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Objective: To investigate glomerular development and expression of insulin and insulin-like growth factor receptors in an experimental model of intrauterine growth restriction (IUGR). Material and Methods: We studied three groups of Sprague-Dawley fetuses: IUGR – restricted by ligation of the right uterine artery; C-IUGR – left horn controls, and EC – external controls (non-manipulated). Body and organs were weighed, and glomerular number and volume were analyzed. Expression of IRβ, IRS-1, IRS-2 and IGF-IRβ was analyzed in liver, intestine and kidneys by immunoblotting. Results: Organ/body weight ratios were similar. In IUGR, glomerular number and volume were increased compared to C-IUGR and EC (p<0.001). In the IUGR liver, increases were found in IGF-IRβ compared to C-IUGR and EC; IRβ compared to EC, and IRS-2 compared to C-IUGR. However, decreases in IRβ were noted in IUGR compared to C-IUGR; IRS-1 compared to C-IUGR and EC, and IRS-2 compared to EC. In IUGR intestine, increases were detected in IRβ, IRS-1 and IGF-IRβ compared to C-IUGR and EC. In IUGR kidneys, increases were observed in IRβ and IGF-IRβ compared to C-IUGR and EC, and IRS-1 compared to EC. Decreased IRS-2 in the intestine and kidney were noticed in IUGR compared to C-IUGR and EC. Conclusion: IUGR fetuses had less glomeruli and alterations in insulin receptors, which may be associated with an increased risk of disease occurrence in adulthood.

PURPOSE: To evaluate the intrauterine growth restriction (IUGR) by the expression of IR-β, IRS-1, IRS-2, IGF-IRβ and Ikappaβ in experimental model of gastroschisis. METHODS: Pregnant rats at 18.5 days of gestation were submitted to surgery to create experimental fetal gastroschisis (term = 22 days) were divided in three groups: gastroschisis (G), control (C) and sham (S). Fetuses were evaluated for body weight (BW), intestinal (IW), liver (LW) and their relations IW/BW and LW/BW. IR-β and IGF-IRβ receptors, IRS-1 and IRS-2 substrates and Ikappaβ protein were analyzed by western blotting. RESULTS: BW was lower in G, the IW and IW / BW were greater than C and S (p<0.05) groups. The liver showed no differences between groups. In fetuses with gastroschisis, compared with control fetuses, the expression of IGF-IRβ (p<0.001) and Ikappaβ (p<0.001) increased in the liver and intestine, as well as IR-β (p<0.001) which decreased in both. In contrast to the intestine, IRS-1 (p<0.001) increased in the liver and IRS-2 decreased (p<0.01). CONCLUSION: The axis of the intestine liver has an important role in inflammation, with consequent changes in the metabolic pathway of glucose can contribute to the IUGR in fetuses with gastroschisis.

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Dedico este trabalho... Ao meu esposo Douglas, pelo amor, incentivo e dedicação em todos os momentos, compartilhando comigo as angústias e ansiedades ao longo de todo caminho. Aos meus pais Norma e Bueno, pelo exemplo de dedicação à família , pelo incentivo e apoio, agradecendo suas lições de vida, seu amor e carinho. Aos meus sogros Anita e Carlos, pelo incentivo e ajuda em tantas cirunstâncias. Aos meus tios Marly e Ramiro, pelo incentivo e carinho. A minha tia Onélia , pelo incentivo e carinho, tornando a jornada menos árdua. À memória de minhas avós Maria e Leonilda, agradecendo seus contínuos estímulos aos meus estudos. vi vii Dedico esta obra aos meus filhos Bruno e Pedro motivos de vida e alegria. viii ix Agradecimentos

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