| 2. |
- Roberts, CT, et al.
(författare)
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Circulating insulin-like growth factor (IGF)-I and IGF binding proteins-1 and-3 and placental development in the guinea-pig
- 2002
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Ingår i: Placenta. - 0143-4004 .- 1532-3102. ; 23:10, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- Restricting maternal nutrition before and throughout pregnancy in the guinea-pig restricts foetal growth in part by altering placental structural determinants of substrate transfer function. The insulin-like growth factors ha c been implicated in mediating these changes. To assess the role of IGF-I in placental adaptation to maternal undernutrition, we examined the associations of circulating IGF-I and IGF binding proteins - 1, -3 and -4 in the mother with placental structural development. In both mid- and late pregnancy, maternal food restriction reduced maternal plasma IGF-I by 56 per cent (P<0.0005) and 50 per cent (P<0.0005) respectively, and plasma IGFBP-3 by 47 per cent (P=0.03) and 55 per cent (P=0.002), respectively. Maternal plasma IGFBP-4 was reduced by 45 per cent (P=0.041) in food restricted guinea-pigs in mid-pregnancy but not late in pregnancy, while IGFBP-I was unaltered at both stages. Late in pregnancy, food restriction reduced the ratio of maternal circulating IGF-I to IGFBP-I by 52 per cent (P=0.011) and increased the ratio of IGF-I to IGFBP-3 in maternal plasma by 10 per cent (P=0.011). The relationships between the maternal IGF axis and structural correlates of placental function were assessed using pooled data from both ad libitum fed and food restricted animals. In mid-pregnancy, the volume density of the maternal blood space in the placental labyrinth correlated positively with both maternal plasma IGF-1 and IGFBP-3, while maternal blood space volume correlated negatively with maternal plasma IGF-I and IGFBP-3, while maternal blood spacevolume correlated positively with both maternal plasma negatively with maternal plasma IGFBP-1. In late preg IGF-1 and IGFBP-4, while the surface area of syncytiotrophoblast and weight of trophoblast correlated positively, and mean syncytiotrophoblast thickness negatively, with maternal plasma IGF-I. Late in pregnancy, the volume density and weight of svncytrotrophoblast, the surface density and total surface area of trophoblast and the volume of the maternal blood space each correlated positively, and syncytiotrophoblast)last thickness correlated negatively with maternal plasma IGFBP-3. Concomitantly, placental weight, placental diameter, placental volume, volume density and weight of syncytiotrophoblast, weight of foetal capillaries, syncytiotrophoblast surface density and total syncytiotrophoblast surface area in the placental labyrinth, each correlated positively with the ratio of IGF-I to IGFBP-1 in maternal plasma, while syncytiotrophoblast thickness correlated negatively with this ratio. In late pregnancy therefore, increased trophoblast abundance and placental vascularity, and a reduced barrier to diffusion between maternal and foetal blood, occurs in association with increased abundance of IGF-I and its major carrier, IGFBP-3, and a reduction in that of IGFBP-I in maternal blood in the guinea-pig. This suggests that systemic IGF-I and modulation of its bioavailability by IGFBPs -1 and -3 N within the mother may influence placental growth and differentiation in an endocrine fashion, particularly when nutrition is limited. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 3. |
- Scherer, SW, et al.
(författare)
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Human chromosome 7: DNA sequence and biology
- 2003
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Tidskriftsartikel (refereegranskat)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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