Profile Of Offspring Research Articles

Safety profiles of offspring born from early-follicular long-acting GnRH agonist protocol and daily mid-luteal GnRH agonist protocol: a retrospective study

BackgroundThe gonadotropin hormone-releasing hormone agonists (GnRH-a) have been widely used for controlled ovarian stimulation in assisted reproductive technology (ART). The early-follicular long-acting GnRH-a long protocol (EFL) and the luteal phase short-acting GnRH-a long protocol (LPS) are commonly used GnRH agonist protocols. We conducted a retrospective analysis to assess and compare the rates of congenital abnormalities and safety profiles in offspring born from the EFL and LPS protocols.MethodsWe conducted a retrospective cohort study to analyze and compare neonatal data from patients who using EFL or LPS protocols at our center between January 1, 2014, and June 30, 2017. The study ultimately included 1810 neonates from 1401 cycles using the EFL protocol and 2700 neonates from 2129 cycles using the LPS protocol.The main outcome measures are gestational age at delivery, birth weight, and congenital anomaly rate.To assess the influence of various factors on congenital abnormalities, a random-effects logistic regression model was employed.ResultsThe EFL and LPS protocols led to similar congenital anomaly rates (1.64% vs. 2.35%, P = 0.149). No significant differences were found between the two groups regarding birth weight and its categories, newborn gender and congenital anomaly rate. The results of the multivariate logistic regression model indicated no association between congenital anomaly and BMI, duration of infertility, treatment protocol, fertilization method, or embryo transfer stage. Compared with singleton pregnancies, the probability of congenital defects in multiple pregnancies was 2.64 times higher (OR: 2.64, 95% CI: 1.72–4.05, P < 0.0001). Newborns with congenital defects were born with a lower gestational age compared with full-term pregnancies.ConclusionIn conclusion, the EFL protocol is considered a safe option for ensuring offspring safety, comparable with the LPS protocol; however, multiple pregnancies represent an independent risk factor for congenital abnormalities. This approach can be widely adopted; however, prioritizing single embryo transfers is strongly recommended to minimize the potential risks associated with multiple pregnancies in offspring.

Circulating Cytokine Levels and Cardiovascular Disease Risk Profile in Young Adult Offspring of Women with Type1 Diabetes.

Cytokines are key players in the development of both type1 diabetes (T1D) and cardiovascular disease (CVD). Offspring of women with T1D are known to have an increased risk of early-onset CVD. We studied whether an increased risk of CVD can be observed in the cytokine profile among young adult offspring of women with T1D. This cross-sectional case-control study included 67 offspring of women with T1D (cases) and 79 control participants (controls). At an age of 18-23years, they participated in a clinical assessment including laboratory tests and questionnaires. Cytokine levels were analyzed from venous blood samples after 10h fasting using Quansys biosciences Q-Plex™ High Sensitivity Human Cytokine Array. Circulating cytokine levels were in general similar between the groups. The circulating levels of interferon-γ (1.78 [IQR 1.20, 2.36] pg/mL versus 2.57 [IQR 1.50, 3.89] pg/mL) (p = 0.006) were lower in cases than controls. The findings did not support our hypothesis that serum cytokine profile, determined in early adulthood, was associated with a more adverse CVD risk profile in offspring of women with T1D. Further studies are warranted to find out whether cytokines could serve as early biomarkers of CVD development or whether changes in the cytokine levels over years could be used to monitor CVD progression in offspring of women with T1D.

Prenatal Maternal Antibiotics Treatment Alters the Gut Microbiota and Immune Function of Post-Weaned Prepubescent Offspring.

This study aimed to investigate the immediate and continual perturbation to the gut microbiota of offspring in the weeks post-weaning and how these may be modulated by treating pregnant C57BL/6J dams with antibiotics (ABX). We used a broad-spectrum antibiotic cocktail consisting of ampicillin 1 mg/mL, neomycin 1 mg/mL, and vancomycin 0.5 mg/mL, or vancomycin 0.5 mg/mL alone, administered ad-lib orally to dams via drinking water during gestation and stopped after delivery. We analyzed the gut microbiota of offspring, cytokine profiles in circulation, and the brain to determine if there was evidence of a gut-immune-brain connection. Computationally predicted metabolic pathways were calculated from 16s rRNA sequencing data. ABX treatment can negatively affect the gut microbiota, including reduced diversity, altered metabolic activity, and immune function. We show that the maternal ABX-treatment continues to alter the offspring's gut microbiota diversity, composition, and metabolic pathways after weaning, with the most significant differences evident in 5-week-olds as opposed to 4-week-olds. Lower levels of chemokines and inflammatory cytokines, such as interleukin (IL)-1α and IL-2, are also seen in the periphery and brains of offspring, respectively. In conclusion, this study shows maternal antibiotic administration alters gut microbiome profiles in offspring, which undergoes a continuous transformation, from week to week, at an early age after weaning.

Issue Information

Maternal excessive folic acid intake induced hyperactivity and a low anxiety state, whereas maternal undernutrition led to hypoactivity. Furthermore, brain monoamine profiles in offspring were transformed by excessive maternal folic acid fortification and undernutrition in different directions. Excessive maternal folic acid fortification and undernutrition may alter offspring behavior through additive or synergistic effects on brain monoamine profiles. Further details can be seen in the article by Ono et al. in this issue.This study is dedicated to Mr. Kodai Hino, who passed away in 2018 after accomplishing its main experiments with us. image

P-046 Effect of different sperm chromatin dispersion type on IVF/ICSI outcome and offspring profile

Abstract Study question Whether the percentage of different sperm chromatin dispersion type are associated with the IVF/ICSI outcome and offspring profile? Summary answer Percentage of different sperm chromatin dispersion type are significantly associated with the embryo cleavage rate, embryo quality, live birth rate and offspring gender. What is known already The sperm DNA fragmentation index (DFI) is increasingly recognized as a key sperm functional parameter for assessing male fertility. Sperm chromatin dispersion (SCD) test is widely used in clinical andrology lab to measure DFI, and according to the size of sperm halo it divides sperm into three categories: big halo sperm, middle halo sperm, small or no halo sperm. Previous study reported that big halo sperm are significantly associated with embryo quality and pregnancy rate. The average halo size of Y-chromosome bearing sperm are significantly smaller than X - chromosome bearing sperm. Study design, size, duration This is a multi-center retrospective study recruited 200 couples underwent IVF/ICSI treatment in Nanfang Hospital and Guangdong Women's and Children's Hospital from May 2018 to May 2019. Participants/materials, setting, methods Patients meet the followed inclusion criteria were recruited: (1) The male partners received sperm chromatin dispersion test; (2) The female partners have normal ovarian reserve (female age &amp;lt; 35 years old, FSH ≤10 IU/L and AFC ≥ 5); (3) Couples received fresh single embryo transfer. The association between sperm chromatin dispersion type and IVF/ICSI outcome and the offspring profile were retrospectively analyzed. Main results and the role of chance Regression analysis showed that the embryo cleavage rate is positively associated with the percentage of sperm with big halo (Adjusted ?????(95% CI) 0.09 (0.01, 0.17), P&amp;lt;0.05), but negatively associated with the percentage of sperm with middle halo (Adjusted ????? (95% CI)- 0.22 (-0.35, -0.09), P&amp;lt;0.001). The good embryo rate is negatively associated with the percentage of sperm with middle halo (Adjusted ????? (95% CI) -0.60 (-1.04, -0.16), P&amp;lt;0.05). Live birth is significantly associated with the percentage of sperm with small halo (Adjusted OR (95% CI) 0.89 (0.80, 1.00), P&amp;lt;0.05). Offspring gender is significantly associated with the percentage of sperm with big halo (Adjusted OR (95% CI) 0.95 (0.91, 0.99), P&amp;lt;0.05) and the percentage of sperm with middle halo (Adjusted OR (95% CI) 1.09 (1.02, 1.17), P&amp;lt;0.05). The area under the receiver operator characteristic (ROC) curve (AUC) of the big halo sperm percentage to predict male offspring is 0.68 (95%CI (0.54, 0.81), P &amp;lt; 0.05). The AUC of middle halo sperm percentage to predict female offspring is 0.66 (95%CI (0.52, 0.80), P &amp;lt; 0.05). Limitations, reasons for caution This is a retrospective study which may have the bias caused by the nature of this type of study. The sample size is relatively small. Wider implications of the findings The percentage of big halo sperm are significantly associated with embryo cleavage rate and male offspring. The percentage of middle halo sperm are significantly associated with embryo cleavage rate, lower good embryo rate and female offspring. The percentage of small halo sperm is significantly associated with live birth. Trial registration number 82101683

Cardiovascular and autonomic profiles in offspring of fructose fed parents: role of anti‐inflammatory cholinergic reflex and exercise training

AimConsidering that anti‐inflammatory cholinergic reflex has been implicated in cardiovascular disorder, and spleen seems to be a critical organ in this reflex, here we evaluated the impact of aerobic exercise training on cardiovascular and autonomic profiles in offspring of rats submitted to fructose overload, as well as, the role of the splenectomy in this condition.MethodsOffspring of Wistar rats treated with fructose or placebo (water) were divided into 5 groups: Sedentary Control (OC), Sedentary Fructose (OF), Trained Fructose (OFT), Splenectomized Sedentary Fructose (OFE) and Splenectomized Trained Fructose (OFST). Fructose overload (10%) was started 30 days after weaning only for the parents and continued until the end of lactation. The offspring received standard feeding and were evaluated 30 days after weaning, at which time the spleen was removed (splenectomy) and the aerobic exercise training was realized on treadmill (1h/d, 5d/week, 4 weeks, moderate intensity). Blood pressure (BP) and heart rate (HR) signals were direct recorded, baroreflex sensitivity (BRS) was measured using increasing doses of phenylephrine and sodium nitroprusside. Oxidative stress was measured in cardiac tissue.ResultsSystolic BP, Diastolic BP and Mean BP increase in OF compared to OC, OFT, OFE and OFST groups (OC: 105±1.3, OF: 112±1.6, OFT: 104±2.4, OFE: 103±3.1, OFST: 104±2 mmHg) HR reduced in the OFT compared to the OC group. Regarding BRS, bradycardic and tachycardic responses were impaired in OF compared to OC group; and OFE, OFT and OFST groups increased these parameters compared to OF group. In the antioxidant profile in cardiac tissue, the activities of catalase and superoxide dismutase were reduced in the OF group compared to the OC group, and increased in the OFE, OFT and OFST groups compared to the OF group. Protein oxidation was increased in the OF group compared to the OC, OFE, OFT and OFST groups (OC: 5.37±0.15, OF: 6.41±0.21, OFT: 4.93±0.3, OFE: 4.94±0.23, OFST: 4.66±0.46 nmol/mg protein). The redox balance of glutathione (GSH/GSSG) was decreased in the OF group compared to the OC and OFT groups.ConclusionThese results demonstrate that fructose exposure in parents induced early changes in offspring BP, BRS and cardiac oxidative stress, that seems to be mediated, at least in part, by the anti‐inflammatory cholinergic reflex. Moreover exercise training seems to prevent/attenuate such dysfunctions.

Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice

ObjectiveThe prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring.MethodsMice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring.ResultsWe show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring.ConclusionMaternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.

Fructooligosaccharide ameliorates high-fat induced intrauterine inflammation and improves lipid profile in the hamster offspring

Maternal high-fat diet (HFD) often results in intrauterine and feto-placental inflammation, and increases the risks of fetal programming of metabolic diseases. Intake of prebiotic is reported beneficial. However, its effects on HFD during pregnancy and lactation is not known. We evaluated the maternal intake of fructooligosaccharide (FOS) and its impact on placental inflammation, offspring's adiposity, glucose, and lipid metabolism in their later life. Female Golden Syrian hamsters were fed with a control diet (CD, 26.4 % energy from fat) or HFD (60.7% energy from fat) in the presence or absence of FOS from preconception until lactation. All pups were switched over to CD after lactation and continued until the end. Placental inflammation was upregulated in HFD-fed dam, as measured by a high concentration of hsCRP in the serum and amniotic fluid. Neutrophil infiltration was significantly increased in the decidua through the chorionic layer of the placenta. The expression of pro-inflammatory cytokines such as COX2, NFκβ, IL-8, TGFβ mRNA was increased in the chorioamniotic membrane (P <.05). The HFD/CD hamsters had more adiposity, higher triglyceride, and low HDL at 12 months of age compared to CD/CD (P <.05). However, HFD+FOS/CD-fed hamsters prevented adverse effects such as placental inflammation, neutrophil infiltration, glucose, and lipid profiles in the offspring (P <.05). Anti-inflammatory and lipid-lowering effects of FOS may reduce placental inflammation by lowering neutrophil infiltration and decreasing the production of pro-inflammatory cytokines. Intake of FOS during pregnancy may be beneficial in maintaining lipid metabolism and preventing excess adiposity for mother and their offspring.

Mothers\u2019 cafeteria diet induced sex-specific changes in fat content, metabolic profiles, and inflammation outcomes in rat offspring

“Western diet” containing high concentrations of sugar and fat consumed during pregnancy contributes to development of obesity and diabetes type 2 in offspring. To mimic effects of this diet in animals, a cafeteria (CAF) diet is used. We hypothesized that CAF diet given to rats before, and during pregnancy and lactation differently influences fat content, metabolic and inflammation profiles in offspring. Females were exposed to CAF or control diets before pregnancy, during pregnancy and lactation. At postnatal day 25 (PND 25), body composition, fat contents were measured, and blood was collected for assessment of metabolic and inflammation profiles. We have found that CAF diet lead to sex-specific alterations in offspring. At PND25, CAF offspring had: (1) higher percentage of fat content, and were lighter; (2) sex-specific differences in levels of glucose; (3) higher levels of interleukin 6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α); (4) sex-specific differences in concentration of IL-6 and TNF-α, with an increase in CAF females; (5) higher level of IL-10 in both sexes, with a more pronounced increase in females. We concluded that maternal CAF diet affects fat content, metabolic profiles, and inflammation parameters in offspring. Above effects are sex-specific, with female offspring being more susceptible to the diet.

Maternal gestational diabetes and childhood hyperlipidemia.

Aim of this study is to assess dyslipidemia risk between children exposed to maternal gestational diabetes mellitus (GDM) and those not exposed. We recruited 1144mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring's age and sex). The age of offspring ranged from 3 to 9years old. We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of maternal GDM with abnormal lipid profiles in offspring. After adjustment for maternal and children's characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40±0.01 vs. 1.50±0.01; p<0.001) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37±0.01 vs. 0.35±0.01; p<0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.11 (95% confidence interval [CI 1.15-3.88]) for low HDL cholesterol and 1.35 (95% CI 1.00-1.81) for high triglycerides/HDL cholesterol ratio, respectively. Maternal GDM was associated with an increased risk of hyperlipidemia in the offspring during early childhood aged from 3 to 9years old.

1079-P: Maternal Gestational Diabetes and Childhood Hyperlipidemia

Very few studies have assessed the impact of maternal gestational diabetes mellitus (GDM) on lipid profiles in the offspring in China. We aim to compare the lipid profile between children exposed to maternal GDM and those not exposed, and assess association between maternal GDM and offspring’s dyslipidemia risk. We recruited 1144 mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring’s age and sex). We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of GDM with abnormal lipid profiles in offspring. After adjustment for maternal and children’s characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40±0.01 vs. 1.50±0.01; P &amp;lt;0.05) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37±0.01 vs. 0.35±0.01; P &amp;lt;0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.07 (95% confidence interval [CI 1.13-3.79]) for low HDL cholesterol and 1.36 (95% CI 1.01-1.82) for high triglycerides/HDL cholesterol ratio, respectively. Exposure to GDM mothers was an independent risk factor for the abnormal lipid profile among children, which can emerge as early as in the preschool period. Disclosure G. Hu: None. Funding Tianjin Women’s and Children’s Health Center; Tianjin Public Health Bureau; European Foundation for the Study of Diabetes/Chinese Diabetes Society/Lilly Programme for Collaborative Research; National Institute of Diabetes and Digestive and Kidney Diseases

Plant Volatile Organic Compounds Evolution: Transcriptional Regulation, Epigenetics and Polyploidy.

Volatile organic compounds (VOCs) are emitted by plants as a consequence of their interaction with biotic and abiotic factors, and have a very important role in plant evolution. Floral VOCs are often involved in defense and pollinator attraction. These interactions often change rapidly over time, so a quick response to those changes is required. Epigenetic factors, such as DNA methylation and histone modification, which regulate both genes and transcription factors, might trigger adaptive responses to these evolutionary pressures as well as regulating the rhythmic emission of VOCs through circadian clock regulation. In addition, transgenerational epigenetic effects and whole genome polyploidy could modify the generation of VOCs’ profiles of offspring, contributing to long-term evolutionary shifts. In this article, we review the available knowledge about the mechanisms that may act as epigenetic regulators of the main VOC biosynthetic pathways, and their importance in plant evolution.

No effect of prior Dengue virus 1 infection in mouse dams on long-term behavioral profiles in offspring infected with Zika virus during gestation

Zika virus (ZIKV) is a mosquito-borne Flavivirus structurally and antigenically related to Dengue virus (DENV). Zika virus has been associated with congenital anomalies and most ZIKV outbreaks have occurred in endemic areas of DENV. The present study investigated the effects of prior DENV serotype 1 (DENV1) immunity in immunocompetent female Swiss mice on gestational ZIKV infection in offspring. Physical/reflex development, locomotor activity, anxiety, visual acuity, and brain-derived neurotrophic factor (BDNF) levels were evaluated in offspring during infancy and adolescence. Anti-DENV1 and anti-ZIKV antibodies were detected in sera of the progenitors, whereas no ZIKV genomes were detected in the offspring brain. Pups from dams with only DENV1 immunity presented alterations of physical/reflex development. Pups from all infected dams exhibited time-related impairments in locomotor activity and anxiolytic-like behavior. Offspring from DENV/ZIKV-infected dams exhibited impairments in visual acuity during infancy but not during adolescence, which was consistent with morphometric analysis of the optic nerve. Pups from DENV1-, ZIKV-, and DENV/ZIKV-infected dams exhibited a decrease in BDNF levels during infancy and an increase during adolescence in distinct brain regions. In summary, we found no influence of prior DENV1 immunity on gestational ZIKV infection in offspring, with the exception of alterations of early visual parameters, and an increase in BDNF levels in the hippocampus during adolescence.

Consequences of maternal psychological stress during pregnancy for the risk of asthma in the offspring.

Asthma is a common lung condition that makes breathing difficult through the inflammation and constriction of the lung airways. Epidemiological evidence supports the presence of a positive association between prenatal maternal psychological stress (PMPS) and asthma in the offspring, suggesting the disease may have developmental origins. T-helper 2 (Th2) cells are a major subtype of T-helper cells, producing Th2 cytokines, which may be the main drivers of asthma symptoms. A Th2 dominant blood cytokine profile may therefore indicate an increased risk of asthma, as studies have shown a link between PMPS and a T-helper 2 (Th2) cytokine profile in offspring. The mechanism by which PMPS may cause Th2 cytokine dominance in the offspring is unclear. Epigenetic modifications in utero can lead to long-lasting effects that persist postnatally and have therefore been implicated in this relationship. Increased maternal blood cortisol levels due to PMPS may increase transfer of cortisol to the foetus, where the temporarily increased levels may induce changes in the epigenome. Evidence from animal studies suggests that genes controlling cytokine production in T cells can be epigenetically modified in a way that increases Th2 cytokine production. Other evidence suggests that methylation of the NR3C1 gene decreases hippocampal glucocorticoid receptor expression, leading to decreased negative regulation of the hypothalamus-pituitary-adrenal axis. This can increase cortisol production which has been shown to increase Th2 cytokine production. Therefore, the link between PMPS and a Th2 offspring cytokine profile, mediated through epigenetic changes, may explain the positive relationship between PMPS and asthma in the offspring.

Effects of microplastics and their adsorption of cadmium as vectors on the cladoceran Moina monogolica Daday: Implications for plastic-ingesting organisms

As pervasive and resilient contaminants, microplastics (MPs) have potential to interact with the toxicity of metals through adsorption on the surface. In this study, we focused on 7-day adsorption of cadmium (5, 10 μg/L) to aged polyethylene-MPs particles (300 μg/L), and further examined 21-day chronic effects of MPs and MPs-Cd on cladoceran Moina monogolica Daday. The effects criteria selected were physiological changes (e.g., parental survival time, somatic growth and reproductive parameters) and nutritional profiles in offspring. Exposure of M. monogolica to both MPs and MPs-Cd can impair the development, reproductive output and fecundity across treatment groups, ultimately leading to parental mortality and poor nutritional status in progeny. Importantly, MPs with adsorbed Cd showed greater adverse dose-dependent effects than bare MPs, likely due to the mechanisms of physico-chemical interactions related to the Cd release from MPs-Cd inside organisms. MPs can pose not only a direct harm to the organisms but also an indirect hazard via adsorption as “transport vector”, having implications for the function and resilience of aquatic ecosystems. Our findings experimentally highlight the importance of characterizing chemical profiling of contaminants adsorbed to field plastics in order to better assess environmentally relevant risks associated with MPs and metals in coastal areas.

Excessive Ingestion Of Parental Fructose Causes Autonomic Dysfunction Since Birth In Offspring: Impact on Adulthood

The aim this study was to evaluate the effects on hemodynamic, autonomic and inflammatory profile in offspring (from birth to adulthood) of parents submitted to chronic fructose overload.The Fructose genitor group was formed by adult Wistar rats (males and females) that underwent a fructose overload (10%) in drinking water for 60 days. The Control genitor group was formed by adult Wistar rats who were only followed for the same period receiving a standard diet. Mating was carried out and the females continued to receive the same diet (fructose or standard) during all gestation and lactation. On the day of birth, the fructose (F) and control (C) offspring were submitted to an electrocardiogram to analyze heart rate variability (n = 10/group). On the day of weaning two groups were evaluated, the CW group (descendants of the control parents, n = 10) and the FW group (descendants of the fructose parents, n = 10). Another two groups were evaluated 30 days after weaning, group C30 (from control parents, n = 10) and the F30 group (from fructose parents, n = 10). During lifespan, all offspring received a standard diet without fructose. Arterial pressure (AP) were recorded directly. Baroreflex sensitivity was evaluated by increasing dosing of phenylephrine and sodium nitroprusside. Cardiovascular autonomic modulation was evaluated by spectral analysis. Inflammatory profile was measured by ELISA in cardiac tissue.Regarding the autonomic evaluations, the fructose groups presented an impairment from birth to adulthood evidenced by a sympathovagal imbalance (LF/HF) when compared to control groups (F: 0.71 ± 0.08; FW: 0.91 ± 0.08 and F30: 0.72 ± 0.09 vs. C: 0.37 ± 0.04; CW: 0.48 ± 0.07 and C30: 0.38 ± 0.04). Additionally, only the F30 group showed higher vascular sympathetic modulation among groups (4.7 ± 0.6 vs. C30: 2.8 ± 0.4; CW: 1.8 ± 0.4 and FW: 2.9 ± 0.4 mmHg2). Moreover, the fructose groups had a worse tachycardic response when compared to control groups at the same time (FW: −2.8 ± 0.3 and F30: −3.1 ± 0.2 vs. CW: −3.9 ± 0.4 and C30: −4.0 ± 0.1 bpm/mmHg). Finally, group F30 presented worse inflammatory profile compared to group C30, evidenced by the increase of IL‐6 (167.2 ± 9.5 vs C30: 104.9 ± 11.9 pg/ml) and decrease of the IL‐10/TNF alpha ratio (P&lt;0.01). The mean, systolic and diastolic AP was increased only in group F30 when compared to the C30 group (mean AP, F30: 109 ± 1.9 vs. C30: 103 ± 1.3 mmHg).In conclusion, the offspring of parents submitted to fructose overload presented autonomic, hemodynamic and inflammatory cardiovascular dysfunctions. Moreover, the results suggest early autonomic dysfunctions, and these seem to precede hemodynamic and inflammatory changes. These findings suggest cardiovascular autonomic variability as a possible early marker of risk of developing disease in offspring of parents exposed to high fructose consumption.Support or Funding InformationFAPESP (2018/17183‐4); CAPES.

Increased Alkaline Phosphatase in Cord Blood of Obese Diabetic Mothers Is Associated to Polyunstaurated Fatty Acid Levels

Introduction: Recent studies indicate that alkaline phosphatase (ALP) may affect expression and activity of fatty acid (FA) transport proteins in placenta and other tissues. Objective: To evaluate if disturbed FA profile in offspring of gestational diabetes mellitus (GDM) with different maternal pregestational weight could be related to maternal or neonatal ALP. Methods: Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 lean-GDM, 20 obese-GDM). Fetal ultrasound was performed. At delivery, FAs were analyzed in placenta, maternal, and venous cord blood. Western blotting analysis of lipid carriers was performed in placenta. Results: Newborns from obese-GDM tended to higher birthweight (p = 0.059) than those from both lean-GDM and controls. ALP in maternal blood tended to be lower in GDM (p = 0.170) while increased significantly in cord blood of obese-GDM with respect to controls (p = 0.039). Saturated FA percentages in cord blood were significantly higher (p < 0.000), while polyunsaturated FA (PUFA) percentages were lower (p = 0.003) in both GDM, which could be due to a lower expression of major family domain 2a receptor (MFSD2a) in the placenta. Plasma ALP in the offspring of obese-GDM was inversely associated to cord essential PUFAs (β = –6.18, p = 0.005) and to placental MFSD2a (β = –38.46, p = 0.014). Conclusions: Cord PUFA and placental MFSD2a are decreased in both lean and obese-GDM pregnancies. Higher ALP in cord blood of obese-GDM could play a role in the FA levels in these pregnancies

Chronic Gestational Inflammation: Transfer of Maternal Adaptation over Two Generations of Progeny.

Changes in the in utero environment result in generational transfer of maladapted physiology in the context of conditions such as stress, obesity, and anxiety. Given the significant contribution of noncommunicable diseases—which are characterised by chronic inflammation—to population mortality, the potential for chronic maternal inflammation mediating foetal programming is a growing concern. The extent of generational transfer in terms of immune functionality and leukocyte glucocorticoid sensitivity was investigated over two generations of offspring (F1 and F2) in a model of chronic LPS-induced maternal inflammation in C57/BL/6 mice. Maternal inflammation resulted in glucocorticoid hypersensitivity (increased glucocorticoid receptor expression levels) in the majority of leukocyte subpopulations in both F1 and F2 offspring. Furthermore, splenocytes stimulated with LPS in vitro exhibited exacerbated inflammatory cytokine responses, which were even more prominent in F2 than F1; this effect could be ascribed to NLRP3 inflammasome hyperactivity in F1 but not F2. Current data illustrates that parental chronic inflammation may mediate the inflammatory profile in offspring, potentially propagating a maladapted proinflammatory phenotype in subsequent generations.

Maternal Restricted- and Over-Feeding During Gestation Result in Distinct Lipid and Amino Acid Metabolite Profiles in the Longissimus Muscle of the Offspring.

Maternal over- and restricted-feeding during gestation have similar negative consequences for the offspring, including decreased muscularity, increased adiposity, and altered metabolism. Our objective was to determine the effects of poor maternal nutrition during gestation (over- and restricted-feeding) on the offspring muscle metabolite profile. Pregnant ewes (n = 47) were fed 60% (RES), 100% (CON), or 140% (OVER) of NRC requirements starting at day 30.2 ± 0.2 of gestation. Offspring sample collection occurred at days 90 and 135 of gestation, and within 24 h of birth. C2C12 myoblasts were cultured in serum collected from offspring at birth (n = 18; 6 offspring per treatment) for analysis of oxidative and glycolytic capacity. Unbiased metabolite analysis of longissimus muscle samples (n = 72; 8 fetuses per treatment per time point) was performed using mass spectrometry. Data were analyzed by ANOVA for main effects of treatment, time point, and their interaction. Cells cultured in serum from RES offspring exhibited increased proton leak 49% (p = 0.01) compared with CON, but no other variables of mitochondrial respiration or glycolytic function were altered. Mass spectrometry identified 612 metabolites. Principle component analysis identified day of gestation as the primary driver of metabolic change; however, maternal diet also altered the lipid and amino acid profiles in offspring. The abundance of 53 amino acid metabolites and 89 lipid metabolites was altered in RES compared with CON (p ≤ 0.05), including phospholipids, sphingolipids, and ceramides within the lipid metabolism pathway and metabolites involved in glutamate, histidine, and glutathione metabolism. Similarly, abundance of 63 amino acid metabolites and 70 lipid metabolites was altered in OVER compared with CON (p ≤ 0.05). These include metabolites involved in glutamate, histidine, lysine, and tryptophan metabolism and phosphatidylethanolamine, lysophospholipids, and fatty acids involved in lipid metabolism. Further, the amino acid and lipid profiles diverged between RES and OVER, with 69 amino acid and 118 lipid metabolites differing (p ≤ 0.05) between groups. Therefore, maternal diet affects metabolite abundance in offspring longissimus muscle, specifically metabolites involved in lipid and amino metabolism. These changes may impact post-natal skeletal muscle metabolism, possibly altering energy efficiency and long-term health.

Autoantibodies, elevated cytokines, and neurocognitive abnormalities in offspring of women with systemic lupus erythematosus: comparison with healthy controls.

Research describes higher incidence of neurodevelopmental disorders and learning disabilities in offspring of women affected by lupus. Factors implied are pregnancy and delivery adversities and exposure to maternal antibodies and cytokines. Little is known about the offspring immunological condition or the relation between offspring and maternal condition. This study was conducted in order to analyze immunological configuration, psychopathology, and neuropsychological performance of young offspring of women with lupus, in comparison with healthy controls and in relation to maternal psychophysical condition. Twenty-one offspring aged 8-17 of 17 women with lupus and 34 controls were recruited. Pregnancy conditions, stress factors, and immunological, psychopathological, and neuropsychological characteristics were compared. Immunological tests included standard lupus screening, lupus-related autoantibodies, antibodies against GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR) (anti-DWEYS Ab), and levels of ten cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GMCSF, IFN-γ, TNF-α). Offspring had lower leukocyte count (p = 0.001) and higher levels of anti-dsDNA Ab (p = 0.022), anti-DWEYS-GluN2 Ab (p < 0.001), and eight cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α-all p < 0.001-and IFN-γ, p = 0.026) than controls. Their cytokine levels did not differ from their mothers'; 23.9% of offspring met the criteria for a clinical psychiatric diagnosis. No differences were found in intelligence measures. Various neuropsychological scores correlated inversely with maternal psychophysical health. Offspring's profile suggests proinflammatory and autoimmune activation. Their rate of psychiatric diagnosis appears higher than in the general population, and their cognitive performance is related to maternal psychophysical health. Longitudinal research might investigate whether immunological and psychosocial conditions influence psychopathology and cognition. Graphical abstract The hypothesized sequence for physical and neuropsychological development for the SLE offspring.