الفهرس | Only 14 pages are availabe for public view |
Abstract Aim of the work 1- Test some of the expected key players controlling kidney development during the intrauterine life which might be affected by Maternal Food restriction. 2- Establishing an ex-vivo kidney explant to investigate the mechanistic explanations behind our results, with a potential for rescuing some of the affected key factors which will open the field for gene therapy. Abstract Intrauterine fetal programming is a process in which stressors during a critical point in gestation impact fetal development with life-long consequences. IUGR refers to a clinical and functional condition and denotes fetuses unable to achieve their own growth potential. Undernutrition is among the most common causes of IUGR specially in the developing countries. Also the ex-vivo kidney explant showed a successful establishment of a growing kidneys model and showed a persistent trend in the reduction of nephron number after three days in the culture. Maternal food restriction resulted in up-regulated mRNA expression for WT1, FGF2, and BMP7, whereas Pax2, GDNF, FGF7, BMP4, WNT4, and WNT11 mRNAs were down-regulated. Protein expression was concordant for WT1, GDNF, Pax2, FGF7, BMP4, and WNT4. In our study maternal food restriction resulted in up-regulated mRNA expression for WT1, FGF2, and BMP7, whereas Pax2, GDNF, FGF7, BMP4, WNT4, WNT11and FLK1 mRNAs were down-regulated. Protein expression was concordant for WT1, GDNF, Pax2, FGF7, BMP4, andWNT4 while VEGF and GFRa1 showed significant reduction despite the minimal change on the mRNA. Our study concluded that dysregulation of critical renal genes (transcription and growth factors) at different stages of development is a key mechanism of the nephropenia induced by maternal FR. |