Background: Preeclampsia (PE) is a critical complication of pregnancy that affects 3% to 5% of all pregnancies and has been linked to aberrant placentation, causing severe maternal and fetal illness and death. Objectives: This systematic review aims to elucidate the association of in-utero endocrine-disrupting chemical (EDC) exposure and microRNAs and their imprinted genes from prenatal and maternal circulation of PE patients. Methods: Databases such as PubMed, PubMed Central, ScienceDirect, the Comparative Toxicogenomics Database (CTD), ProQuest, EBSCOhost, and Google Scholar were utilized to search for articles that investigate the relationships between selected EDCs and epigenetic events such as DNA methylation and microRNAs that are associated with PE. Results: A total of 29 studies were included in the database search. Altered expression of microRNAs (miR-15a-5p, miR-142-3p, and miR-185) in the placenta of PE patients was positively associated with the urinary concentration of phthalates and phenols in the development of the disease in the first trimester. EDCs such as phenols, phthalates, perfluoroalkyl substances (PFOAs), polybrominated diphenyl ethers (PBDEs), and organochlorine phosphates (OCPs) have been reported to be associated with hypertensive disorders in pregnancy. miRNA-31, miRNA-144, miRNA-145, miRNA-210, placental specific clusters (C14MC, and C19MC) may be used as possible targets for PE because of their potential roles in the onset and progression of PE. Conclusions: Prenatal EDC exposure, including exposure to BPA, showed association with signaling pathways including estrogen, sFlt-1/PlGF, ErbB, MAPK/ERK, and cholesterol mechanisms with placental hemodynamics. Even low EDC exposures leave altered epigenetic marks throughout gestation, which might cause PE complications.

Preeclampsia, a pregnancy complication characterized by new-onset hypertension with or without proteinuria and/or end-organ damage, may be influenced by exposure to endocrine-disrupting chemicals present in processed foods and associated with modern lifestyles. This study explores this potential link using a non-animal approach to identify early diagnostic biomarkers for preeclampsia. Seventy pregnant women aged 21-41 years participated, completing questionnaires assessing socio-demographic factors, Suboptimal Health Status Questionnaire scores for fatigue, digestive, cardiovascular, immune, and mental health issues, and exposure to endocrine-disrupting chemicals from processed food consumption and daily product use. Peripheral blood samples were analyzed for hormone profiles, complete blood count, and liver function tests. Statistical analysis revealed that mothers above 27 years old, with a Body Mass Index exceeding 32.25 Kg/m², and a Mean Arterial Pressure of 108.4 ±1.1 mmHg exhibited a potential obesogenic effect on preeclampsia development. Socio-demographic factors like lower economic class, housewife status, primiparous pregnancy, non-graduate education, and rural residence were significantly associated. Analysis of biochemical parameters revealed that serum creatinine, blood urea, total protein, platelet count, blood urea nitrogen, bilirubin profile, LFT profile, and thyroid profile showed potential detrimental effects on kidney, liver, muscle, and thyroid function in preeclampsia patients. Notably, PC, serum urea, bilirubin, total protein, SGOT, ALP, and TSH levels were significantly associated with preeclampsia in individuals reporting higher exposure to EDCs. Minor biochemical alterations were also observed with dairy product consumption. SHS-25 analysis indicated a significant increase in fatigue, and digestive, cardiovascular, immune, and mental health-related issues in patients. Probably, biochemical alterations due to EDC exposure from processed foods and modern lifestyle habits contribute to organ dysfunction in preeclampsia. Identifying these potential biomarkers may pave the way for the development of non-invasive, early diagnostic tools for improved preeclampsia management. This research emphasizes the importance of non-animal testing methods for assessing EDC-related health risks in pregnancy and contributes to the advancement of early PE diagnosis strategies.

Background: Preeclampsia (PE) and gestational diabetes mellitus (GDM) are complex pregnancy disorders characterized by hypertension, proteinuria, increased blood glucose levels, and metabolic dysfunction. Methods: We investigated lymphocyte proliferation, immune function, key antioxidants, and metabolic and mitochondrial enzyme activities in women with PE and PE with GDM compared to normotensive pregnant (NP) controls. Lymphocyte proliferation was assessed following phytohemagglutinin (PHA) stimulation at varying concentrations (0.5, 2.5, and 5 µg/mL). Activities of key antioxidant enzymes, metabolic enzymes, and mitochondrial enzymes were measured. Other stress markers, including nitric oxide (NO) production and lipid peroxidation (TBARS), along with acetylcholine esterase (AChE) activity, and proinflammatory cytokine assays (IL-6 and TNF-α) were also evaluated from the PHA-induced lymphocytes. Results: Lymphocyte proliferation in response to PHA was significantly increased in PE and PE with GDM groups compared to NP, although low-dose PHA (0.5 and 2.5 µg/mL) moderately enhanced proliferation in NP. IL-6 and TNF-α levels were notably elevated in both disease groups. Antioxidant activities of SOD, GST, GPx and AChE, Citrate synthase, Cytochrome c oxidase, and NO production were significantly reduced in PE and PE with GDM, while hexokinase activity involved in glycolysis was elevated in both groups. Further, TBARS levels were elevated in the disease groups, particularly in PE with GDM. Conclusions: The findings arise from a clinical cross-sectional study and highlight significant immune alterations, oxidative stress, and mitochondrial impairment in PE and PE with GDM. The observed elevation in proinflammatory cytokines further underscore the role of immune activation in the pathogenesis of these complications, emphasizing the integrated immunometabolic shifts identified in this study, as potential molecular indicators for early intervention.

Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes.