“Real life” polycyclic aromatic hydrocarbon (PAH) mixtures modulate hCG, hPL and hPLGF levels and disrupt the physiological ratio of MMP-2 to MMP-9 and VEGF expression in human placenta cell lines

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 95; pp. 1 - 10
• Main Authors: Drwal, Eliza, Rak, Agnieszka, Tworzydło, Wacław, Gregoraszczuk, Ewa Łucja
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2020
• Subjects: Cell Line; Chorionic Gonadotropin - metabolism; Female; hCG; hPL; hPLGF; Humans; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Mixture of PAHs; MMPs; Placenta - cytology; Placenta cell line; Placenta Growth Factor - metabolism; Placental Lactogen - metabolism; Polycyclic Aromatic Hydrocarbons - toxicity; Pregnancy; Vascular Endothelial Growth Factor A - metabolism; VEGF; hPL; VEGF; Placenta cell line; MMPs; hPLGF; hCG; Mixture of PAHs
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2020.02.006

•PAH mixtures action on hCG, hPL and hPlGF secretion and expression in placental cells was examined.•In control, PAH mixtures increased hCG and decreased hPlGF levels in both JEG-3 and BeWo cell lines.•PAH mixtures action on basal and hormone-stimulated MMP-2, MMP-9 and VEGF expression was evaluated.•Changed the MMP-2/MMP-9 ratio in favour of MMP-9 in JEG-3 cells, while of MMP-2 in BeWo cells was noted the effect on VEGF expression was cell specific and dependent on the mixture. Using JEG-3 and BeWo cells, we examined the effect of “real life” mixtures of polycyclic aromatic hydrocarbons (PAHs), at doses reported in maternal blood (Mix I) and in placental tissue (Mix II), on human chorionic gonadotropin (hCG), placental lactogen (hPL) and placental growth factor (hPLGF) secretion, protein expression and immunolocalization. Additionally, the action of PAH mixtures on basal and hormone-stimulated matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) protein expression was evaluated. Under basal conditions, the PAH mixtures increased hCG and decreased hPLGF levels in both cell lines, while hPL expression was stimulated in JEG-3 and inhibited in BeWo. There was no effect on the MMP-2/MMP-9 ratio or VEGF expression. In hormone-stimulated cells, PAH mixtures changed the MMP-2/MMP-9 ratio in JEG-3 cells in favor of MMP-9, while in BeWo MMP-2 was favored. The effect on VEGF expression was cell specific and dependent on the mixture. In hCG-treated cells, only Mix II inhibited VEGF expression in JEG-3 cells. Neither PAH mixtures affected this protein in BeWo cells. In hPL-treated cells, Mix I had a stimulatory effect in JEG-3 cells, while Mix II exerted an inhibitory effect in BeWo cells. In hPLGF-treated cells, Mix II decreased in JEG-3 cells, but in BeWo cells, both mixtures increased VEGF expression. Considering that the evaluated protein hormones play crucial roles in angiogenesis and neovascularization in the placenta, “real life” PAH mixtures by disrupting protein hormones levels, the MMP-2/MMP-9 ratio and VEGF expression can lead to insufficiency and many pregnancy-related disorders.