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Plastics found in our everyday environment are becoming an increasing concern for individual and population-level health, and the extent of exposure and potential toxic effects of these contaminants on numerous human organ systems are becoming clear. Microplastics (MPs), tiny plastic particles, appear to have many of the same biological effects as their plastic precursors and have the compounded effect of potential accumulation in different organs. Recently, microplastic accumulation was observed in the human placenta, raising important questions related to the biological effects of these contaminants on the health of pregnancies and offspring. These concerns are particularly heightened considering the developmental origins of health and disease (DOHaD) framework, which postulates that in utero exposure can programme the lifelong health of the offspring. The current review examines the state of knowledge on this topic and highlights important avenues for future investigation.

Preeclampsia (PE), a hypertensive pregnancy disorder, can originate from varied etiology. Placenta malperfusion has long been considered the primary cause of PE. However, we and others have showed that this disorder can also result from heightened inflammation at the maternal-fetal interface. To advance our understanding of this understudied PE subtype, it is important to establish validated rodent models to study the pathophysiology and test therapies. We evaluated three previously described approaches to induce inflammation-mediated PE-like features in pregnant rats: 1) Tumor necrosis factor-α (TNF-α) infusion via osmotic pump from gestational day (GD) 14-19 at 50ng/day/animal; 2) Polyinosinic:polycytidylic acid (Poly I:C) intraperitoneal (IP) injections from GD 10-18 (alternate days) at 10mg/kg/day/animal; and, 3) Lipopolysaccharide (LPS) IP injections from GD 13-18 at 20ug-70ug/kg/day per animal. Maternal blood pressure was measured by tail-cuff. Upon sacrifice, fetal and placenta weights were recorded. Placenta histomorphology was assessed using H&E sections. Placenta inflammation was determined by quantifying TNF-α levels and inflammatory gene expression. Placenta metabolic and mitochondrial health were determined by measuring mitochondrial respiration rates and placenta NAD+/NADH content. Of the three rodent models tested, we found that Poly I:C and LPS decreased both fetal weight and survival; and correlated with a reduction in region specific placenta growth. As the least effective model characterized, TNF-α treatment resulted in a subtle decrease in fetal/placenta weight and placenta mitochondrial respiration. Only the LPS model was able to induce maternal hypertension and exhibited pronounced placenta metabolic and mitochondrial dysfunction, common features of PE. Thus, the rat LPS model was most effective for recapitulating features observed in cases of human inflammatory PE. Future mechanistic and/or therapeutic intervention studies focuses on this distinct PE patient population may benefit from the employment of this rodent model of PE.

Physical activity (PA) and exercise have been associated with a reduced risk of cancer, obesity, and diabetes. In the context of pregnancy, maintaining an active lifestyle has been shown to decrease gestational weight gain (GWG) and lower the risk of gestational diabetes mellitus (GDM), hypertension, and macrosomia in offspring. The main pathways activated by PA include BCAAs, lipids, and bile acid metabolism, thereby improving insulin resistance in pregnant individuals. Despite these known benefits, the underlying metabolites and biological mechanisms affected by PA remain poorly understood, highlighting the need for further investigation. Metabolomics, a comprehensive study of metabolite classes, offers valuable insights into the widespread metabolic changes induced by PA. This narrative review focuses on PA metabolomics research using different analytical platforms to analyze pregnant individuals. Existing studies support the hypothesis that exercise behaviour can influence the metabolism of different populations, including pregnant individuals and their offspring. While PA has shown considerable promise in maintaining metabolic health in non-pregnant populations, our comprehension of metabolic changes in the context of a healthy pregnancy remains limited. As a result, further investigation is necessary to clarify the metabolic impact of PA within this unique group, often excluded from physiological research.

The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational parent/fetal exchange, and ultimately, fetal development and growth. Not surprisingly, in cases of placental dysfunction—where aspects of placental development or function become compromised—adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero–placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

Abstract Background Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. We hypothesized that this heterogeneity is due to the existence of multiple subtypes of PE and, in support of this hypothesis, we recently identified five clusters of placentas within a large gene expression microarray dataset (N = 330), of which four (clusters 1, 2, 3, and 5) contained a substantial number of PE samples. However, while transcriptional analysis of placentas can subtype patients, we propose that the addition of epigenetic information could discern gene regulatory mechanisms behind the distinct PE pathologies, as well as identify clinically useful potential biomarkers. Results We subjected 48 of our samples from transcriptional clusters 1, 2, 3, and 5 to Infinium HumanMethylation450 arrays. Samples belonging to transcriptional clusters 1–3 still showed visible relationships to each other by methylation, but cluster 5, with known chromosomal abnormalities, no longer formed a cohesive group. Within transcriptional clusters 2 and 3, controlling for fetal sex and gestational age in the identification of differentially methylated sites, compared to the healthier cluster 1, dramatically reduced the number of significant sites, but increased the percentage that demonstrated a strong linear correlation with gene expression (from 5% and 2% to 9% and 8%, respectively). Locations exhibiting a positive relationship between methylation and gene expression were most frequently found in CpG open sea enhancer regions within the gene body, while those with a significant negative correlation were often annotated to the promoter in a CpG shore region. Integrated transcriptome and epigenome analysis revealed modifications in TGF-beta signaling, cell adhesion, oxidative phosphorylation, and metabolism pathways in cluster 2 placentas, and aberrations in antigen presentation, allograft rejection, and cytokine-cytokine receptor interaction in cluster 3 samples. Conclusions Overall, we have established DNA methylation alterations underlying a portion of the transcriptional development of “canonical” PE in cluster 2 and “immunological” PE in cluster 3. However, a significant number of the observed methylation changes were not associated with corresponding changes in gene expression, and vice versa, indicating that alternate methods of gene regulation will need to be explored to fully comprehend these PE subtypes.

BACKGROUND:Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. RESULTS:To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. CONCLUSION:Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.