@article {10466, title = {Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility.}, journal = {J Cell Physiol}, volume = {232}, year = {2017}, month = {2017 Jul}, pages = {1681-1688}, abstract = {

Biomarkers have a wide application in research and clinic, they help to choose the correct treatment for diseases. Recent studies, addressing the vaginal microbiome using next generation sequencing (NGS), reported the involvement of bacterial species in infertility. We compared the vaginal microbiome of idiopathic infertile women with that of healthy, including bacterial vaginosis affected women and non-idiopathic infertile women, to identify bacterial species suitable as biomarkers. Information on microorganisms was obtained from the V3-16S rDNA sequencing of cervical-vaginal fluids of 96 women using the Ion Torrent platform. Data were processed with QIIME and classified against the Vaginal 16S rDNA Reference Database. The analysis revealed a significant beta-diversity variation (p < 0.001) between the four groups included in the study. L. iners, L. crispatus, and L. gasseri distinguished idiopathic infertile women from the other groups. In these women, a microbial profile similar to that observed in bacterial vaginosis women has been detected. Our results suggest that the quantitative assessment and identification of specific microorganisms of the cervical-vaginal microflora could increase the accuracy of available tools for the diagnosis of infertility and improve the adoption of therapeutic protocols.

}, keywords = {Adult, Biodiversity, Cervix Uteri, Cohort Studies, Demography, Female, Humans, Infertility, Female, Microbiota, Species Specificity, Vagina, Vaginosis, Bacterial}, issn = {1097-4652}, doi = {10.1002/jcp.25806}, author = {Campisciano, Giuseppina and Florian, Fiorella and D{\textquoteright}Eustacchio, Angela and Stankovi{\'c}, David and Ricci, Giuseppe and De Seta, Francesco and Comar, Manola} } @article {1964, title = {Soluble TRAIL is elevated in recurrent miscarriage and inhibits the in vitro adhesion and migration of HTR8 trophoblastic cells.}, journal = {Hum Reprod}, volume = {27}, year = {2012}, month = {2012 Oct}, pages = {2941-7}, abstract = {

STUDY QUESTION: What is the potential physiopathological role of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in recurrent miscarriage (RM), characterized by at least three consecutive pregnancy losses.

SUMMARY ANSWER: The levels of serum TRAIL immediately after miscarriage in RM patients are significantly elevated with respect to that in first-trimester normal pregnant women, and recombinant TRAIL inhibits the adhesion and migration of HTR8 trophoblastic cells in vitro.

WHAT IS KNOWN ALREADY: Both TRAIL and its trans-membrane receptors (TRAIL-R1, TRAIL-R2, TRAIL-R3~and TRAIL-R4) have been documented in the placenta, but their physiopathological role is incompletely understood.

STUDY DESIGN, SIZE, DURATION: The study populations consisted of RM patients (n = 80) and first-trimester normal pregnant women (n = 80). Blood samples were obtained within 24 h after abortion (RM) or at gestational 12-week (normal pregnant women). As additional controls, third-trimester normal pregnant women (n = 28) were examined before (within 72 h) and after (within 24 h) partum.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The concentrations of TRAIL were analysed in serum samples by ELISA. In parallel, the effect of soluble recombinant TRAIL (0.1-1000 ng/ml) was analysed on the survival of primary extravillus trophoblasts (EVTs) and on the survival, proliferation, adhesion and migration of trophoblastic HTR8 cells.

MAIN RESULTS AND THE ROLE OF CHANCE: The circulating levels of TRAIL in RM women (median: 52.5 pg/ml; mean and SD: 55.5 {\textpm} 24.4 pg/ml) were significantly higher with respect to first-trimester normal pregnant women (median: 44.9 pg/ml; mean and SD: 47 {\textpm} 15.1 pg/ml) and third-trimester normal pregnant women, as assessed before (median: 45.1 pg/ml; mean and SD: 46 {\textpm} 12.4 pg/ml) and after partum (median: 35.4 pg/ml; mean and SD: 38 + 17.5 pg/ml). Both primary EVT and HTR8 cells expressed detectable levels of TRAIL death receptors, but exposure to soluble recombinant TRAIL did not induce cell death of trophoblastic cells. On the other hand, TRAIL dose-dependently inhibited the adhesion of HTR8 cells to decidual endothelial cells (DEC) as well as the migration of HTR8 in transwell assays using either fibronectin or DEC.

LIMITATIONS, REASONS FOR CAUTION: Although this study suggests that TRAIL might have a pathogenic role in RM by inhibiting both the adhesion and migration capabilities of first trimester trophoblastic cells, there is a possibility that the elevated serum levels of TRAIL in RM are not cause but rather the result of RM.

WIDER IMPLICATIONS OF THE FINDINGS: Our current findings together with data of other authors suggest that circulating TRAIL should be further analysed as a potential important biomarker in different physiopathological settings.

STUDY FUNDING/COMPETING INTEREST(S): This study was funded by FIRB projects (RBAP11Z4Z9_002 to Giorgio Zauli and RBAP10447J_002 to Paola Secchiero). The authors have no competing interests to declare.

}, keywords = {Abortion, Habitual, Apoptosis, Cell Adhesion, Cell Line, Cell Movement, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Humans, Pregnancy, Receptors, TNF-Related Apoptosis-Inducing Ligand, TNF-Related Apoptosis-Inducing Ligand, Trophoblasts}, issn = {1460-2350}, doi = {10.1093/humrep/des289}, author = {Agostinis, Chiara and Bulla, Roberta and Tisato, Veronica and De Seta, Francesco and Alberico, Salvatore and Secchiero, Paola and Zauli, Giorgio} }