Effects Of Intrauterine Environment Research Articles

Expression discordance of monozygotic twins at birth: Effect of intrauterine environment and a possible mechanism for fetal programming

Within-pair comparison of monozygotic (MZ) twins provides an ideal model for studying factors that regulate epigenetic profile, by controlling for genetic variation. Previous reports have demonstrated epigenetic variability within MZ pairs, but the contribution of early life exposures to this variation remains unclear. As epigenetic marks govern gene expression, we have used gene expression discordance as a proxy measure of epigenetic discordance in MZ twins at birth in two cell types. We found strong evidence of expression discordance at birth in both cell types and some evidence for higher discordance in twin pairs with separate placentas. Genes previously defined as being involved in response to the external environment showed the most variable expression within pairs, independent of cell type, supporting the idea that even slight differences in intrauterine environment can influence expression profile. Focusing on birthweight, previously identified as a predisposing factor for cardiovascular, metabolic and other complex diseases, and using a statistical model that estimated association based on within-pair variation of expression and birthweight, we found some association between birthweight and expression of genes involved in metabolism and cardiovascular function. This study is the first to examine expression discordance in newborn twins. It provides evidence of a link between birthweight and activity of specific cellular pathways and, as evidence points to gene expression profiles being maintained through cell division by epigenetic factors, provides a plausible biological mechanism for the previously described link between low birthweight and increased risk of later complex disease.

The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis

We tested the hypothesis that diabetic glomerulosclerosis would develop more rapidly in animals with fewer glomeruli. We studied the female offspring of Wistar rats that had been fed a low-protein diet (LPD) containing 6% protein or a normal-protein diet (NPD) containing 18% protein during pregnancy. Streptozotocin diabetes was induced at 12 weeks and animals were killed at 40 weeks. Non-diabetic LPD offspring were of lower birthweight than the NPD offspring (5.19+/-0.64 vs 6.45+/-0.67 g, p<0.001) and had fewer glomeruli (27,402+/-3,137 vs 34,203+/-6,471, p<0.05). Glomerular volume correlated inversely with glomerular number (r=-0.64, p=0.035), but total glomerular filtration surface area was reduced in the LPD animals (4,770+/-541 vs 5,779+/-1,302 mm(2), p=0.05). Other renal structural and functional parameters were similar. In LPD and NPD diabetic animals, glomerular volume and basement membrane width were significantly increased compared to their respective controls. Podocyte density was lowest in the LPD diabetic animals (not significant), and the area covered by each podocyte was greater in the LPD diabetic group (2.40+/-0.693 x10(-3) mm(2)) than in the LPD control group (1.68+/-0.374 x10(-3) mm(2), p<0.001) and in the NPD diabetic animals (1.71+/-0.291 x 10(-3) mm(2), p<0.05). There was no difference in any other structural or functional parameter between the LPD and NPD diabetic animals. A decrease in glomerular number was not deleterious to renal structure and function over 40 weeks in this animal model. Further work in models with progressive renal impairment and hypertension is necessary to clarify the impact of glomerular number on the development of renal disease.

The developmental origin of adult diseases: The effect of intrauterine environment on the vascular proteomic profile in later life

We have previously shown that vascular function in adult mice offspring heterozygous for a non-functioning NOS3 allele depends on whether they developed in a normal mother or one lacking a functional NOS3, independent of the offspring's genomic profile. Our objective was to use proteomics to identify and characterize protein expressions responsible for the altered vascular responses seen in later life in our model of vascular programming.

Seoul Twin Family Study: design, sampling, assessments, and future directions.

The Seoul Twin Family Study seeks to investigate genetic and environmental influences on the development of cognitive abilities and other psychological traits among children and adolescents in Seoul, South Korea. In November, 2001 with the assistance of the Seoul Metropolitan Office of Education, we began to solicit all private and public schools in Seoul to obtain names, addresses, and telephone numbers of the twins enrolled in schools in Seoul. The vast majority of the recruited twins were between 6 and 18 years old. The recruited twins and their non-twin siblings and parents will undergo comprehensive assessment of cognitive abilities, interests, daily activities, personality, and familial and non-familial environments. We plan to reassess the twins and their families every two years as the twins progress through major changes that characterize childhood, adolescence, and adulthood. In addition, medical records of the twins during the prenatal period will be examined to determine the effects of intrauterine environment on individual differences in cognitive abilities and other psychological traits. We also plan to undertake molecular genetic studies to identify genes involved in specific cognitive abilities.

Reciprocal Embryo Transfer Between SHR and WKY II. Effect on Cardiovascular Development

In order to study the in vivo effect of putative hypertensinogenic factors on early development of the cardiovascular system, embryos were reciprocally transferred between WKY and SHR to allow embryonic and fetal development of WKY in a hypertensive intrauterine environment and SHR in a non-hypertensive uterine environment. In one day-old neonates blood vessel dimensions and blood pressures were assessed. Pressures were also measured in animals which matured to the adult stage to determine whether there were any long-term effects on pressure of having developed in an in utero environment different from the one they would have naturally experienced. The data indicate that there are no consistent effects of intrauterine environment on vascular development, as indicated by the fact that normalized wall/lumen ratios were not different between normal and transferred animals, and immediate and long-term pressures were also similar in normal and transferred groups.