Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs

被引:42
作者
Carter, AM
Kingston, MJ
Han, KK
Mazzuca, DM
Nygard, K
Ca, VU [1 ]
机构
[1] Univ Western Ontario, Child Hlth Res Inst, London, ON N6C 2V5, Canada
[2] Univ So Denmark, Dept Physiol & Pharmacol, DK-5000 Odense, Denmark
[3] Child Hlth Res Inst, Dept Paediat, CIHR Grp Fetal & Neonatal Hlth & Dev, London, ON N6A 4GS, Canada
[4] Child Hlth Res Inst, Dept Obstet & Gynaecol, CIHR Grp Fetal & Neonatal Hlth & Dev, London, ON N6A 4GS, Canada
[5] Child Hlth Res Inst, Dept Biochem, CIHR Grp Fetal & Neonatal Hlth & Dev, London, ON N6A 4GS, Canada
[6] Child Hlth Res Inst, Dept Anat & Cell Biol, CIHR Grp Fetal & Neonatal Hlth & Dev, London, ON N6A 4GS, Canada
关键词
D O I
10.1677/joe.1.05781
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth. We hypothesized that intrauterine growth restriction (IUGR) in guinea pigs is mediated by the altered expression of IGFs and/or IGF binding protein (BP) rnRNAs in tissues and is related to growth of specific tissues. IUGR was induced by unilateral uterine artery ligation on day 30 of gestation, and fetal plasma, amniotic fluid and tissue samples were collected at 55-57 days (term about 68 days) from paired IUGR and control fetuses (n = 6). Western ligand blotting and immunoblotting were used to compare IGFBP levels in plasma and amniotic fluid. Total RNA was extracted from placenta and fetal tissues, and the relative abundance of IGF-II and IGFBP-1-6 mRNA was determined by Northern blotting, using species-specific probes where available. IUGR fetuses had decreased (P<0.01, by Student's t-test) placental weight and body weight with an increase in the brain:liver weight ratio. The principal IGFBPs in fetal plasma migrated at 40-35, 30 and 25 kDa and were identified as IGFBP-3, -2 and -4 respectively. IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels. IGFBPs were detected at low levels in amniotic fluid of control fetuses but at higher levels in IUGR fetuses. In IUGR placentae, there was a small increase in IGFBP-4 mRNA (P<0.05). IGFBP-2 mRNA increased (P<0.001) in liver of IUGR fetuses. IGF-II and IGFBP mRNA expression did not change in fetal muscle. The results are consistent with reduced IGF action, directly or through inhibition by IGFBPs, particularly by circulating and tissue IGFBP-2, as a potential causal factor in decreased growth of the placenta and certain fetal tissues.
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页码:179 / 189
页数:11
相关论文
共 46 条
[1]   RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEIN-6 INHIBITS IGF-II-INDUCED DIFFERENTIATION OF L6A1 MYOBLASTS [J].
BACH, LA ;
HSIEH, S ;
BROWN, AL ;
RECHLER, MM .
ENDOCRINOLOGY, 1994, 135 (05) :2168-2176
[2]   SEQUENCE OF A CDNA-ENCODING GUINEA-PIG IGF-I [J].
BELL, GI ;
STEMPIEN, MM ;
FONG, NM ;
SEINO, S .
NUCLEIC ACIDS RESEARCH, 1990, 18 (14) :4275-4275
[3]  
CARTER AM, 1990, J DEV PHYSIOL, V13, P261
[4]   CURRENT TOPIC - RESTRICTION OF PLACENTAL AND FETAL GROWTH IN THE GUINEA-PIG [J].
CARTER, AM .
PLACENTA, 1993, 14 (02) :125-135
[5]  
CHARD T, 1994, GROWTH REGULAT, V4, P91
[6]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[7]  
Clemmons David R., 1997, Cytokine and Growth Factor Reviews, V8, P45, DOI 10.1016/S1359-6101(96)00053-6
[8]   Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice [J].
Crossey, PA ;
Pillai, CC ;
Miell, JP .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 110 (03) :411-418
[9]   INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II - PEPTIDE, MESSENGER RIBONUCLEIC-ACID AND GENE STRUCTURES, SERUM, AND TISSUE CONCENTRATIONS [J].
DAUGHADAY, WH ;
ROTWEIN, P .
ENDOCRINE REVIEWS, 1989, 10 (01) :68-91
[10]   A GROWTH-DEFICIENCY PHENOTYPE IN HETEROZYGOUS MICE CARRYING AN INSULIN-LIKE GROWTH FACTOR-II GENE DISRUPTED BY TARGETING [J].
DECHIARA, TM ;
EFSTRATIADIS, A ;
ROBERTSON, EJ .
NATURE, 1990, 345 (6270) :78-80