Fetal Development Research Articles

Maternal vitamin D3 supplementation in an oxidized-oil diet protects fetus from developmental impairment and ameliorates oxidative stress in mouse placenta and fetus

BackgroundFried food has increased in popularity worldwide. However, deep frying can increase the production of peroxidative toxins in food, which might be harmful to fetal development. The antioxidative effect of vitamin D3 (VD3) has been reported previously. ObjectiveThis study aimed to explore how maternal VD3 supplementation in an oxidized-oil diet during gestation affects fetal antioxidative ability and development. MethodsPregnant mice were randomly assigned into three groups: Control group (diet with fresh soybean oil), OSO group (diet with oxidized soybean oil (OSO)), and OSOV group (diet with OSO and 10000 IU/Kg VD3). Mice were fed with the corresponding diet during gestation. On day 16.5 of gestation, the placenta and fetus were harvested to analyze antioxidative status. ResultsMaternal oxidized-oil diet during gestation significantly reduced placental vessel abundance, labyrinth zone area, and fetal body weight. However, dietary VD3 supplementation prevented these negative effects of oxidized-oil diet. Maternal intake of oxidized-oil diet increased serum concentrations of malondialdehyde, total-nitric oxide synthase (NOS), and inducible-NOS, while VD3 supplementation showed a protection effect on it. Additionally, maternal VD3 supplementation increased the levels of antioxidative enzymes and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2)，thereby protecting placenta and fetus from apoptosis and oxidative stress caused by an oxidized-oil diet. The gene expression and protein levels of a fatty acid transporter solute carrier family 27 member 1 (SLC27A1) in the fetal liver were increased by maternal VD3 supplementation under oxidized-oil diet. Notably, NRF2 could be co-immunoprecipitated with the VD receptor (VDR) in the placenta. ConclusionsMaternal VD3 supplementation could protect fetus from oxidized-oil diet induced developmental impairment by alleviating oxidative stress in the placenta and fetus through the VDR/NRF2 pathway, at least partially. Thus, ensuring adequate levels of VD3 through supplementation is often critical during pregnancy.

Assessment of maternal phthalate exposure in urine across three trimesters and at delivery (umbilical cord blood and placenta) and its influence on birth anthropometric measures

Phthalates, commonly used in plastic manufacturing, have been linked to adverse reproductive effects. Our research from the Saudi Early Autism and Environment Study (2019–2022), involving 671 participants, focused on the impacts of maternal phthalate exposure on birth anthropometric measures. We measured urinary phthalate metabolites in 390 maternal samples collected during each of the three trimesters of pregnancy and in cord serum and placental samples obtained at delivery. We employed various statistical methods to analyze our data. Intraclass correlation coefficients were used to assess the consistency of phthalate measurements, generalized estimating equations were used to explore temporal variations across the trimesters, and linear regression models, adjusted for significant confounders and Bonferroni correction, were used for each birth outcome. Exposure to six phthalates was consistently high across trimesters, with 82 %–100 % of samples containing significant levels of all metabolites, except for mono-benzyl phthalate. We found a 3.15 %–3.73 % reduction in birth weight (BWT), 1.39 %–1.69 % reduction in head circumference (HC), and 3.63 %–5.45 % reduction in placental weight (PWT) associated with a one-unit increase in certain urinary di(2-ethylhexyl) phthalate (DEHP) metabolites during the first trimester. In the second trimester, exposure to MEP, ∑7PAE, and ∑LMW correlated with a 3.15 %–4.5 % increase in the APGAR 5-min score and increases in PWT by 8.98 % for ∑7PAE and 9.09 % for ∑LMW. Our study also highlighted the maternal-to-fetal transfer of DEHP metabolites, indicating diverse impacts on birth outcomes and potential effects on developmental processes. Our study further confirmed the transfer of DEHP metabolites from mothers to fetuses, evidenced by variable rates in the placenta and cord serum, with an inverse relationship suggesting a passive transfer mechanism. Additionally, we observed distinct phthalate profiles across these matrices, adversely impacting birth outcomes. In serum, we noticed increases associated with DEHP metabolites, with birth gestational age rising by 1.01 % to 1.11 %, HC by 2.84 % to 3.67 %, and APGAR 5-min scores by 3.77 % to 3.87 %. Conversely, placental analysis revealed a different impact: BWT decreased by 3.54 % to 4.69 %, HC reductions ranged from 2.57 % to 4.69 %, and chest circumference decreased by 7.13 %. However, the cephalization index increased by 3.67 %–5.87 %. These results highlight the complex effects of phthalates on fetal development, indicating their potential influence on crucial developmental processes like sexual maturation and brain development.

Associations between gestational residential radon exposure and term low birthweight in Connecticut, USA.

Studies suggest biologic mechanisms for gestational exposure to radiation and impaired fetal development. We explored associations between gestational radon exposure and term low birthweight, for which evidence is limited. We examined data for 68,159 singleton full-term births in Connecticut, USA, 2016-2018. Using a radon spatiotemporal model, we estimated ZIP code-level basement and ground-level exposures during pregnancy and trimesters for each participant's address at birth or delivery. We used logistic regression models, including confounders, to estimate odds ratios (ORs) for term low birth weight in four exposure quartiles (Q1 to Q4) with the lowest exposure group (Q1) as the reference. Exposure levels to basement radon throughout pregnancy (0.27-3.02 pCi/L) were below the guideline level set by the US Environmental Protection Agency (4 pCi/L). The ORs for term low birth weight in the second-highest (Q3; 1.01-1.33 pCi/L) exposure group compared to the reference (<0.79 pCi/L) group for basement radon during the first trimester was 1.22 (95% confidence interval [CI]: 1.02, 1.45). The OR in the highest (Q4; 1.34-4.43 pCi/L) quartile group compared to the reference group during the first trimester was 1.26 (95% CI: 1.05, 1.50). Risks from basement radon were higher for participants with lower income, lower maternal education levels, or living in urban regions. This study found increased term low birth weight risks for increases in basement radon. Results have implications for infants' health for exposure to radon at levels below the current national guideline for indoor radon concentrations and building remediations.

Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4.

Fluoride-related changes in the fetal cord blood proteome; a pilot study

BackgroundFluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA.ObjectiveTo identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.MethodsThe proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes.ResultsPathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation.ConclusionMaternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

Exposure to Synthetic Endocrine-Disrupting Chemicals in Relation to Maternal and Fetal Sex Steroid Hormones: A Scoping Review.

Many synthetic endocrine-disrupting chemicals (EDCs) are ubiquitous in the environment and highly detected among pregnant people. These chemicals may disrupt maternal and/or fetal sex steroid hormones, which are critical to pregnancy maintenance and fetal development. Here, we review the epidemiological literature examining prenatal exposure to common synthetic EDCs in relation to maternal and fetal sex steroid hormones. We performed a literature search using PubMed, SCOPUS, and Embase, ultimately identifying 29 articles for full review. Phenols, parabens, and persistent organic pollutants generally showed inverse associations with androgens, estrogens, and progesterone. Phthalates and per-and polyfluoroalkyl substances tended to be inversely associated with progesterone, while evidence regarding androgens and estrogens was mixed. Inconsistent, but noteworthy, differences by fetal sex and timing of exposure/outcome were observed. Overall, the literature suggests EDCs may disrupt maternal and fetal sex steroid activity, though findings are mixed. Given the pervasive, high-volume production of these synthetic chemicals and the critical functions sex steroid hormones play during gestation, additional research is warranted.

Maternal exposure to phenanthrene induces testicular apoptosis and Sertoli cell dysfunction in F1 adult male mice: a histological and molecular study.

Phenanthrene, a polycyclic aromatic hydrocarbon, is found in abundance in environmental pollutants, food, and drinking water. This substance can accumulate in body tissues and exert harmful effects. Moreover, phenanthrene can cross the placental barrier, potentially impacting fetal development. We aimed to explore the impacts of maternal exposure to phenanthrene on testicular tissue and Sertoli cell function in F1 mice. Female rats with vaginal plugs were randomly assigned to one of three groups: control, sham, or phenanthrene. The control group received no intervention during pregnancy. In the sham and phenanthrene groups, corn oil and a phenanthrene solution, respectively, were administered via gavage once every 2 days. Offspring were separated by sex 21 days after birth. At 56 days postnatal, male F1 offspring were euthanized, and their testes were harvested for histological and molecular analyses. Phenanthrene exposure was associated with a lower testicular weight and volume, a smaller diameter of the seminiferous tubules, and a relative thinning of the germinal epithelium. These changes were associated with increased cellular apoptosis, as shown by the upregulation of caspase 3 expression. Additionally, we observed an increase in vacuolization and residual bodies within the tissue. Conversely, the number of Sertoli cells and expression levels of Sox9, as well as the Ocln and Itgb1 genes, were found to be lowered. Maternal exposure to phenanthrene impacts both germ cells and Sertoli cells, disrupting their function and leading to fertility disorders in male F1 offspring mice.

Mucuna pruriens has adverse effects on liver, kidneys and fetal development

Mucuna pruriens has adverse effects on liver, kidneys and fetal development

The effects of in utero exposure to delta-9-tetrahydrocannabinol (THC) on cardiac extracellular matrix expression and vascular transcriptome in rhesus macaques.

Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, remains a schedule I substance, thus safety data regarding the effects on the cardiovascular and prenatal health are limited. Importantly, there is evidence showing prenatal cannabis exposure can negatively impact fetal organ development, including the cardiovascular system. THC can cross the placenta and bind to cannabinoid receptors expressed in the developing fetus, including on endothelial cells. To understand the impact of prenatal THC exposure on the fetal cardiovascular system, we used our rhesus macaque model of prenatal daily edible THC consumption. Prior to conception, animals were acclimated to THC (2.5mg/7kg/day, equivalent to a heavy medical cannabis dose) and maintained on this dose daily throughout pregnancy. Fetal tissue samples were collected at gestational day 155 (full term is 168 days). Our model showed that in utero THC exposure was associated with a decreased heart to body weight ratio in offspring, warranting further mechanistic investigation. Histological examination of the fetal cardiac and vascular tissues did not reveal any significant effect of THC exposure on the maturity of collagen within the fetal heart or the aorta. Total collagen III expression and elastin production and organization were unchanged. However, bulk RNA-sequencing of vascular cells in the umbilical vein, umbilical artery, and fetal aorta demonstrated that THC alters the fetal vascular transcriptome and is associated with upregulated expression of genes involved in carbohydrate metabolism and inflammation. The long-term consequences of these findings are unknown, but suggest that prenatal THC exposure may affect cardiovascular development in offspring.

Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development

Effect of Vitamin D Deficiency on Arterial Stiffness in Pregnant Women with Preeclampsia and Pregnancy-Induced Hypertension and Implications for Fetal Development

Factors influencing high cardiovascular risk in subpopulation of young adults

Abstract Introduction The cardiovascular risk factors determine the development of early atheriosclerotic lesions, and the susceptibility to their proartheriosclerotic action is programmed by external factors and also those present during fetal development. The occurrence of atherosclerotic risk factors depends on an age. In population of children and young adults it seems reasonable to assess the classical risk factors for atherosclerosis in the connection with such additional given as family history being an indirect surrogate of genetic factors, and a low birth weight. Aim of the study was to categorize the study group into two groups - those who exhibit a low-risk and those who exhibit a high-risk of cardiovascular disease, and to determine the factors characteristic for each risk group. Materials and Methods The study was done on 512 volunteers, students in the following Faculties: Health Care Faculty: Nursing Course (178 / 34,7%), Physiotherapy Course (109 / 21,3%), Obstetrics Course (49 / 9,5%), Faculty of Medicine (176 / 34,3%). The questionnaire on cardiovascular risk factors was constructed. According to the results of its assessment the following groups were divided: the group of high risk (10% of investigated with the highest awarding of points) and the group of low risk (10% of investigated with the lowest awarding of points). Results Significant quantitative and qualitative differences were found between the low-risk and high-risk groups. Groups of the high and low risk did not differ in respect of sexes investigated and in respect of the direction of studies. One ascertained essential differences in variable qualitative and quantitative between the group of the low and high risk. Family history of diabetes, arterial hypertension, cardiovascular diseases, lipid disturbances, stroke were indeed greater in the group of high risk. The low birth weight was significantly lower in the group of high risk (p=0,02). The current and chronic stress status grading according to the punctual scale (0-10) was significantly higher in the group of high risk as compared to the low risk group (p=0,01, p=0,03, respectively). The systolic pressure was significantly higher in the high risk group in comparison to the low risk subjects (p=0,01). Conclusions High cardiovascular risk in subgroup of young adults results from high smoking status, low physical activity, diet and family history of cardiovascular disorders. The numerous cardiovascular risk factors that occur in some students are associated with low birth weight and a positive family medical history. The above observations show the influence of genetic and fetal factors on the development of atherosclerosis. Young adults with high cardiovascular risk are characterized by higher subjective stress level. Quantitative differences in high risk Medical family history

Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid.

Development of the respiratory system can be affected by the use of drugs during pregnancy, as the prenatal phase is highly sensitive to pharmacological interventions, resulting in long-term consequences. The deleterious effects of external cannabinoids during gestation may be related to negative interference in central nervous system formation, cardiorespiratory system function, and behavioral disorders. Nevertheless, the impact of external cannabinoids on cardiorespiratory network development, chemosensitivity, and its future consequences in adulthood is still unclear. We evaluated the effects of prenatal exposure to a synthetic cannabinoid (WIN 55,212-2, 0.5 mg.kg-1.day-1) on the cardiorespiratory control and panic-like behavior of male and female rats in adulthood. Exogenous cannabinoid exposure during pregnancy resulted in a sex-dependent difference in breathing control. Specifically, males showed increased chemosensitivity to CO2 and O2, while females exhibited decreased sensitivity. Altered cardiovascular control was evident, with prenatally treated males and females being more susceptible to hypertension and tachycardia under adverse environmental conditions. Moreover, WIN-treated males exhibited higher fragmentation of sleep episodes, while females displayed anxiolytic and panicolytic behavioral responses to CO2. However, no changes were observed in the mechanical component of the respiratory system, and there were no neuroanatomical alterations, such as changes in the expression of CB1 receptors in the brainstem or in the quantification of catecholaminergic and serotonergic neurons. These findings highlight that external interference in cannabinoid signaling during fetal development causes sex-specific long-lasting effects for the cardiorespiratory system and behavioral responses in adulthood.

Deep Learning Techniques for a Comprehensive Analysis of Fetal Biometric Parameters Across Trimesters

The process of creating fetal images from the uterus using sound influence is known as fetal ultrasound imaging. During this scan, measurements such as the gestational sac, biparietal diameter, head circumference, abdominal circumference, and femur length can be taken from the mother, which are further analyzed by the radiologist or gynecologist. These factors allow us to quickly test for anomalies and monitor the fetal growth and development of a baby. This paper delves into the techniques utilized in previous studies for analyzing abnormalities from ultrasound images using machine learning and deep learning techniques. Specifically, we focus on two trimesters and three key fetal parameters: Head Circumference (HC), Abdominal Circumference (AC), and Femur Length (FL). Our proposed method, the Unet segmentation method, not only performs segmentation but also predicts the parameters. We employ various transfer learning techniques for classification. The experiment involves 1,313 medical fetal images, comprising 563 from the second trimester and 750 from the third trimester. In terms of segmentation accuracy, the results for the second trimester's biometric parameters are as follows: AC = 69.09%, FL = 92.02%, and HC = 69.43%. For the third trimester, the accuracy for FL is 90.04%, and for HC, it is 69.76%. Regarding classification methods, MobileNet and XceptionNet yield comparable results. For the second trimester, MobileNet achieves 99.28%, and XceptionNet achieves 99.82%. For the third trimester, both MobileNet and XceptionNet achieve 99.86%.

Maternal Dietary Carbohydrate and Pregnancy Outcomes: Quality over Quantity

Dietary nutrition plays a crucial role in determining pregnancy outcomes, with poor diet being a major contributor to pregnancy metabolic syndrome and metabolic disorders in offspring. While carbohydrates are essential for fetal development, the excessive consumption of low-quality carbohydrates can increase the risk of pregnancy complications and have lasting negative effects on offspring development. Recent studies not only highlighted the link between carbohydrate intake during pregnancy, maternal health, and offspring well-being, but also suggested that the quality of carbohydrate foods consumed is more critical. This article reviews the impacts of low-carbohydrate and high-carbohydrate diets on pregnancy complications and offspring health, introduces the varied physiological effects of different types of carbohydrate consumption during pregnancy, and emphasizes the importance of both the quantity and quality of carbohydrates in nutritional interventions during pregnancy. These findings may offer valuable insights for guiding dietary interventions during pregnancy and shaping the future development of carbohydrate-rich foods.

T2*-Relaxometry MRI to Assess Third Trimester Placental and Fetal Brain Oxygenation and Placental Characteristics in Healthy Fetuses and Fetuses With Congenital Heart Disease.

Congenital heart disease (CHD) has been linked to impaired placental and fetal brain development. Assessing the placenta and fetal brain in parallel may help further our understanding of the relationship between development of these organs. 1) Placental and fetal brain oxygenation are correlated, 2) oxygenation in these organs is reduced in CHD compared to healthy controls, and 3) placental structure is altered in CHD. Retrospective case-control. Fifty-one human fetuses with CHD (32 male; median [IQR] gestational age [GA] = 32.0 [30.9-32.9] weeks) and 30 from uncomplicated pregnancies with normal birth outcomes (18 male; median [IQR] GA = 34.5 [31.9-36.7] weeks). 1.5 T single-shot multi-echo-gradient-echo echo-planar imaging. Masking was performed using an automated nnUnet model. Mean brain and placental T2* and quantitative measures of placental texture, volume, and morphology were calculated. Spearman's correlation coefficient for determining the association between brain and placental T2*, and between brain and placental characteristics with GA. P-values for comparing brain T2*, placenta T2*, and placental characteristics between groups derived from ANOVA. Significance level P < 0.05. There was a significant positive association between placental and fetal brain T2* (⍴ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* ⍴ = -0.65; fetal brain T2* ⍴ = -0.32). Both placental and fetal brain T2* values were significantly reduced in CHD, after adjusting for GA (placental T2*: control = 97 [±24] msec, CHD = 83 [±23] msec; brain T2*: control = 218 [±26] msec, CHD = 202 [±25] msec). Placental texture and morphology were also significantly altered in CHD (Texture: control = 0.84 [0.83-0.87], CHD = 0.80 [0.78-0.84]; Morphology: control = 9.9 [±2.2], CHD = 10.8 [±2.0]). For all fetuses, there was a significant positive association between placental T2* and placental texture (⍴ = 0.46). Placental and fetal brain T2* values are associated in healthy fetuses and those with CHD. Placental and fetal brain oxygenation are reduced in CHD. Placental appearance is significantly altered in CHD and shows associations with placental oxygenation, suggesting altered placental development and function may be related. 3 TECHNICAL EFFICACY: Stage 3.

Synthetic MRI and MR Fingerprinting-Derived Relaxometry of Antenatal Human Brainstem Myelination: A Postmortem-Based Quantitative Imaging Study.

The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting-derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed. In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting-specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities. Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging-derived relaxation times (medulla oblongata [r = -0.459; P = .021]; midbrain [r = -0.413; P = .040]), T2-relaxation times (medulla oblongata [r = -0.625; P < .001]; midbrain [r = -0.571; P = .003]), and MR fingerprinting-derived T1-relaxation times (medulla oblongata [r = -0.433; P = .035]; midbrain [r = -0.386; P = .062]), and T2-relaxation times (medulla oblongata [r =-0.883; P < .001]; midbrain [r = -0.890; P < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351-0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82-0.965) (T1-relaxation times: midbrain). There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development.

Impact of previous pregnancy and BMI on cellular and serum immune activity from early to late pregnancy

Immunological adaptions during pregnancy play a crucial role in healthy fetal development. Aberrant immune modifications however contribute to adverse pregnancy outcomes, which may be driven by maternal factors such as previous pregnancies and BMI. This secondary analysis of the MicrobeMom2 RCT investigates the changes to maternal inflammatory biomarkers derived from serum and stimulated peripheral blood mononuclear cells (PBMCs) during pregnancy, and the effects of previous pregnancies (parity) and BMI on maternal immune responses. Changes in immune and metabolic biomarkers from early (11–15 weeks’ gestation) to late (28–32 weeks’ gestation) pregnancy were compared using paired t-tests. Participants were then split by parity (nulliparous, parous) and BMI (BMI < 25, BMI > = 25), and the relationship between parity and BMI with immune biomarker levels was examined using independent t-tests, paired t-tests, ANCOVA, and linear regression. Equivalent non-parametric tests were used for skewed data. Recruited women (n = 72) were on average 31.17 (SD ± 4.53) years of age and 25.11 (SD ± 3.82) BMI (kg/m2). Of these, 51 (70.8%) had a previous term pregnancy. Throughout gestation, PBMC cytokines displayed contrasting trends to serum, with a dampening of immune responses noted in PBMCs, and enhanced production of cytokines observed in the serum. Significant decreases in PBMC derived TNF-α, IL-10 and IFN-γ were seen from early to late pregnancy. Serum C3, IL-17A, IL-6, TNF-α, CD163, GDF-15 and leptin increased throughout gestation. First pregnancy was associated with higher levels of leptin in late pregnancy, while parous women showed significant decreases in PBMC derived TNF-α, IL10, and IFN-γ with gestation. Differences in levels of C3, IL-17A, TNF-α, GDF-15 and leptin were observed across BMI groups. Overall, serum-derived cytokines exhibit contrasting levels to those derived from stimulated PBMCs. Maternal immune responses undergo significant changes from early to late pregnancy, which are influenced by parity and BMI. These differences aid our understanding as to why first-time mothers are at greater risk of placental disease such as pre-eclampsia and fetal growth restriction.

Maternal obesity and offspring neurodevelopment are associated with hypoxic gene expression in term human placenta.

One third of women in the United States are affected by obesity during pregnancy. Maternal obesity (MO) is associated with an increased risk of neurodevelopmental and metabolic disorders in the offspring. The placenta, located at the maternal-fetal interface, is a key organ determining fetal development and likely contributes to programming of long-term offspring health. We profiled the term placental transcriptome in humans (pre-pregnancy BMI 35+ [MO condition] or 18.5-25 [lean condition]) using single-nucleus RNA-seq to compare expression profiles in MO versus lean conditions, and to reveal potential mechanisms underlying offspring disease risk. We recovered 62,864 nuclei of high quality from 10 samples each from the maternal-facing and fetal-facing sides of the placenta. On both sides in several cell types, MO was associated with upregulation of hypoxia response genes. On the maternal-facing side only, hypoxia gene expression was associated with offspring neurodevelopmental measures, in Gen3G, an independent pregnancy cohort with bulk placental tissue RNA-seq. We leveraged Gen3G to determine genes that correlated with impaired neurodevelopment and found these genes to be most highly expressed in extravillous trophoblasts (EVTs). EVTs further showed the strongest correlation between neurodevelopment impairment gene scores (NDIGSs) and the hypoxia gene score. We reanalyzed gene expression of cultured EVTs, and found increased NDIGSs associated with exposure to hypoxia. Among EVTs, accounting for the hypoxia gene score attenuated 44% of the association between BMI and NDIGSs. These data suggest that hypoxia in EVTs may be a key process in the neurodevelopmental programming of fetal exposure to MO.

The role of iodine in thyroid function and iodine impact on the course of Hashimoto’s thyroiditis - review

Introduction: Iodine is one of the most important micronutrients necessary for the proper functioning of the thyroid gland. It is an essential component of thyroxine and triiodothyronine, hormones produced and secreted by the thyroid gland. Severe iodine deficiency impairs thyroid hormone synthesis and can lead to gland enlargement. This deficiency results in various disorders collectively termed iodine deficiency disorders. Not only iodine deficiency but also excess iodine intake can be harmful and affect thyroid function. Doses of iodine above physiological levels can result in both hypothyroidism and hyperthyroidism. Numerous studies have linked chronic high iodine intake to an increased frequency of autoimmune thyroiditis. This review examines the mechanisms of iodine regulation and the role of excess iodine can play in the development of Hashimoto’s thyroiditis. Aim of the study: The aim of the study is to present and summarize the role of iodine in thyroid function and its impact on the course of Hashimoto’s thyroiditis. This review explains the potential increased risk of thyroid autoimmune disorder connected with iodine over-supplementation. Materials and Methods: For this current literature review, the important studies published from 1986-2024 in PubMed database was searched. The literature available in the PubMed database was reviewed with the following keywords: iodine, Hashimoto’s thyroiditis, autoimmune thyroiditis. Conclusion: Iodine is crucial for thyroid health and fetal development, but its excessive intake can be harmful. Maintaining optimal levels of this microelement is essential to prevent both iodine deficiency and autoimmune disorders. Iodine supplementation is recommended only for pregnant and lactating women.

Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction. Maternal plasma samples were collected from two independent cohorts: (1) Established disease cohort: 50 participants diagnosed with early-onset preeclampsia (< 34 weeks’ gestation), 14 with early-onset fetal growth restriction, and 25 gestation-matched controls. (2) Prospective cohort, collected at 36 weeks’ gestation before diagnosis: 17 participants later developed preeclampsia, 49 delivered infants with fetal growth restriction (birthweight < 5th centile), and 72 randomly selected controls. Metabolic evaluation was performed by Metabolomics Australia on the Agilent 6545 QTOF Mass Spectrometer. In the established disease cohort, 77 metabolites were altered in circulation from participants with preeclampsia – increased l-cysteine (3.73-fold), l-cystine (3.28-fold), l-acetylcarnitine (2.57-fold), and carnitine (1.53-fold) (p < 0.05). There were 53 metabolites dysregulated in participants who delivered a fetal growth restriction infant—including increased levulinic acid, citric acid (1.93-fold), and creatine (1.14-fold) (p < 0.05). In the prospective cohort, 30 metabolites were altered in participants who later developed preeclampsia at term – reduced glutaric acid (0.85-fold), porphobilinogen (0.77-fold) and amininohippuric acid (0.82-fold) (p < 0.05) was observed. There were 5 metabolites altered in participants who later delivered a fetal growth restriction infant – including reduced 3-methoxybenzenepropanoic acid (p < 0.05). Downstream pathway analysis revealed aminoacyl-tRNA biosynthesis to be most significantly altered in the established cohort in preeclampsia (13/48 hits, p < 0.001) and fetal growth restriction (7/48 hits, p < 0.001). The predictive cohort showed no significant pathway alterations. This study observed altered metabolites in maternal plasma collected before and after diagnosis of a preeclampsia or fetal growth restriction. While a significant number of metabolites were altered with established disease, few changes were observed in the predictive cohort. Thus, metabolites measured in this study may not be useful as predictors of preeclampsia or fetal growth restriction.