Lack of Histocompatibility Leukocyte Antigen-G expression in early embryos is not related to germinal defects or impairment of interleukin-10 production by embryos

Abstract

The expression of Histocompatibility Leukocyte Antigen (HLA)-G molecules is a mandatory prerequisite for the development of pregnancy but no hypotheses have yet been advanced regarding the lack of HLA-G modulation expression in a percentage of early embryos obtained by in vitro fertilization (IVF). One possible hypothetical model assumes that the absence of regulation of HLA-G or impaired interleukin (IL)-10 secretion could be related to germinal defects. We investigated the presence of soluble HLA-G antigens in supernatants of single embryo cultures from couples admitted to a second fertilization procedure; these couples showed a complete absence of HLA-G modulation in the first cycle's embryo supernatants (0/31). The results obtained in the second IVF cycle showed embryo supernatants positive for HLA-G (14/40), suggesting that the previous lack of antigen modulation is independent of germinal defects. Furthermore, since it has been reported that oocytes and early embryos can secrete IL-10, an anti-inflammatory cytokine produced by type 2 helper T cells that induces upregulation of HLA-G expression in monocytes and trophoblasts, we investigated the levels of IL-10 and soluble HLA-G in 40 embryo culture supernatants from 21 IVF cycles. No associations were observed between the presence of IL-10 and the production and concentrations of soluble HLA-G, or between IL-10 levels and pregnancy outcome. These results indicate that the lack of HLA-G production in early embryos is not related to germinal defects or to impairment in embryo IL-10 secretion but could be ascribed to possible uncorrected fertilization processes.

Analysis of HLA-G in Maternal Plasma, Follicular Fluid, and Preimplantation Embryos Reveal an Asymmetric Pattern of Expression

“…Criscuoli et al (15) found that patients in whom no sHLA-G was detected in embryo supernatants often had sHLA-G detected in embryo supernatants in a subsequent IVF cycle. sHLA-G expression has not been previously studied in embryos beyond day 3 of development.…”

“…This has been associated with increased cleavage rates and successful implantation of the embryo during in vitro fertilization (IVF) treatment (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In IVF protocols, embryo selection for transfer to the uterus is based on visual assessment of embryo morphology and cleavage rate.…”

The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells

“…Due to the low sHLA-G concentration in embryo cultures (EC), the HLA-G immunodetection method and sample treatment strongly determine the reliability of the sHLA-G measurement in embryo culture supernatants. Technical difficulties have led to very controversial results in the past [100,[104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] but are being resolved. sHLA-G in embryo culture supernatants is mostly measured by sandwich ELISA or ALBIA (addressable laser bead immunoassay) techniques.…”

Genetic association between the HLA-G 14-bp insertion/deletion polymorphism and the recurrent spontaneous abortions in Saudi Arabian women

“…Since its discovery, the crucial role of the nonclassical HLA-G molecule in pregnancy success has been demonstrated (Ellis et al, 1986;Kovats et al, 1990;Carosella et al, 1999Carosella et al, , 2003Rouas-Freiss et al, 2007). Various studies have reported that HLA-G molecules are responsible for maintaining the immune-regulated and tolerogenic environment during pregnancy (Fuzzi et al, 2002;Criscuoli et al, 2005;Noci et al, 2005). Indeed, these molecules are predominately expressed on extravillous cytotrophoblasts at the fetal-maternal interface during pregnancy (Carosella et al, 1999;Bainbridge et al, 2000;Bhalla et al, 2006).…”