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Hum. Reprod. Advance Access originally published online on March 24, 2005
Human Reproduction 2005 20(7):1772-1778; doi:10.1093/humrep/deh849
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

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

Meiyi Tang1, Hugh S. Taylor2 and Siamak Tabibzadeh1,3

1 Department of Obstetrics and Gynecology, Stony Brook University, Stony Brook, NY and 2 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA

3 To whom correspondence should be addressed at: Frontiers in Bioscience, PO Box 160, Searingtown, NY 11507, USA. Email: tabibzadeh{at}bioscience.org

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.

Key words: ebaf/endometrium/lefty/mouse/pregnancy


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