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Dysregulated Expression of ebaf, a Novel Molecular Defect in the Endometria of Patients with Infertility¹

Department of Pathology (S.T., Y.C.) and Viral Vector Laboratory (J.M.M.), Department of Research, North Shore University Hospital, Biomedical Research Center, Manhasset, New York 11030; and Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina (M.J.M., B.L.), Chapel Hill, North Carolina 27599

Address all correspondence and requests for reprints to: S. Tabibzadeh, M.D., Department of Pathology, North Shore University Hospital, Biomedical Research Center, 350 Community Drive, Manhasset, New York 11030. E-mail: tabibzad{at}nshs.edu

We recently described the expression of ebaf, a novel member of the transforming growth factor-ß superfamily in human endometrium. ebaf messenger ribonucleic acid was expressed in late secretory and menstrual endometria. Here, we show that ebaf is secreted as 42-, 34-, 28-, and 14-kDa proteins into the conditioned medium of transfected cells, endometrial fluid, and serum. The amount of secreted proteins was markedly reduced during the implantation window in the endometria and sera of normal fertile subjects. The expression of ebaf was dysregulated in the endometria of a subset of women with infertility during the receptive phase of the menstrual cycle. Abundant secreted protein was present in the endometria of these women during the implantation window. During the critical period of endometrial receptivity, ebaf protein was more abundant in patients with endometriosis who did not conceive than in patients who became pregnant. These findings show that ebaf is a secreted product and is released into body fluids. Some types of infertility are associated with dysregulated expression of ebaf in human endometrium, suggesting that a molecular defect in uterine receptivity may be identified using such a marker protein.

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