Genes associated with embryonic attachment and implantation and the role of progesterone

Implantation in humans is a complex process theft involves embryo appositio n and attachment to the maternal endometrial epithelium, traversing adjacen t cells of the epithelial lining and invasion into the endometrial stroma. These processes involve a variety of molecules that are not unique in thems elves but play unique roles in the process of implantation. Genes important to embryonic attachment include the epidermal growth factor (EGF)family (E GF, heparin-binding EGF-like growth factor and amphiregulin) and the cytoki nes (colony-stimulating factor, leukemia inhibitory factor and interleukin- 1), as well as a variety of cell adhesion Molecules and other glycoproteins . Epithelial factors important in attachment may be regulated by paracrine interactions via the endometrial epithelium and the endometrial stroma, whi ch is a progesterone-responsive tissue. Investigations into genetic knockou t animal models and natural mutations in the mouse have demonstrated that g enes important to the implantation process affect both embryo attachment an d decidualization and include cyclooxygenase-2 and the homeobox gene HOXA-1 0. Calcitonin is believed to play a role in preparing the apical cell pole for contact with the trophoblast. A number of factors contribute to endomet rial regulation by progesterone; some are important in embryo attachment as well as in the invasive phase of implantation. Four specific factors regul ated in the endometrial stroma by progesterone are transforming growth fact or-beta, interleukin-1 and insulin-like growth factor binding protein-1, ti ssue inhibitors of metalloproteinases (TIMPs) (especially TIMP-3) and fibro nectin, all of which have been demonstrated to inhibit trophoblast invasive ness. Current research should provide answers regarding the effects of vari ous levels of progesterone on the implantation process.