• Institute of Biology and Immunology of Reproduction
      "Acad. Kiril Bratanov"

      • Scientific achievements

        Most important scientific achievements (last 5 years)

        • Sperm specific, membrane-bound antigens expressed in various animal species including humans have been identified and characterized using monoclonal and polyclonal antibodies produced by us: antigen 1F10 has shown receptor characteristics; antigen 4B12 – appeared as an adhesive molecule; antigen 3G4 has role in the piruvate – lactate cellular metabolism and antigen 60 participate in functional steps required for sperm-egg fusion process. The antifertile effect of antibodies coresponding to these antigens showed their relevance to the fertilization process and their possible significance for immunocontraception.
        • An increased expression of Hsp70 and αB-Cry stress proteins detected using immunohistochemical, immunochemical and genetic studies have been demonstrated in testes of adult mice under conditions of heat-induced apoptosis. Hsp70 is synthesized in germ cells at all stages of spermatogenesis cycle while the synthesis of αB-Cry starts in puberty during differentiation of germ cells in the pachytene stage of meiotic prophase. These studies are important for elucidating the role of stress proteins during proliferation, differentiation and apoptosis of germ cells and their possible role in modulating the fertile potential of the germ cells. 
        • It was found that the incidence of auto-antibodies against Zona Pellucida (ZP) and Granuloza luteinized cells (AGA) in sera and follicular fluids of infertile women were negatively related to the IVF outcome. The frequency and the level were higher in infertile compared to fertile women.
        • It was demonstrated that in the preovulatory follicle the gonadotropin induced system of Atrial natriuretic peptide – cyclic Guanosine Monophosphate – Progesterone exists and shares a regulatory role in the mechanisms of apoptosis mediating the expression of anti-apoptotic bcl-2 and inhibiting executory caspase-3 activity as well as the expression of pro-apoptotic p53. The rate of expression of immunoreactive Atrial natriuretic peptide (ANP) in Granulosa luteinized cells (GLCs) corresponded to its concentration in respective follicular fluids and in supernatants of cultured GLCs as evidence that these cells are the main source of ovarian ANP in the preovulatory human follicle
        • It was demonstrated that the level of apoptosis in human Granulosa luteinized cells (GLCs) increases with the age in infertile women and is higher in mural GLCs than in Cumulus cells (CCs). The rate of apoptosis in CCs is directly related to the maturity of oocytes. Apoptosis of mural GLSs and CCs may be the potential marker for the hormonal stimulation and the In vitro fertilization outcome in women undergoing assisted reproduction
        • It was proven that during the implantation and early pregnancy of the pig the trophectoderm and endometrial epithelium express the integrins (a5β1, avβ3, av, β3), ECM proteins (fibronectin, vitronectin, laminin, collagen type IV), and MMPs-2,9 in an implantation-time dependent manner, which gave evidence for the molecular events participating in the structural remodeling and establishment of the epitheliochorial placenta.
        • Original data for the presence of T-cell aggregates into endometrial compartments during implantation, named T-cell clusters (TCC), were obtained. Both phenotype and localization of TCC are implantation-phase dependent. Endometrial total T, cytotoxic T, and helper T cells, measured by flow cytometry, are highest in number at the critical phase of the implantation - the time of the attachment of genetically different tissues - trophectoderm and maternal epithelium.
        • It was proven by RT-PCR that during the implantation endometrial immune cells are potent to produce the immunomodulatory Th3 cytokine TGFβ1, a finding supporting the hypothesis about Th3-mediated bystander suppression during implantation.
        • It could be suggested that i) the marked Т-cell response and presence of TCC, ii) the decrease and specific re-distribution of NK cells far from placenta attachment site and iii) the production of immunomodulatory substances during the superficial implantation in pigs are possible “pieces” of the complex mechanism of the maternal immune tolerance towards to the semialogeneic fetus.
        • It has been proved that Са2+ bound protein Secretagogin plays an important role in the synthesis and secretion of insulin and that dexamethazone as a member of the glucocorticoid family disturbs the insulin secretion through influence on the synthesis, the intracellular distribution and secretion of Secretagogin.
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