Reproductive, pregnancy, and placental exposomes influence the fetal neural exposome through toxic stressor interplay, impairing the maternal-placental-fetal (MPF) triad. Neonatal encephalopathy represents different clinical presentations based on complex time-dependent etiopathogenetic mechanisms including hypoxia-ischemia that challenge diagnosis and prognosis. Reproductive, pregnancy, and placental exposomes impair the fetal neural exposome through toxic stressor interplay within the MPF triad. Long intervals often separate disease onset from phenotype. Interdisciplinary fetal-neonatal neurology training, practice, and research closes this knowledge gap. Maintaining reproductive health preserves MPF triad health with life-course benefits.

Coastal areas are affected by urban, industrial and agriculture pollutants runoff, wastewater and stormwater discharges, making this environment the final repository of chemical contaminants. These contaminants have the potential to spread out to the entire food chain, impacting marine life and the quality of their habitat. In this aspect, the concept of marine mammals as bioindicators provides an approach to the degree of contamination in the environment and to the identification and management of multiple sources of contaminants. The present study analyzed several elements like As, Ba, Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb, V and Zn in liver tissue from two dolphin species: Sotalia guianensis, a near-threatened species, and the vulnerable Pontoporia blainvillei. In the study, we also investigated if dolphins (population) recorded using the heaviest urban areas have higher concentrations of contaminants in their tissues. Dolphin samples (n = 40 S. guianensis; n = 97 P. blainvillei) were collected by daily monitoring carried out by Santos Basin Beach Monitoring Project (PMP-BS), from stranded individuals found in São Paulo state. The Spearman\'s rank correlation showed distinct correlations in the accumulation of trace elements by both species, indicating different sources of exposure to the elements studied or distinct biochemical processes between species. Interspecific and intraspecific variations were observed, possibly related to the individual distribution and feeding habits. Correlations were observed between age and concentrations of trace elements, positive for Cd, Hg and Mo. Finally, our findings indicate high levels of Cu, Zn, and concentrations of As, V and Hg in fetuses, in particular, an analysis was performed on a fetus found inside a stranded individual, indicating placental transfer as the first route of exposure for some elements.

Maternal-fetal microchimerism is a fascinating phenomenon in which maternal cells migrate to the tissues of the offspring during both pregnancy and breastfeeding. These cells primarily consist of leukocytes and stem cells. Remarkably, these maternal cells possess functional potential in the offspring and play a significant role in shaping their immune system development. T lymphocytes, a cell population mainly found in various tissues of the offspring, have been identified as the major cell type derived from maternal microchimerism. These T lymphocytes not only exert effector functions but also influence the development of the offspring\'s T lymphocytes in the thymus and the maturation of B lymphocytes in the lymph nodes. Furthermore, the migration of maternal leukocytes also facilitates the transfer of immune memory across generations. Maternal microchimerism has also been observed to address immunodeficiencies in the offspring. This review article focuses on investigating the impact of maternal cells transported within maternal microchimerism on the immune system development of the offspring, as well as elucidating the effector functions of maternal cells that migrate through the placenta and breast milk to reach the offspring.

During development, embryos and foetuses may be exposed to maternally ingested antiseizure medications (ASM), valproate and lamotrigine, essential in some patients to control their epilepsy symptoms. Often, the two drugs are co-administered to reduce required doses of valproate, a known potential teratogen. This study used Genetic Absence Epilepsy Rat from Strasbourg to evaluate transfer of valproate and lamotrigine across late gestation placenta and their entry into cerebrospinal fluid (CSF) and brain of developing rats, in mono- and combination therapies. Animals at embryonic day (E) 19, postnatal day (P) 0, 4 and 21, and adults were administered valproate (30 mg/kg) or lamotrigine (6 mg/kg) with their respective [3H]-tracers, either alone or in combination. In chronic experiments, females consumed valproate-containing diet from 2 weeks prior to mating until offspring were used at E19 and P0. Drugs were injected 30 min before blood, CSF and brain samples were collected from terminally anaesthetised animals. Radioactivity in samples was measured. In acute monotherapy brain entry of valproate was higher in foetal than postnatal animals, correlating with its plasma protein binding. Brain entry of lamotrigine was not age-dependent. Combination therapy enhanced entry of lamotrigine into the adult brain but had no effects on brain and CSF entry of valproate. Following chronic valproate exposure, placental transfer of valproate decreased in combination therapy; however, foetal brain entry increased. Results suggest that during pregnancy, the use of combination therapy of valproate and lamotrigine may mitigate overall foetal exposure to valproate but potential risks to foetal brain development are less clear.

Endocytosis represents a category of regulated active transport mechanisms. These encompass clathrin-dependent and -independent mechanisms, as well as fluid phase micropinocytosis and macropinocytosis, each demonstrating varying degrees of specificity and capacity. Collectively, these mechanisms facilitate the internalization of cargo into cellular vesicles. Pregnancy is one such physiological state during which endocytosis may play critical roles. A successful pregnancy necessitates ongoing communication between maternal and fetal cells at the maternal-fetal interface to ensure immunologic tolerance for the semi-allogenic fetus whilst providing adequate protection against infection from pathogens, such as viruses and bacteria. It also requires transport of nutrients across the maternal-fetal interface, but restriction of potentially harmful chemicals and drugs to allow fetal development. In this context, trogocytosis, a specific form of endocytosis, plays a crucial role in immunological tolerance and infection prevention. Endocytosis is also thought to play a significant role in nutrient and toxin handling at the maternal-fetal interface, though its mechanisms remain less understood. A comprehensive understanding of endocytosis and its mechanisms not only enhances our knowledge of maternal-fetal interactions but is also essential for identifying the pathogenesis of pregnancy pathologies and providing new avenues for therapeutic intervention.

In utero gene editing (IUGE) is a potential treatment for inherited diseases that cause pathology before or soon after birth. Preexisting immunity to adeno-associated virus (AAV) vectors and Cas9 endonuclease may limit postnatal gene editing. The tolerogenic fetal immune system minimizes a fetal immune barrier to IUGE. However, the ability of maternal immunity to limit fetal gene editing remains a question. We investigated whether preexisting maternal immunity to AAV or Cas9 impairs IUGE. Using a combination of fluorescent reporter mice and a murine model of a metabolic liver disease, we demonstrated that maternal anti-AAV IgG antibodies were efficiently transferred from dam to fetus and impaired IUGE in a maternal titer-dependent fashion. By contrast, maternal cellular immunity was inefficiently transferred to the fetus, and neither maternal cellular nor humoral immunity to Cas9 impaired IUGE. Using human umbilical cord and maternal blood samples collected from mid- to late-gestation pregnancies, we demonstrated that maternal-fetal transmission of anti-AAV IgG was inefficient in midgestation compared with term, suggesting that the maternal immune barrier to clinical IUGE would be less relevant at midgestation. These findings support immunologic advantages for IUGE and inform maternal preprocedural testing protocols and exclusion criteria for future clinical trials.

Mammalian reproduction relies on precise maternal-fetal communication, wherein immune modifications foster tolerance toward the semi-allogeneic embryo. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as crucial mediators, transporting molecules like microRNAs securely. EVs influence various reproductive stages, from gamete maturation to implantation, and impact pathologies like pregnancy loss. In the embryo-maternal dialogue, EVs notably affect oviductal interactions, gene expression, and the embryo-endometrial interface, crucial for successful implantation. Key queries persist about EV uptake, cargo delivery, and the specific biomolecules driving communication. Their potential in diagnostics, therapeutics, and understanding environmental impacts on fertility signals an exciting future, reliant on collaborative efforts for transformative strides in reproductive health.

The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus.

This study, conducted by searching keywords such as \"maternal lupus\", \"neonatal lupus\", and \"congenital heart block\" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother\'s uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal-fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal-fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal-fetal interface adapts to pregnancy\'s unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.