In the present study, we investigated the ability of human fetal membranes (amnion and choriodecidua) to regulate human maternal uterine cell functions through the secretion of surfactant protein (SP)-A and SP-D at the end of pregnancy. We detected the expression of both SP-A (SP-A1 and SP-A2) and SP-D by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed that human fetal membranes expressed both SP-A and SP-D. By Western blot analysis, we demonstrated that SP-A protein expression was predominant in choriodecidua, whereas the amnion predominantly expressed SP-D. Only the secretion of SP-A was evidenced in the culture supernatants of amnion and choriodecidua explants by immunodot blot and confirmed by Western blot. Exogenous human purified SP-A induced stress fiber formation in cultured human myometrial cells via a pathway involving Rho-kinase. Conditioned medium from choriodecidua and amnion explants mimicked the SP-A effect. Treatment of myometrial cells with SP-A-depleted conditioned medium from choriodecidua or amnion explants failed to change the actin dynamic. These data indicate that SP-A released by human fetal membranes is able to exert a paracrine regulation of F-actin filament organization in myometrial cells. myometrium; pregnancy REGULATION OF LABOR PROCESSES involves cross-talk between maternal and fetal compartments. Thus, the roles of locally produced factors acting on myometrium need further exploration. The fetal membranes are located in the vicinity of the myometrium and are then ideally positioned to regulate signaling pathways between mother and fetus at the time of labor (for review, see (1,10,15,20,22,31,38) and can be detected as early as 26 wk of pregnancy in amniotic fluid. SP-D levels rise only slightly during pregnancy, whereas SP-A levels rise sharply from 32 wk toward term (29,34) and then decline in spontaneous parturition at term (3). Condon et al. (5) have described SP-A as a link between fetal lung development and the timing of labor in the mouse. Their thesis was that SP-A secreted by the fetal lung into amniotic fluid near term activates macrophages in the amniotic fluid, priming their migration to the maternal uterus and ultimately causing a functional "progesterone withdrawal" and labor through a NF-B-driven inflammation response. However, trafficking of fetal macrophages into the myometrium of women with labor at term does not occur (16,18). In addition, the human fetal membranes are thought to be extrapulmonary sources of SP-A and SP-D (29). To date, only the expression of SP-A1 has been found in human fetal membranes (13), and an induction of SP-A expression by cortisol has been reported in cultured chorionic trophoblasts (40).In the present study, we addressed the question of whether SP-A and SP-D originating from the human fetal membranes can directly regulate human maternal uterine cell functions. We previously reported the ability of SP-A to bind and to serve as a signal in human uterine smooth muscle cells (11). We first analy...