Developmental exposure to endocrine disrupter dichlorodiphenyltrichloroethane alters transcriptional regulation of postnatal morphogenesis of adrenal zona fasciculata

Abstract

The present study is aimed to validate expression of transcriptional factors mediating postnatal development of adrenal zona fasciculata in rats exposed to low doses of endocrine disrupter dichlorodiphenyltrichloroethane prenatally and postnatally. Histological and immunohistochemical examination of the adrenals was performed. Impaired blood circulation, dystrophy and cell death were found in zona fasciculata of pubertal rats after developmental exposure to low doses of dichlorodiphenyltrichloroethane. Reparation of zona fasciculata was associated with increased number of Sonic hedgehog- and Oct4-expressing adrenal cortical cells but not in areas of regeneration. These data suggest that cell death may promote upregulation of factors inducing and maintaining pluripotent state in fasciculata cells for restoration of tissue homeostasis. Termination of growth of the adrenals after puberty was associated with upregulation of antiproliferative factor Hhex and decrease of cell proliferation. Dichlorodiphenyltrichloroethane exposure disrupted transcriptional control of cell proliferation by downregulation of Hhex expression in fasciculata cells. Decrease of proliferation in the exposed rats was mediated by inhibition of Sonic hedgehog and Oct4 expression and suppression of canonical Wnt signaling. The present study elucidated an alternative mechanism of proliferation control activated by endocrine disrupter dichlorodiphenyltrichloroethane through transition of fasciculata cells from pluripotent state and higher proliferative potential to differentiation. Activation of the alternative mechanism of growth control may probably affect maintenance of tissue homeostasis of zona fasciculata in postnatal development.

Keywords

• Dichlorodiphenyltrichloroethane
• Zona fasciculata
• Adrenal gland
• Oct4
• Sonic hedgehog
• Wnt signaling