Proposed model of TGF-β action in estrogen production in trophoblast cells. TGF-β binds to its serine/threonine receptor complex (TβRII and ALK5) to activate Smad2. The phosphorylated Smad2 forms a complex with Smad4 and translocate to the nucleus, where the complex could interact with other transcription factors (TF) and co-repressors to inhibit aromatase gene transcription. TGF-β also decreases aromatase mRNA stability, which contributes to a decrease in aromatase mRNA levels. The decrease in aromatase mRNA may lead to a decrease in aromatase activity and thus estrogen biosynthesis in trophoblast cells.