Disturbances in the LIF pathway in the endometrium among women with unexplained infertility
Received 17 January 2008; received in revised form 8 April 2008; accepted 8 April 2008. published online 05 August 2008.
Objective
To study the expression of leukemia inhibitory factor (LIF), its receptors LIFR and gp130, and its inhibitor SOCS1 in endometria from fertile women and infertile women with unexplained infertility. Signaling through the LIF pathway is involved in maintenance of a receptive state of human endometrium. Impaired endometrial receptivity may be a cause of female infertility.
Design
Prospective clinical study.
Setting
Hospital-based IVF unit and university-affiliated reproductive research laboratories.
Patient(s)
Twenty-six healthy fertile women and 14 women with unexplained infertility.
Intervention(s)
Endometrial biopsy.
Main Outcome Measure(s)
Pinopode formation, expression of LIF, LIFR, gp130, and SOCS1 protein and mRNA in endometrial biopsies.
Result(s)
The expression of LIFR in the endometrium was negatively correlated to the expression of SOCS1 and positively correlated to the formation of pinopodes. In control fertile women, simultaneous intense apical staining of LIFR and gp130 together with faint SOCS1 staining was observed in epithelial cells, whereas the opposite was seen in most women with unexplained infertility.
Conclusion(s)
Unexplained infertility in some women might be explained by disturbances in the LIF pathway in midsecretory-phase endometrium.
aDepartment of Clinical Science Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
bDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California
cDepartment of Women's and Children's Health, Uppsala University, Uppsala, Sweden
Reprint requests: Lusine Aghajanova, M.D., Ph.D., 513 Parnassus Avenue, HSW 1671, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF, San Francisco, CA 94143-0556 (Fax: 415-502-7866).
L.A. has nothing to disclose. S.A. has nothing to disclose. K.B. has nothing to disclose. O.H. has nothing to disclose. B.-M.L. has nothing to disclose. A.S.-E. has nothing to disclose.
Supported by the Swedish Research Council, the Swedish Society of Medicine, Uppsala University, Karolinska Institutet, the Goljes Foundation, the Åke Wibergs Foundation, and R&D grants from Stockholm County Council and Karolinska Institutet (ALF).