The effects os exposure to obesogenic environment at different developmental phases on prostate morphophysiology os Wistar rats

Author(s)

Eloísa Zanin Pytlowanciv

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2015-08-28

Examining board members

Rejane Maira Góes; Cristiane da Fonte Ramos; Flavia Karina Delella; Luis Antonio Justulin Junior; Wellerson Rodrigo Scarano

• Advisor: Rejane Maira Góes

Abstract

Experimental data indicate that the high-fat diet (HFD) affects the proliferative activity and prostate health. However, the consequences of maternal obesity and obesogenic environment (OE) by lipids excess in the diet for the prostate remain inconclusive. This study investigated the effects of the exposure to OE at different developmental phases on prostate morphophysiology of Wistar rats at adulthood and the possible correlations with the metabolic status and regulation by sex steroids. Male Wistar rats (19 weeks-old; n=15) were fed with balanced chow (C; 3% fat, 3.5Kcal/g) or HFD (20% fat, 4.9Kcal/g) during gestation (G), gestation and lactation (GL), from post-weaning to adulthood (WA), from lactation to adulthood (LA) and from gestation to adulthood (GA). The OE during pregnancy included previous induction of maternal obesity by feeding with HFD for 15 weeks. OE led to insulin resistance in all groups, overweight in GL, obesity and decrease in circulating testosterone levels in the WA, LA and GA groups and increased estrogen levels in GA. Moreover, there was an increase in triglycerides and decrease in HDL levels in the obese groups. Regardless the developmental phase, the OE leads to ventral prostate hypertrophy which, except for the G group, also presented an increase in epithelial proliferation activity. The increase in cell proliferation in these groups was concurrent with the decrease in immunopositive cells frequency of androgen receptor, estrogen receptor ? and liver X receptor ? and increase in estrogen receptor ? and peroxisome proliferator-activated receptor ?. Therefore, the increase in cell proliferation induced by the OE is independent of the androgen receptor signaling. The OE increases cell death by desquamation, in acinar epithelium of ventral prostate, in the groups exposed during gestation and/or lactation and to a greater degree in the group exposed throughout life. The morphological changes in the prostate that characterize the earliest, intermediate and final stages of this kind of death were established. Loss of epithelial AR plays a key role in this process. OE exposure before weaning, increased atrophic lesions foci on the ventral prostate, and the exposure after weaning, increased hyperplasia and intraepithelial neoplasia foci, as indicated by the lesions multiplicity analysis. The longer the exposure period to OE, more serious were the lesions found in the ventral lobe. The OE did not promote pronounced alterations on the dorsal and lateral prostate histology, as indicated by microscopic and stereological analyses. Nor alters the androgen receptor frequency, showing that these lobes are less susceptible to the OE exposure and androgen fall, as compared with the ventral lobes. In conclusion, the OE exposure at different developmental phases interferes with ventral prostate morphophysiology proportionally with metabolic impairment and androgen decline, leading to a hypertrophic and hyperproliferative state associated with increased pathological lesions and collective loss of cells by desquamation. The exposure to OE during pregnancy/lactation is as harmful to the ventral prostate proliferation rates as the exposure for a lifetime (AU)

• FAPESP's process: 11/03596-6 - Comparative effect of obesity at different development stages on the rat ventral prostate histophysiology: possible relationships with steroid hormones and the 5 alpha-reductase expression
• Grantee: Eloísa Zanin Pytlowanciv
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)