Pregnancy-related Diseases Research Articles

The effects of Helicobacter pylori infection on pregnancy-related diseases and fetal development in diabetes in pregnancy

BackgroundThis study aimed to determine the association of Helicobacter pylori (H. pylori) infection with pregnancy-related diseases and fetal development in women with diabetes in pregnancy (DIP).MethodsAll the participants were recruited before 16 weeks of gestation. According to their medical history and the results of a 75-g oral glucose tolerance test at the 24th week of pregnancy, the participants were divided into a normal control group (NC group), a gestational diabetes mellitus group (GDM group), and a pre-pregnancy diabetes mellitus group (PGDM group). According to the results of an H. pylori serum antibody detection test, each group was further divided into two subgroups: an H. pylori positive subgroup (HP+ subgroup) and an H. pylori negative group (HP- subgroup). The incidences of pregnancy-related diseases, the fetal developmental status, and the newborn status were compared among the groups.ResultsThis study recruited 356 pregnant women. The infection rates of type I H. pylori were significantly higher in the GDM group and the PGDM group than in the NC group (χ2=6.949, P=0.031). With the exception of the NC-HP+ subgroup, there were higher incidences of pregnancy-related diseases in the HP+ subgroups than in the HP− subgroups (P<0.05). Furthermore, the incidences of pregnancy-induced hypertension (PIH), preeclampsia, and premature delivery were significantly higher in the GDM-HP+ subgroup and the PGDM-HP+ subgroup than in the NC-HP+ subgroup (P<0.05). At the end of pregnancy, all 3 HP− subgroups showed better fetal development than the HP+ subgroups (P<0.05), and the NC-HP+ subgroup showed better fetal development than the GDM-HP+ and PGDM-HP+ subgroups (P<0.05). Meanwhile, the PGDM-HP+ subgroup showed poor fetal development, even in the 2nd trimester of pregnancy.ConclusionsH. pylori infection is extremely common in DIP. For women with DIP, infection with H. pylori can increase the risks of pregnancy-related diseases and poor fetal development. H. pylori screening and eradication therapy before pregnancy may aid in preventing pregnancy-related diseases and improve fetal development.

A Proposal for new Quality attributes for Schedule R of the Indian Drugs and Cosmetics Act, 1940

Original sin is not life but it is a part of life. It establishes psychological, mental and physical health. Statistics reveal several deaths of pregnant mothers, ectopic pregnancy, child deaths or original sin related diseases, apart from lethal consequences which is out of the scope of this article. Use of contraceptive methods may be beneficial in several circumstances avoiding unwanted pregnancies. A few television channels were scrolling the various contraceptive methods and educating the citizens for a good health perspective. The objective of this review is not only to enlighten the various contraceptive methods but also in knowing their failure level methods and some unique evaluation methods that can be included in Schedule R of the Drugs and Cosmetics Act, 1940 so as to append the quality attributes with in-vitro and in-vivo original sin correlated models. The review illustrates role of researchers/pharmacist/medical professionals in problem solving skills and is also expected to answer the general questions experienced and witnessed by the author relating to original sin including gender sensitization. In India, several national level bodies also insist for academic accreditations the contributions relating to gender sensitization and the article meets criteria as well. If the author as a common man sends a sample for current products for assessing abstract attributes, does Central Drugs Laboratory can?, a thought in this direction is needed which in turn indicates role of questionnaires/instruments in the Drugs and Cosmetics Act, 1940 and Rules 1945. Does a need of a statutory warning for original sin products is necessary, a question is raised and a review by persons skilled in art is proposed. The article illustrates either side to the context. The article also helps to overcome barriers from society, professional point of view relating to original sin related research either at the pre-clinical or at the clinical levels.

Pregnancy outcome in women with different rheumatic diseases: a retrospective analysis

Objective: Pregnancy may influence the course of inflammatory rheumatic diseases and, conversely, rheumatic and musculoskeletal diseases (RMDs) can affect the outcome of pregnancy. This study aimed to retrospectively analyse the outcome of pregnancy and disease in women with RMDs. Method: Subjects were patients with high-risk pregnancy and connective tissue diseases (CTDs) or inflammatory joint diseases (IJDs) managed at a specialized rheumatology outpatient clinic from 2007 to 2014. Data from conception to 6 months postpartum were collected from medical records and a questionnaire, and analysed regarding clinical symptoms, medications, pregnancy complications, birth outcomes, and infant development. Generalized estimating equations were used to compare the groups (CTD vs IJD). Results: The eligible 66 pregnancies in 57 RMD patients were divided into two groups by RMD type: CTD (n = 48) or IJD (n = 18). The live birth rate was 97% overall. Pregnancy complications (excluding two twin pregnancies) were incurred in 39.1%: miscarriage (n = 2), premature delivery (n = 12), small-for-gestational-age infants (n = 5), and/or pregnancy-related diseases (n = 14). Three children born to women with CTDs had affected development (autism spectrum disorder, congenital heart disease, bronchopulmonary dysplasia). CTD infants had a significantly lower mean gestational age (in weeks) (p = 0.042), weight (p = 0.009), and length (p = 0.016) at birth than IJD infants. Conclusion: Although the live birth rate was high, complications occurred in 39.1% of pregnancies in this cohort. Therefore, interdisciplinary management of pregnant women with RMDs at specialized clinics is strongly recommended.

PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells.

Autophagy plays an important role in the normal development and function of trophoblast cells and is precisely regulated during pregnancy. Dysregulated autophagy contributes to the abnormal proliferation of trophoblasts, which is closely related to the occurrence of pregnancy-related diseases. Placenta specific 8 (PLAC8, Onzin) is a multifaceted protein proven to promote autophagy and potentiate various tumor progression. Its role in trophoblasts remains elusive. In our present study, PLAC8 expression was detected in tissues of first-trimester placentas (n=5), term placentas (n=5), choriocarcinoma (n=5), and placental site trophoblastic tumor (n=5). PLAC8 expression was increased in gestational neoplasms compared with normal pregnancies. mCherry-EGFP-LC3B reporter and transmission electron microscopy confirmed PLAC8 promoted the autophagic flux of human trophoblast cells. Both gain-of-function and loss-of-function experiments demonstrated PLAC8-regulated autophagy-related genes, including ATG5, ATG12, and Beclin-1. In addition, our data showed that PLAC8 co-localized with p53 and promoted its degradation, and p53 re-expression partially abrogated the PLAC8-induced autophagy activity. Furthermore, the overexpression of PLAC8 promoted cell viability and proliferation, acting as a protective mechanism of trophoblasts against the cytotoxicity of etoposide (VP-16). Such a phenomenon was effectively abrogated by autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ). In conclusion, PLAC8-induced autophagy to promote the proliferation of trophoblasts. This study provided insights into the mechanism of PLAC8-induced autophagy in trophoblasts, which is significant for a wide range of gestational diseases and may contribute to developing novel treatment strategies for trophoblastic diseases.

Cadmium cytotoxicity and possible mechanisms in human trophoblast HTR-8/SVneo cells.

The accumulation of cadmium (Cd) in the human body through food chain can lead to adverse pregnancy outcomes. In this study, Cd cytotoxicity and its mechanisms in HTR-8/SVneo cells were investigated. Cd disrupted the cellular submicrostructure and inhibited the cell viability in a time- and dose-dependent manner. The levels of reactive oxygen species, malondialdehyde content, and the activities of glutathione peroxidase (GSH-Px) and total superoxode dismutase (T-SOD) were concentration-dependently increased by Cd. In addition, Cd dose-dependently inducedcell apoptosis and decreased cell migration and invasion capacities. Finally, Cd significantly upregulated all the genes related to oxidative stress (SOD1, ROS1, and HSPA6), inflammatory response, cell cycle, apoptosis, and migration and invasion. This study will provide insights into the prevention and treatment of pregnancy-related diseases caused by Cd intoxication.

Sex Differences in the Exocrine Pancreas and Associated Diseases.

Differences in pancreatic anatomy, size, and function exist in men and women. The anatomical differences could contribute to the increase in complications associated with pancreatic surgery in women. Although diagnostic criteria for pancreatitis are the same in men and women, major sex differences in etiology are reported. Alcohol and tobacco predominate in men, whereas idiopathic and obstructive etiologies predominate in women. Circulating levels of estrogens, progesterone, and androgens contribute significantly to overall health outcomes; premenopausal women have lower prevalence of cardiovascular and pancreatic diseases suggesting protective effects of estrogens, whereas androgens promote growth of normal and cancerous cells. Sex chromosomes and gonadal and nongonadal hormones together determine an individual’s sex, which is distinct from gender or gender identity. Human pancreatic disease etiology, outcomes, and sex-specific mechanisms are largely unknown. In rodents of both sexes, glucocorticoids and estrogens from the adrenal glands influence pancreatic secretion and acinar cell zymogen granule numbers. Lack of corticotropin-releasing factor receptor 2 function, a G protein–coupled receptor whose expression is regulated by both estrogens and glucocorticoids, causes sex-specific changes in pancreatic histopathology, zymogen granule numbers, and endoplasmic reticulum ultrastructure changes in acute pancreatitis model. Here, we review existing literature on sex differences in the normal exocrine pancreas and mechanisms that operate at homeostasis and diseased states in both sexes. Finally, we review pregnancy-related pancreatic diseases and discuss the effects of sex differences on proposed treatments in pancreatic disease.

Healthcare providers and the oral health of the mother and the unborn child.

One of the main information channels on oral health during pregnancy is direct and regular contact with obstetricians and gynecologists, who are the health professionals that future mothers consult most often during pregnancy. Thus, it would be desirable to promote information campaigns on dental topics aimed at women, starting with pre- and post-partum courses, to prepare them for the changes of the perinatal period. In recent years, health professionals have increasingly focused on maternal health during pregnancy. In a survey conducted in the United States just over ten years ago on a large sample of obstetrician-gynecologists, most respondents recognised the importance of pregnancy care. However, 77% of respondents had not advised the patients to undergo dental checkups, and 73% seldom asked the patients whether they had seen a dentist in the past 12 months [Morgan, 2009]. In light of these discouraging findings, in 2012 the American College of Obstetricians and Gynecologists and the American Dental Academy devised appropriate guidelines [OHRC, 2012]: It would be desirable to promote similar initiatives globally, and we ask our readers to report to us the current status in their own country. Regarding Italy, the recent partnership between the European Federation of Periodontology and the Italian Society of Periodontology has made it possible to offer a wealth of useful information, accessible online, aimed at professionals and expectant mothers as an aid to achieve optimal oral health in pregnancy [EFP and SIdP, 2017]. Thanks to the compliance and the positive attitude of future mothers, as a result of the support of healthcare professionals and widespread dissemination, it is now possible to reduce the incidence of both pregnancy-related and childhood diseases. We are well aware that the paediatric dentist is often consulted too late, in the presence, for instance, of advanced carious lesions. Therefore it is crucial for general and paediatric dentists to inform future mothers on the critical issues that may arise during pregnancy and the first years of their child's life, and to provide them a set of instructions, starting with basic notions such as the recommended frequency of brushing and the correct use of fluorinated toothpastes. Finally, it would be useful to promote programmes that are aimed at evaluating the patients' knowledge about aspects such as prevention and oral health. This would aid in identifying any weaknesses in the current prevention strategies, and help health professionals implement targeted projects supported by both the private sector and the national health system in order to include all the information required to achieve true primary prevention.

Correlation of ultrasound imaging with histopathological findings in gestational trophoblastic disease

Introduction: Gestational trophoblastic diseases include a spectrum of pregnancy-related diseases caused by abnormal proliferation of the placenta. The main aim of this study was to correlate ultrasound imaging with histopathological findings.&#x0D; Method: This is the retrospective chart review of findings of transabdominal ultrasonography in clinically suspected gestational trophoblastic diseases which were confirmed by histopathology after the evacuation of a product of conception during 3 years from 2016 to 2019 at Patan Hospital, Patan Academy of Health Sciences Nepal. The accuracy of sonography was correlated with histopathological findings and analyzed by Fisher’s Exact or Pearson’s Chi-square tests. The study was approved ethically.&#x0D; Result: Among 155 clinically suspected gestational trophoblastic diseases, ultrasonography was accurate in 141(91.0%) and confirmed by histopathology; 14(9.0%) were non-molar miscarriages. In 141 histologically confirmed trophoblastic disease, 110(71.0 %) were partial mole, 15(9.7%) complete mole, 12(7.7%) invasive mole and 3(1.9 %) persistent mole, and 1(0.6%) choriocarcinoma. Snowstorm appearance and absence of fetus were statistically significant ultrasonography findings.&#x0D; Conclusion: The ultrasound is a reliable non-invasive first-line imaging modality for the diagnosis of gestational trophoblastic diseases and had an accuracy of 91% as confirmed by histopathology in this study.

From Midwife-Dominated to Midwifery-Led Antenatal Care: A Meta-Ethnography.

Provision of antenatal care includes risk identification, prevention and management of pregnancy-related diseases, but also health education, health promotion, support and guidance to smooth the transition to parenthood. To ensure good perinatal health, high-quality, free and easily accessed antenatal care is essential. The aim of this study was to identify, integrate and synthesize knowledge of midwives’ experiences of providing antenatal care, attending to clients’ individual needs whilst facing multiple challenges. We conducted a meta-ethnography, which is a seven-step grounded, comparative and interpretative methodology for qualitative evidence synthesis. A lines-of-argument synthesis based on two metaphors was developed, based on refutational themes emerging from an analogous translation of findings in the included 14 papers. The model reflects midwives’ wished-for transition from a midwife-dominated caring model toward a midwifery-led model of antenatal care. Structural, societal and personal challenges seemingly influenced midwives’ provision of antenatal care. However, it emerged that midwives had the willingness to change rigid systems that maintain routine care. The midwifery-led model of care should be firmly based in midwifery science and evidence-based antenatal care that emphasize reflective practices and listening to each woman and her family. The change from traditional models of antenatal care towards increased use of digitalization no longer seems to be a choice, but a necessity given the ongoing 2020 pandemic.

Association of adverse outcomes of intrahepatic cholestasis of pregnancy with zonulin levels

Our aim was to investigate serum zonulin levels in intrahepatic cholestasis of pregnancy (ICP) and to determine the usefulness of zonulin in ICP follow-up. A prospective case-control study was carried out which included 88 pregnant women (44 patients with ICP and 44 controls). Maternal serum samples obtained from all participants and zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Compared with controls, women with ICP had significantly higher zonulin levels (mean 0.728 ± 0.520 ng/mL vs. 1.303 ± 0.63 ng/mL, p <.001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of zonulin levels for ICP, the area under the curve (AUC) was 0.761 (95% CI: 0.661–0.860). Multivariable logistic regression analysis revealed serum zonulin levels was independently associated with adverse perinatal outcomes (OR = 1.278, 95% CI: 0.232–7.041), severity ICP (OR: 7.535, 95% CI: 1.597–13.553) and also unresponsiveness to treatment in ICP (OR: 4.178, 95% CI: 0.929–8.784). IMPACT STATEMENT What is already known on this subject? Zonulin is a regulator protein that increases the intestinal permeability by modulating the intercellular tight junctions (TJ). It is the only physiological protein known to control intestinal permeability and damage of the intestinal barrier is one of the causes of absorption disorders, inflammation and autoimmunity. ICP is a relatively non-threatening condition to women but is linked with a higher risk of preterm delivery, foetal distress and foetal death. What do the results of this study add? This study showed that increased levels of zonulin are associated with adverse perinatal outcomes, severity of ICP and unresponsiveness to treatment in ICP. What are the implications of these findings for clinical practice and/or further research? Focussing on preservation of intestinal permeability may be an alternative preventive strategy to reduce the adverse perinatal outcomes and severity of ICP. Further longitudinal studies are needed to verify the relationships among zonulin levels and pregnancy-related diseases.

Expression and Regulation of Aquaporins in Pregnancy Complications and Reproductive Dysfunctions.

Aquaporins (AQPs), small hydrophobic integral membrane proteins, mediate rapid transport of water and small solutes. The abnormal expressions of AQPs are associated with pregnancy complications and reproductive dysfunctions, including preeclampsia, gestational diabetes mellitus, tubal ectopic pregnancy, intrahepatic cholestasis of pregnancy, preterm birth, chorioamnionitis, polyhydramnios, and oligohydramnios, thus resulting in adverse pregnancy outcomes. This review explains the alterations of AQPs in pregnancy complications and reproductive dysfunctions and summarizes the molecular mechanisms involved in the regulations of AQPs by drugs such as oxytocin, polychlorinated biphenyls, all-trans-retinoic acid, salvia miltiorrhiza, and insulin, or other factors such as oxygen and osmotic pressure. All the research provides evidence that AQPs could be the new therapeutic targets of pregnancy-related diseases.

Analysis of HLA-G long-read genomic sequences in mother\u2013offspring pairs with preeclampsia

Preeclampsia is a pregnancy-induced disorder that is characterized by hypertension and is a leading cause of perinatal and maternal–fetal morbidity and mortality. HLA-G is thought to play important roles in maternal–fetal immune tolerance, and the associations between HLA-G gene polymorphisms and the onset of pregnancy-related diseases have been explored extensively. Because contiguous genomic sequencing is difficult, the association between the HLA-G genotype and preeclampsia onset is controversial. In this study, genomic sequences of the HLA-G region (5.2 kb) from 31 pairs of mother–offspring genomic DNA samples (18 pairs from normal pregnancies/births and 13 from preeclampsia births) were obtained by single-molecule real-time sequencing using the PacBio RS II platform. The HLA-G alleles identified in our cohort matched seven known HLA-G alleles, but we also identified two new HLA-G alleles at the fourth-field resolution and compared them with nucleotide sequences from a public database that consisted of coding sequences that cover the 3.1-kb HLA-G gene span. Intriguingly, a potential association between preeclampsia onset and the poly T stretch within the downstream region of the HLA-G*01:01:01:01 allele was found. Our study suggests that long-read sequencing of HLA-G will provide clues for characterizing HLA-G variants that are involved in the pathophysiology of preeclampsia.

A life-threatening case of pregnancy-related atypical Haemolytic uremic syndrome and successful treatment with Eculizumab

BackgroundPregnancy-related Atypical Haemolytic Uremic Syndrome (P-aHUS) is a rare condition affecting genetically predisposed women during pregnancy. It is often difficult to diagnose and has a significant impact on maternal and foetal outcomes. It is characterised by microangiopathic haemolytic anaemia and kidney injury from thrombotic microangiopathy.Case presentationA 27-year-old female of Lebanese descent presented at 36 weeks’ gestation with foetal death in-utero (FDIU) with placental abruption on a background of previously normal antenatal visits. She was coagulopathic and anaemic with anuric acute kidney injury, requiring emergency Caesarean section, intubation and dialysis. Her coagulopathy rapidly resolved, however, her anaemia and renal dysfunction persisted. A diagnosis of P-aHUS was made, and she was empirically treated with Eculizumab. Her ADAMTS13 level was normal, effectively excluding thrombotic thrombocytopenic purpura. Within 2 weeks of treatment her haematological parameters improved, and her renal function began to recover and within 2 months she became dialysis independent.ConclusionThis case highlights the challenges of a timely diagnosis of P-aHUS from other pregnancy-related diseases. Although our patient is dialysis-independent, her risk of relapse remains high with subsequent pregnancies. Currently we are awaiting her genetic sequencing to complete her assessment for underlying mutations and are determining the safest approach to a future planned pregnancy.

The Role of Contrast-Enhanced Ultrasound in Evaluating Gestational Trophoblastic Neoplasia: A Preliminary Study.

ObjectiveWe aimed to compare the imaging features of gestational trophoblastic neoplasias (GTNs) and benign pregnancy-related uterine diseases on contrast-enhanced ultrasound (CEUS) to explore the clinical value of CEUS in differentiating these two types of uterine lesions.Materials and MethodsIn this prospective study, patients with GTNs before and after chemotherapy and benign pregnancy-related uterine lesions received conventional US and CEUS. The imaging features and parameters of CEUS of the lesions were assessed.ResultsA total of 73 patients were enrolled in this study, including 48 with GTNs and 25 with benign lesions. The enhancement pattern of newly diagnosed GTNs was mainly diffuse enhancement (70.8%), with a non-enhanced area of less than 1/3 of the entire lesion. For the benign group, the enhancement pattern was mainly ring-shaped enhancement (72.0%), and the non-enhanced area was more than 1/2 (68.0%), significantly different from that of GTNs (P = 0.000 and 0.002, respectively). Forty-one lesions demonstrated unclear boundaries on greyscale US but clearly displayed on CEUS. In both the benign and malignant groups, the measurements of lesion size on CEUS were larger than those on greyscale US (P = 0.000). The measurement differences (ΔD: D2-D1) of the malignant cases were higher than those of the benign cases (P = 0.001).ConclusionGTNs and benign pregnancy-related uterine diseases have different imaging characteristics on CEUS. The boundary and involved range of the lesion can be clearly demonstrated on CEUS. CEUS possesses clinical value in diagnosing and evaluating GTNs and benign pregnancy-related diseases.

Methylmercury cytotoxicity and possible mechanisms in human trophoblastic HTR-8/SVneo cells

Methylmercury (MeHg) exposure during pregnancy can lead to adverse outcomes, including miscarriage and intrauterine growth retardation. In this study, MeHg cytotoxicity and its mechanisms in HTR-8/SVneo cells were investigated. MeHg inhibited HTR-8/SVneo cell viability and severely disrupted the cellular submicrostructure, showing a time-dose effect relationship. After MeHg treatment, the reactive oxygen species levels, malondialdehyde content, and superoxide dismutase (SOD) and catalase activities in the HTR-8/SVneo cells increased significantly with increased MeHg concentration (P<0.05). Similarly, MeHg also induced HTR-8/SVneo cell apoptosis in a dose-dependent manner. The proportion of cells in G1 phase decreased with increasing MeHg concentration, while that in the S and G2/M phases gradually increased. Moreover, cell migration and invasion capacities gradually decreased with increasing MeHg concentration, showing a significant difference between the MeHg-treated and control groups. Genes related to oxidative stress (HSPA6, HSPA1A, Nrf2, SOD1, HO-1, NQO1, OSGIN1, and gPX1), cell cycle (P21 and CDC25A), apoptosis (CYCS and AIFM2), and migration and invasion (CXCL8, CXCL3, CLU, IL24, COL3A1, MAPT, and ITGA7) were differentially expressed in the MeHg-treated group, indicating MeHg toxicity and mechanism of action. This study will provide insights into the prevention and treatment of pregnancy-related diseases caused by MeHg.

Roles of HLA-G in the Maternal-Fetal Immune Microenvironment.

During pregnancy, the maternal uterus and fetus form a special microenvironment at the maternal-fetal interface to support fetal development. Extravillous trophoblasts (EVTs), differentiated from the fetus, invade into the decidua and interact with maternal cells. Human leukocyte antigen (HLA)-G is a non-classical MHC-I molecule that is expressed abundantly and specifically on EVTs in physiological conditions. Soluble HLA-G (sHLA-G) is also found in maternal blood, amniotic fluid, and cord blood. The abnormal expression and polymorphisms of HLA-G are related to adverse pregnancy outcomes such as preeclampsia (PE) and recurrent spontaneous abortion (RSA). Here we summarize current findings about three main roles of HLA-G during pregnancy, namely its promotion of spiral artery remodeling, immune tolerance, and fetal growth, all resulting from its interaction with immune cells. These findings are not only of great significance for the treatment of pregnancy-related diseases but also provide clues to tumor immunology research since HLA-G functions as a checkpoint in tumors.

Mining of combined human placental gene expression data across pregnancy, applied to PPAR signaling pathway

IntroductionTo date, we have only an incomplete understanding of how gene expression in the human placenta changes at the genome-wide scale from very early in gestation to term. Our aim was to investigate the dynamic changes in gene expression throughout placentation. MethodsIn our study, gene expression profiles were collected of human placentas from 4 to 40 gestational weeks of age. Simple linear regression and weighted correlation network analysis were applied to identify genes of interest. Analyses of gene enrichment, including gene ontology and pathways from the Kyoto Encyclopedia of Genes and Genomes, were performed using clusterProfiler. Finally, dynamic changes in the expression of individual genes were represented using line graphs of scaled and adjusted gene expression. ResultsOur results highlighted a total of 5173 genes that are involved in different periods of placentation. Downstream annotation of these genes revealed the biological processes and pathways involved, from which we chose to further investigate the PPAR signaling pathway. We were able to detect changes over time in many genes involved in lipid storage/metabolism, including members of the FABP family and LPL. These patterns were corroborated by lipid staining of placental sections, which revealed a significant decrease in lipid droplet content in placentas from early in the first trimester to term. ConclusionOur study provides detailed information on the dynamics of biological processes and pathways across human placentation. These findings give us new clues for deciphering the normal functions of placentation and the ways in which the mis-regulation of these pathways may be linked to pregnancy-related diseases. As an example, our results show that the PPAR signaling pathway mediates a constant decrease in placental lipid content over the course of pregnancy.

The Role of the Gut Microbiota in the Prevention and Management of Gestational Diabetes Mellitus: Are We There Yet?

Current nonpharmacological approaches, including diet and exercise interventions, for preventing and treating gestational diabetes mellitus are effective for less than 50% of women. Recent evidence suggests that the gut microbiome is integrally involved in maternal glucose homeostasis. Changes to the composition and metabolic behavior of the gut microbiota may play a role in the development and persistence of gestational diabetes mellitus. Thus, there is growing interest in targeting the maternal gut microbiome for preventing and managing pregnancy-related diseases including gestational diabetes mellitus. Future progress may come from a systems biology approach to elucidate the role of the gut microbiota in maternal glucose homeostasis.

Downregulation of hsa_circ_0005243 induces trophoblast cell dysfunction and inflammation via the \u03b2-catenin and NF-\u03baB pathways

BackgroundGestational diabetes mellitus (GDM) is a common complication in pregnancy that poses a serious threat to the health of both mother and child. While the specific etiology and pathogenesis of this disease are not fully understood, it is thought to arise due to a combination of insulin resistance, inflammation, and genetic factors. Circular RNAs (circRNAs) are a special kind of non-coding RNA that have attracted significant attention in recent years due to their diverse activities, including a potential regulatory role in pregnancy-related diseases, such as GDM.MethodsWe previously reported the existence of a novel circRNA, hsa_circ_0005243, which was identified by RNA sequencing. In this study, we examined its expression in 20 pregnant women with GDM and 20 normal pregnant controls using quantitative reverse transcription PCR analysis. Subsequent in vitro experiments were conducted following hsa_circ_0005243 knockdown in HTR-8/SVneo cells to examine the role of hsa_circ_0005243 in cell proliferation and migration, as well as the secretion of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Finally, we examined the expression of β-catenin and nuclear factor kappa-B (NF-κB) signaling pathways to assess their role in GDM pathogenesis.ResultsExpression of hsa_circ_0005243 was significantly reduced in both the placenta and plasma of GDM patients. Knockdown of hsa_circ_0005243 in trophoblast cells significantly suppressed cell proliferation and migration ability. In addition, increased secretion of inflammatory factors (TNF-α and IL-6) was observed after hsa_circ_0005243 depletion. Further analyses showed that knockdown of hsa_circ_0005243 reduced the expression of β-catenin and increased nuclear NF-κB p65 nuclear translocation.ConclusionsDownregulation of hsa_circ_0005243 may be associated with the pathogenesis of GDM via the regulation of β-catenin and NF-κB signal pathways, suggesting a new potential therapeutic target for GDM.

Ambient particle radioactivity and gestational diabetes: A cohort study of more than 1 million pregnant women in Massachusetts, USA

BackgroundExposure to ionizing radiation increases the risk of chronic metabolic disorders such as insulin resistance and type 2 diabetes. Internal ionizing radiation from inhaled radioactive aerosol may contribute to the associations between fine particulate matter (PM2.5) and gestational diabetes mellitus (GDM). MethodsWe used the Massachusetts Registry of Vital Records to study 1,061,937 pregnant women from 2001 to 2015 with a singleton pregnancy without pre-existing diabetes. Gross β activity measured by seven monitors of the U.S. Environmental Protection Agency's RadNet monitoring network was utilized to represent ambient particle radioactivity (PR). We obtained GDM status from birth certificates and used logistic regression analyses adjusted for socio-demographics, maternal comorbidities, PM2.5, temperature and relative humidity. We also examined effect modification by smoking habits. ResultsAmbient particle radioactivity exposure during first and second trimester of pregnancy was associated with higher odds of GDM (OR: 1.18 (95% CI 1.10 to 1.22). Controlling for PM2.5 did not substantially change the effects of PR on GDM. In women that reported being former or current smokers, the association between PR and GDM was null. In the full cohort, the overall effect of PM2.5 on GDM without adjusting for PR was not significant. ConclusionThis is the first population-based study to examine the association between particle radioactivity and gestational diabetes mellitus - one of the most common pregnancy-related diseases with lifelong effects for the mother and the fetus. This finding has important public health policy implications because it enhances our understanding about the toxicity of PR, a modifiable risk factor, which to date, has been considered only as an indoor and occupational air quality risk.