H2S Improves the Rate of Migration in Trophoblast Cells

Abstract

IntroductionThe migration of trophoblast cells during the first trimester of pregnancy is crucial to placentation process. Defective migration of trophoblastic cells may affect the remodelling (pseduovasculogenesis) of spiral arteries resulting in Hypoxia/Reoxygenation (H/R) episodes. These repeated H/R events can leads to oxidative stress and release of anti‐angiogenic, anti‐inflammatory and pro‐oxidant factors in maternal circulation causing endothelial dysfunction resulting in adverse pregnancy outcomes like preeclampsia and fetal growth restriction. The anti‐inflammatory, pro‐angiogenic and pro‐migratory effect of H2S on endothelial cells have been documented in literature. So we hypothesized that H2S or its mimics (NaHS) may also affect the migration capacity of trophoblast cells during placentation.MethodsThe immortalized first trimester extravillous trophoblast cell line (HTR‐8/SVneo) were given various treatments like 50μM NaHS, Hypoxia/Reoxygenation [H/R (one and two cycles)] and Hypoxia/Reoxygenation supplemented with 50μM NaHS. The cell migration was assessed using wound scratch assay following these various exposures. The percentage wound area covered was assessed in all groups. The difference in wound covered area was statistically analysed. [ten different zone in triplicate (i.e. thirty) were used for calculating the wound areas]ResultsThe percentage of wound covered area (rate of migration) increased in cells which received 50μM NaHS [control (32.8%), NaHS (67.5%)] whereas it reduced to 8.7% in Hypoxia/Reoxygenation one cycle exposed cells and more so (−18.9%) in the cells which received two cycles of Hypoxia/Reoxygenation. However the cells which received Hypoxia/Reoxygenation (one cycle and two cycles) and showed reduced migration, improved their rate of migration when supplemented with 50μM NaHS. [one cycle H/R (8.7%), one cycle H/R+NaHS (39.8) and two cycles H/R (−18.9%), two cycles H/R+NaHS (29.5%)]. The difference in wound covered area among various groups was statistically significant [(control vs NaHS; p<0.001, control vs one cycle H/R; p<0.001, control vs two cycle H/R; p<0.001, one cycle H/R vs one cycle H/R+NaHS; p <0.001, two cycle H/R vs two cycles H/R+NaHS; p<0.001 (one‐way ANOVA with Bonferroni correction)].ConclusionThese results imply that H2S may promote the migration of trophoblastic cells, which might then lead to adequate conversion of spiral arteries into wider diameter low resistance vessels having good placental perfusion. In future the role of H2S on cellular and molecular factors responsible for cell migration needs to explored.IESC/T‐467/23.12.2014Support or Funding InformationF.8‐397/A‐397/2015/RsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.