Normal Pregnancy Research Articles

Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

Immunological regulation and the role of autophagy in preeclampsia.

Autophagy is a bulk degradation system that maintains cellular homeostasis by producing energy and/or recycling excess proteins. During early placentation, extravillous trophoblasts invade the decidua and uterine myometrium, facing maternal immune cells, which participate in the immune suppression of paternal and fetal antigens. Regulatory T cells will likely increase in response to a specific antigen before and during early pregnancy. Insufficient expansion of antigen-specific Treg cells, which possess the same T cell receptor, is associated with the pathophysiology of preeclampsia, suggesting sterile systemic inflammation. Autophagy is involved in reducing inflammation through the degradation of inflammasomes and in the differentiation and function of regulatory T cells. Autophagy dysregulation induces protein aggregation in trophoblasts, resulting in placental dysfunction. In this review, we discuss the role of regulatory T cells in normal pregnancies. In addition, we discuss the association between autophagy and regulatory T cells in the development of preeclampsia based on reports on the role of autophagy in autoimmune diseases.

The value of Middle cerebral and umbilical arteries Doppler indices in pregestational diabetic versus normal pregnancies in prediction of adverse neonatal outcome

The value of Middle cerebral and umbilical arteries Doppler indices in pregestational diabetic versus normal pregnancies in prediction of adverse neonatal outcome

Serum Vitamin D3 level in spontaneous abortion cases in comparison to ongoing viable pregnancies: A case–control study in a tertiary medical college

Background: The immunoregulatory functions of Vitamin D3 play a vital role in the maintenance of normal pregnancy. Several studies have reported the association of low serum Vitamin D3 levels with spontaneous abortion. Aims and Objectives: The purpose of the study was to determine the association between serum Vitamin D3 level and spontaneous abortion cases in a tertiary medical college. Materials and Methods: The case–control study was conducted at the Department of Gynecology and Obstetrics, Medical College, Kolkata. The study population included 50 women with spontaneous abortion (cases) and 50 women with viable pregnancy beyond 20 weeks of gestation (controls). The cases and controls were matched with respect to age, socioeconomic status, and laboratory parameters. Investigations performed for both groups were ultrasonography for confirmation of abortion and viable pregnancy, serum Vitamin D3, and other biochemical markers. Data were compared between cases and controls using the Chi-square test and unpaired “t” test along with the calculation of odds ratios (OR). Results: About 24% of cases and 10% of controls belonged to Vitamin D3 deficient category. The difference was statistically significant (P=0.009, d.f.=2) (OR: 2.84, 95% confidence intervals [CI]: 0.92–8.80). Bleeding PV was present in 50% of cases and 4% of controls (P=0.0001, d.f.=1) (OR: 24.00, 95% CI: 5.25–109.65). Abdominal pain was complained by 46% of cases and 10% of controls (P=0.0001, d.f.=1) (OR: 7.67, 95% CI: 2.61–22.54). Conclusion: Vitamin D3 deficiency was present more in spontaneous abortion cases in comparison to viable pregnancies. Routine daily supplementation of vitamin D3 during the first trimester of pregnancy should be incorporated into the ongoing national program. Training of health workers to educate pregnant women and their family members regarding the importance of vitamin D3 is the need of the hour.

Factors Related to Husband's Involment in Antenatal Care Visits in High Risk Pregnant Women

High-risk pregnancy is a pregnancy that can cause harm and complications to the mother and fetus during pregnancy, childbirth or after delivery compared to normal pregnancy and childbirth. The aim of this research is to determine "Factors Associated with Husband's Involvement in Antenatal Care Visits for High Risk Pregnant Women". The design in this research is cross-sectional. The sample in the study was 187 people. The validated questionnaire was used in collecting data for this research. and analyzed univariately using frequency distribution, bivariate using chi-square test, and multivariate using logistic regression test. The research results showed that age (p=0.875), education (p=0.004), income (p=0.015). Based on the multivariate results, it was found that the most dominant factor related to husband's involvement in antenatal care visits was education with the highest OR value of 0.139.

Placental and Renal Pathways Underlying Pre-Eclampsia.

Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction. Chronic kidney disease is an established risk factor for the development of pre-eclampsia, as angiogenic homeostasis is altered and the maternal circulation is already hypertensive. Facing pre-eclampsia in the context of chronic kidney disease is a challenging emergency for both the mother and the fetus. The clinical features and the management of this multi-organ disorder are clearly defined in the modern literature but the underlying pathophysiologic mechanisms remain not fully elucidated. Understanding the pathophysiology that mediates the onset of pre-eclampsia itself and in synergy with chronic kidney disease is fundamental for developing prompt prevention strategies, treatment planning, and patient counseling. This review aims to summarize the main molecular mechanisms involved in the process of pre-eclampsia, with a particular focus on the role of the kidneys and hormonal pathways related to renal function in normal pregnancy and pre-eclamptic syndromes.

Risk of Pre-Eclampsia in Women with Low Serum Ionized Magnesium

Background: There are many risk factors of development of preeclampsia among the pregnant women. Objective: The purpose of the present study has set out to assess the relationship between preeclampsia and blood ionized magnesium levels.
 Methodology: This case-control study was performed in the Department of Obstetrics and Gynaecology, Dhaka Medical College and Hospital from January 2020 to December 2021 for a period of 2(two) years. Pregnant patients who showed preeclampsia were all the amounts of ionized magnesium in venous blood collected from patients with preeclampsia. Additionally, the magnesium levels of age-matched, healthy pregnant women were determined.
 Results: A total number of 100 pregant women included in this study of which 50 pregnant women were designated as case and the rest 50 pregnant women were control. It has found that serum levels of ionized magnesium were significantly decreased among preeclamptic cases (0.58 ± 0.06) as compared to normal pregnancies (0.72 ± 0.05) (p < 0.001). Using a cut-off value of 0.7 mmol/l, the serum ionized magnesium level was divided into two groups and was compared between cases and controls. The risk of developing preeclampsia was more than 33 (95% CI = 10.9 – 102.1) times higher in pregnant women with serum magnesium level < 0.7 mmol/L than those pregnant women with serum magnesium level 0.7 or > 0.7 mmol/L.
 Conclusion: Low level of serum ionized magnesium is a risk factor of development of preeclampsia.

HLA-G Expression/Secretion and T-Cell Cytotoxicity in Missed Abortion in Comparison to Normal Pregnancy.

The main role of HLA-G is to protect the semi-allogeneic embryo from immune rejection by proper interaction with its cognate receptors on the maternal immune cells. Spontaneous abortion is the most common adverse pregnancy outcome, with an incidence rate between 10% and 15%, with immunologic dysregulation being thought to play a role in some of the cases. In this study, we aimed to detect the membrane and soluble HLA-G molecule at the maternal-fetal interface (MFI) and in the serum of women experiencing missed abortion (asymptomatic early pregnancy loss) in comparison to the women experiencing normal early pregnancy. In addition, the proportion of T cells and their cytotoxic profile was evaluated. We observed no difference in the spatial expression of HLA-G at the MFI and in its serum levels between the women with missed abortions and those with normal early pregnancy. In addition, comparable numbers of peripheral blood and decidual total T and γδT cells were found. In addition, as novel data we showed that missed abortion is not associated with altered extravilous invasion into uterine blood vessels and increased cytotoxicity of γδT cells. A strong signal for HLA-G on non-migrating extravilous trophoblast in the full-term normal placental bed was detected. In conclusion, HLA-G production at the MFI or in the blood of the women could not be used as a marker for normal pregnancy or missed abortions.

Protective role of complement factor H against the development of preeclampsia.

Pregnancy is an immunologically regulated, complex process. A tightly controlled complement system plays a crucial role in the successful establishment of pregnancy and parturition. Complement inhibitors at the feto-maternal interface are likely to prevent inappropriate complement activation to protect the fetus. In the present study, we aimed to understand the role of Factor H (FH), a negative regulator of complement activation, in normal pregnancy and in a model of pathological pregnancy, i.e. preeclampsia (PE). The distribution and expression of FH was investigated in placental tissues, various placental cells, and in the sera of healthy (CTRL) or PE pregnant women via immunohistochemistry, RT-qPCR, ELISA, and Western blot. Our results showed a differential expression of FH among the placental cell types, decidual stromal cells (DSCs), decidual endothelial cells (DECs), and extravillous trophoblasts (EVTs). Interestingly, FH was found to be considerably less expressed in the placental tissues of PE patients compared to normal placental tissue both at mRNA and protein levels. Similar results were obtained by measuring circulating FH levels in the sera of third trimester CTRL and PE mothers. Syncytiotrophoblast microvesicles, isolated from the placental tissues of PE and CTRL women, downregulated FH expression by DECs. The present study appears to suggest that FH is ubiquitously present in the normal placenta and plays a homeostatic role during pregnancy.

Lipid metabolism during pregnancy: consequences for mother and child.

Accommodating fetal growth and development, women undergo multiple physiological changes during pregnancy. In recent years, several studies contributed to the accumulating evidence about the impact of gestational hyperlipidemia on cardiovascular risk for mother and child. This review aims to provide a comprehensive overview of the current research on lipid profile alterations during pregnancy and its associated (cardiovascular) outcomes for mother and child from a clinical perspective. In a normal pregnancy, total and LDL-cholesterol levels increase by approximately 30-50%, HDL-cholesterol by 20-40%, and triglycerides by 50-100%. In some women, for example, with familial hypercholesterolemia (FH), a more atherogenic lipid profile is observed. Dyslipidemia during pregnancy is found to be associated with adverse (cardiovascular) outcomes for the mother (e.g. preeclampsia, gestational diabetes, metabolic syndrome, unfavorable lipid profile) and for the child (e.g. preterm birth, large for gestational age, preatherosclerotic lesions, unfavorable lipid profile). The lipid profile of women during pregnancy provides a unique window of opportunity into the potential future cardiovascular risk for mother and child. Better knowledge about adverse outcomes and specific risk groups could lead to better risk assessment and earlier cardiovascular prevention. Future research should investigate implementation of gestational screening possibilities.

Влияние дидрогестерона на окситоцинореактивность нейтрофилов венозной крови беременных женщин и родильниц

The ability of steroid hormones to modulate the binding of oxytocin to oxytocin receptors is of great interest. The purpose of this article was to study the effect of oxytocin, dydrogesterone and their mixture on the radical activity of venous blood neutrophils in pregnant women during the 3rd trimester of a normal pregnancy and in women on the 1st day after term delivery. Materials and methods. Using the chemiluminescent method (BChL-07 biochemiluminometer) and cell stimulation with latex particles, we studied non-genomic and genomic effects of dydrogesterone (5∙10–5 g/l), oxytocin (10–7 IU/l) and their mixture on the radical activity of venous blood neutrophils in 20 pregnant women in the 3rd trimester of a normal pregnancy and 10 women on the 1st day after term labour. When the noise level was automatically subtracted, the following were recorded: maximum intensity of the synthesis of reactive oxygen species, time to reach the maximum of synthesis intensity, and area under the chemiluminogram curve, reflecting the total synthesis of radical particles over the course of 30 min. Results. Baseline radical activity of neutrophils in women on the 1st day after term delivery was found to be three times higher than in women during the 3rd trimester of a normal pregnancy. Judging by the area under the chemiluminogram curve and maximum intensity of the synthesis of reactive oxygen species, oxytocin had an equal stimulating effect on venous blood neutrophils both in pregnant women during the 3rd trimester and in puerperae. Dydrogesterone in each group of women equally stimulated the radical activity of neutrophils, both non-genomically and genomically. In both groups, under the action of dydrogesterone through membrane receptors, oxytocin reactivity of neutrophils remained unchanged, while through nuclear receptors, it decreased. Possible mechanisms of progesterone’s involvement in the regulation of oxytocin reactivity of the myometrium and venous blood neutrophils in women during pregnancy and postpartum are considered.

PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development

Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.

Differential 5'-tRNA Fragment Expression in Circulating Preeclampsia Syncytiotrophoblast Vesicles Drives Macrophage Inflammation.

The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5'-tRNA fragments (5'-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy. 5'-tRFs are produced in response to stress. We hypothesized STB-EV 5'-tRF release might change in preeclampsia. We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5'-tRFs in vivo. We quantified 5'-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5'-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses. 5'-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5'-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5'-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5'-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5'-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5'-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells. Increased release of syncytiotrophoblast-derived vesicle-bound 5'-tRF-Glu-CTC contributes to preeclampsia pathophysiology.

Bioinformatics analysis identifies potential autophagy key genes and immune infiltration in preeclampsia.

Preeclampsia (PE) is a disease that seriously threatens maternal and fetal health. Appropriate autophagy can shield the placenta from oxidative stress, but its role in PE is unclear. To identify potential autophagy-related genes in PE. Microarray datasets from the Gene Expression Omnibus database, compassing the test dataset GSE10588, along with validation datasets GSE4707 and GSE60438 GPL10558, were utilized. Differentially expressed genes (DEGs) were identified using the limma R package, intersected with autophagy-related genes. Hub genes were obtained using the Cytoscape software and analyzed via gene set enrichment analysis (GSEA). The diagnostic capability of hub genes was evaluated using receiver operating characteristic (ROC) curve analysis. Analysis of immune cell infiltration was conducted using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT methods. Placental tissues were collected from 10 normal pregnant women and 10 preeclamptic pregnant women, and the expression of hub genes was validated through immunohistochemistry and western blot analysis. Analysis of the microarray data identified 2224 DEGs, among which 26 were autophagy-related DEGs identified through intersection with autophagy genes. Ten hub genes were identified. Immune cell infiltration analysis suggested the potential involvement of T regulatory cells (Tregs), natural killer cells, neutrophils, and T follicular helper cells in the pathogenesis of PE. ROC curve analysis indicated promising diagnostic capabilities for EGFR and TP53. Additionally, levels of EGFR and TP53 were significantly higher in placental tissue from PE pregnancies compared to normal pregnancies. EGFR and TP53 may play a role in PE by influencing autophagy.

Dynamic changes in the gut microbiota during three consecutive trimesters of pregnancy and their correlation with abnormal glucose and lipid metabolism

IntroductionDuring normal pregnancy, changes in the gut microbiota (GM) in response to physiological alterations in hormonal secretion, immune functions and homeostasis have received extensive attention. However, the dynamic changes in the GM during three consecutive trimesters of pregnancy and their relationship with glucose and lipid metabolism have not been reported. In this study, we aimed to investigate the dynamic changes in the diversity and species of the GM during three consecutive trimesters in women who naturally conceived, and their relationships with abnormal fasting blood glucose (FBG) and serum lipid levels.MethodsA total of 30 pregnant women without any known chronic or autoimmune inflammatory disease history before pregnancy were enrolled during the first trimester. Serum and stool samples were collected during the first trimester, the second trimester, and the third trimester. Serum samples were tested for FBG and blood lipid levels, and stool specimens were analyzed by 16S rDNA sequencing.ResultsThe abundance ratio of bacteroidetes/firmicutes showed an increasing tendency in most of the subjects (19/30, 63.3%) from the first to the third trimester. LEfSe analysis showed that the abundance of Bilophila was significantly increased from the first to the third trimester. In addition, at the genus level, the increased relative abundance of Mitsuokella, Clostridium sensu stricto and Weissella were potentially involved in the development of high FBG during pregnancy. The raised relative abundance of Corynebacterium, Rothia and Granulicatella potentially contributed to the occurrence of dyslipidemia during pregnancy.ConclusionsThere are dynamic changes in the GM during the three trimesters, and the alterations in some bacterium abundance may contribute to the development of high FBG and dyslipidemia during pregnancy. Monitoring enterotypes and correcting dysbiosis in the first trimester may become new strategies for predicting and preventing glucolipid metabolism disorders during pregnancy.

Multi-omics analysis reveals the associations between altered gut microbiota, metabolites, and cytokines during pregnancy.

For embryo implantation and fetal development, the maternal immune system undergoes dramatic changes. The mechanisms involved in inducing alterations of maternal immunity have not been fully clarified. Gut microbiome and metabolites were thought to influence the host immune response. During normal pregnancy, notable changes occur in the gut microbiota and metabolites. However, the relationship of these alterations to immune function during pregnancy remains unclear. In this study, we examined gut microbiota, fecal metabolites, plasma metabolites, and cytokines in pregnant women and non-pregnant women. Our findings revealed that, in comparison to non-pregnant women, pregnant women exhibit a significant increase in the relative abundance of Actinobacteriota and notable differences in metabolic pathways related to bile acid secretion. Furthermore, there was a marked reduction in pro-inflammatory cytokines levels in pregnant women. Correlation analyses indicated that these alterations in cytokines may be linked to specific gut bacteria and metabolites. Bacteria within the same microbial modules exhibited consistent effects on cytokines, suggesting that gut bacteria may function as functional groups. Mediation analysis further identified that certain bacteria might influence cytokines through metabolites, such as bile acids and arachidonic acid. Our findings propose potential biological connections between bacteria, metabolites, and immunity, which require further validation in future studies.IMPORTANCEA great number of studies have focused on diseases induced by intestinal microecological disorders and immune imbalances. However, the understanding of how intestinal microbiota interacts with immunity during normal pregnancy, which is fundamental to studying pathological pregnancies related to intestinal microbiota disturbances, has not been well elucidated. Our study employed multi-omics analysis to discover that changes in gut microbiota and metabolites during pregnancy can impact immune function. In addition, we identified several metabolites that may mediate the effect of gut microbes on plasma cytokines. Our study offered new insights into our understanding of the connections between the gut microbiome, metabolome, and the immune system during pregnancy.

Seroepidemiology of Herpes Simplex Viruses Type 1 and 2 in Pregnant Women in Croatia.

Background and Objectives: Herpes simplex viruses (HSV-1 and HSV-2) are one of the most widespread causes of human viral infections. In Croatia, only two published studies have analyzed the seroprevalence of HSV infections in childbearing-aged and pregnant women (2005-2010), while more recent data are lacking. This study aimed to analyze the prevalence and risk factors for HSV-1 and HSV-2 infections among pregnant women in Croatia in the period from 2011 to 2021. Materials and Methods: This study included 667 pregnant women aged 16-45 years submitted for HSV-1 and HSV-2 serology testing. Serum samples were initially screened for HSV-1 and HSV-2 IgM and IgG antibodies using a commercial ELISA test with a confirmation of HSV-2-positive samples using an immunoblot assay. Results: The overall IgG seroprevalence rates were 69.9% for HSV-1 and 3.8% for HSV-2. A significant gradual increase in the HSV-2 seroprevalence with age was observed from 0.5% in participants under 30 years to 8.3% in participants above 40 years. The HSV-1 seroprevalence was stable up to 40 years (70.0 and 68.3%, respectively), with an increase to 86.1%, but this difference did not reach statistical significance. Area of residence (urban or suburban/rural), geographic region (continental or coastal), and obstetric history (normal pregnancy or unfavorable obstetric history) were not associated with HSV-1 and HSV-2 seroprevalence. Older age was found to be a significant risk factor for HSV-2 seropositivity in both univariate and multivariate risk analysis. Conclusions: HSV-1 infection is widely prevalent among pregnant women with a stable trend over time. However, a declining trend in the HSV-2 seroprevalence was observed compared to 2005-2010. Serological screening in pregnant women is important in identifying seronegative women who are susceptible to HSV infection as well as seropositive women who are at risk for genital herpes recurrence during delivery.

Exosomes as modulators of embryo implantation.

Exosomes, known as extracellular vehicles (EVs), are found in biological fluids. They have the capability to carry and transfer signaling molecules, such as nucleic acids and proteins, facilitating intercellular communication and regulating the gene expression profile in target cells. EVs have the potential to be used as biomarkers in diagnosis, prognosis and also as feasible therapeutic targets. The available evidence suggests that exosomes play critical roles in the reproductive system, particularly during implantation, which is widely recognized as a crucial step in early pregnancy. A proper molecular dialogue between a high-quality embryo and a receptive endometrium is essential for the establishment of a normal pregnancy. This review focuses on the key role of exosomes originated from various sources, including the embryo, seminal fluid, and uterus fluid, based on the available evidence. It explores their potential applications as a novel approach in assisted reproductive technologies (ART).

Dynamics of the Gut Microbiota and Faecal and Serum Metabolomes during Pregnancy-A Longitudinal Study.

Normal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that the gut microbiota may have an important role in the progression of pregnancy, these findings have been inconsistent, and the relationship between the gut microbiota and metabolites that change dynamically during and after pregnancy remains to be clarified. In this longitudinal study, we comprehensively profiled the temporal dynamics of the gut microbiota, Bifidobacterium communities, and serum and faecal metabolomes of 31 women during their pregnancies and postpartum periods. The microbial composition changed as gestation progressed, with the pregnancy and postpartum periods exhibiting distinct bacterial community characteristics, including significant alterations in the genera of the Lachnospiraceae or Ruminococcaceae families, especially the Lachnospiraceae FCS020 group and Ruminococcaceae UCG-003. Metabolic dynamics, characterised by changes in nutrients important for fetal growth (e.g., docosatrienoic acid), anti-inflammatory metabolites (e.g., trans-3-indoleacrylic acid), and steroid hormones (e.g., progesterone), were observed in both serum and faecal samples during pregnancy. Moreover, a complex correlation was identified between the pregnancy-related microbiota and metabolites, with Ruminococcus1 and Ruminococcaceae UCG-013 making important contributions to changes in faecal and serum metabolites, respectively. Overall, a highly coordinated microbiota-metabolite regulatory network may underlie the pregnancy process. These findings provide a foundation for enhancing our understanding of the molecular processes occurring during the progression of pregnancy, thereby contributing to nutrition and health management during this period.

Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies.

Preeclampsia (PE) is a serious hypertensive disorder affecting 4-5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.