biostudies-literatureBrown RMNational Institutes of Health, Eunice Kennedy ShriverNICHD NIH HHSNational Institutes of HealthNational Institute of Child Health and Human DevelopmentNIH HHS1000-1010https://www.ebi.ac.uk/biostudies/studies/S-EPMC9113487biostudies-literatureUnknown106(5)Appropriate embryo-uterine interactions are essential for implantation. Besides oocyte abnormalities, implantation failure is a major contributor to early pregnancy loss. Previously, we demonstrated that two members of the Iroquois homeobox transcription factor family, IRX3 and IRX5, exhibited distinct and dynamic expression profiles in the developing ovary to promote oocyte and follicle survival. Elimination of each gene independently caused subfertility, but with different breeding pattern outcomes. Irx3 KO (Irx3LacZ/LacZ) females produced fewer pups throughout their reproductive lifespan which could only be partially explained by poor oocyte quality. Thus, we hypothesized that IRX3 is also expressed in the uterus where it acts to support pregnancy. To test this hypothesis, we harvested Biology of reproductionIrx3 promotes gap junction communication between uterine stromal cells to regulate vascularization during embryo implantation†.PMC9113487R01 HD090066R01HD090066R01HD075079T32HD41921Fu AKannan AJorgensen JSMussar MBrown RMBagchi ICWang LfalseIrx3 promotes gap junction communication between uterine stromal cells to regulate vascularization during embryo implantation†.Appropriate embryo-uterine interactions are essential for implantation. Besides oocyte abnormalities, implantation failure is a major contributor to early pregnancy loss. Previously, we demonstrated that two members of the Iroquois homeobox transcription factor family, IRX3 and IRX5, exhibited distinct and dynamic expression profiles in the developing ovary to promote oocyte and follicle survival. Elimination of each gene independently caused subfertility, but with different breeding pattern outcomes. Irx3 KO (Irx3LacZ/LacZ) females produced fewer pups throughout their reproductive lifespan which could only be partially explained by poor oocyte quality. Thus, we hypothesized that IRX3 is also expressed in the uterus where it acts to support pregnancy. To test this hypothesis, we harvested 2022-01-01T00:00:00Z2022 May2025-04-19T13:32:28.545Z2025-04-19T13:32:28.545ZS-EPMC91134873513835810.1093/biolre/ioac015