Presence of HHV6A in endometrial epithelial cells from women with primary unexplained infertility

摘要

To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women,\uda prospective randomized study was conducted on a cohort of primary unexplained infertile\udwomen and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA\udwas analyzed and the percentage and immune-phenotype of resident endometrial Natural\udKiller (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial\udbiopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA\udwas found in 43% of endometrial biopsies from primary unexplained infertile women, but not\udin control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but\udpresent in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in\udinfertile women with HHV6-A infection compared with infertile women without HHV6-A infection.\udNotably, we observed a lower percentage of endometrial specific CD56brightCD16-\udNK cells. We observed an enhanced HHV-6A-specific endometrial NK cell response in\udHHV-6A positive infertile women, with a marked increase in the number of endometrial NK\udcells activating towards HHV-6A infected cells. The analysis of uterine flushing samples\udshowed an increase in IL-10 levels and a decrease of IFN-gamma concentrations in infertile\udwomen with HHV6-A infection. Our study indicates, for the first time, that HHV-6A infection\udmight be an important factor in female unexplained infertility development, with a possible\udrole in modifying endometrial NK cells immune profile and ability to sustain a successful\udpregnancy.