Shiga toxin type 2 (Stx2) inhibits migration, invasion and tubes formation in trophoblast cells of the first trimester (Swan 71 cell) possible role of inducible nitric oxide synthase (iNOS) in the damage produced by Stx2.

SCALISE MARÍA LUJÁN; IBARRA CRISTINA; SACERDOTI FLAVIA

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Annual de la Sociedad Argentina de Inmunología, Reunión Anual de la Sociedad Argentina de Fisiología.; 2018

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Fisiología, Sociedad de Inmunología

Successful placentation involves migration, invasion and remodeling of uterine arteries by trophoblast cells. Failures in these processes are related to serious obstetric complications, as placental dysfunction or miscarriage. We propose was that Stx2, the main virulence factor of Shiga toxin producing Escherichia coli, can cause feto-placental damages through a misbalance of nitric oxide production by inducible nitric oxide synthase (iNOS). Our aim was to evaluate the effects of Stx2 (0.1 µg/ml) at 24 h on migration, invasion and tubulogenesis of first trimester trophoblast cells and to analyze if aminoguanidine (AG), a selective inhibitor of iNOS can modulate Stx2 effects. Swan 71 cell line was used as a first trimester trophoblast model. Cell migration was determined as percentage of wound closure in wound-healing assays. Invasiveness was evaluated as the number of cells invading Transwells coated with Matrigel. Finally, tubulogenesis were analyzed by counting the number of extremities and branch formation. Stx2 significantly decreased cell migration (64.8 ± 3.1 vs 27.5 ± 6.9 %), cell invasion (nº of invading cells: 107.3 ± 19.5 vs 41.5 ± 6.9) and tubulogenesis (nº of extremities: 538 ± 58 vs 304 ± 28, branch formation: 335 ± 41 vs 139 ± 4). AG partially reverted the Stx2 effects compared to control (n.s.). These results support the hypothesis that Stx2 could impair placenta formation by a process involving iNOS.