Article ; Online: HLA-G isoforms, HLA-C allotype and their expressions differ between early abortus and placenta in relation to spontaneous abortions.
2024 Volume 149, Page(s) 44–53
Abstract: Introduction: Spontaneous abortion (SAB) affects approximately 10% of clinically recognized pregnancies. Fetal trophobalst invasion and remodeling of maternal spiral arteries is reported to be dependent on crosstalk between HLA-C/HLA-G expressed on ... ...
| Abstract | Introduction: Spontaneous abortion (SAB) affects approximately 10% of clinically recognized pregnancies. Fetal trophobalst invasion and remodeling of maternal spiral arteries is reported to be dependent on crosstalk between HLA-C/HLA-G expressed on extra villous trophoblast (EVTs)and Killer cell Immunoglobin like receptors (KIRs) of decidual NK (dNK). Immune dysfunction in decidua contributes to early miscarriage. Methodology: The study used mother neonate paired cord blood and term placenta samples (n = 46), elective abortus (n = 17,gestational age = 10-12 weeks of pregnancy) and SAB abortus (n = 24, gestational age = 12-15 weeks of pregnancy) for HLA-G, KIR2D and HLA-C. In addition, term placenta was collected from women with history of spontaneous pregnancy loss (n = 24) and women with history of live birth (n = 32). SSP-PCR was used for genotyping, RT-PCR for gene expression, copy number variation (CNVs) and HLA-C allotyping and ELISA for protein expression studies. Results: Membrane bound HLA-G4 isoform proportion was higher 39.28%, p = 0.02) in term placenta. SAB abortus had higher proportion of HLA-G3 (50%),while elective abortus exhibited higher proportion of soluble isoforms (HLA-G5, = 5.9, HLA-G6 = 5.9%, HLA-G7 = 11.8%). Higher inhibitory KIR2DL1 content and copy numbers with lower HLA-C2 in SAB contrasted with higher copy numbers of KIR2DS1(p = 0.001), KIR2DS1 Conclusion: Our data supports lower cognate receptor ligand KIR2DS1+/2DL1+ HLA-C2 together with predominance of HLA-G3 isoform in SAB as confounding factors in spontaneous pregnancy loss. HLA-G isoforms and expression differed between first trimester abortus and term placenta suggesting temporal modulation and marks novelty of the study. |
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| MeSH term(s) | Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Abortion, Spontaneous/genetics ; Abortion, Spontaneous/metabolism ; Decidua/metabolism ; DNA Copy Number Variations ; HLA-C Antigens/genetics ; HLA-G Antigens/genetics ; HLA-G Antigens/metabolism ; Killer Cells, Natural ; Placenta/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Trophoblasts/metabolism |
| Chemical Substances | HLA-C Antigens ; HLA-G Antigens ; Protein Isoforms |
| Language | English |
| Publishing date | 2024-03-11 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 603951-0 |
| ISSN | 1532-3102 ; 0143-4004 |
| ISSN (online) | 1532-3102 |
| ISSN | 0143-4004 |
| DOI | 10.1016/j.placenta.2024.02.009 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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