Abstract:The epigenetic nature of development mandates the observation of the effect of any exogenous substance, especially those with estrogenic activities, during critical phases of development. The submandibular gland (SMG) presents as a great model due to extensive postnatal development, and is known to be regulated and affected by hormones as well as growth factors. Herein, we observed postnatal development following low doses of Biochanin A (BCA) and 17β estradiol (E2) in rats. The pups were randomly divided into four groups: control, BCA, E2, and dimethyl sulfoxide (DMSO), and euthanized at the 6th, 15th, 30th, and 60th postnatal days (PND). SMG morphogenesis was assessed. The nuclear expression of estrogen receptor beta (ERβ) was evaluated immunohistochemically; ERβ expression was up-regulated by BCA and down-regulated by E2. Similarly, caspase three gene expression, assessed by real time polymerase chain reaction was increased in the BCA group but decreased in the E2 group. A significant decrease in epidermal growth factor gene expression was noted at PND 30. The results presented by this study provide evidence that the effect of a postnatal exposure of the SMG to Biochanin A during development could be linked to sex hormone-dependent disorders.