The decidua is a specialized, highly modified endometrium [of pregnancy]. It is essential for hemochorial placentation, that is, one in which maternal blood contacts trophoblast. This relationship requires trophoblast invasion. Decidualization, that is, transformation of secretory endometrium to decidua, is dependent on estrogen and progesterone and factors secreted by the implanting blastocyst. The special relationship that exists between the decidua and the invading trophoblast seemingly defies the laws of transplantation immunology. [The success of this unique semiallograft not only is of great scientific interest but may involve processes that harbor insights leading to more successful transplantation surgery and perhaps even immunological treatment of neoplasia (Billingham, 1986; Lala, 2002).
Decidual Structure
The decidua is classified into three parts based on anatomical location. Decidua directly beneath blastocyst implantation is modified by trophoblast invasion and becomes the decidua basalis. The decidua capsularis overlies the enlarging blastocyst and initially separates the conceptus from the rest of the uterine cavity (Fig. 5-6). This portion is most prominent during the second month of pregnancy and consists of decidual cells covered by a single layer of flattened epithelial cells. Internally, it contacts the avascular, extraembryonic fetal membrane—the chorion laeve. The remainder of the uterus is lined by decidua parietalis. During early pregnancy, there is a space between the decidua capsularis and parietalis because the gestational sac does not fill the entire uterine cavity. By 14 to 16 weeks’ gestation, the expanding sac has enlarged to completely fill the uterine cavity. The resulting apposition of the decidua capsularis and parietalis creates the decidua vera, and the uterine cavity is functionally obliterated.
Three portions of the decidua—the basalis, capsularis, and parietalis—are illustrated.
In early pregnancy, the decidua begins to thicken, eventually attaining a depth of 5 to 10 mm. With magnification, furrows and numerous small openings, representing the mouths of uterine glands, can be detected. Later in pregnancy, the decidua becomes thinner, presumably because of pressure exerted by the expanding uterine contents.
The decidua parietalis and basalis are composed of three layers. There is a surface or compact zone—zona compacta; a middle portion or spongy zone—zona spongiosa—with remnants of glands and numerous small blood vessels; and a basal zone—zona basalis. The zona compacta and spongiosa together form the zona functionalis. The basal zone remains after delivery and gives rise to new endometrium.
In human pregnancy, the decidual reaction is completed only with blastocyst implantation. Predecidual changes, however, commence first during the midluteal phase in endometrial stromal cells adjacent to the spiral arteries and arterioles. Thereafter, they spread in waves throughout the uterine endometrium and then from the implantation site. The endometrial stromal cells enlarge to form polygonal or round decidual cells. The nuclei become round and vesicular, and the cytoplasm becomes clear, slightly basophilic, and surrounded by a translucent membrane. Each mature decidual cell becomes surrounded by a pericellular membrane. Thus, the human decidual cells clearly build walls around themselves and possibly around the fetus. The pericellular matrix surrounding the decidual cells may allow attachment of cytotrophoblasts through cellular adhesion molecules. The cell membrane also may provide decidual cell protection against selected cytotrophoblastic proteases.
As a consequence of implantation, the blood supply to the decidua capsularis is lost as the embryo-fetus grows. Blood supply to the decidua parietalis through spiral arteries persists. These arteries retain a smooth-muscle wall and endothelium and thereby remain responsive to vasoactive agents.
In contrast, the spiral arterial system supplying the decidua basalis directly beneath the implanting blastocyst, and ultimately the intervillous space, is altered remarkably. These spiral arterioles and arteries are invaded by cytotrophoblasts. During this process, the vessel walls in the basalis are destroyed. Only a shell without smooth muscle or endothelial cells remains. Importantly, as a result, these vascular conduits of maternal blood—which become the uteroplacental vessels—are not responsive to vasoactive agents. Conversely, the fetal chorionic vessels, which transport blood between the placenta and the fetus, contain smooth muscle and thus do respond to vasoactive agents.
Early in pregnancy, the zona spongiosa of the decidua consists of large distended glands, often exhibiting marked hyperplasia and separated by minimal stroma. At first, the glands are lined by typical cylindrical uterine epithelium with abundant secretory activity that contributes to blastocyst nourishment. As pregnancy progresses, the epithelium gradually becomes cuboidal or even flattened and later degenerates and sloughs to a greater extent into the gland lumens. With advanced pregnancy, the glandular elements largely disappear. In comparing the decidua parietalis at 16 weeks’ gestation with the early proliferative endometrium of a nonpregnant woman, there is marked hypertrophy but only slight hyperplasia of the endometrial stroma during decidual transformation.
The decidua basalis contributes to formation of the placental basal plate (Fig. 5-7). It differs histologically from the decidua parietalis in two important respects. First, the spongy zone of the decidua basalis consists mainly of arteries and widely dilated veins, and by term, glands have virtually disappeared. Second, the decidua basalis is invaded by many interstitial trophoblast cells and trophoblastic giant cells. Although most abundant in the decidua, the giant cells commonly penetrate the upper myometrium. Their number and invasiveness can be so extensive as to resemble choriocarcinoma.
Section through a junction of chorion, villi, and decidua basalis in early first-trimester pregnancy. (Photograph contributed by Dr. Kurt Benirschke.)
The Nitabuch layer is a zone of fibrinoid degeneration in which invading trophoblasts meet the decidua basalis. If the decidua is defective, as in placenta accreta, the Nitabuch layer is usually absent (Chap. 41, Maternal and Perinatal Outcomes). There is also a more superficial, but inconsistent, deposition of fibrin—Rohr stria—at the bottom of the intervillous space and surrounding the anchoring villi. McCombs and Craig (1964) found that decidual necrosis is a normal phenomenon in the first and probably second trimesters. Thus, necrotic decidua obtained through curettage after spontaneous abortion in the first trimester should not necessarily be interpreted as either a cause or an effect of the pregnancy loss.
Both deciduas contain numerous cell types whose composition varies with gestational stage (Loke, 1995). The primary cellular components are the true decidual cells, which differentiated from the endometrial stromal cells, and numerous maternal bone marrow–derived cells.
Early in pregnancy, a striking abundance of large, granular lymphocytes termed decidual natural killer (NK) cells are present in the decidua. In peripheral blood, there are two subsets of NK cells. Approximately 90 percent are highly cytolytic. Ten percent show less cytolytic ability but increased cytokine secretion. In contrast to peripheral blood, 95 percent of NK cells in decidua secrete cytokines, and about half of these unique cells also express angiogenic factors. These decidua NK cells likely play an important role in trophoblast invasion and vasculogenesis.
In addition to placental development, the decidua potentially provides other functions. The decidua is the source of prolactin that is present in enormous amounts in amnionic fluid (Golander, 1978; Riddick, 1979). Decidual prolactin is not to be confused with placental lactogen (hPL), which is produced only by syncytiotrophoblast. Rather, decidual prolactin is a product of the same gene that encodes for anterior pituitary prolactin. And although the amino-acid sequence of prolactin in both tissues is identical, an alternative promoter is used within the prolactin gene to initiate transcription in decidua (Telgmann, 1998). This may explain the different mechanisms that regulate expression in the decidua versus pituitary (Christian, 2002a,b).
Prolactin preferentially enters amnionic fluid, and little enters maternal blood. Consequently, prolactin levels in amnionic fluid are extraordinarily high and may reach 10,000 ng/mL at 20 to 24 weeks’ gestation (Tyson, 1972). This compares with fetal serum levels of 350 ng/mL and maternal serum levels of 150 to 200 ng/mL. As a result, decidual prolactin is a classic example of paracrine function between maternal and fetal tissues.
The exact physiological roles of decidual prolactin are still unknown. Its action is mediated by the relative expression of two unique prolactin receptors and by the amount of intact or full-length prolactin protein compared with the truncated 16-kDa form (Jabbour, 2001). Receptor expression has been demonstrated in decidua, chorionic cytotrophoblasts, amnionic epithelium, and syncytiotrophoblast (Maaskant, 1996). There are several possible roles for decidual prolactin. First, most or all of this protein hormone enters amnionic fluid. Thus, it may serve in transmembrane solute and water transport and in amnionic fluid volume maintenance. Second, there are prolactin receptors in several bone marrow-derived immune cells, and prolactin may stimulate T cells in an autocrine or paracrine manner (Pellegrini, 1992). This raises the possibility that decidual prolactin may act in regulating immunological functions during pregnancy. Prolactin may play a role in angiogenesis regulation during implantation. Last, decidual prolactin has been shown in the mouse to have a protective function by repressing expression of genes detrimental to pregnancy maintenance (Bao, 2007).
Regulation of decidual prolactin is not clearly defined. Most agents known to inhibit or stimulate pituitary prolactin secretion—including dopamine, dopamine agonists, and thyrotropin-releasing hormone—do not alter decidual prolactin secretion either in vivo or in vitro. Brosens and colleagues (2000) demonstrated that progestins act synergistically with cyclic adenosine monophosphate on endometrial stromal cells in culture to increase prolactin expression. This suggests that the level of progesterone receptor expression may determine the decidualization process, at least as marked by prolactin production. Conversely, various cytokines and growth factors—endothelin-1, IL-1, IL-2, and epidermal growth factor—decrease decidual prolactin secretion (Chao, 1994; Frank, 1995). Studies in decidualized human endometrial cells in culture have led to identification of several transcription factors that regulate decidual prolactin (Jiang, 2011; Lynch, 2009).