In vivo gene transfer of lefty leads to implantation failure in mice.

BACKGROUND Endometrium is a unique tissue that is prepared for implantation of blastocyst during each menstrual cycle. In humans, if implantation does not occur or fails, endometrium is shed. METHODS AND RESULTS We identified ebaf/lefty, as a key cytokine, highly expressed in human endometrium during the non-receptive phase of tissue remodelling. Lefty was increased in the endometria of a number of patients with 'unexplained infertility' during the receptive phase, suggesting dysregulation of lefty as a potential factor contributing to infertility. Here, we showed that induction of a similar state of lefty overexpression in endometrium, by in vivo gene delivery, decreased implantation in pregnant mice. This state of overexpression could be induced by a retroviral vector transducing lefty or by liposome-mediated introduction of a lefty expression vector. Analysis of endometrium showed increased lefty after in vivo gene transfer. CONCLUSION These findings suggest that induction of a state of lefty overexpression in endometrium leads to reduced implantation.