Fetal Placenta Research Articles

Genomic Insights into Gestational Weight Gain: Uncovering Tissue-Specific Mechanisms and Pathways.

Increasing gestational weight gain (GWG) is linked to adverse outcomes in pregnant persons and their children. The Early Growth Genetics (EGG) Consortium identified previously genetic variants that could contribute to early, late, and total GWG from fetal and maternal genomes. However, the biologic mechanisms and tissue-Specificity of these variants in GWG is unknown. We evaluated the association between genetically predicted gene expression in five relevant maternal (subcutaneous and visceral adipose, breast, uterus, and whole blood) from GTEx (v7) and fetal (placenta) tissues and early, late, and total GWG using S-PrediXcan. We tested enrichment of pre-defined biological pathways for nominally (P < 0.05) significant associations using the GENE2FUNC module from Functional Mapping and Annotation of Genome-Wide Association Studies. After multiple testing correction, we did not find significant associations between maternal and fetal gene expression and early, late, or total GWG. There was significant enrichment of several biological pathways, including metabolic processes, secretion, and intracellular transport, among nominally significant genes from the maternal analyses (false discovery rate p-values: 0.016 to 9.37×10). Enriched biological pathways varied across pregnancy. Though additional research is necessary, these results indicate that diverse biological pathways are likely to impact GWG, with their influence varying by tissue and weeks of gestation.

Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Homeostatic Type I IFN Response at the Placenta Contributes to Sex-biased Neurodevelopmental Outcome

Abstract The maternal-fetal interface, placenta, plays pivotal roles in fetal development. Recent evidence shows that the placenta contributes to the sex-biased prevalence of some developmental disorders such as neurodevelopmental disorders. Commencing an exploration into the molecular intricacies of fetal sex-specific transcriptional changes within the placenta, our study leveraged single-cell RNA sequencing. We uncovered a diminished expression of interferon (IFN)-responsive genes (ISGs) in male fetus-associated trophoblasts compared to female, which have pivotal roles in the process of spiral artery remodeling. We further found maternal NK cells associated with male fetus placenta showed a reduction in the interferon production pathway. The introduction of maternal immune activation (MIA), which induces neurodevelopmental abnormalities in male offspring, it reversed these sex-specific disparities in the placenta. In pursuit of unraveling the potential link between sex-specific ISGs expression and neurodevelopmental outcomes in MIA offspring, we selectively removed IFN alpha and beta receptor subunit 1 (IFNAR1) in a trophoblast-specific manner. Blunting IFNAR1 in the placenta protected male offspring from MIA-induced behavioral abnormalities. Our data suggests the intricate landscape of sex-specific IFN response at the maternal-fetal interface and underscore its role in shaping the sex-bias observed in MIA-induced neurodevelopmental phenotypes.

Determination of the vimentin marker in the placenta of cows in normal and delayed afterbirth

Modern dairy enterprises suffer financial losses due to the high morbidity of the dairy herd after calving. The current study presents the distribution of the extracellular matrix of the ratio of mesenchymal elements of the placenta in cows during physiological and complicated labor with retained placenta. Caruncle and cotyledon tissues were collected every 6 hours after spontaneous labor until the membranes were released. Depending on the time of release of membranes after birth, the samples were classified as follows: 1 - control group, in which the membranes were released within 6 hours after birth, considered complete, spontaneous and physiological (Partus normalis); 2 - experimental group, in which the membranes were released 9-12 hours after the fetus was delivered, the birth was considered pathological with retention of the placenta (Retenzio sekundarium). Identification of changes in the content of vimentin-containing elements involves the development of a system for express diagnostics of reproductive pathologies in dairy cattle during labor and after calving. Samples of placenta from cows undergoing physiological labor and placenta retention were subjected to standard histological procedures. Paraffin sections of the placenta, 5 µm thick, were mounted on glasses treated with poly-L-lysine (Menzel). Using immunohistochemical and immunofluorescence double staining, the immunolocalization of antibodies to vimentin was studied using clone EPR3776 (rabbit, monoclonal, Taiwan, GeneTex, Int. Corp). The localization of the content of intermediate filaments of the mesenchymal phenotype in the cow placenta was studied, in which the presence of a large number of small capillaries was revealed both in the villi of the cotyledons and in the caruncular crypts during normal pregnancy and childbirth, as well as the equilibrium ratio of mesenchymal structures in the placenta. In childbirth complicated by placenta retention, a decrease in the vascularization of chorionic villi in the cotyledons and degradation of filaments involved in the formation of cellular contacts between the cytotrophoblasts of the chorionic villi of the cotyledons of the fetal part of the placenta and endothelial and epithelial cells of the crypts of the caruncles of the maternal part of the placenta were demonstrated. Pronounced expression of vimentin was found in the cells lining the crypts of caruncles, as well as in the cytoplasmic membrane of villous cytotrophoblasts. A study of the ratio of mesenchymal elements using the immunofluorescent method of double staining of antibodies to vimentin showed that a significant decrease in them both in the cytotrophoblasts of cotyledons and in the epithelial cells of caruncles is observed in the placenta of cows with the development of a state of placental insufficiency, leading to a complication of labor by retention of the placenta. The present study provides the first evidence that vimentin is expressed in bovine placentomes during the gestational, prenatal, and parturient periods and suggests that this filament may, in combination with steriodogenic homones, mediate the separation of the fetal placenta from the maternal placenta.

Ferroptosis is involved in trophoblast cells cytotoxicity induced by black phosphorus nanoparticles

Black phosphorus (BP) is a new type of nanomaterial, which has been widely used in many biomedical fields due to its superior properties, but there are few studies on the toxicity of BP, especially in the reproductive system. To explore the effects of BP exposure on reproduction and reveal its molecular mechanism, we firstly investigated the potential toxicity of black phosphorus nanoparticles (BPNPs) in vivo. The results showed that BP exposure in pregnant mice can reduce the weight of fetal mice and placenta. H&E staining further indicated the changes of placental cross-section and vascular remodeling after BP treatment. Then, human exvillous trophoblast HTR8/SVneo was treated with different concentrations of BPNPs. We found that BPNPs induced significant cytotoxicity, including dose-dependent reduction of cell viability and proliferation. Trophoblast cell migration and invasion were also impaired by BPNPs exposure. Moreover, pretreatment with Cytochalasin D (Cyto-D), a classical phagocytic inhibitor, alleviated the decline of cell viability induced by BPNPs. Transcriptome sequencing showed that BPNPs exposure led to ferroptosis. Subsequently, the related indexes of ferroptosis were detected, including increase of iron ion concentration, decrease of the ferroptosis marker, GPX4 (Glutathione Peroxidase 4), increase of FTL (Ferritin Light Chain), and increase of lipid peroxidation indexes (MDA level and decrease of GSH level). In addition, ferroptosis inhibitors (Fer-1 and DFO) pretreatment can alleviate both the cytotoxic effects and functional impairment induced by BPNPs. In summary, our study confirmed the reproductive toxicity of BPNPs for the first time, and constructed BPNPs injury model in vitro using human villus trophoblast cells and revealed the role of ferroptosis in this process, which deepened our understanding of the biosafety of black phosphorus nanomaterials.

Gender associations between phthalate exposure and biomarkers of oxidative stress: A prospective cohort study.

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.

Gross as well as microscopic anatomy and physiological functions of fetal placenta in Jaffrabadi buffaloes

The present study was conducted to know the gross morphology and histo-morphological structure of fetal placenta in Jaffrabadi buffaloes. Parameters like calf weight, placental weight, numbers, and size of cotyledons were observed in Jaffrabadi buffaloes and morphologically, fetal cotyledons were convex and non-pendunculated in Jaffrabadi buffaloes were found. Histological studies of small and large cotyledons showed extensive branching of secondary and tertiary villi that were longer, slender, and well developed in Jaffrabadi buffalo. A less developed basal lamina was seen in small cotyledon whereas developed basal lamina with numerous capillaries and connective tissue were observed in the large cotyledon. The diameter of trophoblast giant cells (TGC) in larger cotyledons were significantly (P&lt;0.05) than the small cotyledons in expelled placenta at full term in Jaffrabadi buffaloes. A distinct distribution of carbohydrate and lipids in cotyledons were observed between large and small cotyledons as evident by acid mucopolysaccharides, neutral polysaccharides, and sudanophilic staining. Specific staining for calcium with Alizarin red stain showed that calcium is not present in a noticeable amount in small and large cotyledons. Isolation and culture of Jaffrabadi placental cells in M-199 medium with antibiotics and 2% FBS results in the efficient production of progesterone, estrogen, and testosterone. This study has shown that trophoblast cells are the actual sites for steroid hormone production. These cultured placental cells (1x106 cells/ ml) produce Progesterone, Estradiol-17β and Testosterone in the range of 1.72 to 2.12, 16.03 to 19.51 and 0.51 to 0.58 ng/ml, respectively in Jaffrabadi buffalo.

Paternal DDT exposure induces sex-specific programming of fetal growth, placenta development and offspring’s health phenotypes in a mouse model

Mounting evidence suggests that environmentally induced epigenetic inheritance occurs in mammals and that traits in the progeny can be shaped by parental environmental experiences. Epidemiological studies link parental exposure to environmental toxicants, such as the pesticide DDT, to health phenotypes in the progeny, including low birth and increased risk of chronic diseases later in life. Here, we show that the progeny of male mice exposed to DDT in the pre-conception period are born smaller and exhibit sexual dimorphism in metabolic function, with male, but not female, offspring developing severe glucose intolerance compared to controls. These phenotypes in DDT offspring were linked to reduced fetal growth and placenta size as well as placenta-specific reduction of glycogen levels and the nutrient sensor and epigenetic regulator OGT, with more pronounced phenotypes observed in male placentas. However, placenta-specific genetic reduction of OGT only partially replicates the metabolic phenotype observed in offspring of DDT-exposed males. Our findings reveal a role for paternal pre-conception environmental experiences in shaping placenta development and in fetal growth restriction. While many questions remain, our data raise the tantalizing possibility that placenta programming could be a mediator of environmentally induced intergenerational epigenetic inheritance of phenotypes and needs to be further evaluated.

Altered placental immune cell composition and gene expression with isolated fetal spina bifida.

Fetal spina bifida (SB) is more common in pregnant people with folate deficiency or anomalies of folate metabolism. It is also known that fetuses with SB have a higher risk of low birthweight, a condition that is typically placental-mediated. We therefore hypothesized that fetal SB would associate with altered expression of key placental folate transporters and an increase in Hofbauer cells (HBCs), which are folate-dependent placental macrophages. Folate receptor-α (FRα), proton coupled folate receptor (PCFT), and reduced folate carrier (RFC) protein localization and expression (immunohistochemistry) and HBC phenotypes (HBC abundance and folate receptor-β [FRβ] expression; RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases; n=12) and in term (n=10) and gestational age (GA) - and maternal body mass index - matched (n=12) controls without congenital anomalies. Cases had a higher proportion of placental villous cells that were HBCs (6.9%vs. 2.4%, p=.0001) and higher average HBC FRβ expression (3.2 mRNA molecules per HBC vs. 2.3, p=.03) than GA-matched controls. HBCs in cases were largely polarized to a regulatory phenotype (median 92.1% of HBCs). In sex-stratified analyses, only male cases had higher HBC levels and HBC FRβ expression than GA-matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabeling. HBC abundance and FRβ expression by HBCs are increased in placentae of fetuses with SB, suggesting immune-mediated dysregulation in placental phenotype, and could contribute to SB-associated comorbidities.

Point-of-care ultrasound, today, tomorrow, and the future – the place for task sharing

Background: Maternal and neonatal morbidity and mortality remain public health concerns. A study onmortality in Kenyan hospitals found that neonates comprise two-thirds of deaths in the pediatric agegroup (0–13 years). These deaths are caused by preventable conditions or those, which can bemanaged better if diagnosed early, such as placenta insufficiency, placenta previa, severe fetal growthrestriction, congenital abnormalities, multiple pregnancies, and breech presentation; these can all beidentified using point-of-care ultrasound (POCUS). Obstetrical ultrasound availability is limited to level 4and higher facilities, yet most women access lower levels of health care. Implementation of POCUS iscurrently limited because of a lack of appropriate training, limited scope of practice for frontline workers,and legal framework.Objective: The POCUS project is being undertaken to develop national guidelines to facilitate the roll outand scale-up of obstetrical POCUS.Methods: A collaborative participatory approach is planned for the development of the national POCUSguidelines. The key in this process is the identification of suitable frontline workers who, with adjustmentto their scope of practice, appropriate training, implementation of a supervision/referral system, canundertake obstetrical POCUS and gain buy-in from regulatory bodies, the inclusion of voices of relevantstakeholders, and leadership from government. A landscape and stakeholders analysis will also beundertaken as part of the process of the guideline development.Results: Narrative literature review shows that the WHO recommends effective and reliable antenatalultrasound services to be available to all pregnant women to optimize maternal and newborn healthoutcomes and at least one ultrasound scan up to 24 weeks of pregnancy. That there are deliberateefforts in Kenya to introduce POCUS with pilot training and implementation. Where obstetrical POCUS isimplemented, it is useful in diagnosing fetal malpresentation, placenta previa, congenital malformations,or multiple pregnancies. Appropriate interventions, such as reduction of cesarean delivery, induction oflabor, reduction of small for gestational age, low birthweight, preterm birth, and stillbirths, can improve thehealth outcome of the mother and neonate. There is a need to develop national POCUS guidelines.Conclusions: Implementation of POCUS may be riddled with difficulties, particularly where frontlineworkers’ current scope of practice may not allow them to perform such procedures, regulatoryframework, lack of knowledge, awareness, negative attitude, or behavior. The proposed guidelines willaddress these barriers.

A training program for obstetrics point-of-care ultrasound to rural health care providers in Kenya

Background: Ultrasound is a crucial and effective diagnostic tool in medicine. Recent advancements in technology have led to the increased use of point-of-care ultrasound (POCUS). Access to ultrasound equipment and training programs in low- and middle-income countries (LMICs) is limited. Despite the World Health Organization’s (WHO) recommendations for universal antenatal ultrasounds, POCUS for reproductive health has not been widely used in LMICs. We describe the implementation of obstetrics POCUS training for high-risk conditions in rural public health care facilities in Kenya. Methods: As part of the initiation of a large-scale implementation study of obstetrics-POCUS, clinician trainees were recruited from rural Kenyan hospitals to participate in a series of five-day POCUS workshops. Trainers provided brief didactic lessons followed by hands-on training with live models and at regional clinical sites for five obstetrics POCUS applications. Instructor-observed assessments of students’ scanning and image interpretation were performed during the training period. Assessment of knowledge and confidence was performed via an online pretest and posttest and objective structured clinical examinations. Results: 514 midlevel health care providers were trained over three months, with a trainer: trainee ratio of 1:5. Of the 514 trained HCPs, 468 were from 8 rural counties with poor maternal and neonatal outcomes, while the remaining 46 were from nearby facilities. Obstetrics POCUS topics covered included malpresentation, multiple gestation, fetal cardiac activity, placenta, and amniotic fluid volume. There was a marked improvement in the posttraining test scores. Conclusion: Our implementation description serves as a guide for the successful rapid dissemination of obstetrics POCUS training for midlevel providers. Our experience demonstrates the feasibility of a short intensive POCUS training to rapidly establish specific POCUS skills in efforts to rapidly scale POCUS access and services. There is a widespread need for expanding access to ultrasound during pregnancy through accessible obstetrics POCUS training programs.

Does the birth plan match what is relevant to women? Preferences of Spanish women when giving birth

BackgroundTo support women in making shared decisions, it is important to know what is relevant to them. The aim is to explore which of the options included in birth plans (BP) are of most interest to women, and which are more controversial. In addition, the possible association of this variability with personal characteristics.MethodsThe data are part of a cross-sectional descriptive study, carried out in xxx, on the clinimetric characteristics of two instruments to measure women’s needs in labour and postpartum. Women were recruited consecutively by their midwives during pregnancy check-ups, receive a link to a digital questionnaire and were allowed to provide links to the questionnaires to other pregnant women. Women were asked to determine their level of agreement with statements about the birth environment, accompaniment, pain relief, medical intervention and neonatal care. The relationship between agreement with each statement, socio-demographic variables and fear of childbirth (W-DEQ-A) was analysed using a combination of descriptive statistics to analyse frequencies, and regression models to test the effect of socio-demographic variables and fear of childbirth on those items with the greatest variability.ResultsTwo hundred forty-seven women responded. More than 90% preferred a hospital delivery, with information about and control over medical intervention, accompanied by their partner and continuous skin-to-skin contact with the newborn. There are other questions to which women attach less importance or which show greater variability, related to more clinical aspects, like foetal monitoring, placenta delivery, or cord clamping… Various factors are related to this variability; parity, nationality, educational level, risk factor or fear of childbirth are the most important.ConclusionsSome items referring to the need for information and participation are practically unanimous among women, while other items on technical interventions generate greater variability. That should make us think about which ones require a decision after information and which ones should be included directly. The choice of more interventional deliveries is strongly associated with fear of childbirth.

MFO-TL: modified firefly optimal transfer learning based motion correction of fetal brain and placenta MRI for thyroid prediction

MFO-TL: modified firefly optimal transfer learning based motion correction of fetal brain and placenta MRI for thyroid prediction

PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses.

This study aimed to develop a physiologically based pharmacokinetic (PBPK) model that simulates metabolically cleared compounds' pharmacokinetics (PK) in pregnant subjects and fetuses. This model accounts for the differences in tissue sizes, blood flow rates, enzyme expression levels, plasma protein binding, and other physiological factors affecting the drugs' PK in both the pregnant woman and the fetus. The PBPKPlus™ module in GastroPlus® was used to model the PK of metoprolol, midazolam, and metronidazole for both non-pregnant and pregnant groups. For each of the three compounds, the model was first developed and validated against PK data in healthy non-pregnant volunteers and then applied to predict the PK in the pregnant groups. The model accurately described the PK in both the non-pregnant and pregnant groups and explained well the differences in the plasma concentration due to pregnancy. When available, the fetal plasma concentration, placenta, and fetal tissue concentrations were also predicted reasonably well at different stages of pregnancy. The work described the use of a PBPK approach for drug development and demonstrates the ability to predict differences in PK in pregnant subjects and fetal exposure for metabolically cleared compounds.

Maternal selenium dietary supplementation alters sociability and reinforcement learning deficits induced by in utero exposure to maternal immune activation in mice

Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model.Selenium was administered via drinking water (1.5 ppm) to pregnant dams from gestational day (GD) 9 to birth, and MIA was induced at GD17 using polyinosinic:polycytidylic acid (poly-I:C, 20 mg/kg via intraperitoneal injection). Foetal placenta and brain cytokine levels were assessed using a Luminex assay and brain elemental nutrients assessed using inductively coupled plasma- mass spectrometry. Adult offspring were behaviourally assessed using a reinforcement learning paradigm, the three-chamber sociability test and the open field test. MIA elevated placental IL-1β and IL-17, and Se supplementation successfully prevented this elevation. MIA caused an increase in foetal brain calcium, which was prevented by Se supplement. MIA caused in offspring a female-specific reduction in sociability, which was recovered by Se, and a male-specific reduction in social memory, which was not recovered by Se. Exposure to poly-I:C or selenium, but not both, reduced performance in the reinforcement learning task. Computational modelling indicated that this was predominantly due to increased exploratory behaviour, rather than reduced rate of learning the location of the food reward.This study demonstrates that while Se may be beneficial in ameliorating sociability deficits caused by MIA, it may have negative effects in other behavioural domains. Caution in the use of Se supplementation during pregnancy is therefore warranted.

Role of paralogs in the sex-bias transcriptional and metabolic regulation of the brain-placental axis in mice

IntroductionDuplicated genes or paralogs play important roles in the adaptive function of eukaryotic genomes. Animal studies have shown evidence for the functional role of paralogs in pregnancy, but our knowledge about the role of paralogs in the fetoplacental regulation remains limited. In particular, if fetoplacental metabolic regulation is modulated by differential expression of paralogs remains unexamined. MethodsIn this study, gene expression profiles of day-15 placenta and fetal brain were compared to identify families or groups of paralogous genes expressed in the placenta and brain of male versus female fetuses in mice. A Bayesian modeling was applied to infer directional relationship of transcriptional variation of the paralogs relative to the phylogenetic variation of the genes in each family. Gas chromatography-mass spectrometry (GC-MS) was used to perform untargeted metabolomics analysis of day-15 placenta and fetal brain of both sexes. ResultsWe identified paralog groups that were expressed in a sex and/or tissue biased manner between the placenta and fetal brain. Bayesian modeling showed evidence for directional relationship between expression and phylogeny of specific paralogs. These relationships were sex specific. GC-MS analysis identified metabolites that were expressed in a sex-bias manner between the placenta and fetal brain. By performing integrative analysis of the metabolomics and gene expression data, we showed that specific groups of metabolites and paralogous genes were expressed in a coordinated manner between the placenta and fetal brain. DiscussionThe findings of this study collectively suggest that paralogs play an influential role in the regulation of the brain-placental axis in mice.

Maternal nano-titanium dioxide inhalation exposure alters placental cyclooxygenase and oxidant balance in a sexually dimorphic manner

The placenta plays a critical role in nutrient-waste exchange between the maternal and fetal circulation, and thus impacts fetal growth and development. We have previously shown that nano-titanium dioxide (nano-TiO2) inhalation exposure during gestation decreased fetal female pup and placenta mass [1], which persists in the following generation [2]. In utero exposed females, once mated, their offspring's placentas had increased capacity for H2O2 production. Generation of oxidants such as hydrogen peroxide (H2O2), have been shown to impact cyclooxygenase activity, specifically metabolites such as prostacyclin (PGI2) or thromboxane (TXA2). Therefore, we hypothesized that maternal nano-TiO2 inhalation exposure during gestation results in alterations in placental production of prostacyclin and thromboxane mediated by enhanced H2O2 production in a sexually dimorphic manner. Pregnant Sprague-Dawley rats were exposed to nano-TiO2 aerosols or filtered air (sham-control) from gestational day (GD) 10–19. Dams were euthanized on GD 20, and fetal serum and placental tissue were collected based on fetal sex. Fetal placental zones (junctional zone (JZ) and labyrinth zone (LZ)) were assessed for xanthine oxidoreductase (XOR) activity, H2O2, and catalase activity, as well as 6-keto-PGF1α and TXB2 levels. Nano-TiO2 exposed fetal female LZ demonstrated significantly greater XOR activity compared to exposed males. Exposed fetal female LZ also demonstrated significantly diminished catalase activity compared to sham-control females. Exposed fetal female LZ had significantly increased abundance of 6-keto-PGF1α compared to sham-control females and increased TXB2 compared to exposed males. In the aggregate these data indicate that maternal nano-TiO2 inhalation exposure has a greater impact on redox homeostasis and PGI2/TXA2 balance in the fetal female LZ. Future studies need to address if treatment with an XO inhibitor during gestation can prevent diminished fetal female growth during maternal nano-TiO2 inhalation exposure.

Indications and Outcomes of Maternal and Neonatal Health among Emergency Cesarean Section- a Retrospective Study

Introduction: The rate of cesarean sections is rising globally, with varying indications and outcomes. This study aims to analyze the indications and outcomes of emergency cesarean sections in a Bangladeshi context, focusing on maternal and neonatal health. Methods: This retrospective observational study was conducted at Netrokona Medical College, Bangladesh, from July 2021 to June 2022. It included 100 cases of emergency cesarean sections, excluding elective cases and those with incomplete records. Data on maternal age, gravidity, socioeconomic status, gestational age, BMI, indications for cesarean section, and maternal and neonatal outcomes were collected and analyzed. Result: The majority of cesarean sections were performed on women aged 21-30 (67%). The most common indication was a previous cesarean section (42%), followed by fetal distress (16%) and placenta previa (11%). Maternal outcomes showed 82% of women had no complications, with fever (12%) and excessive blood loss (8%) being the most common issues. Neonatal outcomes were generally positive, with 97% having APGAR scores ≥7. The gender distribution was 59% male and 41% female, and most neonates had normal or healthy birth weights. Conclusion: The study highlights a high prevalence of emergency cesarean sections among younger women, primarily due to previous cesarean sections. While maternal and neonatal outcomes were largely favorable, the presence of postoperative complications indicates the need for enhanced care. These findings underscore the importance of careful assessment in emergency cesarean sections and postoperative monitoring, particularly in resource-limited settings like Bangladesh.

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of invivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of invivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

Effects of paracetamol/acetaminophen on the expression of solute carriers (SLCs) in late-gestation fetal rat brain, choroid plexus and the placenta.

Solute carriers (SLCs) regulate transfer of a wide range of molecules across cell membranes using facilitative or secondary active transport. In pregnancy, these transporters, expressed at the placental barrier, are important for delivery of nutrients to the fetus, whilst also limiting entry of potentially harmful substances, such as drugs. In the present study, RNA-sequencing analysis was used to investigate expression of SLCs in the fetal (embryonic day19) rat brain, choroid plexus and placenta in untreated control animals and following maternal paracetamol treatment. In the treated group, paracetamol (15mg/kg) was administered to dams twice daily for 5 days (from embryonic day15 to 19). In untreated animals, overall expression of SLCs was highest in the placenta. In the paracetamol treatment group, expression of several SLCs was significantly different compared with control animals, with ion, amino acid, neurotransmitter and sugar transporters most affected. The number of SLC transcripts that changed significantly following treatment was the highest in the choroid plexus and lowest in the brain. All SLC transcripts that changed in the placenta following paracetamol treatment were downregulated. These results suggest that administration of paracetamol during pregnancy could potentially disrupt fetal nutrient homeostasis and affect brain development, resulting in major consequences for the neonate and extending into childhood.