Abstract
Group B Streptococcus (GBS) infection during pregnancy is involved in maternal sepsis, chorioamnionitis, prematurity, fetal infection, neonatal sepsis, and neurodevelopmental alterations. The GBS-induced chorioamnionitis leads to a plethora of immune and trophoblast cells alterations that could influence endothelial cells to respond differently to angiogenic mediators and alter placental vascular structure and function in pregnant women. In this context, preventive measures are needed to reduce such dysfunctions. As such, we evaluated the effects of a non-lethal exposure to inactivated GBS on trophoblast cells and chorionic villi explants, and if the treatment with uvaol would mitigate these effects. The concentration of 106 CFU of GBS was chosen since it was unable to reduce the HTR-8/SVneo cell line nor term chorionic villi explant viability. Raman spectroscopy of trophoblast cells showed significant alterations in their biochemical signature, mostly reverted by uvaol. GBS exposure increased HTR-8/SVneo cells IL-1β and IFN-γ production, phagocytosis, oxidative stress, and decreased trophoblast cell migration. The Ea.hy926 endothelial cell line produced angiopoietin-2, CXCL-8, EGF, FGF-b, IL-6, PlGF, sPECAM-1, and VEGF in culture. When co-cultured in invasion assay with HTR-8/SVneo trophoblast cells, the co-culture had increased production of angiopoietin-2, CXCL-8, FGF-b, and VEGF, while reduced sPECAM-1 and IL-6. GBS exposure led to increased CXCL-8 and IL-6 production, both prevented by uvaol. Chorionic villi explants followed the same patterns of production when exposed to GBS and response to uvaol treatment as well. These findings demonstrate that, even a non-lethal concentration of GBS causes placental inflammation and oxidative stress, reduces trophoblast invasion of endothelial cells, and increases CXCL-8 and IL-6, key factors that participate in vascular dysregulation observed in several diseases. Furthermore, uvaol treatment prevented most of the GBS-provoked changes. Hence, uvaol could prevent the harmful effects of GBS infection for both the mother and the fetus.
Highlights
Group B Streptococcus (GBS) or Streptococcus agalactiae is a gram-positive bacterium responsible for a great number of maternal and fetal morbidity and mortality
Placental explants incubated with GBS at 106 colony-forming units (CFU) alone or after uvaol treatment had no statistically significant changes in overall viability concerning control (Figure 1A)
To perform spectral data analysis and classification, the Raman spectra were divided into three groups: (i) cells without treatment; (ii) cells treated with uvaol; (iii) cells incubated with GBS at 106 CFU (GBS); and (iv) cells treated with uvaol and incubated with GBS
Summary
Group B Streptococcus (GBS) or Streptococcus agalactiae is a gram-positive bacterium responsible for a great number of maternal and fetal morbidity and mortality This bacterium is part of the vaginal and/or gastrointestinal tract of 10– 30% of pregnant women, where the colonization is usually asymptomatic. Latin American countries still do not have effective guidelines, and a recent study has shown that less than 15% of pregnant women are, screened for GBS, except Uruguay, where 65% of them are screened In the latter country, GBS colonization was found in 18.5% of women, while the highest prevalence was found in black women, older women, and women without primary education (HogenEsch et al, 2021). The biggest and more populated country of the region, Brazil, does not even have GBS screening and prophylaxis guidelines consensus in its National Healthcare Public System (Nascimento et al, 2019)
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