Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia’s effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD’s cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD’s impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD’s complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.

Background: In healthy pregnancies, components of the Renin-Angiotensin system (RAS) are present in the placental villi and contribute to invasion, migration, and angiogenesis. At the same time, soluble fms-like tyrosine kinase 1 (sFlt-1) production is induced after binding of ANG-II to its receptor (AT-1R) in response to hypoxia. As RAS plays an essential role in the pathogenesis of COVID-19, we hypothesized that angiogenic marker (sFlt-1) and RAS components (ANG-II and ACE-2) may be related to adverse outcomes in pregnant women with COVID-19; Methods: Prospective cohort study. Primary outcome was severe pneumonia. Secondary outcomes were ICU admission, intubation, sepsis, and death. Spearman’s Rho test was used to analyze the correlation between sFlt-1 and ANG-II levels. The sFlt-1/ANG-II ratio was determined and the association with each adverse outcome was explored by logistic regression analysis and the prediction was assessed using receiver-operating-curve (ROC); Results: Among 80 pregnant women with COVID-19, the sFlt-1/ANG-II ratio was associated with an increased probability of severe pneumonia (odds ratio [OR]: 1.31; p = 0.003), ICU admission (OR: 1.05; p = 0.007); intubation (OR: 1.09; p = 0.008); sepsis (OR: 1.04; p = 0.008); and death (OR: 1.04; p = 0.018); Conclusion: sFlt-1/ANG-II ratio is a good predictor of adverse events such as pneumonia, ICU admission, intubation, sepsis, and death in pregnant women with COVID-19.

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Emerging evidence implicates gut and vaginal microbiota dysbiosis in preeclampsia pathogenesis through its roles in immune regulation, inflammation, and placental function. This review explores the mechanisms linking microbiota alterations to preeclampsia and evaluates the therapeutic potential of microbiota-targeted interventions. A systematic search using MeSH terms related to “preeclampsia”, “microbiota”, and “dysbiosis” identified studies on microbiota and preeclampsia pathophysiology. Data extraction focused on microbial alterations and mechanistic insights. Gut dysbiosis, characterized by reduced beneficial bacteria and short-chain fatty acid production, weakens the intestinal barrier, exacerbates systemic inflammation, and impairs placental development. Vaginal dysbiosis, marked by reduced Lactobacillus species, promotes local inflammation, increasing placental dysfunction risk. Therapeutic strategies, including probiotics, prebiotics, and dietary modifications, show promise in restoring microbial balance and mitigating preeclampsia risk. Microbiota dysbiosis significantly contributes to preeclampsia pathogenesis through inflammation, endothelial dysfunction, and placental impairment. Interventions targeting microbial balance, such as probiotics and dietary modifications, show promise for prevention, but further research and large-scale trials are essential to validate their efficacy and safety.

Cardiomyocyte injury and troponin T elevation has been reported within COVID-19 patients and are associated with a worse prognosis. Limited data report this association among COVID-19 pregnant patients. Objective: We aimed to analyze the association between troponin T levels in severe COVID-19 pregnant women and risk of viral sepsis, intensive care unit (ICU) admission, or maternal death. Methods: We performed a prospective cohort of all obstetrics emergency admissions from a Mexican National Institute. All pregnant women diagnosed by reverse transcription-polymerase chain reaction (RT-qPCR) for SARS-CoV-2 infection between October 2020 and May 2021 were included. Clinical data were collected, and routine blood samples were obtained at hospital admission. Seric troponin T was measured at admission. Results: From 87 included patients, 31 (35.63%) had severe COVID-19 pneumonia, and 6 (6.89%) maternal deaths. ROC showed a significant relationship between troponin T and maternal death (AUC 0.979, CI 0.500–1.000). At a cutoff point of 7 ng/mL the detection rate for severe pneumonia was 83.3% (95%CI: 0.500–0.100) at 10% false-positive rate. Conclusion: COVID-19 pregnant women with elevated levels of troponin T present a higher risk of death and severe pneumonia.

Oxidative stress (OS) induced by SARS-CoV-2 infection may play an important role in COVID-19 complications. However, information on oxidative damage in pregnant women with COVID-19 is limited. Objective: We aimed to compare lipid and protein oxidative damage and total antioxidant capacity (TAC) between pregnant women with severe and non-severe COVID-19. Methods: We studied a consecutive prospective cohort of patients admitted to the obstetrics emergency department. All women positive for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction (RT-qPCR) were included. Clinical data were collected and blood samples were obtained at hospital admission. Plasma OS markers, malondialdehyde (MDA), carbonylated proteins (CP), and TAC; angiogenic markers, fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF); and renin-angiotensin system (RAS) markers, angiotensin-converting enzyme 2 (ACE-2) and angiotensin-II (ANG-II) were measured. Correlation between OS, angiogenic, and RAS was evaluated. Results: In total, 57 pregnant women with COVID-19 were included, 17 (28.9%) of which had severe COVID-19; there were 3 (5.30%) maternal deaths. Pregnant women with severe COVID-19 had higher levels of carbonylated proteins (5782 pmol vs. 6651 pmol; p = 0.024) and total antioxidant capacity (40.1 pmol vs. 56.1 pmol; p = 0.001) than women with non-severe COVID-19. TAC was negatively correlated with ANG-II (p < 0.0001) and MDA levels (p < 0.0001) and positively with the sFlt-1/PlGF ratio (p = 0.027). Conclusions: In pregnant women, severe COVID-19 is associated with an increase in protein oxidative damage and total antioxidant capacity as a possible counterregulatory mechanism.