title: Uterine DCs are crucial for decidua formation during embryo implantation in mice.
abstract: Implantation is a key stage during pregnancy, as the fate of the embryo is often decided upon its first contact with the maternal endometrium. Around this time, DCs accumulate in the uterus; however, their role in pregnancy and, more specifically, implantation, remains unknown. We investigated the function of uterine DCs (uDCs) during implantation using a transgenic mouse model that allows conditional ablation of uDCs in a spatially and temporally regulated manner. Depletion of uDCs resulted in a severe impairment of the implantation process, leading to embryo resorption. Depletion of uDCs also caused embryo resorption in syngeneic and T cell-deficient pregnancies, which argues against a failure to establish immunological tolerance during implantation. Moreover, even in the absence of embryos, experimentally induced deciduae failed to adequately form. Implantation failure was associated with impaired decidual proliferation and differentiation. Dynamic contrast-enhanced MRI revealed perturbed angiogenesis characterized by reduced vascular expansion and attenuated maturation. We suggest therefore that uDCs directly fine-tune decidual angiogenesis by providing two critical factors, sFlt1 and TGF-beta1, that promote coordinated blood vessel maturation. Collectively, uDCs appear to govern uterine receptivity, independent of their predicted role in immunological tolerance, by regulating tissue remodeling and angiogenesis. Importantly, our results may aid in understanding the limited implantation success of embryos transferred following in vitro fertilization.
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Vicki
authors.initials: V
authors.lastname: Plaks
authors.forename: Tal
authors.initials: T
authors.lastname: Birnberg
authors.forename: Tamara
authors.initials: T
authors.lastname: Berkutzki
authors.forename: Shay
authors.initials: S
authors.lastname: Sela
authors.forename: Adi
authors.initials: A
authors.lastname: BenYashar
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Kalchenko
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.forename: Nava
authors.initials: N
authors.lastname: Dekel
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D010064:Embryo Implantation / Q000235:genetics / Q000276:immunology*; D020964:Embryo Loss / Q000235:genetics / Q000276:immunology; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D004717:Endometrium / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D011247:Pregnancy / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000276:immunology
chemical_list: D053773:Transforming Growth Factor beta1; D040281:Vascular Endothelial Growth Factor Receptor-1