Identification of novel endometrial targets for contraception.

Successful embryo implantation is a critical step in establishing pregnancy and requires appropriate preparation of the endometrium to provide a transient state of "uterine receptivity." The most essential of the molecular events determining receptivity may therefore provide potential targets for postcoital contraception. Using the mouse as a model, we identified molecules specifically regulated in the endometrium at very early implantation: these were monoclonal nonspecific suppressor factor beta (MNSFbeta), splicing factor SC35, a novel protease of the HtrA family, termed HtrA3, calcium-binding protein (CaBP)-d9k (calbindin d9k) and proprotein convertase 6 (PC6). All of these molecules were also expressed in human endometrium, with the exception of CaBP-d9k, which was represented by the functionally similar CaBP-d28k. Appropriate spatial and temporal expressions of mRNA and protein were demonstrated for all five candidate molecules in mouse and primate (human and rhesus monkey) endometrium during the menstrual cycle and early pregnancy. Functional studies in mice established that blocking production of the CaBPs and PC6 within the endometrium completely prevented implantation and thus provided proof of principle that these molecules are potential contraceptive targets.