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: Vicki Plaks, Tal Birnberg, Tamara Berkutzki, Shay Sela, Adi BenYashar, Vyacheslav Kalchenko, Gil Mor, Eli Keshet, Nava Dekel, Michal Neeman, Steffen Jung
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 118 Issue 12 Pg. 3954-65 (Dec 2008) ISSN: 0021-9738 [Print] United States
• PMID: 19033665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transforming Growth Factor beta1
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Animals
• Cell Differentiation (immunology)
• Cell Proliferation
• Dendritic Cells (cytology, immunology)
• Embryo Implantation (genetics, immunology)
• Embryo Loss (genetics, immunology)
• Embryo, Mammalian (cytology, embryology, immunology)
• Endometrium (blood supply, cytology, immunology)
• Female
• Immune Tolerance (physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Neovascularization, Physiologic (genetics, immunology)
• Pregnancy (genetics, immunology)
• T-Lymphocytes (cytology, immunology)
• Transforming Growth Factor beta1 (genetics, immunology)
• Vascular Endothelial Growth Factor Receptor-1 (genetics, immunology)