Fetal Programming Effects Research Articles

Effect of gestational naural pasture allowance on muscle development of lambs

To study the effects of gestational undernutrition induced by a lower natural pasture allowance on myogenesis and meat production in lambs, two experiments were carried out. In the first, Corriedale sheep were fed contrasting natural pasture allowances (23 days before conception until gestation day 122) and myogenesis was evaluated in 70-day-old fetuses and newborns. In the second, similar ewes were fed with contrasting natural pasture allowances (day 30 of gestation until parturition) and the productive performance, quantity and quality of meat and muscular characteristics in 200-day-old lambs were evaluated. A lower pasture allownace affected fetal myogenesis (fewer secondary fibers) and was associated with reduced mitotic and myoblastic fusion activity in some muscles. In newborns, maternal undernutrition affected muscle histology, fibrillar biological and contractile properties (MyHC-I and GLUT-4). Likewise, undernutrition strongly reduced muscle IGF-1 and could compromise neonatal hypertrophic compensation. On the other hand, maternal undernutrition from day 30 to parturition affected growth, carcass quality and muscle weights at 200 days, although these effects were mainly sex-dependent, with males being the most affected. Maternal undernutrition affected fibrillar composition (greater oxidative activity) in all muscles at 200 days. Biochemical and meat quality characteristics were also affected, although these effects depended on both muscle and sex. In summary, a lower gestational pasture allowance negatively affected fetal myogenesis and neonatal muscle characteristics (worse hypertrophic capacities), and induced fetal programming effects on muscle mass and muscle characteristics at 200 days. This implies that, regardless of postnatal conditions, intrauterine alterations induce muscular changes, which may be related to the ability to grow and the quality of the meat produced. Likewise, our results highlight the importance of considering the sex of the animal and the muscle when studying these effects.

Fetal programming and lactation: modulating gene expression in response to undernutrition during intrauterine life.

Adverse environmental conditions during intrauterine life, known as fetal programming, significantly contribute to the development of diseases in adulthood. Fetal programming induced by factors like maternal undernutrition leads to low birth weight and increases the risk of cardiometabolic diseases. We studied a rat model of maternal undernutrition during gestation (MUN) to investigate gene expression changes in cardiac tissue using RNA-sequencing of day 0-1 litters. Moreover, we analyzed the impact of lactation at day 21, in MUN model and cross-fostering experiments, on cardiac structure and function assessed by transthoracic echocardiography, and gene expression changes though qPCR. Our analysis identified specific genes with altered expression in MUN rats at birth. Two of them, Agt and Pparg, stand out for being associated with cardiac hypertrophy and fibrosis. At the end of the lactation period, MUN males showed increased expression of Agt and decreased expression of Pparg, correlating with cardiac hypertrophy. Cross-fostering experiments revealed that lactation with control breastmilk mitigated these expression changes reducing cardiac hypertrophy in MUN males. Our findings highlight the interplay between fetal programming, gene expression, and cardiac hypertrophy suggesting that lactation period is a potential intervention window to mitigate the effects of fetal programming. Heart remodeling involves the alteration of several groups of genes and lactation period plays a key role in establishing gene expression modification caused by fetal programming. We could identify expression changes of relevant genes in cardiac tissue induced by undernutrition during fetal life. We expose the contribution of the lactation period in modulating the expression of Agt and Pparg, relevant genes associated with cardiac hypertrophy. This evidence reveal lactation as a crucial intervention window for preventing or countering fetal programming.

Maternal nutrition and fetal imprinting of the male progeny

The global population as well as the demand for human food is rapidly growing worldwide, which necessitates improvement of efficiency in livestock operations. In this context, environmental factors during fetal and/or neonatal life have been observed to influence normal physical and physiological function of an individual during adulthood, and this phenomenon is called fetal or developmental programming. While numerous studies have reported the impact of maternal factors on development of the female progeny, limited information is available on the potential effects of fetal programming on reproductive function of the male offspring. Therefore, the objective for this review article was to focus on available literature regarding the impact of maternal factors, particularly maternal nutrition, on reproductive system of the male offspring. To this end, we highlighted developmental programming of the male offspring in domestic species (i.e., pig, cow and sheep) as well as laboratory species (i.e., mice and rat) during pregnancy and lactation. In this sense, we pointed out the effects of maternal nutrition on various functions of the male offspring including hypothalamic–pituitary axis, hormonal levels, testicular tissue and semen parameters.

Fetal Programming Influence on Microbiome Diversity and Ruminal and Cecal Epithelium in Beef Cattle.

We explored the influence of maternal nutritional strategies on the development of the rumen and cecum in offspring. Additionally, we investigated the potential repercussions of prenatal nutrition on the rumen and fecal microbiota composition, utilizing metagenomic 16S techniques, to understand the effects of fetal programming (FP) in Nellore cattle. A total of 63 bulls submitted to different prenatal nutrition strategies, namely, non-programming (NP), partial programming (PP), and complete programming (CP), were evaluated. The rumen epithelium was methodically evaluated based on the presence of rumenitis and structural irregularities. The assessment of cecum lesions was conducted post-evisceration, whereby all thoroughly cleaned ceca were methodically evaluated. Samples from 15 animals of rumen fluid at slaughter and feces during the finishing phase were collected, respectively. All DNA extraction were carried out using the Macherey Nagel NucleoSpin Tissue®, and 16S sequencing was conducted using the V4 primers on the MiSeq platform. Within the ruminal ecosystem, an estimated range of 90 to 130 distinct amplicon sequence variants was discerned, as distributed across 45,000 to 70,000 sequencing reads. Our metagenomic exploration unveils microbial communities that distinctly mirror gastrointestinal tract microenvironments and dietary influences. In sum, this comprehensive study advances our comprehension of FP, highlighting the interplay of maternal nutrition, gastrointestinal development, and microbial communities, contributing significantly to the fields of animal science.

Fetal programming effect of rumen-protected methionine on primiparous Angus × Simmental offspring's performance and skeletal muscle gene expression.

Primiparous Angus × Simmental dams (n = 22) with an average body weight (BW) of 449 ± 32kg of BW were divided based on two nutritional treatments: control (CTRL) and rumen-protected methionine (RPM). The control group received bermudagrass hay, corn gluten, and soybean hulls pellets supplementation (base diet); whereas the RPM group received the base diet in addition to 0.07% of DM of RPM at a fixed rate during the last trimester of gestation and the first ~80d of lactation, in which calves (n = 17) were early weaned. Only male calves were included in this study. After weaning, calves born to RPM dams also received RPM from weaning (day 1) to day 100. Blood sampling and skeletal muscle biopsies for subsequent quantitative polymerase chain reaction (PCR) analysis were conducted on days 1, 25, 50, and 100 on calves. Quantitative PCR data were analyzed using GLIMMIX, and blood metabolites concentrations, BW, and body condition score (BCS) were analyzed using the MIXED procedure of SAS. There was no difference in maternal BW and BCS between treatments. Glucose and blood metabolites that served as biomarkers for liver health (e.g., aspartate transaminase, albumin, alkaline phosphatase, and alanine transaminase) were in the normal levels for all calves (P > 0.40). Calves in the RPM group had a greater expression of adipogenic genes (e.g., PPARG, LPL, and CEBPD) at day 100 compared with CTRL (P < 0.01). In addition, DNA methylation (DNMT1) and oxidative stress-related genes (SOD2 and NOS3) in the RPM group were upregulated at day 100 compared with CTRL (P < 0.01). These results may suggest that calves born to primiparous dams exposed to RPM supplementation are more prone to develop greater adipose tissue than CTRL calves. Furthermore, RPM supplementation may improve methylation processes, as shown by the upregulation of DNMT1. The results shown in our study aim at expanding the knowledge on fetal programming and early-life growth and development of beef cattle under supplementation with RPM.

The impact of exposure to tobacco smoking and maternal trauma in fetal life on risk of migraine.

Prenatal period is the key time in human development. Many prenatal factors are well-known and increase the risk of developing diseases' after birth. Few studies indicated the link between the prenatal period and the prevalence of migraine in childhood and adolescence so far. We decided to broaden current knowledge and investigate whether the prenatal factors influence the prevalence of migraine in adulthood. The objective of this study is to provide evidence of relationship between in utero environment and risk of migraine. In total 266 females (136 in the migraine group, 130 in the control group) and 80 males (35 in the migraine group, 45 in the control group), aged 18-65 participated in the study. The quality of prenatal environment was characterized on the basis of mother's and father's education, tobacco smoke exposure, alcohol consumption, and traumatic event during pregnancy, which are considered as prenatal factors and affect on fetal development. Migraine occurrence in adulthood was significantly associated with maternal tobacco smoking during pregnancy (OR 3.42, 95% CI 1.54-7.61, p = 0.036) and traumatic event during pregnancy (OR 2.27, 95% CI 1.24-4.13, p = 0.020). Our study suggests that the fetal programming effect of tobacco smoking exposure and maternal trauma is not limited to prenatal life and is suggested as having a role in adulthood. Our findings support evidence that migraine adulthood can be partly influenced by early life conditions.

Influence of maternal hyperglycemia on rat daughters and granddaughters

This study evaluated the influence of maternal diabetes on the reproductive outcomes of adult daughters during full-term pregnancy in rats. The local ethics committee approved all experimental protocols. The adult female pups of nondiabetic (control – CP) and diabetic (DP) mothers were subjected to mating with healthy male rats for reproductive analysis. On day 17 of pregnancy, both groups underwent an oral glucose tolerance test (OGTT) to evaluate glucose tolerance. At the end of pregnancy, the rats were anesthetized for laparotomy and exposure of maternal organs. Uterine horns, ovaries, fetuses, and placentas were weighed to classify fetal weight and placental efficiency. P&lt;0.05 was considered a statistically significant limit, and Pearson's correlation was used. Higher maternal fasting blood glucose was correlated with a lower number of live fetuses and, consequently, with a lower litter weight. Thus, maternal fasting glucose during pregnancy is a relevant biomarker related to the poor reproductive outcome of daughters of rats. Furthermore, these findings show the detrimental effects of fetal programming induced by maternal diabetes in adulthood in the subsequent generation.

Transcriptomic survey of key reproductive and metabolic tissues in mouse models of polycystic ovary syndrome

Excessive androgen production and obesity are key to polycystic ovary syndrome (PCOS) pathogenesis. Prenatal androgenized (PNA), peripubertal androgenized, and overexpression of nerve growth factor in theca cells (17NF) are commonly used PCOS-like mouse models and diet-induced maternal obesity model is often included for comparsion. To reveal the molecular features of these models, we have performed transcriptome survey of the hypothalamus, adipose tissue, ovary and metaphase II (MII) oocytes. The largest number of differentially expressed genes (DEGs) is found in the ovaries of 17NF and in the adipose tissues of peripubertal androgenized models. In contrast, hypothalamus is most affected in PNA and maternal obesity models suggesting fetal programming effects. The Ms4a6e gene, membrane-spanning 4-domains subfamily A member 6E, a DEG identified in the adipose tissue in all mouse models is also differently expressed in adipose tissue of women with PCOS, highlighting a conserved disease function. Our comprehensive transcriptomic profiling of key target tissues involved in PCOS pathology highlights the effects of developmental windows for androgen exposure and maternal obesity, and provides unique resource to investigate molecular mechanisms underlying PCOS pathogenesis.

Immune Responses to SARS-CoV-2 in Pregnancy: Implications for the Health of the Next Generation.

Widespread SARS-CoV-2 infection among pregnant individuals has led to a generation of fetuses exposed in utero, but the long-term impact of such exposure remains unknown. Although fetal infection is rare, children born to mothers with SARS-CoV-2 infection may be at increased risk for adverse neurodevelopmental and cardiometabolic outcomes. Fetal programming effects are likely to be mediated at least in part by maternal immune activation. In this review, we discuss recent evidence regarding the effects of prenatal SARS-CoV-2 infection on the maternal, placental, and fetal immune response, as well as the implications for the long-term health of offspring. Extrapolating from what is known about the impact of maternal immune activation in other contexts (e.g., obesity, HIV, influenza), we review the potential for neurodevelopmental and cardiometabolic morbidity in offspring. Based on available data suggesting potential increased neurodevelopmental risk, we highlight the importance of establishing large cohorts to monitor offspring born to SARS-CoV-2-positive mothers for neurodevelopmental and cardiometabolic sequelae.

Maternal exposure of rats to sodium saccharin during gestation and lactation on male offspring†.

We investigated the effects of fetal programming in Sprague-Dawley rats through the maternal consumption of sodium saccharin on the testicular structure and function in male offspring. Feed intake and efficiency, organ and fat weight, quantification and expression of androgen receptor (AR), and proliferating cell nuclear antigen (PCNA) proteins, sperm count, and hormone levels were determined. Consumption alterations were found in the final weeks of the experiment. Decreases in AR and PCNA expression and quantification, tubular diameter, and luminal volume, and increases in epithelial and interstitial relative volumes were observed. Lower sperm count and transit, and lower estradiol concentration were also found. Sodium saccharin consumption by dams programmed male offspring by affecting the hypothalamic-pituitary-gonad axis with alterations in the Sertoli cell population, in spermatogonia proliferation, the expression and quantification of AR, and in sperm count. We hypothesized that these changes may be due to an estradiol reduction that caused the loosening of adhesion junctions of the blood-testis barrier, causing cell losses during spermatogenesis, also reflected by a decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. We conclude that maternal sodium saccharin consumption during pregnancy and lactation programmed alterations in the reproductive parameters of male offspring, thus influencing spermatogenesis.

PSIV-B-14 Fetal Programming Effects on Weight Gain and Backfat Thickness in Nellore Heifers

Abstract Few studies have investigated the effects of fetal programming on the performance of heifers in the rearing phase This study evaluated the effects of maternal nutrition on performance and backfat thickness (BFT) of beef cattle heifers. The study comprised pregnant 126 Nellore dams, which were fixed time artificially inseminated (FTAI) with semen of four bulls. The animals were separated into three treatments: Not Programmed (NP), without protein-energy supplementation; Partially Programmed (PP), supplementation offered in the final third of gestation; and Full Programmed (FP), supplementation during the whole gestation. Animals were allocated to pasture paddocks with access to the supplement (0.03% live weight for NP, and 0.3% live weight for PP and FP) and water ad libitum. After calving, protein-energy supplementation ceased (average 220 days old), regardless of the treatment. After weaning, the female progeny (55 heifers) remained on the pasture until the beginning of the reproductive season at 24 months old. The performance of heifers was evaluated in the periods of weaning, year, 18 months and 24 months, measuring weight and backfat thickness (BFT). The effects of treatments (NP, PP, and FP) on phenotypes were evaluated using the analysis of variance and the means compared by the Tukey-Kramer test, with contrasts considered significant when p&amp;lt; 0.05. The weight of the animals showed a significant difference over time (p = 0.017). The weight of the heifers in the three treatments was similar in all periods evaluated (p &amp;gt; 0.05); however, when an analysis was carried out over time, a significant difference occurred among the treatments (p = 0.017). Fetal programming did not affect the weight and fat thickness of the heifers throughout the rearing period.

Effect of perfluoroalkyl exposure in pregnancy and infancy on intrauterine and childhood growth and anthropometry. Sub study from COPSAC2010 birth cohort.

Perfluoroalkyl substances PFOS and PFOA are persistent and bioaccumulative exogenous chemicals in the human body with a range of suspected negative health effects. It is hypothesised that exposure during prenatal and early postnatal life might have particularly detrimental effects on intrauterine and childhood growth. In a Danish longitudinal mother-child cohort we investigate effect of PFOS and PFOA in pregnancy and infancy on intrauterine and childhood growth and anthropometry. COPSAC2010 is an ongoing population based mother-child cohort of 738 pregnant women and their children followed from 24 week gestation with longitudinal deep clinical phenotyping until age 10 years. In this observational cohort sub study plasma PFOS and PFOA concentrations were semi-quantified by untargeted metabolomics in the mothers at week 24 and 1 week postpartum and in the children at ages 6 and 18 months and calibrated using a targeted pipeline. We examined associations to intrauterine and childhood growth and anthropometry, including interactions with child sex. Untargeted and targeted blood metabolomics profiles were integrated to investigate underlying mechanisms. Pregnancy plasma PFOA concentrations were associated with lower birth size -0.19 [-0.33; -0.05] BMI z-score per 1-ng/mL and increased childhood height (z-scored) at age 6: 0.18 [0.05; 0.31], but there was no association between childs' own infancy plasma PFOA concentration and height. Pregnancy plasma PFOS concentrations were also associated with lower birth BMI (-0.04 [-0.08; -0.01]), but in childhood pregnancy plasma PFOS concentration interacted with child sex on BMI and fat percentage at 6 years with negative associations in girls and positive in boys. The effect of maternal plasma PFOS concentration on lower girl BMI was borderline mediated through increasing child plasma lactosyl-ceramide levels (p-mediation=0.08). Similarly the effect of maternal plasma PFOS concentration on higher boy fat percentage was borderline mediated through increasing child plasma lactosyl-ceramide levels (p-mediation=0.07). Infancy concentrations of plasma PFOS associated with lower height in childhood, -0.06 z-score at age 6 [-0.19; -0.03]. Higher PFOS and PFOA plasma concentrations during pregnancy had detrimental effects on fetal growth. The effects on childhood growth were not similar as PFOA increased child height, opposite of PFOS in multipollutant models suggesting a differing fetal programming effect. Sex specific growth effects were borderline mediated through an altered lactosyl-ceramide metabolism, proposing a possible mechanism of PFOS that has long-lasting health consequences in this observational study. All funding received by COPSAC are listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Novo Nordic Foundation (Grant nos NNF20OC0061029, NNF170C0025014, NNF180C0031764) The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (Grant no 0603-00280B) and The Capital Region Research Foundation have provided core support to the COPSAC research center. Effort from JALS is supported by R01HL123915, R01HL141826, and R01HL155742 from NIH/NHLBI. CEW was supported by the Swedish Heart Lung Foundation (HLF 20180290, HLF 20200693). BC has received funding for this project from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 946228). The funding agencies did not have any role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, or approval of the manuscript.

The Impact of Fetal Programming in Ewe Nutrition with Chromium Propionate or Calcium Salts of Palm Oil on the Meat Quality and Bone of the Progeny.

This study aimed to evaluate the inclusion of chromium propionate or calcium salts of palm oil in ewes' diet during the final third of gestation and lactation on progeny performance, carcass characteristics, non-carcass components, and bone density. Forty-three ewe, Santa Inês and Dorper breed, three ± one-year-old, and body weight 57 ± 10 kg were used. The experimental design was in casual blocks in three treatments, CTL treatment (n = 15) with starch from corn; CR (n = 15) diet CTL plus chromium propionate; PF (n = 13) diet CTL plus calcium salts of palm oil. After weaning, 23 male lambs from these ewes were confined in individual stalls, with the same diet for 60days, slaughtered. The data were analyzed using the SAS program, PROC GLM, and compared the means using Tukey's test at 5% probability. The maternal diet did not alter the dry matter intake, feeding efficiency, and average daily weight gain. Therefore, weights (weaning and slaughter) and carcass yield were higher for CR and PF groups than for CTL (P < 0.05). The treatment did not influence the loin eye area and fat thickness (P > 0.05). The spleen and the respiratory tract were smaller for PF and larger for CTL (P < 0.05). Leg weight was higher for CR. The perimeter and depth of the shank for the CR and PF lambs were higher, indicating an effect of maternal nutrition in this commercial cut. The CR group had a smaller epiphysis measurement and femur length than the CTL group. We concluded that the fetal programming effect in ewes fed with Cr propionate and Ca salts of palm oil benefited the progeny by increasing their body weight, better carcass yield, and a higher proportion of prime cuts.

Childhood cardiovascular morphology and function following abnormal fetal growth

Studies examining the link between abnormal fetal growth and cardiac changes in childhood have presented conflicting results. We studied the effect of abnormal fetal growth on cardiac morphology and function during childhood, while controlling for body size, composition and postnatal factors. We report on the follow-up of 90 children (median age 5.81 years, IQR 5.67; 5.95) born appropriate for gestational age (AGA, N = 48), small for gestational age (SGA, N = 23), or large for gestational age (LGA, N = 19); SGA and LGA defined as birth weight Z-score < − 2 and > + 2, respectively. We examined the heart using echocardiography, including Doppler and strain imaging, in relation to anthropometrics, body composition, blood pressure, physical activity, and diet. Although groupwise differences in body size decreased during the first year after birth, LGA remained larger at follow-up, with higher lean body mass and BMI, while SGA were smaller. Slight changes in left ventricular diastolic function were present in SGA and LGA, with SGA showing increased mitral diastolic E- and A-wave peak flow velocities, and increased septal E/E′ ratio, and LGA showing larger left atrial volume adjusted for sex and lean body mass. In univariate analyses, lean body mass at follow-up was the strongest predictor of cardiac morphology. We found no groupwise differences at follow-up for ventricular sphericity, cardiac morphology adjusted for lean body mass and sex, or blood pressure, diet, or physical activity. Cardiac morphology is predicted by lean body mass during childhood, even in the setting of abnormal fetal growth. Our results are consistent with a limited effect of fetal programming on cardiac dimensions during childhood. Minor changes in diastolic function are present in both SGA and LGA children, however, the clinical significance of these changes at this stage is likely small.

Developmental programming: prenatal and postnatal consequences of hyperthermia in dairy cows and calves

With global warming, the incidence of heat stress in dairy cows is increasing in many countries. Temperatures outside the thermoneutral zone (heat stress) are one of the environmental factors with the greatest impact on milk production and reproductive performance of dairy cows. In addition to several biological mechanisms that may contribute to the effects of fetal programming, epigenetic modifications have also been investigated as possible mediators of the observed associations between maternal heat stress during late gestation and performance and health later in life. In utero programming of these offspring may coordinate changes in thermoregulation, mammary gland development, and milk production ability at different developmental stages. This review examines the effects of prenatal and postnatal hyperthermia on the developmental outcomes of dairy cows, as well as the physiological and molecular mechanisms that may be responsible for the negative phenotypic consequences of heat stress that persist throughout the neonatal and adult periods and may have multigenerational implications. The physiological and molecular mechanisms underlying the negative phenotypic consequences of heat stress are discussed. Research challenges in this area, future research recommendations, and therapeutic applications are also discussed. In summary, strategies to reduce heat stress during the dry period should consider not only the productivity of the pregnant cow but also the well-being of the newborn calf.

Prematurity and Low Birth Weight in Neonates as a Risk Factor for Obesity, Hypertension, and Chronic Kidney Disease in Pediatric and Adult Age.

Low weight at birth may be due to intrauterine growth restriction or premature birth. Preterm birth is more common in low- and middle-income countries: 60% of preterm birth occur in sub-Saharan African or South Asian countries. However, in some higher-income countries, preterm birth rates appear to be increasing in relation to a reduction in the lower threshold of fetal viability. The cutoff is at 22–23 weeks, with a birth weight of approximately 500 g, although in developed countries such as Japan, the viability cutoff described is 21–22 weeks. There is evidence of the long-term consequences of prenatal programming of organ function and its relationship among adult diseases, such as hypertension (HT), central obesity, diabetes, metabolic syndrome, and chronic kidney disease (CKD). Premature delivery before the completion of nephrogenesis and intrauterine growth restriction leads to a reduction in the number of nephrons that are larger due to compensatory hyperfiltration and hypertrophy, which predisposes to the development of CKD in adulthood. In these patients, the long-term strategies are early evaluation and therapeutic interventions to decrease the described complications, by screening for HT, microalbuminuria and proteinuria, ultrasound monitoring, and renal function, with the emphasis on preventive measures. This review describes the effects of fetal programming on renal development and the risk of obesity, HT, and CKD in the future in patients with low birth weight (LBW), and the follow-up and therapeutic interventions to reduce these complications.

Arterial health during early childhood following abnormal fetal growth

BackgroundAbnormal fetal growth is associated with increased cardiovascular risk in adulthood. We investigated the effect of fetal programming on arterial health and morphology during early childhood.MethodsWe examined 90 children (median age 5.81 years, interquartile range: 5.67; 5.95), born small for gestational age with fetal growth restriction, large or appropriate for gestational age (SGA, N = 23, LGA, N = 19, AGA N = 48). We measured body composition, anthropometrics, blood pressure, pulse wave velocity (PWV), lipids, glucose and inflammatory markers, and assessed carotid, brachial, radial and femoral arterial morphology and stiffness using very-high resolution ultrasound (46–71 MHz).ResultsLGA showed increased anthropometry, lean body mass and body mass index. SGA displayed decreased anthropometry and lean body mass. Blood pressure, PWV, carotid artery stiffness and blood work did not differ groupwise. Differences in lumen diameters, intima-media thicknesses (IMT) and adventitia thicknesses disappeared when adjusted for lean body mass and sex. In multiple regression models arterial dimensions were mainly predicted by lean body mass, with birth weight remaining associated only with carotid and brachial lumen dimensions, and not with IMTs. Carotid-femoral PWV was predicted by height and blood pressure only. No independent effect of adiposity was observed.ConclusionsArterial dimensions in childhood associate with current anthropometrics, especially lean body mass, and sex, explaining differences in arterial layer thickness. We found no signs of fetal programming of cardiovascular risk or arterial health in early childhood.

Inter- and trans-generational effects of gestational ghrelin imbalance on development and reproduction in the mouse.

We have demonstrated that ghrelin (Ghrl) participates in fetal programming, since intragestational hyperghrelinaemia increased pup's growth and a Ghrl-receptor antagonist accelerated offspring's sexual maturation and impaired their adult reproductive function. Now, we aim to analyse if these phenotypic changes (found in F1) also occurred in F2 and/or F3 generations. We treated mice dams (F0), with 4nmol/animal/day of Ghrl or 6nmol/animal/day of an antagonist [Ant:(d -Lys3)GHRP6] from day 1 of pregnancy until delivery. When F1 female pups reached adulthood, they were paired to obtain F2, and subsequently, F2 females were paired to obtain F3. Parameters evaluated in F2 and F3 pups were: growth, physical development, neurobiological maturation, puberty onset and in adulthood, reproductive function. The F2 and F3 Ant groups showed a significant increase in litter size. Although no differences were detected in the weight of these pups at birth, in adulthood, they were heavier. At F3, pups from the Ant group showed advanced incisors eruption and eye opening compared to controls. Furthermore, F3 male pups from the Ant group showed earlier testis descent, although in adulthood, these males exhibited reduced sperm concentration in comparison to Ghrl. No differences were detected in F2 or F3 females regarding puberty onset or reproduction. Some fetal programming effects of Ghrl seen in F1, also appeared transgenerationally. Since many women at reproductive age suffer from conditions with reduced Ghrl levels (i.e. obesity or polycystic ovarian syndrome), these results could be relevant to the health of their descendants.

Fetal programming: could intrauterin life affect health status in adulthood?

Intrauterine life is one of the most important periods of life. As the development of the fetus continues, the mechanisms that affect adult health also begin to mature. With the hypothesis denoted “fetal programming,” it is thought that the presence of endocrinological disorders, toxins, infectious agents, the nutritional status of a mother, and nutrients related to placental functionality all have an effect on future life. Therefore, the fetus must adapt to the environment for survival. These adaptations may be involved the redistribution of metabolic, hormonal, or cardiac outputs in an effort to protect the brain, which is one of the important organs, as well as the slowing of growth to meet nutritional requirements. Unlike lifestyle changes or treatments received in adult life, the early developmental period tends to have a lasting effect on the structure and functionality of the body. In this review, fetal programming and the effects of fetal programming are discussed.

Metabolomic Profile of Young Adults Born Preterm.

Prematurity is a risk factor for the development of chronic adult diseases. Metabolomics can correlate the biochemical changes to a determined phenotype, obtaining real information about the state of health of a subject at that precise moment. Significative differences in the metabolomic profile of preterm newborns compared to those born at term have been already identified at birth. An observational case–control study was performed at the University Hospital of Siena. The aim was to evaluate and compare the metabolomic profiles of young adults born preterm to those born at term. Urinary samples were collected from 67 young adults (18–23 years old) born preterm (mean gestational age of 30 weeks, n = 49), and at term of pregnancy (mean gestational age of 38 weeks, n = 18). The urinary spectra of young adults born preterm was different from those born at term and resembled what was previously described at birth. The Random Forest algorithm gave the best classification (accuracy 82%) and indicated the following metabolites as responsible for the classification: citrate, CH2 creatinine, fumarate and hippurate. Urine spectra are promising tools for the early identification of neonates at risk of disease in adulthood and may provide insight into the pathogenesis and effects of fetal programming and infants’ outcomes.