title: Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility.
abstract: To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune-phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA was found in 43% of endometrial biopsies from primary unexplained infertile women, but not in control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but present in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in infertile women with HHV6-A infection compared with infertile women without HHV6-A infection. Notably, we observed a lower percentage of endometrial specific CD56brightCD16- NK cells. We observed an enhanced HHV-6A-specific endometrial NK cell response in HHV-6A positive infertile women, with a marked increase in the number of endometrial NK cells activating towards HHV-6A infected cells. The analysis of uterine flushing samples showed an increase in IL-10 levels and a decrease of IFN-gamma concentrations in infertile women with HHV6-A infection. Our study indicates, for the first time, that HHV-6A infection might be an important factor in female unexplained infertility development, with a possible role in modifying endometrial NK cells immune profile and ability to sustain a successful pregnancy.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Gynecology and Obstetrics, University of Ferrara, Ferrara, Italy.|School of Medicine, University of Geneve, Geneve, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marci
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gentili
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Bortolotti
authors.affiliation: Human Reproduction Centre-Brunico Hospital, Brunico (BZ), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lo Monte
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caselli
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolzani
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Rotola
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Di Luca
authors.affiliation: Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism; D004717:Endometrium / Q000473:pathology*; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D015654:Herpesvirus 6, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007247:Infertility, Female / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D007694:Killer Cells, Natural / Q000276:immunology; D010641:Phenotype; D011247:Pregnancy; D014599:Uterus / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines