Email this article The role of the HLA-G gene and its expression in the genesis of recurrent miscarriage
- Authors: Bakleycheva M.O.1, Bespalova O.N.1, Ivashchenko T.E.1
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Affiliations:
- The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- Issue: Vol 71, No 1 (2022)
- Pages: 101-108
- Section: Reviews
- URL: https://journals.rcsi.science/jowd/article/view/76384
- DOI: https://doi.org/10.17816/JOWD76384
- ID: 76384
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Abstract
This review summarizes the results of modern foreign and domestic clinical studies that provide information on the importance of the main histocompatibility complex (HLA), in general, and the expression of non-classical HLA-G molecules on trophoblast cells, in particular, in the physiological course of early pregnancy. The HLA-G gene has central functions in the processing and presentation of antigen and inhibits the receptor of NK cells, which leads to a decrease in the immune response at the fetal-maternal interface and provides immune tolerance to the fetus from the maternal body. HLA-G expression is dependent on combinations of transcription factors, miRNAs, and environmental factors. Based on this, more than a hundred studies have been put into clarifying how HLA-G expression influences the development of pregnancy complications, such as recurrent pregnancy losses, in which immunological factors are believed to play a crucial role.
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##article.viewOnOriginalSite##About the authors
Margarita O. Bakleycheva
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: bakleicheva@gmail.com
ORCID iD: 0000-0002-0103-8583
Scopus Author ID: 57203248029
MD, junior research schientist of Department of obstetrics and perinatology
Russian Federation, 3, Mendeleevskaya Line, Saint Petersburg, 199034Olesya N. Bespalova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN-code: 4732-8089
MD, Dr. Sci. (Med.)
Russian Federation, 3, Mendeleevskaya Line, Saint Petersburg, 199034Tatyana E. Ivashchenko
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Author for correspondence.
Email: tivashchenko2011@mail.ru
ORCID iD: 0000-0002-8549-6505
PhD, Dr. Sci. (Biol.), Professor
Russian Federation, 3, Mendeleevskaya Line, Saint Petersburg, 199034References
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Fig. 1. Schematic representation of the fetus, placenta, decidual tissue, and the functional significance of protein molecules of HLA-G expression. The rectangular inset indicates an enlarged view of the maternal-fetal interface showing the localization of trophoblast cell populations. Cytotrophoblast cells are precursors of differentiated trophoblast cell populations; extravillous trophoblast (EVT) cells express HLA-E, HLA-G, and possibly HLA-F on their surface; syncytiotrophoblast cells can express the soluble form of HLA-G protein molecules together with villous trophoblast cells. The arrows on the round inset indicate the interactions of HLA-G with various receptors on the cell surface, namely natural killer (NK) cells of the uterus, CD8+ T cells. ILT — immunoglobulin-like transcript [1]
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Fig. 2. Scheme illustrating the hypothesis of the relationship between a decreased HLA-G gene expression and dysfunction of decidual natural killer (NK) dysfunction in recurrent miscarriage (recurrent fetal loss). Lower KIR2DL4 expression in decidual NK cells in patients with recurrent miscarriage may suppress the proinvasion and secretion of pro-angiogenic cytokines in these cells. Additionally, reduced HLA-G gene expression by miRNA-133a in the trophoblast cell line, HTR-8/SVneo, may affect the secretion capacity of decidual NK cells when bound to KIR2DL4. Decreased levels of cytokines may affect trophoblast invasion and angiogenesis. EVT — extravillous trophoblast cells; VEGF — vascular endothelial growth factor [23]
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Fig. 3. The similarity of different populations for the G*0101–0107 alleles of the HLA-G gene. Clustering by Ward’s method using the Euclid distance measure [25]
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