Em conjunto, os efeitos biométricos, metabólicos e hormonais da exposição ao ambiente obesogênico (AO) induzido por consumo de dieta hiperlipídica variam de acordo com o período de exposição, promovendo níveis progressivos de comprometimento, já que os animais expostos durante a gestação foram resistentes à insulina, durante a gestação e lactação foram resistentes à insulina e apresentaram sobrepeso, e os expostos pós-desmame foram considerados obesos além de resistentes à insulina.
Na próstata ventral, o AO induz a hipertrofia prostática independente do período de exposição. Essa hipertrofia é resultado em parte do aumento de proliferação epitelial, que acontece por vias independentes de andrógenos. O aumento nos níveis de leptina, insulina e estrógeno combinados com o desequilíbrio nos receptores de estrógeno (ERα e β), receptor X do fígado (LXRα) e o receptor de ativação da proliferação dos peroxissomos (PPARγ) parecem coordenar o aumento da proliferação epitelial e da hipertrofia do órgão. A morte celular por apoptose não variou entre os grupos. Entretanto, o AO induziu a morte celular por descamação, principalmente quando ocorre na vida toda. A morte celular por descamação foi encontrada em todos os grupos experimentais, evidenciando que se trata de um componente importante da fisiologia prostática, que pode ser estimulado em situação de excesso de lipídeos e queda androgênica.
Quanto às alterações histológicas, o AO também promove aumento do tecido estromal em detrimento do lúmen acinar em todos os períodos de exposição e aumento na frequência do epitélio acinar nos grupos expostos pós-nascimento. As alterações no estroma envolvem reorganização estromal, caracterizada por diminuição na frequência relativa da musculatura lisa que envolve os ácinos prostáticos e aumento do conteúdo de fibras colágenas no estroma, independente da fase de exposição. Essas alterações encontradas mesmo na próstata dos animais que foram expostos somente durante a gestação sugerem que o compartimento estromal é afetado antes que o epitelial. Ainda, o aumento da angiogênese encontrado no estroma dos grupos expostos durante a amamentação e/ou a vida adulta pode ser um fator de risco para o desenvolvimento de situações patológicas em idades mais avançadas.
A exposição ao AO antes do desmame aumentou os focos de lesões atróficas no lobo ventral e, em períodos após o desmame, aumentou os focos de hiperplasia, conforme indicado pela análise da multiplicidade de lesões. Quanto maior o período de exposição ao
AO, mais graves as lesões encontradas no lobo ventral, visto que os grupos expostos durante a lactação até a idade adulta apresentaram aumento de neoplasias intraepiteliais (NIP) de baixo e alto grau. Também foi observado aumento na incidência e multiplicidade de NIP de alto grau no grupo exposto somente durante a gestação/lactação, mostrando que o AO nessa fase é tão prejudicial para as para a próstata ventral quanto à exposição por toda a vida.
Os lobos dorsal e lateral são menos responsivos às alterações hormonais induzidas pela exposição ao AO quando comparados ao lobo ventral. A próstata lateral se mostrou mais suscetível à insulina, enquanto que o lobo dorsal é mais suscetível a drásticas alterações nos níveis de testosterona, cuja resposta é, respectivamente, aumento e diminuição dos índices proliferativos.
Conclui-se que o AO em diferentes fases da vida interfere na morfofisiologia da próstata ventral de modo proporcional ao comprometimento metabólico e à queda androgênica, levando a um estado hipertrófico e hiperproliferativo associado ao aumento de lesões patológicas e a perda coletiva de células por descamação.
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