Disease relevance of Fetal Growth Retardation

• Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI-1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR) [1].
• The mutant pups exhibited many of the clinical features of Zellweger syndrome patients, including intrauterine growth retardation, severe hypotonia, failure to feed, and neonatal death [2].
• It has been demonstrated that intrauterine growth retardation, defined as birth weight below the 10th percentile, gives rise to a reduction in nephron number [3].
• The five subjects with permanent neonatal diabetes due to glucokinase deficiency identified to date are characterized by intrauterine growth retardation, permanent insulin-requiring diabetes from the first day of life, and hyperglycemia in both parents [4].
• We previously identified a transgenic mouse model that developed pregnancy-associated hypertension (PAH) and intrauterine growth restriction (IUGR) by mating females expressing human angiotensinogen (hANG) with males expressing human renin (hRN) [5].

Psychiatry related information on Fetal Growth Retardation

• To further define the neuroendocrine consequences of intrauterine growth retardation (IUGR), we have used a rat model of maternal protein restriction throughout pregnancy to examine the pattern of corticosterone and GH secretion under basal conditions and in response to psychological stress in male offspring at 4, 9, and 18 months of age [6].
• Hoyeraal-Hreidarsson syndrome (HHS) includes intrauterine growth retardation, microcephaly, mental retardation, cerebellar malformation, and pancytopenia [7].
• Developmental disability, intrauterine growth retardation, renal anomalies, and dysmorphic features have been described in offspring of women who abuse toluene during pregnancy [8].
• Since thyroid hormone effects are mediated through binding to specific nuclear thyroid hormone receptors (TRs), we have defined the pattern of TR isoform expression in the CNS throughout normal human development and have compared TR expression in the CNS of normal fetuses with those affected by IUGR [9].
• In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness [10].

High impact information on Fetal Growth Retardation

• Intrauterine growth retardation, perinatal death, and maternal homocysteine levels [11].
• Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation [12].
• Overexpression of TP in the vasculature under the control of the pre-proendothelin-1 promoter results in a murine model of intrauterine growth retardation (IUGR), which is rescued by timed suppression of Tx synthesis with indomethacin [12].
• Instead, Hs3st1(-/-) mice exhibited genetic background-specific lethality and intrauterine growth retardation, without evidence of a gross coagulopathy [13].
• These observations also suggest, for the first time, the existence of a cross-talk between AT1 or AT2 receptors in trophoblast and that the reduction in placental AT1 receptors in IUGR may, in part, account for poor placental function in this disorder [14].

Chemical compound and disease context of Fetal Growth Retardation

• IUGR animals were glucose-intolerant and insulin-resistant at an early age [15].
• This pattern of maturation in our patients was unaffected by intrauterine growth retardation, postnatal illness, or concurrent xanthine administration [16].
• CONCLUSION: Our findings suggest that mild MTHFR deficiency, low dietary folate, or both in the dams increase the incidence of fetal loss, intrauterine growth retardation, and heart defects [17].
• In the light of evidence for altered NO production in the feto-placental unit in preeclampsia and intrauterine growth restriction (IUGR), we investigated gestational changes in human placental L-arginine transport by systems y(+) and y(+)L in purified microvillous plasma membrane vesicles [18].
• Exaggerated cell death was recorded in PE and IUGR explants exposed to TNFalpha and 3% O2 [19].

Biological context of Fetal Growth Retardation

• AT1 receptor binding was significantly reduced (P < 0. 02) in intraeuterine growth restriction (IUGR) pregnancies [14].
• In conclusion, maternal and placental pathologies in intrauterine growth retardation are associated with various alterations of placental EGFR, pointing out the importance of EGFR ligands in the regulatory pathway of placental and fetal growth [20].
• Possible narrowed assignment of the loci of monosomy 21-associated microcephaly and intrauterine growth retardation to a 1.2-Mb segment at 21q22.2 [21].
• Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life [22].
• These data represent the first evidence for the role of PKB alpha and endothelial nitricoxide synthase in regulating placental development and provide an animal model for intrauterine growth retardation [23].

Anatomical context of Fetal Growth Retardation

• Ribonucleotide protection assays showed no significant change in the expression of Ang-2 mRNA between gestationally matched normal and IUGR placentas; however, immunoblots revealed that Ang-2 protein was significantly decreased in IUGR, suggesting that this may contribute to the abnormal development of the villous vasculature [24].
• When compared to controls, female offspring of our IUGR rat model exhibit higher expression (mRNA) of ANP and the atrial isoform of the myosin light chain, lower levels of Na+,K+-ATPase beta1 protein, increased cardiomyocyte depth and volume, increased sarcomere length, diminished cardiomyocyte contractility and lower aconitase activity [25].
• Fetuses with IUGR therefore may benefit from arginine supplementation [26].
• Elevated maternal serum alpha-fetoprotein with normal amniotic fluid alpha-fetoprotein was found to be associated with an increased incidence of intrauterine growth retardation and nonneural tube congenital anomalies [27].
• The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS) [28].

Gene context of Fetal Growth Retardation

• Intrauterine growth retardation and postnatal acute diabetes result from insulin deficiency in double homozygous null mutants for Ins1 and Ins2 (Duvillié B, et al., Proc. Natl. Acad. Sci. USA 94:5137-5140, 1997) [29].
• During the frequently sampled iv glucose tolerance test, the magnitude of the AIR in short normal subjects was related to the fall in IGFBP-1 levels (P = 0.03); however, no relationship was seen between AIR and fall in IGFBP-1 in IUGR subjects (P = 0.24) [30].
• Maternal serum-soluble vascular endothelial growth factor receptor-1 in early pregnancy ending in preeclampsia or intrauterine growth retardation [31].
• Nonobese subjects of normal height had higher plasma IGF-I (117 +/- 9 microg/liter; P < 0.0001) and IGFBP-3 (2.34 +/- 0.12 mg/liter) values than the IUGR group (P < 0.0005) [30].
• PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36) [32].

Analytical, diagnostic and therapeutic context of Fetal Growth Retardation

• Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample [1].
• To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed [1].
• After stimulation, TUNEL and Annexin V binding of CTs were significantly raised in PE and IUGR as compared with normal pregnancy [33].
• First phase insulin release in the iv glucose tolerance test, adjusted for insulin sensitivity, did not significantly differ between IUGR and control groups (442 +/- 284 vs. 391 +/- 209 pmol/L; P = 0.86) [34].
• In a case-control study that investigated the effect of intrauterine growth retardation (IUGR) on glucose homeostasis, 20-yr-old adults born with IUGR were shown to be hyperinsulinemic in an oral glucose tolerance test, suggestive of insulin resistance [34].

References