High Amounts of Total and Extracellular Vesicle-Derived Soluble HLA-G are Associated with HLA-G 14-bp Deletion Variant in Women with Embryo Implantation Failure

• Published in: American journal of reproductive immunology (1989) Vol. 75; no. 6; pp. 661 - 671
• Main Authors: Nardi, Fabiola da Silva, Slowik, Renata, Michelon, Tatiana, Manvailer, Luis Felipe dos Santos, Wagner, Bettina, Neumann, Jorge, Horn, Peter, Bicalho, Maria da Graça, Rebmann, Vera
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.06.2016; Wiley Subscription Services, Inc
• Subjects: 14-bp ins/del polymorphism; 3' Untranslated Regions - genetics; Adult; extracellular vesicles; Extracellular Vesicles - metabolism; Female; Fertilization in Vitro; Gene Frequency; Genes; Genetic Association Studies; Genotype; HLA-G Antigens - genetics; HLA-G Antigens - metabolism; human leukocyte antigen-G; Humans; implantation failure; Infertility, Female - genetics; Infertility, Female - therapy; Polymorphism; Polymorphism, Genetic; Pregnancy; Sequence Deletion - genetics; soluble HLA-G; Treatment Failure; vesicular sHLA-G; 14-bp ins/del polymorphism; implantation failure; human leukocyte antigen-G; extracellular vesicles; vesicular sHLA-G; soluble HLA-G
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.12507

Problem Human leukocyte antigen‐G (HLA‐G) expression is related to 14‐bp insertion/deletion polymorphism at the 3′UTR of the HLA‐G gene. Soluble forms of HLA‐G are released as free molecules or via extracellular vesicles (EVs). Due to the crucial role of HLA‐G during pregnancy, we analyzed the 14‐bp polymorphism and the two secreted forms in implantation failure women (IF) and in fertile women (FW). Method of study For the genetic analysis, 49 IF and 34 FW were genotyped. For sHLA‐G quantification, serum samples from 35 IF and 23 FW were available. ExoQuick™ kit was used for EVs precipitation. The total soluble HLA‐G (sHLA‐Gtot) and vesicular sHLA‐GEV were quantified by ELISA. The EVs size and concentration were determined by nanoparticle tracking analysis (NTA). Results An increased proportion of IF presented high levels of sHLA‐Gtot (P = 0.02) and vesicular sHLA‐GEV (P = 0.0003) compared to FW. The 14‐bp deletion allele is more frequent in IF (P = 0.0002) and associated with high levels of sHLA‐Gtot and vesicular sHLA‐GEV. Conclusion The high expression of sHLA‐Gtot and sHLA‐GEV, together with the presence of the 14‐bp deletion allele, might be involved in implantation failure.