Passive immunization with a mouse monoclonal antibody against progesterone, designated DB3, blocks pregnancy in several species. We have previously reported that DB3 localizes in the mouse uterine epithelium shortly before normal implantation. This phenomenon is pregnancy dependent and specific for the progesterone antibody. In this study we demonstrate that DB3 is present in the lumen of the uterus 36 h after an i.p. injection; this correlates with the time of maximum antibody reaction on the uterine epithelium. Incubation of DB3 with free progesterone, progesterone-hemisuccinate or progesterone-bovine serum albumin before administration prevented its localization on the epithelium, indicating that the localization requires free progesterone-binding sites and thus probably depends upon progesterone binding. In addition, studies in vitro show that DB3 can effectively bind to progesterone carried by high-affinity progesterone-binding protein purified from coypu plasma. We suggest that specific targeting of DB3 may be through progesterone associated with a progesterone-binding molecule on the membrane of the uterine epithelia. This may be an important part of the mechanism of antibody action against implantation.

Summary Of primary importance for the establishment of pregnancy is the maintenance or prolongation of corpus luteal function. In large domestic animals this is achieved by a blastocyst‐derived signal which disarms the uterine luteolytic mechanism some time before there is any structural association between embryonic and maternal tissues. This is not the case in all mammals because, in certain instances, maternal recognition of pregnancy, as defined by luteal response in terms of maintained or prolonged function, may correspond with the onset of nidation and even post date the time of attachment and implantation. Evidence for the importance of blastocyst‐derived signals and their intensity has been examined but the hypothesis requires further testing to elucidate the relationship between stimulus (signal) and response (luteal function). Studies of the mechanisms by which progesterone action can be blocked in early pregnancy currently focus on target cell epithelia in the uterus and the nature of surface antigens associated with the onset of the implantation process. To date, proof is lacking for a uterus‐specific growth factor with unique functions which forms an essential component of histotrophe; but there is substantial evidence that polypeptide growth factors are detectable at significant concentrations in the uterus. The development of specific peptide antagonists should help to reveal the functions of polypeptide mitogens in uterine physiology and their role in the complex cellular signalling and recognition that occurs between embryo and mother in the early stages of gestation (Brigstock et al 1989).