The expression of nuclear retinoid receptors in human implantation.

Vitamin A and retinoids play an important role during development. They affect morphogenesis, cell growth and differentiation by interacting with two types of receptor, the RARs and the RXRs. Despite the well known established teratogenic effects of retinoids during human pregnancy, little is known about the effect of retinoids on human placental development. We studied the possible involvement of retinoids during the implantation process by investigating the spatial distribution of retinoid receptors in the human implantation site by in situ hybridization and immunohistochemistry. For in situ hybridization, we used digoxigenin-labelled antisense riboprobes. Immunochemical staining was performed with specific antibodies against the various retinoid receptors and a streptavidin-alkaline phosphatase immunostaining kit. We found that only two types of receptors were expressed at the implantation site: RARalpha and RXRalpha. Both types of receptors were present in the proliferative intermediate trophoblast, the invasive extravillous trophoblast and decidual cells. Both receptors were also present in the villous cytotrophoblasts. The presence of this retinoid receptor in the cytotrophoblasts suggests a key role for all-trans retinoic acid and/or 9-cis retinoic acid in the development of human placenta.