Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of ‘embryo competency’ and IVF outcome

Sher, Geoffrey; Keskintepe, Levent; Nouriani, M.; Roussev, Roumen G.; Batzofin, Joel

doi:10.1016/s1472-6483(10)62113-x

Cited by 120 publications

(85 citation statements)

References 26 publications

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“…No pregnancies were obtained in the patients whose embryos did not secrete HLA-G, but 18 of 75 of the patients whose embryos produced soluble HLA-G became pregnant, suggesting that soluble HLA-G secretion is a prerequisite for successful implantation. In more recent studies, only embryos that had been cultured singly were examined, making the data easier to interpret (7,8). In one study, 72 of 101 (71%) of women under 39 years old who had at least one HLA-G secreting embryo transferred achieved a pregnancy, compared with 13 of 58 (22%) in the soluble HLA-G-negative group (7).…”

Section: Discussionmentioning

confidence: 99%

“…In more recent studies, only embryos that had been cultured singly were examined, making the data easier to interpret (7,8). In one study, 72 of 101 (71%) of women under 39 years old who had at least one HLA-G secreting embryo transferred achieved a pregnancy, compared with 13 of 58 (22%) in the soluble HLA-G-negative group (7). In the other, no pregnancies were obtained in 26 of 66 women whose transferred embryos did not secrete soluble HLA-G, while nine pregnancies occurred in the 40 of 66 women whose embryos did secrete soluble HLA-G (8).…”

Section: Discussionmentioning

confidence: 99%

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Differential Expression of Alternatively Spliced Transcripts of HLA-G in Human Preimplantation Embryos and Inner Cell Masses

Yao

Barlow

Sargent

2005

The Journal of Immunology

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It has been reported that preimplantation human embryos secrete HLA-G, and the levels may be predictive of their ability to implant. However, it is not known which of the membrane-bound (HLA-G 1–4) and soluble (HLA-G 5–6) alternatively spliced forms are present, nor the developmental stage at which they appear. Therefore, we have investigated HLA-G mRNA isoform expression on single embryos at the two-, four-, six-, and eight-cell, morula, and blastocyst stages. The percentage of embryos expressing each HLA-G isoform mRNA increased with developmental stage, but contrary to expectation, HLA-G5 mRNA was not detected in single two- to eight-cell embryos and was only expressed by 20% of morulae and blastocysts. Similarly, soluble HLA-G6 mRNA was not detected until the blastocyst stage and then in only one-third of embryos. In contrast, labeling with MEM G/9 Ab (specific for HLA-G1 and -G5) was observed in 15 of 20 two- to eight-cell embryos and 5 of 5 blastocysts. This disparity between mRNA and protein may be due to HLA-G protein remaining from maternal oocyte stores produced before embryonic genome activation and brings into question the measurement of soluble HLA-G for clinical evaluation of embryo quality. Although HLA-G is expressed in the preimplantation embryo, later it is primarily expressed in the invasive trophoblast of the placenta rather than the fetus. Therefore, we have investigated whether down-regulation of HLA-G first occurs in the inner cell mass (precursor fetal cells) of the blastocyst and, in support of this concept, have shown the absence HLA-G1 and -G5 protein and mRNA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential Expression of Alternatively Spliced Transcripts of HLA-G in Human Preimplantation Embryos and Inner Cell Masses

Yao

Barlow

Sargent

2005

The Journal of Immunology

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“…An increased pregnancy rate of 63-64% and implantation rate of 32% was reported for embryo transfers in which at least one embryo selected for embryo transfer was positive for sHLA-G compared with lower pregnancy rates of 36% decreased implantation rates of 19% in patients receiving only embryos whose culture media was negative for sHLA-G. Expression of sHLA-G was also related to increasing cell stage [40,41]. Figures 4 and 5 show the pregnancy outcomes of 326 embryos from 49 couples undergoing IVF and embryo transfer in whom embryos were selected for transfer based on both embryo culture sHLA-G concentrations and embryo morphology [42].…”

Section: Evaluation Of Hla-g Gene Polymorophismsmentioning

confidence: 98%

HLA-G and its role in implantation (review)

Roussev

Coulam

2007

J Assist Reprod Genet

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Background Human leukocyte antigen G (HLA-G) is thought to play a key role in implantation by modulating cytokine secretion to control trophopblastic cell invasion and to maintain a local immunotolerance. Method of study The literature is reviewed to provide a description of the genetic background, properties of the protein, and the function of HLA-G. Data are presented on potential clinical applications of HLA-G including the use of evaluation of HLA-G gene polymorphisms in the diagnosis of patients experiencing recurrent pregnancy loss and evaluation and testing of soluble HLA-G (sHLA-G) in embryo culture media for the selection of embryos for transfer after in vitro fertilization (IVF). Results The literature supports a central role of HLA-G for successful implantation. Of couples experiencing recurrent pregnancy loss, 32% demonstrated the -1725G HLA-G polymorphism. Our data showed that when embryos were selected for transfer after IVF based on culture media concentrations of sHLA-G≥2 U/ml and good morphologic grade, a 65% pregnancy rate compared with a 0% pregnancy rate in those with <2 U/ml sHLA-G. Conclusions HLA-G is important for successful implantation in human beings. The HLA-G -725 promoter polymorphism is a risk factor for recurrent miscarriage. Measurement of sHLA-G in embryo culture media can help select embryos for transfer after IVF allowing fewer embryos to be transferred in an attempt to lower multiple gestation rates.

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“…The decline in the level of sHLA-G1 in amniotic fluid may stimulate a maternal immune response against the fetus and contribute to the initiation of parturition. In this regard, sHLA-G was detected in eight cell-stage embryo culture supernatants obtained by in vitro fertilization (IVF), and positive embryo implantation occurred only in women with sHLA-G1/ -G5 molecules in embryo culture supernatants [42][43][44].…”

Section: Expression Of Shla-g In Physiological Conditionsmentioning

confidence: 99%

Soluble HLA-G: Are they clinically relevant?

Pistoia¹,

Morandi²,

Wang³

et al. 2007

Seminars in Cancer Biology

162

182

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HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main function in physiological conditions is to abrogate maternal NK cell activity against foetal tissue and to establish immune tolerance at maternal-foetal interface. HLA-G is expressed not only as a membrane bound molecule on the surface of cells, but also as a soluble moiety in body fluids. The major isoforms of HLA-G present in serum are soluble HLA-G1 and HLA-G5 which are generated by shedding or proteolytic cleavage of the membrane bound isoform and by secretion of a soluble isoform, respectively.Here we review the data about soluble HLA-G (sHLA-G) serum levels in different pathological conditions, including immune-mediated disorders, transplantation, and malignancies. In particular, we focus on sHLA-G expression and function in human neuroblastoma, a pediatric tumor, with special emphasis on a novel potential immuno escape mechanism utilized by NB to instruct monocytes to produce and release sHLA-G. Finally, the potential clinical relevance of sHLA-G serum levels is discussed.

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Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of ‘embryo competency’ and IVF outcome

Cited by 120 publications

References 26 publications

Differential Expression of Alternatively Spliced Transcripts of HLA-G in Human Preimplantation Embryos and Inner Cell Masses

Differential Expression of Alternatively Spliced Transcripts of HLA-G in Human Preimplantation Embryos and Inner Cell Masses

HLA-G and its role in implantation (review)

Soluble HLA-G: Are they clinically relevant?

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