Reinaldo Marín

Magnesium is crucial for enzymatic and genetic functions, and demand increases for both the mother and the foetus during pregnancy. Inadequate magnesium intake is linked to adverse outcomes, including foetal growth restriction and preeclampsia. This narrative review characterizes the global prevalence of insufficient magnesium intake and status among pregnant women and examines its relationship with deficiency symptoms and preeclampsia. Current magnesium requirements based on recent studies and public health guidelines to identify new hallmarks for prevention and treatment are also assessed. A literature search over the past five years revealed evidence of widespread dietary magnesium inadequacy among pregnant populations. In the absence of a validated, pregnancy-specific biomarker, the true prevalence of physiological magnesium deficiency remains difficult to establish. Serum magnesium levels often appear normal despite this dietary shortfall, which may mask an underlying insufficiency. International guidelines differ on routine supplementation, and current evidence does not support universal supplementation for all pregnant women; targeted supplementation may be warranted for those with documented insufficiency or recognized risk factors, while ensuring adequate magnesium status through a varied diet remains the appropriate strategy for the broader population. Persistent dietary inadequacy nonetheless represents a significant public health concern. Current research confirms that magnesium sulphate (MgSO4) remains the cornerstone pharmacological intervention for preeclampsia with severe features and eclampsia, and its use has been associated with a significant reduction in maternal and foetal morbidity. Further prospective research is needed to clarify pregnancy-specific magnesium requirements, validate diagnostic biomarkers, and solidify clinical guidelines and best practices for pregnancy nutrition.

The objective of the Research Topic "Maternal-Fetal Interface: New Insights in Placenta Research Volume II" was to bring together original research articles and reviews highlighting recent advances in understanding placental functions and its impact on the health of the mother and her future child. This collection encompasses a diverse range of contributions, including six original articles, a mini-review, three reviews, and a systematic review.A striking theme emerging from current research is the central role of specialized cellular projections-podosomes and invadopodia-in trophoblast invasion at the maternal-fetal interface (Patel and Dash 2012). These "invasive feet" are crucial for normal placental development, yet their classification remains debated due to the discovery of hybrid structures that blur conventional definitions (Patel and Dash 2012). This conceptual ambiguity highlights the need to re-evaluate how these invasive mechanisms are defined and studied, particularly in the context of pregnancy complications such as placenta accreta and preeclampsia, where trophoblast invasion is either excessive or insufficient.Epigenetic regulation has become a central focus in understanding the immune microenvironment at the maternal-fetal interface. Mechanisms such as DNA methylation, histone modifications, and non-coding RNA activity are now recognized as crucial for orchestrating the immune balance required for successful implantation and placental development (Inbar-Feigenberg et al. 2013). Disruptions in these epigenetic processes have been associated with a range of placenta-related complications, highlighting the potential of targeted interventions that modulate gene expression without altering the underlying DNA sequence (Puvvula et al. 2025).The placenta's capacity to regulate protein folding and respond to cellular stress is a critical factor in ensuring a healthy pregnancy (Chowdhury et al. 2024). The unfolded protein response (UPR), activated by endoplasmic reticulum (ER) stress, plays a dual role: while a basal level of UPR activity is essential for normal placental development, prolonged or excessive ER stress can lead to cellular dysfunction and adverse pregnancy outcomes (Garip et al. 2022, Soczewski et al. 2023). This "stress paradox" illustrates the delicate balance between physiological adaptation and pathological disruption, emphasizing the importance of ER homeostasis for both maternal and fetal well-being. Preeclampsia (PE) remains one of the most formidable challenges in obstetric medicine, due not only to its acute clinical risks but also to its long-term health implications. Recent work suggests that trained innate immunity (TRIM)-a process by which exposure to danger signals during PE epigenetically reprograms maternal immune cells-may provide a mechanistic link between pregnancy complications and future cardiovascular disease (Romao-Veiga et al. 2022). This persistent pro-inflammatory state, driven by epigenetic changes, may help explain the elevated risk of hypertension, heart disease, and stroke observed in women with a history of PE. Advancing our understanding of TRIM could open novel avenues for prevention and therapy, both during pregnancy and beyond.Maternal metabolic status, particularly overweight and obesity, is increasingly recognized as a key modifier of placental and vascular structure (Louwen et al. 2024). Research has demonstrated that maternal overweight is associated with significant remodeling of the umbilical vein, including increased wall thickness and collagen deposition. These structural alterations may compromise the efficiency of nutrient and oxygen delivery to the fetus, potentially influencing long-term health outcomes. Such findings reinforce the importance of optimizing maternal health before and during pregnancy, not only for favorable perinatal outcomes but also for mitigating intergenerational health risks.Environmental factors are increasingly recognized as significant threats to placental function. Microplastics, once considered as pollutants affecting marine ecosystems, have now been detected in human placental tissue (Ragusa et al. 2021). Experimental studies demonstrate that exposure to polystyrene microplastics induces cytotoxicity, oxidative stress, and metabolic disturbances in placental explants, raising serious concerns about their potential to impair fetal development and contribute to pregnancy complications. Given the pervasive presence of microplastics in the environment, further research into their impact on human health is both urgent and essential.Research into placental oxidative stress has expanded significantly, with growing emphasis on the mechanisms governing antioxidant defenses, gene expression regulation, and the pathophysiology of pregnancy-related diseases (Vornic et al. 2024, Wu et al. 2016). Bibliometric analyses reveal a shift toward investigating emerging risk factors, environmental exposures, and the complex interplay between inflammation, stem cells, and immune regulation. These trends reflect a broader understanding that placental health is influenced by an intricate network of genetic, epigenetic, metabolic, and environmental factors.Advances in reproductive technology, such as preimplantation genetic testing for aneuploidy (PGT-A), are also reshaping our understanding of pregnancy complications (Hou et al. 2021). Emerging evidence suggests that PGT-A may reduce the risk of preeclampsia in pregnancies involving male fetuses, although this protective effect does not appear to extend to female fetuses. This sex-specific difference underscores the complexity of fetal-maternal interactions and highlights the importance of personalized approaches in fertility treatment and pregnancy management.Finally, the interaction between inflammation and placental function in the context of maternal diabetes provides valuable insights into the roles of Hofbauer cells, unique and specialized fetal immune...

Magnesium sulfate (MgSO₄) is a therapeutically versatile agent used across various medical conditions. This review integrates experimental and computational findings to elucidate the clinical, cellular, molecular, and electronic mechanisms underlying MgSO₄’s therapeutic effects, focusing on its antioxidant properties. MgSO₄ remains the gold standard treatment for preeclampsia and eclampsia, preventing seizures and mitigating oxidative damage. In preterm birth, it offers fetal neuroprotection, although its efficacy as a tocolytic agent is limited. MgSO₄ also shows promise in treating respiratory conditions, notably severe asthma, where it acts as a bronchodilator. Its applications extend to anesthesia, pain management, and cardiac arrhythmias, reflecting its diverse pharmacological actions. Advanced computational methods, including molecular dynamics simulations and quantum chemistry calculations, have revealed how MgSO₄ interacts with cell membranes and neutralizes hydroxyl radicals. These studies suggest that MgSO₄’s antioxidant effects stem from its ability to stabilize membrane structures and modulate electron transfer processes. The therapeutic effects are mediated through multiple pathways, including calcium channel modulation, NMDA receptor antagonism, and anti-inflammatory mechanisms. Although generally safe, MgSO₄ requires careful monitoring due to its narrow therapeutic window. Future research should focus on precision dosing strategies, innovative delivery systems, and expanded therapeutic applications. A comprehensive understanding of MgSO₄’s molecular mechanisms and clinical applications will further optimize its therapeutic use. Graphical abstract

Preeclampsia, a pregnancy-specific syndrome with multisystem involvement, significantly contributes to maternal and fetal morbidity and mortality. This study compared physiological, fetal, and placental parameters between preeclamptic women and salt-loaded pregnant rats, an established animal model for preeclampsia. We evaluated lipid peroxidation levels in both placental homogenates and red blood cell ghosts, and Ca-ATPase activity in placental homogenates. Additionally, we assessed the effects of magnesium sulfate (MgSO4) treatment on these parameters. Salt-loaded pregnant rats received 1.8% NaCl solution ad libitum for seven days starting from the 15th day of pregnancy. For analysis, blood and placental samples were obtained from preeclamptic women and the rat model. Results showed that salt-loaded pregnant rats exhibited similar characteristics to preeclamptic women, including increased lipid peroxidation, and lowered Ca-ATPase activity in placental and red blood cell ghosts. MgSO4 treatment in preeclamptic women and salt-loaded rats modified Ca-ATPase activity and lipid peroxidation levels in red blood cell membranes and placental membranes, bringing values closer to normal values. The reduction in lipid peroxidation by MgSO4 may account for increased Ca-ATPase activity. This study validates the salt-loaded pregnant rat model as a valuable tool for investigating preeclampsia, offering insights into the condition's pathophysiology and potential therapeutic interventions.

Editorial: Maternal-fetal interface: new insight in placenta research