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.[1]References
- In vivo gene transfer of lefty leads to implantation failure in mice. Tang, M., Taylor, H.S., Tabibzadeh, S. Hum. Reprod. (2005) [Pubmed]
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