MATERNAL IL-11R-ALPHA FUNCTION IS REQUIRED FOR NORMAL DECIDUA AND FETOPLACENTAL DEVELOPMENT IN MICE

In eutherian mammals, implantation and establishment of the chorioalla ntoic placenta are essential for embryo development and survival, As a maternal response to implantation, uterine stromal cells proliferate, differentiate, and generate the decidua, which encapsulates the conce ptus and forms the maternal part of the placenta. Little is known abou t decidual functions and the molecular interactions that regulate its development and maintenance. Here we show that the receptor far the cy tokine interleukin-11 (IL-11R alpha) is required specifically for norm al establishment of the decidua. Females homozygous for a hypomorphic IL-11R alpha allele are fertile and their blastocysts implant and elic it the decidual response. Because of reduced cell proliferation, howev er, only small deciduae form. Mutant deciduae degenerate progressively , and consequently embryo-derived trophoblast cells generate a network of trophoblast giant cells but fail to form a chorioallantoic placent a, indicating that the decidua is essential for normal fetoplacentatio n. IL-11R alpha is expressed in the decidua as well as in numerous oth er tissues and cell types, including the ovary and lymphocytes. The di fferentiation state and proliferative responses of B and T-lymphocytes in mutant females were normal, and wild-type females carrying IL-11R alpha mutant ovaries had normal deciduae, suggesting that the decidual ization defects do not arise secondarily as a consequence of perturbed IL-11R alpha signaling defects in lymphoid organs or in the ovary, Th erefore, IL-11R alpha signaling at the implantation site appears to be required for decidua development.