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

• Grant number: 13/24230-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2014
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Luis Antonio Justulin Junior
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Jaqueline de Carvalho Rinaldi ; Sérgio Luis Felisbino

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. (AU)

Scientific publications

(4)

(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)

COLOMBELLI, KETLIN T.; SANTOS, SERGIO A. A.; CAMARGO, ANA C. L.; CONSTANTINO, FLAVIA B.; BARQUILHA, CAROLINE N.; RINALDI, JAQUELINE C.; FELISBINO, SERGIO L.; JUSTULIN, LUIS A.. Impairment of microvascular angiogenesis is associated with delay in prostatic development in rat offspring of maternal protein malnutrition. General and Comparative Endocrinology, v. 246, p. 258-269, MAY 15 2017. (13/24230-5)

CAMARGO, ANA C. L.; CONSTANTINO, FLAVIA B.; SANTOS, SERGIO A. A.; COLOMBELLI, KETLIN T.; DAL-PAI-SILVA, MAELI; FELISBINO, SERGIO L.; JUSTULIN, LUIS A.. Influence of postnatal prolactin modulation on the development and maturation of ventral prostate in young rats. REPRODUCTION FERTILITY AND DEVELOPMENT, v. 30, n. 7, p. 969-979, JUN 2018. (13/24230-5)

CONSTANTINO, FLAVIA B.; CAMARGO, ANA C. L.; SANTOS, SERGIO A. A.; COLOMBELLI, KETLIN T.; MARTIN, LAURA F.; SILVA, MARCIA G.; FELISBINO, SERGIO L.; JUSTULIN, LUIS A.. The prostate response to prolactin modulation in adult castrated rats subjected to testosterone replacement. Journal of Molecular Histology, v. 48, n. 5-6, p. 403-415, DEC 2017. (13/24230-5)

SANTOS, SERGIO A. A.; CAMARGO, ANA C.; CONSTANTINO, FLAVIA B.; COLOMBELLI, KETLIN T.; MANI, FERNANDA; RINALDI, JAQUELINE C.; FRANCO, SUELEN; PORTELA, LUIZ M. F.; DURAN, BRUNO O. S.; SCARANO, WELLERSON R.; et al. Maternal Low-Protein Diet Impairs Prostate Growth in Young Rat Offspring and Induces Prostate Carcinogenesis With Aging. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, v. 74, n. 6, p. 751-759, JUN 2019. (14/08531-8, 17/01063-7, 13/24230-5)