Bortolotti Daria, Soffritti Irene, D'Accolti Maria, Gentili Valentina, Di Luca Dario, Rizzo Roberta, Caselli Elisabetta
Section of Microbiology and Medical Genetics, Department of Medical Sciences, University of Ferrara, via Luigi Borsari 46, 44121, Ferrara, Italy.
Reprod Sci. 2020 Mar;27(3):779-786. doi: 10.1007/s43032-019-00102-8. Epub 2020 Jan 1.
We recently reported that human herpesvirus 6 (HHV-6) infection is frequently present in endometrial tissue of women with unexplained infertility, and that virus infection induces a profound remodulation of miRNA expression in human cells of different origin. Since specific miRNA patterns have been associated with specific pregnancy outcomes, we aimed to analyze the impact of HHV-6A infection on miRNAs expression and trophoblast receptivity in human endometrial cells. To this purpose, a human endometrial cell line (HEC-1A) was infected with HHV-6A and analyzed for alterations in the expression of miRNAs and for permissiveness to the attachment of a human choriocarcinoma trophoblast cell line (JEG-3). The results showed that HHV-6A infection of endometrial cells up-modulates miR22 (26-fold), miR15 (19.5-fold), and miR196-5p (12.1 fold), that are correlated with implant failure, and down-modulates miR18 (11.4 fold), miR101-3p (4.6 fold), miR181-5p (4.9 fold), miR92 (3.3 fold), and miR1207-5p (3.9 fold), characterized by a low expression in preeclampsia. Moreover, HHV-6A-infected endometrial cells infected resulted less permissive to the attachment of trophoblast cells. In conclusion, collected data suggest that HHV-6A infection could modify miRNA expression pattern and control of trophoblast cell adhesion of endometrial cells, undermining a correct trophoblast cell attachment on endometrial cells.
我们最近报道，人类疱疹病毒6型（HHV-6）感染在不明原因不孕症女性的子宫内膜组织中经常存在，并且病毒感染会在不同来源的人类细胞中引起miRNA表达的深刻重塑。由于特定的miRNA模式与特定的妊娠结局相关，我们旨在分析HHV-6A感染对人类子宫内膜细胞中miRNA表达和滋养层细胞接受性的影响。为此，用人子宫内膜细胞系（HEC-1A）感染HHV-6A，并分析miRNA表达的变化以及对人绒毛膜癌滋养层细胞系（JEG-3）附着的允许性。结果表明，子宫内膜细胞的HHV-6A感染上调了与植入失败相关的miR22（26倍）、miR15（19.5倍）和miR196-5p（12.1倍），并下调了子痫前期中低表达的miR18（11.4倍）、miR101-3p（4.6倍）、miR181-5p（4.9倍）、miR92（3.3倍）和miR1207-5p（3.9倍）。此外，HHV-6A感染的子宫内膜细胞对滋养层细胞的附着允许性降低。总之，收集的数据表明，HHV-6A感染可能会改变miRNA表达模式并控制子宫内膜细胞的滋养层细胞黏附，破坏滋养层细胞在子宫内膜细胞上的正确附着。
