From endometrial receptivity to infertility

Implantation of the blastocyst in endometrium requires establishment of a c oordinated molecular dialogue between the embryo and the endometrium. Facto rs instrumental in the preparation of a receptive endometrium ave derived f rom the hypothalamic-pituitary-gonadal axis. These factors modulate the exp ression of genes that drive the endometrium throughout the characteristic m enstrual cycles. During each menstrual cycle, a series of coordinated, arch itectural, morphological, cytochemical, and molecular changes ultimately le ad to the preparation of a receptive endometrium during the putative "recep tive period" or "implantation window." It is during this critical period th at a proper dialogue can be established between an intrusive blastocyst and a receptive endometrium. If,for any reason, this dialogue is not establish ed or is perturbed, the embryo is aborted. The natural fate of the receptiv e endometrium, in the absence of implantation, is development of a second s et of changes that ultimately lead to menstruation. The identity of the mol ecular repertoire that makes endometrium receptive to implantation and/or l ead to menstruation is being revealed and broadly includes cytokines, heat shock factors, adhesion molecules and matrix metalloproteases. We identifie d a novel gene of the transforming growth factor-beta, superfamily of molec ules, the so-called endometrial bleeding-associated factor or ebaf, whose e xpression is confined to the late secretory and menstrual phases. Various f orms of female infertility were associated with dysregulated expression of ebaf during the implantation window. The findings show an occult molecular defect of endometrial receptivity that seems to be due to dysregulated and premature expression of a member of the premenstrual molecular repertoire. The dysregulated expression of ebaf may assist in the identification, progn ostication, and monitoring of treatment of infertile women.