Human Villous Trophoblasts (HVT)

Specific PPARγ Agonist and Antagonist Regulate H3K4me³ and H3K9ac in Human Trophoblast Cells

Preeclampsia stands as a common pregnancy disorder which emerges after 20 weeks of gestation through hypertension and organ dysfunction and causes high death rates among mothers and newborns. Because existing therapies fail to cure PE researchers must explore the root causes of the disease. Meister et al. analyzed the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients.

Researchers evaluated PPARγ's effects on histone modifications H3K4me³ and H3K9ac in trophoblasts by using Ciglitazone as PPARγ agonist and T0070907 as antagonist. After 24 hours of incubating Human Villous Trophoblasts (HVT) and EVT cells with these compounds, researchers performed histone modification and PPARγ level analysis through double immunofluorescence. HVT cells showed reduced PPARγ levels following Ciglitazone treatment but higher levels when treated with T0070907 as indicated in Figure 1. Ciglitazone treatment led to significant reduction of H3K4me³ fluorescence intensity with p-value of 0.04 while T0070907 treatment caused significant increase (Fig. 2A and B). H3K9ac intensity demonstrated equivalent patterns where it decreased with Ciglitazone (p = 0.005) and increased with T0070907 (p = 0.004; Fig. 2C and D).

Fig. 1. Examples of staining results of the immunofluorescence of PPARγ and H3K4me³ in control (A,C) and PE placentas (B,D) in the syncytiotrophoblast (A,B) and the decidua (C,D) (Meister S, Hahn L, et al., 2021).

Fig. 2. Staining results of histonemodifications H3K4me³ (A,B) and H3K9ac (C,D) and PPARγ after incubation with Ciglitazone (A,C) (20 mM) and T0070907 (B,D) (Meister S, Hahn L, et al., 2021).

Gal-2 Promotes the Histone Modifications H3K4me³ and H3K9ac in HVT Cells

Preeclampsia represents a significant pregnancy health threat because researchers have yet to understand its pathophysiology or develop effective treatments. Hahn et al. investigated how galectin-2 (Gal-2) affects reduced transcription-promoting histone modifications (H3K4me³, H3K9ac) in PE for understanding its role in trophoblasts and syncytialisation.

They found that Gal-2 promotes the histone modifications H3K4me³ and H3K9ac in BeWo cells. Based on the results of the BeWo cell culture, incubation with Gal-2 was repeated with Human Villous Trophoblasts (HVT) cells (Fig. 3). A significant increase in H3K4me³ was observed compared to untreated controls (p = 0.020, Mann–Whitney U test), with individual group differences (p = 0.044, Kruskal–Wallis test) and a strong correlation with Gal-2 levels (r = 0.735, p < 0.001, Spearman's Rho). However, no significant changes were noted for H3K9ac expression between treated and untreated HVT cells (p = 0.684, Mann–Whitney U test), nor between individual groups (p = 0.900, Kruskal–Wallis test), and no correlation with Gal-2 (p = 0.769, Spearman's Rho). Despite this, a descriptive analysis indicated increased H3K9ac after Gal-2 treatment (1.52 ± 0.822 vs. 1.25 ± 0.540) and slight elevation with varying Gal-2 concentrations.

Fig. 3. Induction of H3K4me³ and H3K9ac by increasing the concentration of Gal-2 in HVT cells: staining results of immunocytochemistry of HVT cells (Hahn L, Meister S, et al., 2022).