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. 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 Hoxa 10 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 of implantation sites. Transfection with a plasmid which constitutively expresses Hoxa10 optimized survival of implanted embryos resulting in increased litter size. These results demonstrate that maternal Hoxa10 expression is essential for implantation and is the first report of the maternal alteration of a gene known to affect implantation specifically. We also demonstrate that DNA/liposome complexes containing the same Hoxa10 constructs that alter fertility in mice, can affect Hoxa10 expression in a human endometrial cell line. Alteration of human endometrial HOXA10 via liposome-mediated gene transfection is a potential contraceptive agent or fertility treatment.
Bagot
C N
CN
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA.
Troy
P J
PJ
Taylor
H S
HS
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005801:Genes, Homeobox; D015316:Genetic Therapy / Q000379:methods*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D006801:Humans; D007247:Infertility, Female / Q000628:therapy*; D008081:Liposomes; D008098:Litter Size; D051379:Mice; D008815:Mice, Inbred Strains; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D011247:Pregnancy; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; C092119:Hoxa10 protein, mouse; D004247:DNA