The aim of this study was to analyze 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. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.

There are several open questions to be answered regarding the pathophysiology of the development of preeclampsia (PE). Numerous factors are involved in its genesis, such as defective placentation, vascular impairment, and an altered immune response. The activation of the adaptive and innate immune system represents an immunologic, particularity during PE. Proinflammatory cytokines are predominantly produced, whereas immune regulatory and immune suppressive factors are diminished in PE. In the present study, we focused on the recruitment of regulatory T cells (Tregs) which are key players in processes mediating immune tolerance. To identify Tregs in the decidua, an immunohistochemical staining of FoxP3 of 32 PE and 34 control placentas was performed. A clearly reduced number of FoxP3-positive cells in the decidua of preeclamptic women could be shown in our analysis (p = 0.036). Furthermore, CCL22, a well-known Treg chemoattractant, was immunohistochemically evaluated. Interestingly, CCL22 expression was increased at the maternal-fetal interface in PE-affected pregnancies (p_{syncytiotrophoblast} = 0.035, p_decidua = 0.004). Therefore, the hypothesis that Tregs undergo apoptosis at the materno-fetal interface during PE was generated, and verified by FoxP3/TUNEL (TdT-mediated dUTP-biotin nick end labeling) staining. Galectin-2 (Gal-2), a member of the family of carbohydrate-binding proteins, which is known to be downregulated during PE, seems to play a pivotal role in T cell apoptosis. By performing a cell culture experiment with isolated Tregs, we could identify Gal-2 as a factor that seems to prevent the apoptosis of Tregs. Our findings point to a cascade of apoptosis of Tregs at the materno-fetal interface during PE. Gal-2 might be a potential therapeutic target in PE to regulate immune tolerance.

Preeclampsia (PE) is a severe pregnancy disorder with a pathophysiology not yet completely understood and without curative therapy. The histone modifications H3K4me³ and H3K9ac, as well as galectin-2 (Gal-2), are known to be decreased in PE. To gain a better understanding of the development of PE, the influence of Gal-2 on histone modification in trophoblasts and in syncytialisation was investigated. Immunohistochemical stains of 13 PE and 13 control placentas were correlated, followed by cell culture experiments. An analysis of H3K4me³ and H3K9ac was conducted, as well as cell fusion staining with E-cadherin and β-catenin—both after incubation with Gal-2. The expression of H3K4me³ and H3K9ac correlated significantly with the expression of Gal-2. Furthermore, we detected an increase in H3K4me³ and H3K9ac after the addition of Gal-2 to BeWo/HVT cells. Moreover, there was increased fusion of HVT cells after incubation with Gal-2. Gal-2 is associated with the histone modifications H3K4me³ and H3K9ac in trophoblasts. Furthermore, syncytialisation increased after incubation with Gal-2. Therefore, we postulate that Gal-2 stimulates syncytialisation, possibly mediated by H3K4me³ and H3K9ac. Since Gal-2, as well as H3K4me³ and H3K9ac, are decreased in PE, the induction of Gal-2 might be a promising therapeutic target.

Purpose: There are different studies worldwide, which have shown a higher risk of mental disorders due to the COVID-19 pandemic. One aim of this study was to identify influencing factors of the psychological burden related to the COVID-19 pandemic and the impact on the development of postpartum depression. Further, the role of individual stress and coping strategies was analyzed in this context. Materials and methods: Between March and October 2020, 131 women in obstetric care at the LMU Clinic Munich completed a questionnaire at consecutive stages during their perinatal period. The times set for the questionnaire were before birth, 1 month, 2 months, and 6 months after birth. The questionnaire was designed to evaluate the psychological burden related to the COVID-19 pandemic. For this a modified version of the Stress and coping inventory (SCI) and the Edinburgh Postnatal Depression Scale (EPDS) was used. Results: We could show that the psychological burden related to the COVID-19 pandemic influenced the EPDS score 1, 2 and 6 months after birth. In addition, the prenatal stress and individual coping strategies affected the EPDS and the burden related to the COVID-19 pandemic before and after birth significantly. Conclusion: An association of the psychological burden related to the COVID-19 pandemic with the risk of developing postpartum depressive symptoms could be shown in this study. In this context, the separation of the partner and the family was recognized as an important factor. Furthermore, the SCI was identified as an effective screening instrument for identifying mothers with an increased risk of postpartum depression. Hereby allowing primary prevention by early intervention or secondary prevention by early diagnosis.

Background/Objectives: Histone modifications play a key role in the regulation of gene transcription, with alterations in these modifications influencing trophoblast invasion and migration, crucial for placental development. Previously, we observed reduced trimethylated histone H3K4me3 and acetylated H3K9ac levels in the placentas of women with preeclampsia, associated with impaired transcriptional access. This study aims to investigate the impact of SARS-CoV-2 infection on histone modifications in placentas. Methods: Immunohistochemical Staining and Double-staining Immunofluorescence were performed on placentas of patients during after a SARS-CoV-2 infection during pregnancy as well as vaccinated and not vaccinated controls. Results: Our findings reveal that both H3K4me3 and H3K9ac are significantly reduced in placentas following SARS-CoV-2 infection during pregnancy, with more pronounced alterations observed compared to infections during birth. Additionally, vaccination did not exhibit a stronger effect than infection itself on histone modifications. Conclusions: Reduced H3K9ac and H3K4me3 suggest a more repressive chromatin state, likely silencing key placental genes through increased HDAC activity. These epigenetic changes may impair placental function and lead to pregnancy complications, underscoring the need for further research.