Risk Of Later Disease Research Articles

Update on Adrenarche-Still a Mystery.

Adrenarche marks the timepoint of human adrenal development when the cortex starts secreting androgens in increasing amounts, in healthy children at age 8-9 years, with premature adrenarche (PA) earlier. Because the molecular regulation and significance of adrenarche are unknown, this prepubertal event is characterized descriptively, and PA is a diagnosis by exclusion with unclear long-term consequences. We searched the literature of the past 5 years, including original articles, reviews, and meta-analyses from PubMed, ScienceDirect, Web of Science, Embase, and Scopus, using search terms adrenarche, pubarche, DHEAS, steroidogenesis, adrenal, and zona reticularis. Numerous studies addressed different topics of adrenarche and PA. Although basic studies on human adrenal development, zonation, and zona reticularis function enhanced our knowledge, the exact mechanism leading to adrenarche remains unsolved. Many regulators seem involved. A promising marker of adrenarche (11-ketotestosterone) was found in the 11-oxy androgen pathway. By current definition, the prevalence of PA can be as high as 9% to 23% in girls and 2% to 10% in boys, but only a subset of these children might face related adverse health outcomes. New criteria for defining adrenarche and PA are needed to identify children at risk for later disease and to spare children with a normal variation. Further research is therefore required to understand adrenarche. Prospective, long-term studies should characterize prenatal or early postnatal developmental pathways that modulate trajectories of birth size, early postnatal growth, childhood overweight/obesity, adrenarche and puberty onset, and lead to abnormal sexual maturation, fertility, and other adverse outcomes.

Segregated by Wealth, Health, and Development: An Analysis of Pre-School Child Health in a Medium-Sized German City.

The School Entry Examination (SEE) can be used to identify children with current health issues, developmental delays, and risk factors for later diseases. This study analyzes the health status of preschool children in a German city with considerable socio-economic differences among its quarters. We used secondary data from SEEs 2016-2019 from the entire city (8417 children), which we divided into quarters with low (LSEB), medium (MSEB), and high socioeconomic burden (HSEB). In HSEB quarters, 11.3% of children were overweight as opposed to 5.3% in LSEB quarters. In HSEB quarters, 17.2% of children had sub-par cognitive development in contrast to 1.5% in LSEB quarters. For overall sub-par development, LSEB quarters had a prevalence of 3.3%, whereas, in HSEB quarters, 35.8% of children received this result. Logistic regression was used to determine the influence of the city quarter on the outcome of overall sub-par development. Here, considerable disparities among HSEB and LSEB quarters remained after adjustment for parents' employment status and education. Pre-school children in HSEB quarters showed a higher risk for later disease than children in LSEB quarters. The city quarter had an association with child health and development that should be considered in the formulation of interventions.

RF13 | PMON59 Tracking and Cumulative Lifetime Exposure to Circulating IGF-I in 6,459 Healthy Individuals and in SGA Children Treated with GH

Abstract Background: /objective Insulin-like-growth-factor-I (IGF-I) levels in the lower or upper normal range have been proposed as a biomarker of risk for later disease in healthy adults, specifically cardiovascular disease and cancer. In addition, concern has been raised about the frequently observed supraphysiological IGF-I levels in non-growth-hormone-deficient children treated with growth hormone (GH). However, whether a single IGF-I measurement is a valid indicator of cumulative lifetime exposure to IGF-I and thus disease risk is not established. We aimed to evaluate intra-individual longitudinal tracking of IGF-I and IGF-binding-protein-3 (IGFBP-3) levels and to estimate cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals. We hypothesized that individuals follow a certain IGF-I trajectory throughout life and that GH therapy in childhood does not increase lifetime IGF-I exposure substantially. Methods We performed a combined cross-sectional (n=5,326) and longitudinal (n=1,133) study of 6,459 healthy participants (49% male) aged 0­­­–76 years recruited as part of six Danish population-based studies, resulting in a total of 9,963 serum samples. In addition, we included 238 samples from nine short children born small-for-gestational-age (SGA) before, during and after GH treatment. Serum samples were analyzed for IGF-I and IGFBP-3 with the IDS-iSYS immunoassay and anthropometric measures were obtained. Intra-individual tracking was determined by intraclass correlation coefficients (ICC) derived from a linear mixed model with IGF-I (SDS) or IGFBP-3 (SDS) as dependent variable and subject as random effect, unadjusted and adjusted for BMI-changes. Cumulative lifetime exposure to IGF-I was estimated by calculating area under the curve of the predicted SD trajectory from 0-76 years. Results Sex- and age-specific reference curves for IGF-I and IGFBP-3 were established. For IGF-I, ICCs were 0.50 (95% CI: 0.47–0.53) and 0.53 (0.50–0.56) for male and female participants, respectively. ICCs for IGFBP-3 were 0.52 (0.49–0.55) for male participants and 0.59 (0.56–0.62) for female. Cumulative lifetime IGF-I exposure was significantly higher in female (mean ± SD, 12,723 ± 3,691) than in male participants (12,563 ± 3,393); p=0.02. The SGA patients had a mean (range) GH-treatment duration of 9.2 years (5.2–11.9). Treatment caused an increase in estimated cumulative lifetime IGF-I exposure of 1,759 ± 556 shifting them from a mean estimated lifetime exposure without treatment of 9,512 ± 1,889 to 11,271 ± 1,689 with treatment. This corresponded to a rise in IGF-I trajectory (SDS) of 0.55 SD ± 0.18, from -0.89 SD ± 0.57 to -0.35 SD ± 0.49. Conclusion Our results suggest that IGF-I and IGFBP-3 levels are tracking throughout life and that a single measurement reliably reflects lifetime exposure. We, for the first time, estimated lifetime exposure to IGF-I in healthy individuals and show that pediatric GH therapy only slightly increases lifetime exposure and not beyond levels commonly found in the reference population. Presentation: Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Raising the bar for measuring childhood adversity

Awareness about the harmful effects of adverse childhood experiences (ACEs) has increased in the past decade among paediatric providers and researchers. Hundreds of observational studies have documented the prevalence and consequences of childhood adversity,1 showing that childhood adversity can at least double the risk of later disease in childhood, adolescence, and adulthood, and explain up to 40% of morbidity and premature mortality across the lifecourse.1 Screening young people for ACEs and intervening could be key to buffering the effects of these experiences and reducing future morbidities.

Tracking and Cumulative Lifetime Exposure to IGF-I in 6459 Healthy Individuals and in SGA Children Treated With GH.

Supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations have been a matter of concern in children treated with GH because high IGF-I levels were associated with risk of later disease in former epidemiological studies. To determine whether a single IGF-I measurement reliably reflects lifetime IGF-I exposure we evaluated intraindividual longitudinal tracking of IGF-I and IGF-binding protein-3 (IGFBP-3) levels and we estimated cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals. We included 6459 healthy participants (cross-sectional = 5326; longitudinal = 1133) aged 0-76 years (9963 serum samples) and 9 patients born small-for-gestational-age (SGA) with 238 serum samples during GH treatment. Intraindividual tracking of IGF-I and IGFBP-3 (SD score [SDS]) was determined by intraclass correlation coefficients (ICCs). Cumulative lifetime IGF-I exposure was estimated by area under the curve of the predicted SDS trajectory from 0 to 76 years. For IGF-I (SDS), ICCs were 0.50 (95% CI, 0.47-0.53) for male and 0.53 (0.50-0.56) for female participants. Lifetime IGF-I exposure was significantly higher in female (mean 12 723 ± 3691 SD) than in male participants (12 563 ± 3393); P = 0.02. In SGA children, treatment with GH increased the lifetime exposure to IGF-I from 9512 ± 1889 to 11 271 ± 1689, corresponding to an increase in lifetime IGF-I trajectory from -0.89 SD ± 0.57 to -0.35 SD ± 0.49. Because IGF-I and IGFBP-3 levels track throughout life, a single measurement reliably reflects lifetime exposure. GH therapy increased the lifetime exposure to IGF-I only slightly and it remained below the average lifetime exposure in the reference population.

Clinical Implications

Clinical Implications

Early life socioeconomic circumstances and cardiometabolic health in childhood: Evidence from the Generation XXI cohort

Social adversity is thought to become biologically embedded during sensitive periods of development which could set children on a trajectory of increased risk for later diseases. This study estimated the association between early socioeconomic circumstances and cardiometabolic biomarkers during childhood.We analyzed data from 2962 participants in the birth cohort Generation XXI. Early socioeconomic circumstances included parental education and occupation and household income measured at the child's birth; cardiometabolic biomarkers included a set of parameters that were determined at seven and 10years old. The association between early socioeconomic circumstances and cardiometabolic biomarkers in children aged seven and 10years old was estimated using generalized estimating equations.We observed, after adjustment for birth weight, sex, five-a-day fruit and vegetable intake and sedentary activity, that children with low educated mothers presented higher body mass index z-score (β=0.22; 95%CI: 0.12, 0.33), higher waist circumference (β=1.14; 95%CI: 0.55, 1.73) and increased systolic blood pressure z-score (β=0.15; 95%CI: 0.08, 0.22) at the age of seven. At 10years, children with mothers with low education, presented higher body mass index z-score (β =0.32; 95%CI: 0.21, 0.43), higher waist circumference (β=2.79; 95%CI: 1.94, 3.64), increased diastolic blood pressure z-score (β=0.11; 95%CI: 0.06, 0.17) and increased systolic blood pressure s-score (β=0.20; 95%CI: 0.12, 0.28). When repeated measures of cardiometabolic biomarkers were taken into account, the association between socioeconomic circumstances and cardiometabolic biomarkers remained significant.Low socioeconomic circumstances have a possible detrimental effect on children's cardiometabolic health. Thus, socioeconomic adversity might impact health outcomes already in the first decade of life, emphasizing the early social patterning of cardiometabolic health and the need of social policies targeting children and families to modify or reverse its negative impact on health.

The effects of early life adversity on growth, maturation, and steroid hormones in male and female rats.

Early life adversity is a risk factor for psychiatric disorders, yet the mechanisms by which adversity increases this risk are still being delineated. Here, we used a limited bedding and nesting (LBN) manipulation in rats that models a low resource environment to examine effects on growth, developmental milestones, and endocrine endpoints. In LBN, dams and pups, from pups' postnatal days 2-9, are exposed to an environment where dams lack proper materials to build a nest. This manipulation is compared to control housing conditions, where rat dams have access to ample nesting materials and enrichment throughout pups' development. We found that the LBN condition altered maternal care, increasing pup-directed behaviors while reducing self-care. This, perhaps compensatory, increase in nursing and attention to pups did not mitigate against changes in metabolism, as LBN reduced weight gain in both sexes and this effect persisted into adulthood. Although adult stress hormone levels in both sexes and vaginal opening and estrous cycle length in females were not disrupted, there was other evidence of endocrine dysregulation. Compared to controls, LBN rats of both sexes had shortened anogenital distances, indicating reduced androgen exposure. LBN males also had higher plasma estradiol levels in adulthood. This combination of results suggests that LBN causes a demasculinizing effect in males that could contribute to lasting changes in the brain and behavior. Importantly, alterations in metabolic and endocrine systems due to early life adversity could be one mechanism by which stress early in life increases risk for later disease.

Self-rated health (SRH) in young people and causes of death and mortality in young adulthood. A prospective registry-based Norwegian HUNT-study

BackgroundSelf-rated health (SRH), which is frequently used in epidemiological research, has consistently been shown to be a strong predictor of morbidity and mortality, even after controlling for demographic, social and medical risk factors. However, less is known about the relationship between SRH and all-cause and cause-specific mortality in young adulthood. ObjectiveTo investigate SRH in young people (13–35 years-old) as a predictor of all-cause mortality in young adulthood (deaths before age 54) and examine the associated causes of death. MethodsWe used data from two large population-based cohort studies (N = 23,679): Young-HUNT1 (1995–1997, persons 13 to 20 years old, participation rate = 90%) and HUNT2 (1995–1997, persons 20 to 35 years old, participation rate = 70%). These data were linked to the Norwegian Cause of Death Registry up to 2014, and 247 deaths were identified. Other predictors we examined included age, gender, baseline smoking, physical activity and physical and mental disability. ResultsParticipants reporting ‘not so good’/‘poor’ SRH had approximately twice the risk of death compared to those reporting ‘good’ or ‘very good’ SRH at baseline. The association between low SRH and risk of death was attenuated when the models were adjusted for other predictors, but remained statistically significant. The causes of death differed somewhat between SRH levels. Most of the deaths for people reporting ‘very good’ SRH at baseline were mostly due to neoplasms (34%) and other external causes (30%). The causes of death were more varied for people reporting ‘not so good’/‘poor’ SRH, with suicide (23%), other external causes (21%) and other/unknown causes of death (17%) being the most frequent causes. ConclusionSRH predicts all-cause mortality in young adulthood, with poor SRH being associated with death in young adulthood. The findings also indicate different causes of death for different SRH. This knowledge is important for identifying groups at risk for later disease, which can potentially be used to prevent morbidity in the adult population.

Renal function and blood pressure in 11 year old children born extremely preterm or small for gestational age.

BackgroundPreterm birth and low birth weight are associated with reduced nephron numbers and increased risk of hypertension and kidney disease in later life.AimsWe tested the hypothesis that extremely preterm birth and intrauterine growth restriction is associated with decreased renal function in mid childhood.MethodsAt 11 years of age the following measures were obtained in a regional cohort of children born extremely premature (EP, i.e. < 28 weeks gestational age—GA) or with extremely low birth weight (ELBW, i.e. BW < 1000 grams) and in matched controls born at term with appropriate BW (AGA): Height, weight, abdominal circumference, triceps and subscapular skin fold thicknesses, blood pressure, plasma levels of creatinine, cystatin C and symmetric dimethyl arginine (SDMA). Small for gestational age (SGA) was defined as a BW < 10th percentile for GA. Glomerular filtration rate (GFR) was estimated according to the equations by Schwartz, Zappitelli and Gao.ResultsFifty-seven of 61 eligible EP/ELBW children, 20 (35%) born SGA, and 54 controls, were assessed. Estimated GFR decreased while plasma SDMA increased from the children born AGA at term through those born preterm AGA to preterm SGA. Systolic BP was correlated to fat mass indices (p<0.03), but not to renal function (p>0.2) and did not differ between the groups.ConclusionsChildren born EP/ELBW, particularly those born SGA, had impaired renal function at age 11 years as judged from estimated GFRs and plasma levels of SDMA. Since reduced renal function is associated with an increased risk of later disease, these children should be followed in order to minimize additional risk factors.

Human Milk Adiponectin and Leptin and Infant Body Composition over the First 12 Months of Lactation.

Human milk (HM) adipokines may influence infant feeding patterns, appetite regulation, and body composition (BC). The associations between concentrations/calculated daily intakes (CDI) of HM adipokines in the first 12 months postpartum and maternal/term infant BC, and infant breastfeeding parameters were investigated. BC of breastfeeding dyads (n = 20) was measured at 2, 5, 9, and/or 12 months postpartum with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). 24-h milk intake and feeding frequency were measured along with whole milk adiponectin and skim and whole milk leptin (SML and WML) and CDI were calculated. Statistical analysis used linear regression/mixed effects models; results were adjusted for multiple comparisons. Adipokine concentrations did not associate with infant BC. Higher CDI of adiponectin were associated with lower infant fat-free mass (FFM; p = 0.005) and FFM index (FFMI; p = 0.009) and higher fat mass (FM; p < 0.001), FM index (FMI; p < 0.001), and %FM (p < 0.001). Higher CDI of SML were associated with higher infant FM (p < 0.001), FMI (p < 0.001), and %FM (p = 0.002). At 12 months, higher CDI of WML were associated with larger increases in infant adiposity (2–12 month: FM, p = 0.0006; %FM, p = 0.0004); higher CDI of SML were associated with a larger decrease in FFMI (5–12 months: p = 0.0004). Intakes of HM adipokines differentially influence development of infant BC in the first year of life, which is a critical window of infant programming and may potentially influence risk of later disease via modulation of BC.

Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization

The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P= .009). Smoking (P= .003), but not use of recreational drugs (P= .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P= .007). In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later.

Epigenetics of Skeletal Diseases.

Epigenetic mechanisms modify gene activity in a stable manner without altering DNA sequence. They participate in the adaptation to the environment, as well as in the pathogenesis of common complex disorders. We provide an overview of the role of epigenetic mechanisms in bone biology and pathology. Extensive evidence supports the involvement of epigenetic mechanisms (DNA methylation, post-translational modifications of histone tails, and non-coding RNAs) in the differentiation of bone cells and mechanotransduction. A variety of epigenetic abnormalities have been described in patients with osteoporosis, osteoarthritis, and skeletal cancers, but their actual pathogenetic roles are still unclear. A few drugs targeting epigenetic marks have been approved for neoplastic disorders, and many more are being actively investigated. Advances in the field of epigenetics underscore the complex interactions between genetic and environmental factors as determinants of osteoporosis and other common disorders. Likewise, they help to explain the mechanisms by which prenatal and post-natal external factors, from nutrition to psychological stress, impact our body and influence the risk of later disease.

Relationships between Breastfeeding Patterns and Maternal and Infant Body Composition over the First 12 Months of Lactation.

Breastfeeding has been implicated in the establishment of infant appetite regulation, feeding patterns and body composition (BC). A holistic approach is required to elucidate relationships between infant and maternal BC and contributing factors, such as breastfeeding parameters. Associations between maternal and breastfed term infant BC (n = 20) and feeding parameters during first 12 months of lactation were investigated. BC was measured at 2, 5, 9 and/or 12 months postpartum with ultrasound skinfolds (US; infants only) and bioimpedance spectroscopy (infants and mothers). 24-h milk intake (MI) and feeding frequency (FFQ) were measured. Higher FFQ was associated with larger 24-h MI (p ≤ 0.003). Higher 24-h MI was associated with larger infant fat mass (FM) (US: p ≤ 0.002), greater percentage FM (US: p ≤ 0.008), greater FM index (FMI) (US: p ≤ 0.001) and lower fat-free mass index (FFMI) (US: p = 0.015). Lower FFQ was associated with both larger FFM (US: p ≤ 0.001) and FFMI (US: p < 0.001). Greater maternal adiposity was associated with smaller infant FFM measured with US (BMI: p < 0.010; %FM: p = 0.004; FMI: p < 0.011). Maternal BC was not associated with FFQ or 24-h MI. These results reinforce that early life is a critical window for infant programming and that breastfeeding may influence risk of later disease via modulation of BC.

Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth.

Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.

The placenta is the culprit in programming chronic disease

s / Placenta 36 (2015) A1eA60 A2 IFPASA. FETAL MEMBRANES e A FOCUS FOR THE FUTURE OR A LEGACY FROM THE PAST? A.M. Carter. University of Southern Denmark, Denmark The fetal membranes of amniotes are allantois, amnion, chorion and yolk sac. The manner of their development and contribution to placentation varies greatly acrossmammals. This is true also of the cavities they enclose, which are the allantoic sac, amniotic sac and exocoelom. In human development, there is an allantoic stalk, but no allantoic sac; the yolk sac is a short-lived structure and the exocoelom is obliterated in the second trimester by expansion of the amnion. The mouse is commonly used as a model of human placentation. Here, too, there is no allantoic sac and the exocoelom does not persist to term. In contrast, the inverted vascular yolk sac supports the embryo until the chorioallantoic placenta is formed and it acts as an accessory placenta through term. It has a string of important functions yet frequently is discarded or ignored either through ignorance or because it has no obvious equivalent in human pregnancy. In ruminants, which are important to veterinary research and as models in fetal physiology, there is yet another pattern that includes transient yolk sac placentation and a persistent allantoic sac. Embryologists of the late 19C, like Hubrecht and Selenka, uncovered the role of fetal membranes in early development and placentation. They feature prominently in the mid-20C accounts of Amoroso and Mossman. This legacy seems largely to have slipped from the collective consciousness of 21C placentologists. Yet the mouse yolk sac may harbour clues to overall placental function and human yolk sac play a critical role in embryonic development. Medical as well as veterinary research might be well served by a closer focus on fetal membranes. KEY1. THE PLACENTA IS THE CULPRIT IN PROGRAMMING CHRONIC DISEASE K. Thornburg, S. Louey. Melinda Pierce and Kevin Kolahi Center for Developmental Health, Knight Cardiovascular Institute, School of Medicine, Oregon Health and Science University, Portland, USA For the first time in US history, a sustained decrease in life expectancy is predicted. The abrupt change in the upward trajectory in life expectancy is related to increases in the prevalence of obesity, diabetes and uncontrolled hypertension, all of which have been increasing since the ‘90s. Children in the US are now the 3rd generation of people who have consumed mostly processed foods to satisfy their energy requirements. Processed foods are generally high in calories and low in nutrients. It is now well known that babies born at the extremes of birthweights are especially prone to developing chronic disease later in life. Because the placenta is the gatekeeper for nutrients entering the fetus and because the vascular bed of the placenta sets the loading conditions of the embryo/fetal heart, the placenta plays a central role in determining risk for later disease. The size and shape of the placenta interact with maternal phenotypic features to determine risk of coronary heart disease, heart failure and sudden death. Lung and colorectal cancers are predicted by placental size and shape. The number of placental cotyledons predicts blood pressure in children and umbilical cord length is associated with an elevated risk for rheumatic heart disease. Placental size, shape and efficiency in a population vary over time for unknown reasons. One can fairly speculate that population level dietary changes over time are the drivers of placentation; animal data are sparse but support the idea. Sex-specific features of placental function have been shown in humans and animals but the role of diet in altering functional changes is unknown. Understanding the interactions between maternal diet, stress, phenotype and sex-specific placental form and function should be a high priority for scientists and funding agencies. Healthy placentas make healthy babies. Healthy babies are the foundation of a healthy population KEY3. AGING AND THE PLACENTA Roger Smith. Mothers and Babies Research Centre, HMRI, Newcastle, NSW,

Excessive Salt Intake Putting Children at Risk for Later Diseases

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Environmental Health Factors and Sexually Dimorphic Differences in Behavioral Disruptions.

Mounting evidence suggests that environmental factors-in particular, those that we are exposed to during perinatal life-can dramatically shape the organism's risk for later diseases, including neurobehavioral disorders. However, depending on the environmental insult, one sex may demonstrate greater vulnerability than the other sex. Herein, we focus on two well-defined extrinsic environmental factors that lead to sexually dimorphic behavioral differences in animal models and linkage in human epidemiological studies. These include maternal or psychosocial stress (such as social stress) and exposure to endocrine-disrupting compounds (such as one of the most prevalent, bisphenol A [BPA]). In general, the evidence suggests that early environmental exposures, such as BPA and stress, lead to more pronounced behavioral deficits in males than in females, whereas female neurobehavioral patterns are more vulnerable to later in life stress. These findings highlight the importance of considering sex differences and developmental timing when examining the effects of environmental factors on later neurobehavioral outcomes.

Evaluating chemical effects on mammary gland development: A critical need in disease prevention.

Although understanding the environmental factors that contribute to breast cancer could improve disease prevention, standard chemical testing protocols do not adequately evaluate chemicals' effects on breast development. Evidence suggests: (1) mammary gland (MG) development is a complex process that extends from gestation through fetal and neonatal growth, puberty, and pregnancy; (2) altered MG development can increase the risk of breast cancer and other adverse outcomes; and (3) chemical exposures during susceptible windows of development may alter the MG in ways that increase risk for later disease. Together, these highlight the need to better understand the complex relationship between exposure to endocrine disrupting compounds (EDCs) and the alterations in MG morphology and gene expression that ultimately increase disease risk. Changing guideline toxicity testing studies to incorporate perinatal exposures and MG whole mounts would generate critical knowledge about the effects of EDCs on the MG and could ultimately inform disease prevention.

Impact of gestational diabetes and lactational insulin replacement on structure and secretory function of offspring rat ventral prostate

Clinical and experimental studies have shown that exposure to adverse conditions during the critical stages of embryonic, fetal or neonatal development lead to a significantly increased risk of later disease. Diabetes during pregnancy has been linked to increased risk of obesity and diabetes in offspring. Here, we investigated whether mild gestational diabetes mellitus (GDM) followed or not by maternal insulin replacement affects the ventral prostate (VP) structure and function in male offspring at puberty and adulthood. Pregnant rats were divided into the following 3 groups: control (CT); streptozotocin (STZ)-induced diabetes (D); and D plus insulin replacement during lactation (GDI). The male offspring from different groups were euthanized at postnatal day (PND) 60 and 120. Biometrical parameters, hormonal levels and prostates were evaluated. Mild-GDM promoted reduction in the glandular parenchyma and increased collagen deposition. Insulin replacement during lactation restored the VP morphology. Most importantly, mild-GDM decreased the androgen-induced secretory function as determined by prostatein expression, and insulin replacement reversed this effect. Our results demonstrated that mild GDM impairs VP parenchyma maturation, which is associated with an increase in the fibromuscular stroma compartment. Functionally, the reduction in the VP parenchyma decreases the glandular secretory activity as demonstrated by low expression of prostatein, a potent immunosuppressor factor that protects sperm from immunologic damage into the feminine reproductive tract. This change could lead to impairment of reproductive function in male offspring from diabetic mothers. Maternal insulin replacement during the weaning period apparently restores the prostate function in male offspring.