Fetal Organ Research Articles

Sex-bias metabolism of fetal organs, and their relationship to the regulation of fetal brain-placental axis.

The placenta plays influential role in the fetal development of mammals. But how the metabolic need of the fetal organs is related to that of the placenta, and whether this relationship is influenced by the sex of the fetus remain poorly understood. This study used pigs to investigate metabolomic signatures of male and female fetal organs, and determine the relevance of gene expression of the placenta and brain to the metabolism of peripheral organs. Untargeted metabolomics analysis was performed with the day-45 placenta, kidney, heart, liver, lung and brain of male and female pig fetuses to model sex differences in themetabolism of the peripheral organs relative to that of the brain and placenta. Transcriptomic analysis was performed to investigate the expression of metabolic genes in the placenta and fetal brain of both sexes. The results of this study show that the fetoplacental metabolic regulation was not only influenced by the fetal sex but also dependent on the metabolic requirement of theindividual organs of the fetus. Neural network modeling of metabolomics data revealed differential relationship of the metabolic changes of the peripheral organs with the placenta and fetal brain between males and females. RNA sequencing further showed that genes associated with themetabolism of the peripheral organs were differentially expressed in the placenta and fetal brain. The findings of this study suggest a regulatory role of the fetal brain and placenta axis in the sex-bias metabolism of the peripheral organs.

Artificial intelligence assisted common maternal fetal planes prediction from ultrasound images based on information fusion of customized convolutional neural networks

Ultrasound imaging is frequently employed to aid with fetal development. It benefits from being real-time, inexpensive, non-intrusive, and simple. Artificial intelligence is becoming increasingly significant in medical imaging and can assist in resolving many problems related to the classification of fetal organs. Processing fetal ultrasound (US) images increasingly uses deep learning (DL) techniques. This paper aims to assess the development of existing DL classification systems for use in a real maternal-fetal healthcare setting. This experimental process has employed two publicly available datasets, such as FPSU23 Dataset and Fetal Imaging. Two novel deep learning architectures have been designed in the proposed architecture based on 3-residual and 4-residual blocks with different convolutional filter sizes. The hyperparameters of the proposed architectures were initialized through Bayesian Optimization. Following the training process, deep features were extracted from the average pooling layers of both models. In a subsequent step, the features from both models were optimized using an improved version of the Generalized Normal Distribution Optimizer (GNDO). Finally, neural networks are used to classify the fused optimized features of both models, which were first combined using a new fusion technique. The best classification scores, 98.5 and 88.6% accuracy, were obtained after multiple steps of analysis. Additionally, a comparison with existing state-of-the-art methods revealed a notable improvement in the suggested architecture’s accuracy.

Optimizing lipid nanoparticles for fetal gene delivery in vitro, ex vivo, and aided with machine learning

There is a clinical need to develop lipid nanoparticles (LNPs) to deliver congenital therapies to the fetus during pregnancy. The aim of these therapies is to restore normal fetal development and prevent irreversible conditions after birth. As a first step, LNPs need to be optimized for transplacental transport, safety on the placental barrier and fetal organs and transfection efficiency. We developed and characterized a library of LNPs of varying compositions and used machine learning (ML) models to delineate the determinants of LNP size and zeta potential. Utilizing different in vitro placental models with the help of a Random Forest algorithm, we could identify the top features driving percentage LNP transport and kinetics at 24 h, out of a total of 18 input features represented by 41 LNP formulations and 48 different transport experiments. We further evaluated the LNPs for safety, placental cell uptake, transfection efficiency in placental trophoblasts and fetal lung fibroblasts. To ensure the integrity of the LNPs following transplacental transport, we screened LNPs for transport and transfection using a high-throughput integrated transport-transfection in vitro model. Finally, we assessed toxicity of the LNPs in a tracheal occlusion fetal lung explant model. LNPs showed little to no toxicity to fetal and placental cells. Immunoglobin G (IgG) orientation on the surface of LNPs, PEGylated lipids, and ionizable lipids had significant effects on placental transport. The Random Forest algorithm identified the top features driving LNPs placental transport percentage and kinetics. Zeta potential emerged in the top driving features. Building on the ML model results, we developed new LNP formulations to further optimize the transport leading to 622 % increase in transport at 24 h versus control LNP formulation. To induce preferential siRNA transfection of fetal lung, we further optimized cationic lipid percentage and the lipid-to-siRNA ratio. Studying LNPs in an integrated placental and fetal lung fibroblasts model showed a strong correlation between zeta potential and fetal lung transfection. Finally, we assessed the toxicity of LNPs in a tracheal occlusion lung explant model. The optimized formulations appeared to be safe on ex vivo fetal lungs as indicated by insignificant changes in apoptosis (Caspase-3) and proliferation (Ki67) markers. In conclusion, we have optimized an LNP formulation that is safe, with high transplacental transport and preferential transfection in fetal lung cells. Our research findings represent an important step toward establishing the safety and effectiveness of LNPs for gene delivery to the fetal organs.

Transplacental Transfer of Oxytocin and Its Impact on Neonatal Cord Blood and In Vitro Retinal Cell Activity.

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23-42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood-retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP.

Maternal Glycemic Status and Longitudinal Fetal Body Composition and Organ Volumes Based on Three-Dimensional Ultrasonography.

Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth as measured by two-dimensional ultrasonography. Whether fetal three-dimensional (3D) soft tissue and organ volumes provide additional insight into fetal overgrowth is unknown. We prospectively evaluated longitudinal 3D fetal body composition and organ volumes in a diverse US singleton pregnancy cohort (2015-2019). Women were diagnosed with GDM, impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Up to five 3D ultrasound scans measured fetal body composition and organ volumes; trajectories were modeled using linear mixed models. Overall and weekly mean differences in fetal 3D trajectories were tested across glycemic status, adjusted for covariates. In this sample (n = 2,427), 5.2% of women had GDM, and 3.0% had IGT. Fetuses of women who developed GDM compared with NGT had larger fractional arm and fractional fat arm volumes from 26 to 35 weeks, smaller fractional lean arm volume from 17 to 22 weeks, and larger abdominal area from 24 to 40 weeks. Fetuses of women with IGT had similar growth patterns, which manifested later in gestation and with larger magnitudes, and had larger fractional lean arm volume. No overall differences were observed among thigh or organ volumes across glycemic status. Body composition differed in fetuses of GDM-complicated pregnancies, including larger arm and abdominal measures across the second and third trimesters. Patterns were similar in IGT-complicated pregnancies except that they occurred later in gestation and with larger magnitudes. Future research should explore how lifestyle and medication may alter fetal fat accumulation trajectories among hyperglycemic pregnancies.

Measurement of apparent diffusion coefficient (ADC) in fetal organs and placenta using 3 Tesla magnetic resonance imaging (MRI) across gestational ages

Diffusion-weighted imaging (DWI) is a technique used to probe the random microscopic motion of water protons in living tissue, represented by a parameter measurement of apparent diffusion coefficient (ADC) values. This study aimed to measure the ADC values of various fetal organs and placenta using 3T at various gestational ages. This was a prospective observational study. A total of 103 singleton pregnancies from 20 to 38 weeks of gestational age were included. Diffusion-weighted imaging was performed in the axial plane from the fetal head to the trunk with the following parameters: TR: 2000–2500 ms; TE: 88 ms; FOV: 250 mm; 256 matrix; slice thickness: 4 mm with a 0 mm gap; acquisition time: 1 min, 18 s. Diffusion gradient values were b = 0 and b = 700 s/mm2. ADC was measured in fetal brain regions (frontal white matter, occipital white matter, centrum semiovale, pons, thalamus, cerebellum, and fetal organs (lungs, kidney, and placenta). ANOVA was used to calculate the mean ADC values. Karl Pearson’s coefficient of correlation was used to evaluate the correlation between ADC values and increasing gestational age. The mean ADC values of brain regions were: frontal white matter (1.64 ± 0.08 × 10− 3 mm2 /s, F-39.10,p-<0.001), occipital white matter (1.64 ± 0.06 × 10− 3 mm2/s, F-26.14, p-<0.001), centrum semiovale (1.62 ± 0.03 × 10− 3 mm2/s, F-49.88,p-<0.001, pons (1.23 ± 0.09 × 10− 3 mm2/s F-9.14,p-<0.001) ), Thalamus (1.21 ± 0.07 × 10− 3 mm2/s, F-13.54,p-<0.001) and cerebellum (1.36 ± 0.10 × 10− 3 mm2 /s, F-4.19,p-<0.001). The mean ADC values of fetal organs were lung (1.92 ± 0.15 × 10− 3 mm2 /s, F-28.24, p-<0.001), kidney (1.34 ± 0.11 × 10− 3 mm2 /s, F-1.05, p- 0.37) and placenta (1.94 ± 0.11 × 10− 3 mm2 /s, F-160.33, p-<0.001). White-matter regions showed a significant positive correlation with increasing gestational age. Statistically, a negative correlation was observed between increasing gestational age and ADC measurements obtained in the thalamus, cerebellum, pons, and kidney. This will be one of the first few studies to provide the ADC values of the fetal brain and fetal organs using 3T MRI. The current study shows that diffusion-weighted MRI can offer a promising technique to evaluate the structural development of fetal organs and can potentially lead to a biomarker for predicting the functionality of the fetal organs in abnormalities.

Genetic characteristics and pathogenicity of variant porcine parvovirus 1 in northern China

Porcine parvovirus type 1 (PPV1) can lead to reproductive disorders in pregnant sows, including stillbirth, mummification, embryonic death, and infertility (SMEDI syndrome). In this study, we isolated and identified 10 PPV1 strains in northern China, with genomes around 5 kb long and minor deletions in the 127-nt repeat region. The sequence analysis results showed that compared with strain NADL-2 (Reference strain), eight amino acid substitutions on the NS1 protein and fourteen amino acid substitutions on the VP2 protein were found in the ten isolates. Because the JX strain exhibited reduced neutralizing activity induced by commercially available vaccines in vitro, it was selected for challenge experiments in sows at 35 days of gestation. Mutant strain JX not only caused viremia, but also mild edema and mild inflammation in the trachea, lungs, lymph nodes, reproductive organs, and some intestines of the pregnant sows. Strain JX also caused fetal congestion and organ infection after penetrating the placental barrier. In conclusion, this study focused on the variation and evolution of PPV1 in northern China, screened a strain with reduced neutralizing activity, and determined that it has a certain degree of pathogenicity.

Practical Evaluation of the Fetal Cardiac Function.

The fetal heart adapts dynamically to nutrient and oxygen needs from all fetal organs. These continuous changes make it difficult to define normal/abnormal cardiac function based only on the evaluation of a few cycles. Many signs of fetal cardiac dysfunction have been suggested; however, very few can stand as true manifestations of cardiac deterioration, and none has emerged as a single reliable marker of cardiac dysfunction. It is the combination of abnormal findings that provides a more accurate assessment of the status of the fetal heart function.

The Research Progress of DNA Methylation in the Development and Function of the Porcine Placenta.

The pig is the most widely consumed domestic animal in China, providing over half of the meat supply in food markets. For livestock, a key economic trait is the reproductive performance, which is significantly influenced by placental development. The placenta, a temporary fetal organ, is crucial for establishing maternal-fetal communication and supporting fetal growth throughout pregnancy. DNA methylation is an epigenetic modification that can regulate the gene expression by recruiting proteins involved in gene silencing or preventing transcription factor binding. To enhance our understanding of the molecular mechanisms underlying DNA methylation in porcine placental development, this review summarizes the structure and function of the porcine placenta and the role of DNA methylation in placental development.

Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations

Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations.

Tritrichomonas foetus testing in bulls.

To provide a video tutorial on how to perform preputial scraping for the testing of Tritrichomonas foetus in bulls. Postpubertal bulls. A preputial scraping device is inserted in the prepuce, and back-and-forth scraping movements are made to collect smegma and T foetus organisms. The sample is placed in an appropriate media and prepared for shipment to the diagnostic laboratory. Preputial sampling is an effective method for diagnosing T foetus in infected bulls. Bulls are the primary carriers of T foetus, a protozoan parasite responsible for bovine trichomoniasis. By sampling and testing bulls, veterinarians can identify infected animals and implement control measures to prevent the spread of the disease within herds. Trichomoniasis can lead to significant reproductive problems in cattle, including infertility, embryonic death, and abortions. Sampling bulls allows for the detection of infection, enabling prompt intervention to protect the reproductive health of the entire herd. Trichomoniasis outbreaks can result in substantial economic losses for cattle producers due to reduced conception rates, increased calving intervals, and decreased calf crops. Sampling bulls helps to mitigate these losses by identifying and removing infected animals from the breeding pool, thereby minimizing the spread of the disease and its associated reproductive inefficiencies. In many regions, T foetus testing in bulls is a regulatory requirement for cattle movement and trade. Sampling bulls and obtaining negative test results are often necessary for obtaining health certificates and complying with interstate or international movement regulations.

A genome-wide association study reveals candidate genes and regulatory regions associated with birth weight in pigs.

Piglet birth weight is associated with preweaning survival, and its related traits have been included in the breeding program. Thus, understanding its genetic basis is essential. This study identified four birth weight-associated genomic regions on chromosomes 2, 4, 5, and 7 through genome-wide association study analysis in 7286 pigs from three different pure breeds using the FarmCPU model. The genetic and phenotypic variance explained by the four candidate regions is 8.42% and 1.85%, respectively. Twenty-eight candidate genes were detected, of which APPL2, TGFBI, MACROH2A1, and SEC22B have been reported to affect body growth or development. In addition, 21 H3K4me3-enriched peaks overlapped with the birth weight-associated genomic regions were identified by integrating the genome-wide association study results with our previous ChIP-seq and RNA-seq data generated in the pig placenta, a fetal organ relevant to birth weight, and three of the regulatory regions influence TGFBI, MACROH2A1, and SEC22B expression. This study provides new insights into understanding the mechanisms for birth weight. Further investigating the variants in the regulatory regions would help identify the functional variants for birth weight in pigs.

Clinical, Morphological and Multiplex Analysis of a Case of COVID-19-Associated Placental and Fetal Organ Damage at 16 Weeks Gestation

Abstract. COVID-19-associated damage to the placenta and fetal organs is possible among infected pregnant women. This phenomenon is associated with the presence of the virus in the placental tissue itself and transplacental transmission of SARS-CoV-2 from mother to fetus and occurs in case of severe course of the disease in the mother. However, reliable and clinically significant morphological changes in COVID-19-associated placental damage are still a subject of controversy and speculation. The aim of this article is to present a clinical case analysis and evaluation of the morphological features and results of multiplex analysis of COVID-19- associated fetal and placental tissue damage. Materials and methods. Placental and fetal tissue samples were examined using routine histological methods and immunohistochemical studies of the expression of antibodies to CD15 (MMA), CD3 (MRQ-39), CD68 (KP-1), CD138 (DB-A38). The spectroscopic study was performed using the InSpectr M spectrometer with an excitation wavelength of 532 nm. Results The study revealed an inflammatory infiltrate in the fetal membranes, in the umbilical vein wall, in the stroma of the villi, basal plate and intervillous space, forming thrombi of the vessels of the villi, chorionic plate, intervillous space, trophoblast necrosis, abundant deposition of perivillous fibrin. Spectroscopically, signs of changes in the quantitative and qualitative composition of the amino acids proline, phenylalanine, tyrosine and tryptophan, as well as the appearance of non-standard amino acids (hydroxyproline) and protein isoforms, signs of instability of the acid-base balance were revealed. Conclusion. Among the identified changes, both those characteristic of COVID-19-associated placental damage and non-specific ones associated with the body's inflammatory/cytokine response to COVID-19 and persistent placental infection are determined. The results of the multiplex analysis identified a promising direction in understanding the biological basis and essence of this pathology.

Detection Rate of Fetal Anomalies in Early Mid-Trimester Compared to Late Mid-Trimester Detailed Scans: Possible Implications for First-Trimester Sonography.

Objective: A late mid-trimester fetal organ scan (lMTS) is recommended between 18 and 22 weeks of pregnancy. Evidence has been accumulating on the effectiveness of first-trimester anatomy scans. Early mid-trimester fetal scans (eMTSs; 14-17 weeks) may have the advantage of visualization of most organs, hence allowing earlier genetic assessment and decision making. Our aim is to examine the effectiveness of eMTSs in identifying fetal anomalies compared to lMTSs. Methods: A retrospective study was conducted based on data from the multidisciplinary prenatal diagnosis clinic in a tertiary center. During the study period (2011-2021), an out-of-pocket eMTS in a community setting was offered routinely to the general population. Women who had previously undergone an eMTS and were later assessed due to a fetal anomaly in our clinic were included in the study. The cohort was divided into two groups according to whether the anomaly had been detected during the eMTS. We then compared the groups for factors that may be associated with anomaly detection in eMTSs. We used t-tests and chi-square tests, for quantitative and qualitative variables, respectively, to determine variables related to eMTS anomaly detection, and logistic regression for multivariate analysis. Results: Of 1525 women assessed in our multidisciplinary clinic, 340 were included in the study. The anomaly detection rate of the eMTS compared to the lMTS was 59.1% The eMTS detection rates for specific organ systems were as follows: skeletal, 57%; cardiac, 52%; congenital anomalies of the kidneys and urinary tract (CAKUT), 44%; central nervous system, 32.4%; chest, 33%; and abdominal, 28%. In multivariate analysis, abnormal first-trimester screening (aOR 3.2; 95%CI 1.26-8.08) and multiple anomalies (aOR 1.86; 95%CI 1.02-3.37) were found to be associated with eMTS anomaly detection. Conclusions: The eMTS detection rate was nearly 60% and was most accurate in detecting skeletal, cardiac, and CAKUT anomalies. Since the eMTS was community-based, this rate likely reflects a "real-world" scenario. Our findings support consideration of performing an eMTS or first-trimester scan routinely for earlier diagnosis and decision making, as an adjunctive to lMTSs. Future studies will examine the cost-effectiveness of early scans.

Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health.

Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cell mass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear.

Fetal body organ T2* relaxometry at low field strength (FOREST)

Fetal Magnetic Resonance Imaging (MRI) at low field strengths is an exciting new field in both clinical and research settings. Clinical low field (0.55T) scanners are beneficial for fetal imaging due to their reduced susceptibility-induced artifacts, increased T2* values, and wider bore (widening access for the increasingly obese pregnant population). However, the lack of standard automated image processing tools such as segmentation and reconstruction hampers wider clinical use. In this study, we present the Fetal body Organ T2* RElaxometry at low field STrength (FOREST) pipeline that analyzes ten major fetal body organs. Dynamic multi-echo multi-gradient sequences were acquired and automatically reoriented to a standard plane, reconstructed into a high-resolution volume using deformable slice-to-volume reconstruction, and then automatically segmented into ten major fetal organs. We extensively validated FOREST using an inter-rater quality analysis. We then present fetal T2* body organ growth curves made from 100 control subjects from a wide gestational age range (17–40 gestational weeks) in order to investigate the relationship of T2* with gestational age. The T2* values for all organs except the stomach and spleen were found to have a relationship with gestational age (p<0.05). FOREST is robust to fetal motion, and can be used for both normal and fetuses with pathologies. Low field fetal MRI can be used to perform advanced MRI analysis, and is a viable option for clinical scanning.

Progesterone promotes CXCl2-dependent vaginal neutrophil killing by activating cervical resident macrophage-neutrophil crosstalk.

Vaginal infections in women of reproductive age represent a clinical dilemma with significant socioeconomic implications. The current understanding of mucosal immunity failure during early pathogenic invasions that allows the pathogen to grow and thrive is far from complete. Neutrophils infiltrate most tissues following circadian patterns as part of normal repair, regulation of microbiota, or immune surveillance and become more numerous after infection. Neutrophils are responsible for maintaining vaginal immunity. Specific to the vagina, neutrophils continuously infiltrate at high levels, although during ovulation, they retreat to avoid sperm damage and permit reproduction. Here we show that, after ovulation, progesterone promotes resident vaginal macrophage-neutrophil crosstalk by upregulating Yolk sac early fetal organs (FOLR2+) macrophage CXCl2 expression, in a TNFA-patrolling monocyte-derived macrophage-mediated (CX3CR1hiMHCIIhi-mediated) manner, to activate the neutrophils' capacity to eliminate sex-transmitted and opportunistic microorganisms. Indeed, progesterone plays an essential role in conciliating the balance between the commensal microbiota, sperm, and the threat of pathogens because progesterone not only promotes a flurry of neutrophils but also increases neutrophilic fury to restore immunity after ovulation to thwart pathogenic invasion after intercourse. Therefore, modest progesterone dysregulations could lead to a suboptimal neutrophilic response, resulting in insufficient mucosal defense and recurrent unresolved infections.

Prenatal glucocorticoids exposure and adverse cardiovascular effects in offspring.

Glucocorticoids (GCs) are steroid hormones fundamental to the body's normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother's cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11β hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring's cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring's cardiovascular system.

Linoleic and Arachidonic Fatty Acids and their Potential Relationship with Inflammation, Pregnancy, and Fetal Development.

To summarize the evidence of maternal, placental, and fetal alterations that an excessive intake of n-6 polyunsaturated FAs (PUFAs), LA, and AA, could produce during pregnancy. A thorough review of the literature regarding the effects of n-6 PUFAs during pregnancy and lactation including in vivo and in vitro models, was carried out using the PubMed database from the National Library of Medicine-National Institutes of Health. An elevated intake of n-6 PUFA, specifically LA, during pregnancy influences children's motor, cognitive, and verbal development during infancy and early childhood. Similarly, they could harm the placenta and the development of other fetal organs such as the fat tissue, liver, and cardiovascular system. Maternal diet, specifically LA intake, could have significant repercussions on fetal development and long-term consequences in the offspring, including the possibility of future metabolic and mental diseases. It would be necessary to focus on the prevention of these alterations through timely dietary interventions in the target population.

Impact of Ionizing Radiation Exposure on Placental Function and Implications for Fetal Programming.

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.