Background: At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis.Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs.Methods: Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. Forin vivoVPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C.) diluted with normal saline at E12. To analyze the cell death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression level of proteins was investigated by Western blot and immunocytochemical assays. The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL gene promoter and NF-κB p65 was investigated by ChIP assay.Results: In this study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed that VPA protects cultured NPCs from cell death after growth factor withdrawal both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The protective effect of prenatally injected VPA was also observed in E16 embryonic brain. Treatment of VPA decreased the level of IκBα and increased the nuclear translocation of NF-κB, which subsequently enhanced expression of anti-apoptotic protein Bcl-XL.Conclusion: To the best of our knowledge, this is the first report to indicate the reduced death of NPCs by VPA at developmentally critical periods through the degradation of IκBα and the activation of NF-κB signaling. The reduced NPCs death might underlie the neurodevelopmental defects collectively called fetal valproate syndrome, which shows symptoms such as mental retardation and autism-like behavior.

Placental Hofbauer cells (HBCs) are specialized macrophages present in the human placenta that play a crucial role in maintaining a healthy pregnancy. These cells are derived from the fetal mesoderm and are responsible for various functions, including immune regulation, angiogenesis, and nutrient transport. In normal pregnancies, HBCs primarily exhibit an M2 or immunomodulatory phenotype, which helps maintain a tolerant and antiinflammatory environment at the maternal-fetal interface. However, in pregnancies complicated by conditions such as immunological disorders, inflammation, or infection, the phenotype and function of HBCs may be altered. Although emerging evidence has highlighted the vital role of HBCs in both normal pregnancies and those with complications, such as chorioamnionitis, gestational diabetes, preeclampsia, and viral infections, their role remains unclear. Recent research also suggests a relationship between HBCs and the development of diseases in offspring. Understanding the role of HBCs in pregnancy could provide insights into the pathophysiology of various pregnancy-related disorders and offer potential therapeutic targets for improving maternal and fetal outcomes. This review explores the functions of HBCs in normal pregnancy and their involvement in complications, emphasizing their potential as biomarkers or targets for interventions aimed at reducing the incidence of adverse pregnancy outcomes. Additionally, we reviewed their potential for perinatal research in recent studies.