The Endocrinology of Uterine Decidualization

Abstract

Although there is a rather broad degree of species variation, initiation of implantation leads to proliferation and differentiation of steroid-primed uterine stromal cells, culminating in the formation of a morphologically and biochemically distinct endocrine tissue, the decidua (1). Decidualization is common among mammals, but the complex cellular processes leading to the formation of the decidua remains poorly understood. In humans, distinct morphological changes can be seen among uterine stromal cells at focal sites during the late secretory stage of the menstrual cycle in the absence of an active implantation process. In rats and mice, the conversion of stromal cells into predecidual cells in response to progesterone exposure alone does not occur, but a pseudodecidual reaction can be induced following mechanical stimulation in a steroid-primed uterus. Establishment of normal pregnancy in these animals requires that the conceptus initiate the uterine decidual response and the full process of decidualization relies on contact with the embryo during the invasive processes of implantation and placentation. Among rodents, primates or humans, steroid priming and the more specific action of progesterone is critical to the process of decidualization. Support for this position comes from studies that demonstrate that mice lacking progesterone receptors cannot elicit a decidual response (2) and the use of antiprogestins such as RU-486, which rapidly terminate human pregnancies (3). The ultimate success of implantation and initiation of a viable pregnancy does not rest on any single factor, but rather it rests on the establishment of complex endocrine and paracrine inter-relationships among the ovary, the conceptus, and the decidua. Failure to establish these early relationships expeditiously during the implantation process leads to a blunted decidual response, and the onset of pregnancy termination.