In vivo dendritic cell depletion reduces breeding efficiency, affecting implantation and early placental development in mice
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.
KeywordsDendritic cells Implantation Natural killer cells Placentation
This work was supported by research grants from the Charité (AF-2007-011) to S.M.B. G.B. and R.C-R. received a scholarship from the German Student Exchange Program (Deutscher Akademischer Austauschdienst). S.M.B is a fellow of the Habilitation program at the Charité, University Medicine Berlin. P.C.A. and S.M.B. are part of the EMBIC Network of Excellence, co-financed by the European Commission throughout the FP6 framework program Life Science, Genomics and Biotechnology for Health.
G.K. performed all the experiments and contributed to manuscript writing; V.S. designed and performed proteomics experiments. P.F., G.B., and P.M. performed histological analysis and animal experiments; R.C-R. and F.R. assisted with the PCR experiments; I.C. and M.M. assisted with MALDI-MS experiments; B.F.K and N.F provided advice, P.C.A. contributed with reagents and S.M.B. supervised the work, designed the experiments and wrote the manuscript.
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