title: Differential ontogenetic exposure to obesogenic environment induces hyperproliferative status and nuclear receptors imbalance in the rat prostate at adulthood.
abstract: BACKGROUND
  Experimental data indicate that high-fat diet (HFD) may alter proliferative activity and prostate health. However, the consequences of HFD exposure during different periods of ontogenetic development on prostate histophysiology remain to be elucidated. Herein, we compare the influence of obesogenic environment (OE) due to maternal obesity and HFD at different periods of life on proliferative activity and nuclear receptors frequency in the rat ventral prostate and a possible relationship with metabolic and hormonal alterations.
  
  
  METHODS
  Male Wistar rats (19 weeks old), treated with balanced chow (Control group-C; 3% high-fat, 3.5 Kcal/g), were compared with those exposed to HFD (20% high-fat, 4.9 kcal/g) during gestation (G-maternal obesity), gestation and lactation (GL), from post-weaning to adulthood (WA), from lactation to adulthood (LA) and from gestation to adulthood (GA). After the experimental period, the ventral prostate lobes were removed and analyzed with different methods.
  
  
  RESULTS
  Metabolic data indicated that G and GL rats became insulin resistant and WA, LA, and GA became insulin resistant and obese. There was a strong inverse correlation between serum testosterone (∼133% lower) and leptin levels (∼467% higher) in WA, LA, and GA groups. Estrogen serum levels increased in GA, and insulin levels increased in all groups, especially in WA (64.8×). OE-groups exhibited prostatic hypertrophy, since prostate weight increased ∼40% in G, GL, LA, and GA and 31% in WA. As indicated by immunohistochemistry, all HFD-groups except G exhibited an increase in epithelial cell proliferation (PCNA-positive) and a decrease in frequency of AR- and ERβ-positive epithelial cells; there was also an increment of ERα-positive stromal cells in comparison with control. Cells containing PPARγ increased in both epithelium and stroma of all OE groups and those expressing LXRα decreased, particularly in groups OE-exposed during gestation (G, GL and GA).
  
  
  CONCLUSIONS
  OE leads to prostate hypertrophy regardless of the period of development and, except when restricted to gestation, leads to a hyperproliferative status which was correlated to downregulation of AR and LXRα and upregulation of ERα and PPARγ signaling.
authors: Department of Structural and Functional Biology, Institute of Biology, Campinas State University-UNICAMP, Campinas, São Paulo, Brazil.
authors: Eloísa Zanin
authors: EZ
authors: Pytlowanciv
authors: Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Univ Estadual Paulista-UNESP, São José do Rio Preto, São Paulo, Brazil.
authors: Maria Etelvina
authors: ME
authors: Pinto-Fochi
authors: Department of Structural and Functional Biology, Institute of Biology, Campinas State University-UNICAMP, Campinas, São Paulo, Brazil.
authors: Vanessa
authors: V
authors: Reame
authors: Department of Structural and Functional Biology, Institute of Biology, Campinas State University-UNICAMP, Campinas, São Paulo, Brazil.
authors: Marina Guimarães
authors: MG
authors: Gobbo
authors: Histology Sector, Institute of Biomedical Sciences, Federal University of Uberlândia-UFU, Uberlândia, MG, Brazil.
authors: Daniele Lisboa
authors: DL
authors: Ribeiro
authors: Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Univ Estadual Paulista-UNESP, São José do Rio Preto, São Paulo, Brazil.
authors: Sebastião Roberto
authors: SR
authors: Taboga
authors: Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Univ Estadual Paulista-UNESP, São José do Rio Preto, São Paulo, Brazil.
authors: Rejane Maira
authors: RM
authors: Góes
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D059305:Diet, High-Fat; D015536:Down-Regulation; D004967:Estrogens / Q000097:blood; D005260:Female; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D000071518:Liver X Receptors; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000473:pathology*; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D015854:Up-Regulation
chemical_list: D004967:Estrogens; D020738:Leptin; D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone
keywords: LXRalpha; PPAR gamma; androgen receptor; estrogen receptors; high-fat diet; prostate hypertrophy