On this basis, we hypothesized that RSA patients might present de

On this basis, we hypothesized that RSA patients might present deficiencies in the VIP/VPAC system among other factors required for a suitable Metformin supplier homeostasis control at the interface. Certainly, the reduction of VPAC1 and VIP expression in maternal PBMCs after trophoblast interaction observed only in RSA patients might underlie failures in VIP-activated pathways. In this sense, RSA patients displayed a significantly lower frequency of CD4+VIP+ endometrial cells in comparison with fertile women, suggesting

a negative precondition of endometrium before embryo implantation. To our knowledge, this is the first report showing that deficiencies in VIP production could be associated with recurrent pregnancy loss. In line with this, in NOD mice, which show pregnancy complications and an increased rate of embryo resorption at the prediabetic stage, the local expression of VIP mRNA was diminished at viable implantation sites compared with control mice [20]. Given the action of VIP in the development of Treg and the efficacy of these cells

to control inflammatory processes, this peptide could arise as a promising candidate as a diagnostic or surrogate biomarker in current treatment of early pregnancy losses as recurrent spontaneous abortions. Research in the past few years has provided a clearer understanding of the molecular mechanisms leading to immune tolerance and homeostasis, but the definitive cellular and molecular interactions underlying the embryo–uterine cross-talk remain to be resolved. Although further BMN 673 order Selleck Venetoclax studies are required to assess the clinical, diagnostic and therapeutic applications of VIP in the human maternal–fetal interface, these observations might contribute to the design of novel therapeutic

strategies to prevent fetal rejection. This study was supported by grants to R.R. (CONICET PIP 2659, UBACyT 2010–2012) and C.P.L. (UBACyT 2011–2014 and PICT 2011-0144 from ANPCyT). We thank Dr Gil Mor, who kindly gave us the Swan 71 cell line. We also thank Dr E. Lombardi and PROEGRE (Research Program from the Argentinean Society of Gynecological and Endocrinological Reproduction) for continuous support. The authors have no financial conflict of interest. “
“Citation Rodríguez-Martínez H, Kvist U, Ernerudh J, Sanz L, Calvete JJ. Seminal Plasma Proteins: What Role Do They Play? Am J Reprod Immunol 2011; 66 (Suppl. 1): 11–22 Problem  Semen is a heterogenous and complex cell suspension in a protein-rich fluid with different functions, some of them well known, others still obscure. Method of study  This paper reviews, comparatively, our current knowledge on the growing field of proteomics of the SP and its relevance in relation to the in vivo situation, for the sake of reproductive biology, diagnostics and treatment.

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