PMID- 34685432 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211026 IS - 2075-1729 (Print) IS - 2075-1729 (Electronic) IS - 2075-1729 (Linking) VI - 11 IP - 10 DP - 2021 Oct 9 TI - Histocompatibility Antigen, Class I, G (HLA-G)'s Role during Pregnancy and Parturition: A Systematic Review of the Literature. LID - 10.3390/life11101061 [doi] LID - 1061 AB - INTRODUCTION: Immune homeostasis of the intrauterine cavity is vital for pregnancy maintenance. At term or preterm, fetal and maternal tissue inflammation contributes to the onset of labor. Though multiple immune-modulating molecules are known, human leukocyte antigen (HLA)-G is unique to gestational tissues and contributes to maternal-fetal immune tolerance. Several reports on HLA-G's role exist; however, ambiguity exists regarding its functional contributions during pregnancy and parturition. To fill these knowledge gaps, a systematic review (SR) of the literature was conducted to better understand the expression, localization, function, and regulation of HLA-G during pregnancy and parturition. METHODS: A SR of the literature on HLA-G expression and function reported in reproductive tissues during pregnancy, published between 1976-2020 in English, using three electronic databases (SCOPE, Medline, and ClinicalTrials.gov) was conducted. The selection of studies, data extraction, and quality assessment were performed in duplicate by two independent reviewers. Manuscripts were separated into three categories: (1) expression and localization of HLA-G, (2) regulators of HLA-G, and (3) the mechanistic roles of HAL-G. Data were extracted, analyzed, and summarized. RESULTS: The literature search yielded 2554 citations, 117 of which were selected for full-text evaluation, and 115 were included for the final review based on our inclusion/exclusion criteria. HLA-G expression and function were mostly studied in placental tissue and/or cells and peripheral blood immune cells, while only 13% of the studies reported data on amniotic fluid/cord blood and fetal membranes. Measurements of soluble and membranous HLA-G were determined mostly by RNA-based methods and protein by immunostaining, Western blot, or flow cytometric analyses. HLA-G was reported to regulate inflammation and inhibit immune-cell-mediated cytotoxicity and trophoblast invasion. Clinically, downregulation of HLA-G is reported to be associated with poor placentation in preeclampsia and immune cell infiltration during ascending infection. CONCLUSIONS: This SR identified several reports supporting the hypothesized role of immune regulation in gestational tissues during pregnancy. A lack of rigor and reproducibility in the experimental approaches and models in several reports make it difficult to fully elucidate the mechanisms of action of HLA-G in immune tolerance during pregnancy. FAU - Tantengco, Ourlad Alzeus G AU - Tantengco OAG AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. AD - Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila 1101, Philippines. FAU - Richardson, Lauren AU - Richardson L AUID- ORCID: 0000-0001-8392-2833 AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. FAU - Lee, Alan AU - Lee A AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. FAU - Kammala, Ananthkumar AU - Kammala A AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. FAU - Silva, Mariana de Castro AU - Silva MC AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. AD - Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista, UNESP, Botucatu 18618-687, Sao Paulo, Brazil. FAU - Shahin, Hend AU - Shahin H AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. FAU - Sheller-Miller, Samantha AU - Sheller-Miller S AUID- ORCID: 0000-0002-3991-1747 AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. FAU - Menon, Ramkumar AU - Menon R AUID- ORCID: 0000-0001-9213-6105 AD - Division of Basic and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77551, USA. LA - eng GR - R01 HD100729/National Institute of Child Health and Human Development/ GR - 1UG3TR003283/National Center for Advancing Translational Sciences/ GR - STAR RD84003201/States Environmental Protection Agency/ GR - T32 ES026568/Regulatory Science in Environmental Health and Toxicology Training Grant/ PT - Journal Article PT - Review DEP - 20211009 PL - Switzerland TA - Life (Basel) JT - Life (Basel, Switzerland) JID - 101580444 PMC - PMC8537334 OTO - NOTNLM OT - antigen OT - fetal membranes OT - immune tolerance OT - placenta OT - pregnancy COIS- We state no conflict of interest. EDAT- 2021/10/24 06:00 MHDA- 2021/10/24 06:01 PMCR- 2021/10/09 CRDT- 2021/10/23 01:22 PHST- 2021/07/30 00:00 [received] PHST- 2021/09/18 00:00 [revised] PHST- 2021/10/05 00:00 [accepted] PHST- 2021/10/23 01:22 [entrez] PHST- 2021/10/24 06:00 [pubmed] PHST- 2021/10/24 06:01 [medline] PHST- 2021/10/09 00:00 [pmc-release] AID - life11101061 [pii] AID - life-11-01061 [pii] AID - 10.3390/life11101061 [doi] PST - epublish SO - Life (Basel). 2021 Oct 9;11(10):1061. doi: 10.3390/life11101061.