Smad 3 regulates proliferation of the mouse ovarian surface epithelium

Smad 3 is a signaling intermediate for the transforming growth factor beta (TGFbeta) family; however, little is known about the role this protein plays in the regulation of the ovarian surface epithelium (OSE). Using a transgenic mouse model, we found that in the absence of Smad 3 there was a distinct morphological alteration of OSE cells. Wild-type (WT) OSE was flat with thin cells, while Smad 3-deficient (Smad 3 -/-) OSE was thick with plump cuboidal cells. WT OSE had less immunostaining for proliferating cell nuclear antigen (PCNA) and estrogen receptor alpha (ERalpha) than Smad 3 -/- OSE. However, there were no differences in the number of apoptotic cells or Bax and Bcl-2 levels between WT and Smad 3 -/- OSE. Although WT mice had higher levels of serum estradiol than Smad 3 -/- mice, WT and Smad 3 -/- mice had similar levels of progesterone. These data suggest that Smad 3 regulates OSE morphological appearance and proliferation in the absence of high serum estradiol levels or alterations in progesterone levels.