Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation

Mice with a targeted mutation of the Hoxa10 gene demonstrate uterine factor infertility. If is unclear if the defect in the uterine environment arises due to the absence of Hoxa10 expression during embryonic development or in the adult. We have recently demonstrated that HOXA10 expression in human e ndometrium rises dramatically at the time of implantation, suggesting mater nal expression of Hoxa10/HOXA10 may be essential to the process. To assess the importance of maternal Hoxa10 expression, the uteri of day 2 pregnant m ice were injected with a DNA/liposome complex containing constructs designe d to alter maternal Hoxa10 expression before implantation. Transfection wit h a Hoxa10 antisense oligodeoxyribonucleotide significantly decreased the n umber of implantation sites. Transfection with a plasmid which constitutive ly expresses Hoxa10 optimized survival of implanted embryos resulting in in creased titter size. These results demonstrate that maternal Hoxa10 express ion is essential for implantation and is the first report of the maternal a lteration of a gene known to affect implantation specifically. We also demo nstrate that DNA/liposome complexes containing the same Hoxa10 constructs t hat alter fertility in mice, can affect Hoxa10 expression in a human endome trial cell line. Alteration of human endometrial HOXA10 via liposome-mediat ed gene transfection is a potential contraceptive agent or fertility treatm ent.