Original Article

Journal of Molecular Medicine

, Volume 86, Issue 9, pp 999-1011

In vivo dendritic cell depletion reduces breeding efficiency, affecting implantation and early placental development in mice

  • Gesa KreyAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
  • , Pierre FrankAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
  • , Valerie ShaiklyAffiliated withDepartment of Biological Sciences, University of Essex
  • , Gabriela BarrientosAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
  • , Rosalia Cordo-RussoAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
  • , Frauke RingelAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
  • , Petra MoschanskyAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
  • , Igor V. ChernukhinAffiliated withDepartment of Biological Sciences, University of Essex
  • , Metodi MetodievAffiliated withDepartment of Biological Sciences, University of Essex
    • , Nelson FernándezAffiliated withDepartment of Biological Sciences, University of Essex
    • , Burghard F. KlappAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
    • , Petra C. ArckAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin
    • , Sandra M. BloisAffiliated withCharité Centrum 12 für Innere Medizin und Dermatologie, Reproductive Immunology Research Group, University Medicine of Berlin Email author 

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Abstract

Implantation of mammalian embryos into their mother’s uterus ensures optimal nourishment and protection throughout development. Complex molecular interactions characterize the implantation process, and an optimal synchronization of the components of this embryo-maternal dialogue is crucial for a successful reproductive outcome. In the present study, we investigated the role of dendritic cells (DC) during implantation process using a transgenic mouse system (DTRtg) that allows transient depletion of CD11c+ cells in vivo through administration of diphtheria toxin. We observed that DC depletion impairs the implantation process, resulting in a reduced breeding efficiency. Furthermore, the maturity of uterine natural killer cells at dendritic cell knockout (DCKO) implantation sites was affected as well; as demonstrated by decreased perforin expression and reduced numbers of periodic-acid-Schiff (PAS)-positive cells. This was accompanied by disarrangements in decidual vascular development. In the present study, we were also able to identify a novel DC-dependent protein, phosphatidylinositol transfer protein β (PITPβ), involved in implantation and trophoblast development using a proteomic approach. Indeed, DCKO mice exhibited substantial anomalies in placental development, including hypocellularity of the spongiotrophoblast and labyrinthine layers and reduced numbers of trophoblast giant cells. Giant cells also down-regulated their expression of two characteristic markers of trophoblast differentiation, placental lactogen 1 and proliferin. In view of these findings, dendritic cells emerge as possible modulators in the orchestration of events leading to the establishment and maintenance of pregnancy.

Keywords

Dendritic cells Implantation Natural killer cells Placentation