Down-regulation of HLA-G gene expression as an immunogenetic contraceptive therapy

HLA-G is a nonclassical HLA immunotolerogenic molecule expressed in different human cell types. Successful embryo implantation is a consequence of information exchange between the uterus and the blastocyst. It is widely accepted that HLA-G expression by the fetus promotes the establishment of several mechanisms that, ultimately, would protect the developing embryo from maternal immune rejection and seems to be essential to both an adequate implantation and a healthy pregnancy. MicroRNAs miR-148a and miR-152 down-regulate HLA-G expression. The levels of both microRNAs in the placenta are very low. Although various contraceptive methods are available in the market, several of the most popular are based on hormone administration, an approach that have been causing concerns regarding their adverse effects. This scenario has led the research and development of new contraceptive methods meant to induce low disturbances in women body. Based on this context, we hypothesize that the delivery of miR-148a and miR-152 microRNAs, carried by liposomes, into the uterus, would locally induce a down-regulation of the immunotolerogenic HLA-G molecule. In this sense, a local concentration increase of both miR-148a and miR-152 would counteract HLA-G expression and therefore prevent pregnancy development, being a potential tool for the development of a new contraceptive therapy. (C) 2017 Elsevier Ltd. All rights reserved.