Impact of intrauterine fetal programming by low protein diet on rat prostate morphogenesis and stem cells

• Grant number: 13/09649-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2013
• Effective date (End): August 31, 2016
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Jaqueline de Carvalho Rinaldi
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 14/10965-6 - Estrogen receptors in adult prostate Stem-Progenitor cells, BE.EP.PD

Abstract

Intrauterine fetal programming by low protein diet (IFP) impairs growth and maturation of rat prostate. Moreover, this kind of fetal programming increases the incidence of proliferative lesions in adult rat prostates, mainly lesions containing stem cells markers. Recent studies emphasize the role of stem cells in the initiation and progression of prostate cancer. Thus, the aim of this project is to investigate the impact of fetal programming by low protein diet on genes involved in prostatic morphogenesis and on prosatic stem cells proliferation/diferenciation. In this sense, the male offspring that born from rats fed a standard diet (group NP) or low protein diet (RP group) will be sacrificed at 3, 5, 10, 21 and 35 days of age. The ventral prostatic lobes (VP) will be dissected; the epithelial bud and the stem cells niche will be analysed throught free-floating imunofluorescence. The gene expression involved in prostatic morphogenesis and stem cells proliferation e/or differentiation (Sca-1, ABCG2, Nanog, CD133, CD117, Nkx3.1, BMP4, BMP7, FGF10, Hoxa13, Wnt2, Wnt5a, IGF-1R e Notch 1) will be investigated by qRT-PCR and western blotting. Moreover, the VP from NP and RP animals at day 10 postnatal will be cultured ex vivo for 11 days under exposure of diferente hormones (testosterone, estradiol and IGF-1) to analyse the stem cell proliferation and ductal morphogenesis. These results may help to elucidate some mechanisms by which IFP affects the prostate stem cells population and morphogenesis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RINALDI, J. C.; SANTOS, S. A. A.; COLOMBELLI, K. T.; BIRCH, L.; PRINS, G. S.; JUSTULIN, JR., L. A.; FELISBINO, S. L. Maternal protein malnutrition: effects on prostate development and adult disease. JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, v. 9, n. 4, p. 361-372, AUG 2018. Web of Science Citations: 0.