowns smaller than two times the standard deviation from the population means. Both the deciduous and permanent teeth are involved. The dimensions of the few fragmentary bones were compared with those of medieval Danish and Norwegian samples and the measurements of the teeth with a number of medieval and modern samples. The gracile skull was of normal size except for the low symphyseal mandibular height. The clavicle and the scapular fragment were of very small dimensions suggesting an extremely slender figure. No long bones were found. The dentition was characterized by congenital absence of nine teeth (4 M³₃, 3 P²₂, 1 P₁, 1 I²) with retained deciduous teeth and by microdontia. With few exceptions the shape of the teeth was within the normal range of variation. The lengths of the roots were normal. The relationship between partial anodontia and tooth size is discussed. The establishment of the crown-size of deciduous molars during intrauterine life is documented. Possible causes for generalized microdontia is reviewed and it is concluded that in the present case, the evidence indicates an intrauterine growth retardation (IU.G.R.) which was partly outgrown during childhood. The nature of IU.G.R. and its incidence are briefly mentioned.