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.


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.


CONCLUSIONS
These findings suggest that induction of a state of lefty overexpression in endometrium leads to reduced implantation.
Tang
Meiyi
M
Department of Obstetrics and Gynecology, Stony Brook University, Stony Brook, NY, USA.
Taylor
Hugh S
HS
Tabibzadeh
Siamak
S
D000818:Animals; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D055458:Left-Right Determination Factors; D008297:Male; D051379:Mice; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000235:genetics*
C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; C526162:Lefty2 protein, mouse; D016212:Transforming Growth Factor beta