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

Abstract

Mice with a targeted mutation of the Hoxa10 gene demonstrate uterine factor infertility. It 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 endometrium rises dramatically at the time of implantation, suggesting maternal expression of Hoxa10/HOXA10 may be essential to the process. To assess the importance of maternal Hoxa10 expression, the uteri of day 2 pregnant mice were injected with a DNA/liposome complex containing constructs designed to alter maternal Hoxa10 expression before implantation. Transfection with a Hoxa10 antisense oligodeoxyribonucleotide significantly decreased the number

Maternal Hoxa10 is required for pinopod formation in the development of mouse uterine receptivity to embryo implantation

“…We have previously shown that this leads to increased Hoxa10 mRNA in the mouse uterus and increased litter size (Bagot et al, 2000); however, we found no uterine histologic changes at the light microscopy level. The uteri of these mice were examined with TEM for evidence of altered pinopod formation.…”

“…We have shown previously that this results in decreased Hoxa10 expression and decreased implantation rates (Bagot et al, 2000). Uteri of the Hoxa10 antisense transfected mice were examined by TEM at 90 hr after vaginal plug detection, the time of implantation.…”

“…Transfection with Hoxa10 antisense also does not result in any identifiable changes in the endometrium at the histologic level (Bagot et al, 2000). We speculated that changes might be observed at the level of subcellular organelles.…”

“…Experiments previously performed demonstrated functional changes in implantation induced by alteration of Hoxa10 expression (Bagot et al, 2000). Despite the functional significance of altered Hoxa10, in early maternal-fetal interaction, no changes were seen in the endometrial histology.…”

“…In the background of normal embryonic Hoxa10 expression and, therefore, normal uterine development, Hoxa10 expression was altered in the adult uterus (Bagot et al, 2000). Hoxa10 antisense treatment reduces maternal Hoxa10 expression and reduces litter size, demonstrating that maternal Hoxa10 is necessary for endometrial receptivity to blastocyst implantation.…”