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

KREY G; FRANK P; SHAIKLY V; BARRIENTOS G; CORDO RUSSO R; RINGEL F; MOSCHANSKY P; CHERNUKHIN IV; METODIEV M; FERNÁNDEZ N; KLAPP BF; ARCK PC; BLOIS SM

JOURNAL OF MOLECULAR MEDICINE (BERLIN, GERMANY)

Springer International

Año: 2008 vol. 86 p. 999 - 1011

0946-2716

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 beta (PITPbeta), 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.