Fig 2: Progesterone caused histological changes in the placenta, affected cell proliferation and invasion, and the PI3K/AKT signaling pathway. In the Normal, Normal+ progesterone, preeclampsia, preeclampsia+ progesterone groups. (A) Morphological photograph of placenta tissues stained with HE. (B) Cyclin D1 and PCNA expression in placenta tissues. (C) MMP-2 and MMP-9 expression in placenta tissues. (D) AKT and p-AKT expression in placenta tissues. Scale bar = 100 µm; The magnification was 100 times and 400 times respectively; Pro: progesterone; PE: preeclampsia; HE: Hematoxylin-Eosin; PCNA: p?roliferating cell nuclear antigen; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9; AKT: protein kinase B; p-AKT: phosphorylation of protein kinase B. *P <0.05 vs Normal group; #P <0.05 vs preeclampsia group.

Fig 3: Effects of different concentrations of progesterone on blood pressure, urinary protein, cell invasion, progesterone levels and inflammatory factors in preeclampsia rats. In the Normal, Normal+10-8mol/L progesterone, Normal+10-6mol/L progesterone, Normal+10-4mol/L progesterone, preeclampsia, preeclampsia+10-8mol/L progesterone, preeclampsia+10-6mol/L progesterone, preeclampsia+10-4mol/L progesterone groups. (A) Blood pressure of rats from 0 to 20 days. (B) Urine protein of rats from 0 to 20 days. (C) MMP-2 and MMP-9 levels in serum from 0-20 days. (D) ELISA was used to detect the level of progesterone in serum from 0 to 20 days. (E) Pro-inflammatory factors TNF-a and IL-1ß levels in serum were detected by ELISA. (F) Anti-inflammatory factors IL-4, IL-10 and IL-13 levels. ns: not significant; Pro: progesterone; PE: preeclampsia; ELISA: Enzyme-Linked Immunosorbent Assay; IL: i?nterleukin; TNF: t?umor necrosis factor; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9. *P <0.05 vs Normal group; #P <0.05 vs PE group.

Fig 4: Progesterone promoted HTR-8/Svneo cell proliferation and invasion. (A) CCK-8 was performed to detect cell proliferation in the Normal, Normal+10-8mol/L progesterone, Normal+10-6mol/L progesterone, Normal+10-4mol/L progesterone, preeclampsia, preeclampsia+10-8mol/L progesterone, preeclampsia+10-6mol/L progesterone, preeclampsia+10-4mol/L progesterone groups. In the Normal, Normal+ progesterone, preeclampsia, preeclampsia+ progesterone groups. (B) Transwell assay was applied to measure cell invasion. (C) Quantitative detection of cell invasion rate. (D) MMP-2 and MMP-9 levels. Scale bar = 100 µm; The magnification was 100 times; Pro: progesterone; PE: preeclampsia; CCK-8: Cell Counting Kit 8; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9; OD: optical density. *P <0.05 vs Normal group; #P <0.05 vs preeclampsia group.

Fig 5: Progesterone acted on HTR-8/Svneo cells via the PI3K/AKT signaling pathway. In the Normal, Normal+LY, preeclampsia, preeclampsia+LY, Normal+ progesterone, Normal+LY+ progesterone, preeclampsia+ progesterone, preeclampsia+LY+ progesterone groups. (A) CCK-8 was performed to measure cell proliferation. (B) Transwell assay was applied to evaluate cell invasion. (C) MMP-2 and MMP-9 levels. (D) AKT, p-AKT, PI3K, and p-PI3K expressions. Pro: progesterone; PE: preeclampsia; CCK-8: Cell Counting Kit 8; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9; OD: optical density; p-PI3K: phosphorylation of phosphoinositide 3-kinase; PI3K: phosphorylation of phosphoinositide 3-kinase; AKT: protein kinase B; p-AKT: phosphorylation of protein kinase B; LY: LY294002. *P <0.05 vs Normal group; #P <0.05 vs preeclampsia group; &P <0.05 vs Normal+progesterone group; @P <0.05 vs preeclampsia+progesterone group.