biostudies-literatureZhao QEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD NIH HHSHHS | National Institutes of Health (NIH)NIAID NIH HHSHHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Institutes of Healthe70291https://www.ebi.ac.uk/biostudies/studies/S-EPMC11706222biostudies-literatureUnknown39(1)At the maternal-fetal interface, tightly regulated levels of retinoic acid (RA), the physiologically active metabolite of vitamin A, are required for embryo implantation and pregnancy success. Herein, we utilize mouse models, primary human cells, and pharmacological tools to demonstrate how depletion of RA signaling via RA receptor (RAR) disrupts implantation and progression of early pregnancy. To inhibit RAR signaling during early pregnancy, BMS493, an inverse pan-RAR agonist that prevents RA-induced differentiation, was administered to pregnant mice during the peri-implantation period. Attenuation of RA/RAR signaling prior to embryo implantation results in implantation failure, whereas attenuation of RA/RAR signaling after embryo implantation disrupts the post-implantation decidual vascuFASEB journal : official publication of the Federation of American Societies for Experimental BiologySignaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization.PMC11706222R01 HD109152R01HD109152T32HD087166R01 AI148695R01AI148695Loia RArora RDouglas NCCheung EKZhao QChemerinski AMassri NZhang XBabwah AVTimmins PWu TSamuels CAfalseSignaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization.At the maternal-fetal interface, tightly regulated levels of retinoic acid (RA), the physiologically active metabolite of vitamin A, are required for embryo implantation and pregnancy success. Herein, we utilize mouse models, primary human cells, and pharmacological tools to demonstrate how depletion of RA signaling via RA receptor (RAR) disrupts implantation and progression of early pregnancy. To inhibit RAR signaling during early pregnancy, BMS493, an inverse pan-RAR agonist that prevents RA-induced differentiation, was administered to pregnant mice during the peri-implantation period. Attenuation of RA/RAR signaling prior to embryo implantation results in implantation failure, whereas attenuation of RA/RAR signaling after embryo implantation disrupts the post-implantation decidual vascu2025-01-01T00:00:00Z2025 Jan2026-06-02T16:13:34.88Z2025-04-07T00:31:42.265ZS-EPMC117062223977780010.1096/fj.202400766R