HLA-G in the human placenta: expression and potential functions

Bouteiller, P. Le

doi:10.1042/bst0280208

Cited by 47 publications

(24 citation statements)

References 10 publications

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“…2G) and not in the trophoblasts within the decidua that had stained positively for both CK-7 and Cdx-2 in serial sections (data not shown). This result agrees well with published work that reports strong expression of the sHLA-G at the fetal-maternal interface (Le Bouteiller et al, 1999), where it has been suggested to contribute to the elimination of potentially harmful maternal cytotoxic allogenic T cells during pregnancy (Le Bouteiller, 2000). This result suggests that the EVTs may stop secreting sHLA-G as they enter the decidua and that HLA-G expression may be restricted to the cellassociated membrane form found on InEVTs and EnEVTs in vivo .…”

Section: Dunk Et Alsupporting

confidence: 83%

A Novel In Vitro Model of Trophoblast-Mediated Decidual Blood Vessel Remodeling

Dunk

Petković

Baczyk

et al. 2003

Laboratory Investigation

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SUMMARY:In vivo the extravillous trophoblasts (EVTs) penetrate the decidua and the first third of the myometrium to remodel the uterine spiral arteries and achieve the high-flow, low-resistance circulation characteristic of the intervillous space of the term placenta. Much of our understanding of these processes comes from histologic analysis of placental bed biopsies, a limited tissue source and one that can provide only a snapshot of a dynamic process. To better characterize these cellular interactions, we have developed an in vitro co-culture system in which first trimester villous explants are cultured at low oxygen tension in contact with 2-mm 2 sections of decidua parietalis from the same patient. Hematoxylin eosin counterstaining of paraffin sections shows that EVT columns form at the tips of the placental villi and adhere and penetrate the decidual surface. The decidual blood vessels in the path of the EVT show morphologic disruption. Immunohistochemical analysis of the co-cultures using both an endothelial specific anti-CD31 and an anti-smooth muscle actin antibody show a disruption of the integrity of the vessel lining together with a complete loss of organized smooth muscle actin surrounding the blood vessels. In contrast control decidua samples in the absence of placental villi exhibit blood vessels with a complete endothelial lining and an organized muscular sheath. Using both an anti-cytokeratin-7 and anti-Cdx-2 antibody specific to trophoblasts, we show that these changes coincide with invasion of the vessels by endovascular trophoblasts and penetration of the decidua by interstitial EVTs. No EVTs were found in the control decidua. Thus we conclude that this in vitro model mimics the physiologic change observed in vivo during trophoblast invasion into maternal decidual tissues, and as such it may provide useful information concerning the interactions between EVTs and decidual cells and vessels during early gestation. (Lab Invest 2003, 83:1821-1828.

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Section: Dunk Et Alsupporting

confidence: 83%

A Novel In Vitro Model of Trophoblast-Mediated Decidual Blood Vessel Remodeling

Dunk

Petković

Baczyk

et al. 2003

Laboratory Investigation

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“…HLA-G may (39) or may not (40) be expressed in the human preimplantation embryo; however, the immediate postimplantation stages of development are not available for evaluation with human pregnancy. The pattern of Mamu-AG expression predominantly in cytotrophoblasts invading the maternal vessels and endometrium strongly resembles the localization of HLA-G in the human placenta at 6-12 weeks of gestation, where HLA-G expression is restricted to cytotrophoblasts that have differentiated along the invasive pathway (5,6,8). Trophoblast invasion into the arterial wall, accompanied by displacement of the endothelial basement membrane and loss of smooth muscle cells (27,41), limits the contractile capacity of endometrial arteries and permits a substantial and constant blood flow to the placenta and fetus.…”

Section: Discussionmentioning

confidence: 99%

Placental expression of the nonclassical MHC class I molecule Mamu-AG at implantation in the rhesus monkey

Slukvin

Lunn

Watkins

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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During human implantation trophoblasts mediate attachment of the embryo to the uterine epithelium and invade and reorganize vessels of the maternal endometrium to initiate blood flow to the intervillous space. Expression of the nonclassical MHC class I molecule HLA-G by invading trophoblasts may play a central role in their protection from recognition by the maternal immune system; however, the ontogeny of trophoblast HLA-G expression during the earliest stages of implantation is difficult to evaluate in human pregnancy. We previously identified a novel nonclassical MHC class I molecule, Mamu-AG, which is expressed in the rhesus monkey placenta and shares many unique characteristics of HLA-G. Immunocytochemical analysis with a Mamu-AG-specific mAb and locus-specific in situ hybridization of rhesus implantation sites 7-12 days after embryo attachment (days 14 -19 of pregnancy) demonstrated that Mamu-AG molecules are expressed predominantly in cytotrophoblasts invading the maternal vessels and endometrium, whereas syncytiotrophoblasts covering trophoblastic lacunae or newly formed chorionic villi remained largely Mamu-AGnegative. By day 36 of pregnancy, Mamu-AG glycoprotein also was expressed in villous syncytiotrophoblasts, and accumulation of Mamu-AG glycoprotein was noted at the border between maternal decidua and fetal trophoblasts. The ontogeny of a nonclassical MHC class I molecule at the implantation site supports the hypothesis that its expression is important for the establishment of maternal-fetal immune tolerance.

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“…shown to be expressed on the surface of invasive extravillous trophoblasts of the human placenta, with potential significance for regulation of the maternal immune response to pregnancy (1)(2)(3)(4)(5)(6). As with other MHC class I molecules, HLA-G is expressed on the cell surface complexed with ␤ 2 -microglobulin and interacts with a variety of receptors on cells of the innate immune system, including NK cells and monocytes (7)(8)(9)(10)(11).…”

Section: T He Nonclassical Mhc Class I Molecule Hla-g Has Beenmentioning

confidence: 99%

“…The membrane was washed twice with TBS and blocked with a 0.2% nonfat dry milk/TBS solution overnight at 4°C. Following blocking, the membrane was washed three times with a 0.1% 4 Abbreviations used in this paper: ISH, in situ hybridization; HA, hemagglutinin. The six nucleotides at the 3Ј terminus (GTAAAG) are derived from intron 4 of Mamu-AG (GenBank accession no.…”

Section: Recombinant Mamu-ag5 Expression and Western Blottingmentioning

confidence: 99%

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Ryan¹,

Grendell²,

Geraghty

et al. 2002

The Journal of Immunology

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The nonclassical MHC class I locus HLA-G is expressed primarily in the placenta, although other sites of expression have been noted in normal and pathological situations. In addition, soluble HLA-G isoforms have been detected in the serum of pregnant and nonpregnant women as well as men. The rhesus monkey placenta expresses a novel nonclassical MHC class I molecule Mamu-AG, which has features remarkably similar to those of HLA-G. We determined that the rhesus placenta expresses Mamu-AG mRNA (Mamu-AG5), retaining intron 4 as previously noted in HLA-G5. Immunostaining experiments with Ab 16G1 against the soluble HLA-G5 intron 4 peptide demonstrated that an immunoreactive protein(s) was present in the syncytiotrophoblasts of the chorionic villi of the rhesus placenta, within villous cytotrophoblasts, and occasionally within cells of the villous stroma. The Mamu-AG5 mRNA was readily detected in rhesus testis (although not in ejaculated sperm). Whereas an Ab against membrane-bound Mamu-AG stained few cells, primarily in the interstitium of the testis, there was consistent immunostaining for Mamu-AG5 in cells within the seminiferous tubules, which was corroborated by localization of Mamu-AG mRNA by in situ hybridization. While primary spermatocytes were negative, Sertoli cells, spermatocytes, and spermatids were consistently positive for 16G1 immunostaining. The specific recognition of the soluble Mamu-AG isoform was confirmed by Western blotting of Mamu-AG5 expressed in heterologous cells. The results demonstrate that a soluble nonclassical MHC class I molecule is expressed in the rhesus monkey placenta and testis, and confirm and extend the unique homology between HLA-G and the rhesus nonclassical molecule Mamu-AG.

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HLA-G in the human placenta: expression and potential functions

Cited by 47 publications

References 10 publications

A Novel In Vitro Model of Trophoblast-Mediated Decidual Blood Vessel Remodeling

A Novel In Vitro Model of Trophoblast-Mediated Decidual Blood Vessel Remodeling

Placental expression of the nonclassical MHC class I molecule Mamu-AG at implantation in the rhesus monkey

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

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