Zhongying Huang

CTLA4Ig gene transfer alleviates abortion in mice by expanding CD4+CD25+ regulatory T cells and inducing indoleamine 2,3-dioxygenase

Successful pregnancy requires a state of immunological tolerance since normally the maternal immune system does not reject the semi-allogeneic conceptus. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a ligand for B7, delivers negative signals to antigen presenting cells (APCs) to compete with CD28 for binding to B7 molecules and down-regulate proinflammatory responses, thus inhibiting T cell activation. Using CBA/J x DBA/2 matings as an abortion-prone model, we observed that adenovirus-mediated CTLA4Ig (Ad-CTLA4Ig) gene transfer improves pregnancy outcome. Ad-CTLA4Ig therapy skewed the ability of serum cytokine production toward a Th2 bias. Flow cytometry revealed that Ad-CTLA4Ig administration expanded peripheral CD4(+)CD25(+) regulatory T cell populations in CBA/J x DBA/2 matings. Furthermore, Ad-CTLA4Ig administration induced indoleamine 2,3-dioxygenase (IDO) and Foxp3 mRNA expression at the materno-fetal interface. Our results demonstrate that adenovirus-mediated CTLA4Ig gene transfer improves pregnancy outcome in a murine model of abortion by expanding the CD4(+)CD25(+) regulatory T cell population and inducing IDO mRNA expression.

ASSOCIATION BETWEEN INTERLEUKIN-10 PROMOTER POLYMORPHISMS AND ENDOMETRIOSIS: A META-ANALYSIS

To investigate the influence of the interleukin-10 gene promoter polymorphisms on the susceptibility of endometriosis, we examined the association by performing a meta-analysis. The PubMed, Embase, HuGE Navigator and CNKI were searched to identify eligible studies. We then conducted a meta-analysis to examine the association between interleukin-10 gene promoter polymorphisms and endometriosis. Eight case-control studies which examined the association between the IL-10 gene promoter polymorphisms and the susceptibility to endometriosis were finally included in the meta-analysis. Meta-analysis of the IL-10 -592 A/C polymorphisms showed a significant increased risk of endometriosis in the overall and Asian population in all genetic models and allele contrast. However, meta-analysis of the IL-10 -1082 A/G and IL-10 -819 T/C polymorphisms showed no association with endometriosis in all genetic models and allele contrast in the overall and Asian population samples. In addition, there was not a significant association between the IL-10 -592 A/C gene promoter polymorphisms with the severity of endometriosis. In conclusion, this meta-analysis suggests that the IL-10 -592 A/C polymorphisms conferred susceptibility to endometriosis. However, no associations were found between the IL-10 -1082 A/G and -819 T/C polymorphisms and susceptibility to endometriosis. Further studies are required to elucidate these associations more clearly.

Recombinant Luteinizing Hormone supplementation in poor responders undergoing IVF: a systematic review and meta-analysis

Abstract The results of several studies about the effectiveness of recombinant luteinizing hormone (rLH) supplementation in poor responder in vitro fertilization (IVF) patients were conflicting. To evaluate the current available data regarding the efficacy of rLH supplementation in poor responders, a meta-analysis was performed. A systemic search was performed without language limitation but restricted to randomized controlled trial (RCT). We mainly explored MEDLINE, EMBASE, CNKI and Cochrane Library for the relevant studies. Three studies were considered eligible for inclusion. The meta-analysis indicated that rLH supplementation did not increase the ongoing pregnancy rate in poor responders (OR 1.30, 95% CI: 0.80, 2.11). Furthermore, there was no significant difference in the number of oocytes retrieved, total dose of rFSH used, total duration of stimulation, number of retrieved metaphase II oocytes and cycle cancellation rate between the study and control groups. In conclusions, the available evidence does not support the addition of rLH in poor responders treated with rFSH and GnRHa for IVF. It was inconclusive. Future research should be based on strict criteria to define poor responders, and large, well-designed RCTs are necessary to definitively answer the important question of whether there was need to use rLH in poor responders undergoing IVF.

Transforming growth factor β1 promotes invasion of human JEG-3 trophoblast cells via TGF-β/Smad3 signaling pathway

Transforming growth factor (TGF)-β1 is involved invasion of human trophoblasts. However, the underlying mechanisms remain unclear. In this study, we performed Transwell assay and found that TGF-β1 promoted the invasion of trophoblast cell line JEG-3. Treatment with TGF-β1 up-regulated the expression of receptor-regulated Smad transcription factors Smad2 and Smad3, and two invasive-associated genes, namely, matrix metallopeptidase (MMP)-9 and MMP-2, in JEG-3 cells. Over-expressing activin receptor-like kinase (ALK) 5, the TGF-β type I receptor (TβRI) enhanced the up-regulation of Smad2, Smad3, MMP-9, and MMP-2 induced by TGF-β1, whereas application of TβRI inhibitor SB431542 diminished the stimulatory effects of TGF-β1 on these genes. Furthermore, transfection of Smad3 and ALK-5 seperately or in combination into JEG-3 cells before TGF-β1 treatment significantly increased the expression of MMP-9 and MMP-2. By contrast, silencing Smad3 and Smad2 by siRNAs significantly decreased the expression of MMP-9 and MMP-2, with Smad3 silence having a more potent inhibitory effect. Inhibiting TβRI with SB431542 or knockdown of Smad3, but not Smad2, abolished the stimulatory effect of TGF-β1 on the invasion of JEG-3 cells. Taken together, the results indicate that TGF-β1 activates the Smads signaling pathway in JEG-3 trophoblast cells and Smad3 play a key role in TGF-β1-induced invasion of JEG-3 and up-regulation of MMP-9 and MMP-2 expression.

Association between the (TAAAA)n SHBG polymorphism and PCOS: a systematic review and meta-analysis.

Abstract Human sex hormone-binding globulin (SHBG) is a specific plasma transport glycoprotein for sex steroid hormones, and serum SHBG levels were decreased in polycystic ovary syndrome (PCOS) patients. To clarify the conflicting data in the literature concerning the association between PCOS and the (TAAAA)n SHBG polymorphism, and influence of the (TAAAA)n SHBG polymorphism on serum SHBG levels of PCOS patients, a systematic review and meta-analysis was performed in this study. Literature search was conducted through PubMed, EMBASE and China National Knowledge Infrastructure. Five studies were included, representing 1595 individuals. No statistically significant associations were found between the (TAAAA)n SHBG allele and genotype with PCOS risk. Moreover, because the influence of the (TAAAA)n SHBG polymorphism on serum SHBG levels of PCOS patients in studies included in our review was investigated in different way to classify the alleles, we were unable to perform a meta-analysis and hence could not draw any conclusions. In conclusion, this study indicates that there is insufficient evidence to demonstrate a conclusive association between the (TAAAA)n SHBG polymorphism with the risk of PCOS, which needs to be further confirmed by further studies.