Offspring Body Research Articles

Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet.

Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy. Male, but not female offspring of HFSSD-fed founders were heavier than those of control-diet-fed counterparts (p < 0.05 and p = 0.066 in males and females, respectively). Both male and female offspring of HFSSD-fed founders were longer compared with control (p < 0.01 for both sexes). Folate treatment of the pregnant dams abolished the effect of the paternal diet on the offspring's body length (p˂0.05). Female offspring of HFSSD-fed founders developed impaired glucose tolerance, which was restored by folate treatment of the dams during pregnancy. The beta cell density per pancreatic islet was decreased in offspring of HFSSD-fed rats (-20% in male and -15% in female F1 offspring, p˂0.001 vs controls). Folate treatment significantly increased the beta cell density (4.3% and 3.3% after folate supplementation given to dams and founders, respectively, p˂0.05 vs the offspring of HFSSD-fed male rats). Changes in liver connective tissue of female offspring of HFSSD-fed founders were ameliorated by treatment of dams with folate (p˂0.01). Hepatic Ppara gene expression was upregulated in female offspring only (1.51-fold, p˂0.05) and was restored in the female offspring by folate treatment (p˂0.05). We observed an increase in hepatic Lcn2 and Tmcc2 expression in female offspring born to male rats exposed to an unhealthy diet during spermatogenesis before mating (p˂0.05 vs controls). Folate treatment of the corresponding dams during pregnancy abolished this effect (p˂0.05). Analysis of DNA methylation levels of CpG islands in the Ppara, Lcn2 and Tmcc2 promoter regions revealed that the paternal unhealthy diet induced alterations in the methylation pattern. These patterns were also affected by folate treatment. Total liver DNA methylation was increased by 1.52-fold in female offspring born to male rats on an unhealthy diet prior to mating (p˂0.05). This effect was abolished by folate treatment during pregnancy (p˂0.05 vs the offspring of HFSSD-fed male rats). Folate treatment of pregnant dams restores effects on female offspring's glucose metabolism induced by pre-conception male founder HFSSD.

Maternal nutrient restriction in guinea pigs as an animal model for studying growth-restricted offspring with postnatal catch-up growth.

We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs with fetal growth restriction (FGR) on offspring body and organ weights, hypothesizing that FGR-MNR animals will show catch-up growth but with organ-specific differences. Guinea pig sows were fed ad libitum (Control) or 70% of the control diet from 4 weeks preconception, switching to 90% at midpregnancy (MNR). Control newborns >95 g [appropriate for gestational age (AGA); n = 37] and MNR newborns <85 g (FGR; n = 37) were monitored until neonatal (~25 days) or adult (~110 days) necropsy. Birth weights and body/organ weights at necropsy were used to calculate absolute and fractional growth rates (FRs). FGR-MNR birth weights were decreased ~32% compared with the AGA-Controls. FGR-MNR neonatal whole body FRs were increased ~36% compared with Controls indicating catch-up growth, with values negatively correlated to birth weights indicating the degree of FGR leads to greater catch-up growth. However, the increase in organ FRs in the FGR-MNR neonates compared with Controls was variable, being similar for the brain and kidneys indicating comparable catch-up growth to that of the whole body and twofold increased for the liver but negligible for the heart indicating markedly increased and absent catch-up growth, respectively. While FGR-MNR body and organ weights were unchanged from the AGA-Controls by adulthood, whole body growth rates were increased. These findings confirm early catch-up growth in FGR-MNR guinea pigs but with organ-specific differences and enhanced growth rates by adulthood, which are likely to have implications for structural alterations and disease risk in later life.

Restraint stress in lactating mice alters the levels of sulfur-containing amino acids in milk.

It is well known that maternal stress during the gestation and lactation periods induces abnormal behavior in the offspring and causes a lowering of the offspring’s body weight. Various causes of maternal stress during the lactation period, relating to, for example, maternal nutritional status and reduced maternal care, have been considered. However, little is known about the effects on milk of maternal stress during the lactation period. The current study aimed to determine whether free amino acids, with special reference to sulfur-containing amino acids in milk, are altered by restraint stress in lactating mice. The dams in the stress group were restrained for 30 min at postnatal days 2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of lactating mice. The concentration of taurine and cystathionine in milk was significantly higher in the stress group, though stress did not alter their concentration in maternal plasma. The ratio of taurine concentration in milk to its concentration in maternal plasma was significantly higher in the stress group, suggesting that stress promoted taurine transportation into milk. Furthermore, taurine concentration in milk was positively correlated with corticosterone levels in plasma. In conclusion, restraint stress in lactating mice caused the changes in the metabolism and in the transportation of sulfur-containing amino acids and resulted in higher taurine concentration in milk. Taurine concentration in milk could also be a good parameter for determining stress status in dams.

Maternal pre-pregnancy BMI and offspring body composition in young adulthood: the modifying role of offspring sex and birth order.

To investigate if the association between maternal pre-pregnancy BMI and offspring's body composition in late adolescence and young adulthood varies by offspring birth order and sex. Family cohort study, with data from registers, questionnaires and physical examinations. The main outcome under study was offspring body composition (percentage fat mass (%FM), percentage lean mass (%LM)) measured by dual-energy X-ray absorptiometry. Uppsala, Sweden. Two hundred and twenty-six siblings (first-born v. second-born; average age 19 and 21 years) and their mothers. In multivariable linear regression models, maternal pre-pregnancy BMI was positively associated with daughter's %FM, with stronger estimates for first-born (β=0·97, 95 % CI 0·14, 1·80) v. second-born daughters (β=0·64, 95 % CI 0·08, 1·20). Mother's BMI before her first pregnancy was associated with her second-born daughter's body composition (β=1·05, 95 % CI 0·31, 1·79 (%FM)) Similar results albeit in the opposite direction were observed for %LM. No significant associations were found between pre-pregnancy BMI and %FM (β=0·59, 95 % CI-0·27, 1·44 first-born; β=-0·13, 95 % CI-0·77, 0·52 second-born) or %LM (β=-0·54, 95 % CI-1·37, 0·28 first-born; β=0·11, 95 % CI-0·52, 0·74 second-born) for sons. A higher pre-pregnancy BMI was associated with higher offspring %FM and lower offspring %LM in late adolescence and young adulthood, with stronger associations for first-born daughters. Preventing obesity at the start of women's reproductive life might reduce the risk of obesity in her offspring, particularly for daughters.

Parental body mass index and its association with body composition, physical fitness and lifestyle factors in their 4-year-old children: results from the MINISTOP trial.

To examine the association between parental body mass index (BMI) and their offspring's body composition, physical fitness and lifestyle factors (that is, sedentary time, physical activity and diet). A total of 307 preschoolers (4.5±0.1 years) and their parents (fathers: 38.1±5.1 years and mothers: 35.6±4.2 years) participated in this study. Parental BMI was calculated using self-reported weight and height. Preschoolers body composition was assessed using: BMI, fat mass percentage, fat mass index, fat-free mass index (measured via air-displacement plethysmography) and waist circumference. Physical fitness was assessed by the PREFIT fitness battery. Lifestyle factors were assessed using the ActiGraph wGT3x-BT (sedentary time and physical activity), and the mobile-phone based tool for energy balance in children (diet). Parental BMI were positively associated with their offspring's BMI (paternal BMI: standardised beta, β=0.233, P<0.001; maternal BMI: β=0.186, P=0.001), fat mass index (paternal BMI: β=0.130, P=0.026; maternal BMI: β=0.163, P=0.005), fat-free mass index (paternal BMI: β=0.214, P<0.001; maternal BMI: β=0.119, P=0.036) and waist circumference (paternal BMI: β=0.178, P=0.001; maternal BMI: β=0.179, P=0.001). A negative association was found between maternal BMI and their offspring's standing long jump test (β=-0.132, P=0.022). Paternal BMI was associated with their offspring's sedentary time (β=0.100, P=0.026), whereas parental BMI was not associated with neither physical activity nor diet (all P⩾0.104). Parental BMI was positively associated with their offspring's BMI, fat as well as fat-free mass index and waist circumference. Moreover, a higher paternal and maternal BMI were related to higher levels of sedentary time and a lower performance in the standing long jump test of their offspring, respectively.

Plasma fatty acid patterns during pregnancy and child's growth, body composition, and cardiometabolic health: The Generation R Study

Exposure to different concentrations of fatty acids during fetal life may affect growth and metabolism. However, most studies examined individual fatty acids, whereas concentrations highly correlate and may interact with each other. We aimed to evaluate patterns of plasma fatty acids during pregnancy and their associations with growth, body composition, and cardiometabolic health of the 6-year-old offspring. This study was performed in 4830 mother-child pairs participating in a population-based cohort in the Netherlands. Around 20 weeks of gestation, we measured plasma phospholipid concentrations of 22 fatty acids, in which we identified three fatty acid patterns using principal component analysis: a 'high n-6 polyunsaturated fatty acid (PUFA)' pattern, a 'monounsaturated and saturated fatty acid (MUFA and SFA)' pattern, and a 'high n-3 PUFA' pattern. When the children were 6 years old, we measured their anthropometrics and detailed body composition (using dual-energy X-ray absorptiometry), and we calculated their body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI). At the same age, children's blood pressure, and serum insulin, HDL-cholesterol, and triacylglycerol were measured. After adjustment for confounders and the other patterns, a higher score for the 'high n-6 PUFA' pattern during pregnancy was associated with a higher height, BMI, and FFMI in the offspring at 6 years, but not independently with cardiometabolic outcomes. The 'MUFA and SFA' pattern was not consistently associated with child body composition or cardiometabolic health. A higher score for the 'high n-3 PUFA' pattern was associated with a lower FMI, higher FFMI, higher HDL-cholesterol, and lower triacylglycerol. Our results suggest that plasma fatty acid patterns during pregnancy may affect offspring's body composition and cardiometabolic health. Specifically, a pattern characterized by high n-3 PUFA levels was associated with a more favorable body composition and blood lipid profile.

Placental and lactational transfer of decabromodiphenyl ether and 2,2′,4,4′-tetrabromodiphenyl ether in dam-offspring pairs of Sprague-Dawley rats

Although several studies have conducted maternal transfer of individual PBDE congener in experimental animals, there is a paucity of research on differences in maternal transfer of PBDE congeners. The purpose of the study was to investigate and compare placental and lactational transfer of BDE 47, -209 and its metabolites in rat dam-offspring pairs following repeated administration of BDE 47 and -209. 13C-BDE 47, BDE 209 and its debrominated congeners were detected both in dam serum and offspring body, which indicates that PBDEs can be maternally transferred. In addition, BDE 196 and -197 appeared in offspring body earlier than in maternal serum, which suggests that debromination can be occur in offspring body. BDE 209 increased in both dam and offspring while levels of 13C-BDE 47 was not increased in dam serum. 13C-BDE 47 seems to be stored in breast milk rather than in maternal serum, which can be assumed through the drastic increase of the congener in suckling pups. The magnitude of lactational transfer of the administered congeners was greater than that of placental transfer. And 13C-BDE 47 was relatively more transferred to suckling pups than BDE 209 through breastfeeding.

Developmental Toxicity of Nanoparticles on the Brain

The toxicity of nanoparticles (nanotoxicology) is being investigated to understand both the health impacts of atmospheric ultrafine particles-the size of which is a fraction (<0.1 μm aerodynamic diameter) of that of PM2.5 (<2.5 μm diameter)-and the safer use of engineered nanomaterials. Developmental toxicity of nanoparticles has been studied since their transfer from pregnant body to fetal circulation and offspring body was first reported. Here we reviewed the developmental toxicity of nanoparticles on the brain, one of the most important organs in maintenance of mental health and high quality of life. Recently the dose- and size-dependency of transplacental nanoparticle transfer to the fetus was reported. It is important to understand both the mechanism of direct effect of nanoparticles transferred to the fetus and offspring and the indirect effect mediated by induction of oxidative stress and inflammation in the pregnant body. Locomotor activity, learning and memory, motor coordination, and social behavior were reported as potential neurobehavioral targets of maternal nanoparticle exposure. Histopathologically, brain perivascular cells, including perivascular macrophages and surrounding astrocytes, have an important role in waste clearance from the brain parenchyma. They are potentially the most sensitive target of maternal exposure to low-dose nanoparticles. Further investigations will show the detailed mechanism of developmental toxicity of nanoparticles and preventive strategies against intended and unintended nanoparticle exposure. This knowledge will contribute to the safer design of nanoparticles through the development of sensitive and quantitative endpoints for prediction of their developmental toxicity.

Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

Dietary intervention in obese dams protects male offspring from WAT induction of TRPV4, adiposity, and hyperinsulinemia.

One major risk factor for childhood overweight is maternal obesity. The underlying molecular mechanisms are ill-defined, and effective prevention strategies are missing. Diet-induced obese mouse dams were changed to standard chow during pregnancy and lactation as an intervention against predisposition for obesity and metabolic sequelea in the offspring. Expression of adipokines and TRPV4, a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis, in offspring's white adipose tissue (WAT) was assessed. Pathological effects on offspring's body weight, fat content, and serum insulin were fully reversed in intervention offspring on postnatal day 21. In WAT, a sixfold increase of Trpv4 mRNA expression in offspring consuming high-fat-containing diet was found, which was completely blunted in the intervention group. Simultaneously, WAT adipokine, interleukin-6, and peroxisome proliferator-activated receptor-γ mRNA and UCP1 protein expression were largely returned to control levels in intervention offspring. Improvement of maternal nutrition offers a powerful strategy to improve offspring's metabolic health. Targeting TRPV4-linked aspects of WAT metabolic function during early development might be a promising approach to prevent long-term adverse metabolic effects of maternal high-fat nutrition.

Variation in parental rearing expenditure triggers short‐term physiological effects on offspring in a long‐lived seabird

Parental care in long‐lived bird species involves a trade‐off between the benefits of increasing the effort expended on current offspring and the costs that this represents for future reproductive output. Under regimes of high environmental variability, long‐lived seabirds can adjust their breeding effort to buffer the negative effects of this variability on their offspring. However, the potential impacts of variation in breeding effort on offspring physiology in the short term and on longer‐term survival are poorly understood. In this study, we manipulated brood age through a cross‐fostering experiment to assess whether increasing or decreasing parental reproductive expenditure led to costs in Blue‐footed Booby Sula nebouxii chicks. Specifically, we tested the consequences of altered parental reproductive expenditure on the offspring's physiological condition (plasma metabolites, heterophil to lymphocyte ratio (H/L) and body condition index (BCI)) and survival. Offspring from broods in which parental investment was experimentally increased showed a lower BCI and lower alkaline phosphatase levels and higher H/L ratios than controls. Conversely, offspring showed the opposite pattern when reproductive expenditure was experimentally decreased. We observed no effects of manipulation of parental investment on triglyceride levels or on survival rates. Although our findings suggest that Blue‐footed Booby parents have the ability to adjust their breeding effort according to the demands of their offspring, parental effort could influence the effect of hatching order by suppressing the aggressive tendency of the senior chick.

Intake of carbohydrates during pregnancy in obese women is associated with fat mass in the newborn offspring

Transmission of obesity across generations is of concern. Offspring of obese women have short- and long-term increased morbidities. A high intake of carbohydrate during pregnancy combined with impaired glucose tolerance is postulated to result in high birth weight, which is linked to subsequent metabolic disease. The objective was to examine the association between carbohydrate intake in obese pregnant women and their offspring's body composition. Secondary analyses were performed in an observational setting of 222 pregnant women with a pregestational BMI (in kg/m(2)) ≥30 participating in a randomized controlled trial. Diet was assessed at gestational weeks 11-14 and 36-37 by using a semiquantitative food-frequency questionnaire. Body composition in the offspring was assessed at birth by dual-energy X-ray absorptiometry. Relative fat mass (%) was the primary outcome. Absolute measures (total fat, abdominal fat, and lean body mass) were secondary outcomes. Mean ± SD weight and absolute and relative fat mass in the offspring at birth were 3769 ± 542 g, 436 ± 214 g, and 11% ± 4%, respectively. Maternal intake of digestible carbohydrates was associated with the offspring's relative fat mass in late (P-trend = 0.006) but not early (P-trend = 0.15) pregnancy. A comparison of mothers in the highest (median: 238 g/d) compared with the lowest (median: 188 g/d) quartile of digestible carbohydrate intake showed a mean adjusted higher value in the offspring's relative fat mass of 2.1% (95% CI: 0.6%, 3.7%), which corresponded in absolute terms to a 103-g (95% CI: 27, 179-g) higher fat mass. Abdominal fat mass was also higher. In a strata of women with well-controlled glucose (2-h glucose values ≤6.6 mmol/L), no association between carbohydrate intake and offspring fat mass was observed, but the associations became significant and increased in strength with higher intolerance (strata with 2-h glucose values between 6.7-7.7 and ≥7.8 mmol/L). In obese women, even those without gestational diabetes but with impaired glucose tolerance, a lower carbohydrate intake at moderate levels in late gestation is associated with a lower fat mass in their offspring at birth. The TOP study was registered at clinicaltrials.gov as NCT01345149.

Association of Parental History of Diabetes Mellitus with the Offspring's Incidence is Modified by Offspring's Body Weight, Findings from a Japanese Worksite-Based Cohort.

Association of Parental History of Diabetes Mellitus with the Offspring's Incidence is Modified by Offspring's Body Weight, Findings from a Japanese Worksite-Based Cohort.

Association between parental history of diabetes and the incidence of type 2 diabetes mellitus differs according to the sex of the parent and offspring's body weight: A finding from a Japanese worksite-based cohort study

ObjectiveTo investigate differences in the association of parental history of diabetes with the risk of type 2 diabetes mellitus (T2DM) in the offspring according to the sex of the parent and the offspring's body weight. MethodsA prospective cohort study of 4446 middle-aged non-diabetic Japanese men and women were followed in Aichi Prefecture, central Japan, from 2002 to 2011. Subjects were categorized by their self-reported parental history of diabetes (“no parental history,” “father only,” “mother only,” and “both”). The association of parental history of diabetes and incidence in the offspring was examined according to overweight status adjusted for age, sex, birth weight, smoking, alcohol consumption, physical activity, total energy intake, body mass index, and number of metabolic syndrome components. ResultsDuring follow-up (median 8.9years), 277 subjects developed T2DM. Parental history of diabetes was positively associated with T2DM incidence. However, stratified analysis by overweight status revealed that only maternal history was associated with increased T2DM incidence in non-overweight subjects (hazard ratio=2.35, 95% confidence interval: 1.41–3.91). While in overweight subjects, paternal history was significantly associated with higher T2DM incidence (hazard ratio=1.98, 95% confidence interval: 1.19–3.28). ConclusionsOur results suggest that parental history of diabetes mellitus is associated with the incidence of T2DM in offspring differently according to the sex of the affected parent and the offspring's body weight.

Leptin in pregnancy and development: a contributor to adulthood disease?

Emerging research has highlighted the importance of leptin in fetal growth and development independent of its essential role in the maintenance of hunger and satiety through the modulation of neuropeptide Y and proopiomelanocortin neurons. Alterations in maternal-placental-fetal leptin exchange may modify the development of the fetus and contribute to the increased risk of developing disease in adulthood. In addition, leptin also plays an important role in reproductive functions, with plasma leptin concentrations rising in pregnant women, peaking during the third trimester. Elevated plasma leptin concentrations occur at the completion of organogenesis, and research in animal models has demonstrated that leptin is involved in the development and maturation of a number of organs, including the heart, brain, kidneys, and pancreas. Elevated maternal plasma leptin is associated with maternal obesity, and reduced fetal plasma leptin is correlated with intrauterine growth restriction. Alterations in plasma leptin during development may be associated with an increased risk of developing a number of adulthood diseases, including cardiovascular, metabolic, and renal diseases via altered fetal development and organogenesis. Importantly, research has shown that leptin antagonism after birth significantly reduces maturation of numerous organs. Conversely, restoration of the leptin deficiency after birth in growth-restricted animals restores the offspring's body weight and improves organogenesis. Therefore, leptin appears to play a major role in organogenesis, which may adversely affect the risk of developing a number of diseases in adulthood. Therefore, greater understanding of the role of leptin during development may assist in the prevention and treatment of a number of disease states that occur in adulthood.

Abstract LB-244: Paternal obesity alters daughters' mammary gland development and increases markers of breast cancer risk in a mouse model

Abstract Introduction: While several epidemiologic and animal studies indicate that maternal nutrition and body weight during pregnancy lead to reprogramming of breast cancer risk in the offspring, no studies have investigated the impact of fathers’ obesity or dietary habits on offspring's breast cancer risk. The goal of the current study is to investigate whether peri-conceptional paternal obesity can epigenetically reprogram father's germ-line and increase their daughters’ likelihood of developing breast cancer, using a carcinogen-induced mouse model of this disease. Methodology: Male mice were fed a control diet or obesity-inducing diet from weaning until sexual maturity; at this point, all males were switched to the control diet and housed together with female rats reared on control diet. Once a vaginal plug was detected, males were removed from female cages and euthanized for sperm collection. Pregnant dams were fed the control diet for the extent of pregnancy and after giving birth. Pups were weaned on postnatal day (PND)21 and fed the control diet throughout the experiment. Offspring's body weight was determined shortly after birth and at weaning. A subset of female offspring was euthanized on PND50 for mammary tissue harvesting. Mammary gland whole-mounts harvested on PND50 were processed and the number of TEBs and ductal elongation blindly examined. Using miRNA arrays, we also investigated whether misregulation of miRNAs expression is involved in mediating the effects of paternal obesity on offspring's mammary gland morphology. Another subset of female offspring was treated with 9,12-dimethylbenz[a]anthracene to induce mammary tumors and is currently being monitored. Results: We found that, compared to control offspring, the offspring of obese fathers had higher birth weight (p=0.02). Birth weight has been positively associated with breast cancer risk in epidemiologic and animal studies. Body weight of daughters (p=0.03), but not sons (p=0.6), of obese fathers were also higher at weaning. Daughters of obese fathers had higher numbers of terminal end buds (TEBs; p=0.03) _ which are targets for malignant transformation and markers of increased breast cancer risk_ in their mammary glands compared to control daughters. Mammary gland ductal elongation (p=0.004) in daughters of obese fathers was also increased. In addition, we found that paternal obesity led to changes in the miRNA expression profile in their sperm. Paternal obesity was also associated with changes in miRNA expression in daughters’ mammary tissue. Conclusions:This study provides critical evidence that fathers’ body weight around conception affects not only their daughters’ body weight at birth and weaning, but it also leads to changes in their daughters’ mammary gland development and miRNA expression profile, and likely their mammary cancer risk. Studies to confirm whether these findings are causally related to increased mammary cancer risk in daughters of obese fathers are currently underway. Citation Format: Chao Yin, Idalia Cruz, Leena Hilakivi-Clarke, Sonia M. de Assis. Paternal obesity alters daughters' mammary gland development and increases markers of breast cancer risk in a mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-244. doi:10.1158/1538-7445.AM2014-LB-244

Exposure to nicotine during pregnancy and altered learning and memory in the rat offspring.

Prenatal exposure to nicotine can cause many fetal developmental problems. This study determined the influence of nicotine during pregnancy on the development of cognitive behavior in the offspring. Nicotine was administered to pregnant rats through implanted osmotic mini-pumps at 6mg/kg/day and flow rate of 60 μl/day for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze; Learning and memory-related receptors were measured. The results showed that exposure to prenatal nicotine (PN) not only caused fetal growth restriction, but also had long-term effects on learning and memory in the offspring. The PN offspring exhibited longer escape latency regardless of sex. The number of passing the platform was significantly less in the PN offspring than that of the control. The expression of messenger RNA (mRNA) and protein of N-methyl-D-aspartic acid receptor (NMDAR) in the hippocampus was significantly increased, whereas alpha7 nicotinic acetylcholine receptor (α7 nAChR) protein was decreased with unchanged α7 nAChR mRNA in the PN offspring. The data provided novel information on the PN-affected development in learning and memory in the offspring, suggesting that α7 nAChR and NMDAR1 in the hippocampus might be the targets for actions of PN in association with memory impairment.

Maternal prepregancy BMI and lipid profile during early pregnancy are independently associated with offspring's body composition at age 5-6 years: the ABCD study.

BackgroundThere is growing evidence that disturbances in maternal metabolism and, subsequently, intrauterine conditions affect foetal metabolism. Whether this has metabolic consequences in offspring later in life is not fully elucidated. We investigated whether maternal pre-pregnancy body mass index (pBMI) is associated with offspring's adiposity at age 5–6 years and whether this association is mediated by the mother's lipid profile during early pregnancy.MethodsData were derived from a multi-ethnic birth cohort, the Amsterdam Born Children and their Development (ABCD) study (inclusion 2003–2004). During early gestation mothers completed a questionnaire during pregnancy (pBMI) and random non-fasting blood samples were analysed for total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total free fatty acids (FFA) in early gestation. At age 5–6 years, child's BMI, waist-to-height-ratio (WHtR) and fat% were assessed.ResultsOnly non-diabetic mothers with at term-born children were included(n = 1727). Of all women, 15.1% were overweight(BMI: 25–29.9 kg/m2) and 4.3% were obese(BMI≥30 kg/m2). After adjustments for confounders, every unit increase in pBMI was linearly associated with various offspring variables: BMI(β 0.10; 95% CI 0.08–0.12), WHtR*100(β 0.13; 95% CI 0.09–0.17), fat%(β 0.21; 95% CI 0.13–0.29) and increased risk for overweight(OR:1.15; 95% CI 1.10–1.20). No convincing proof for mediation by maternal lipid profile during early gestation was found. Moreover, maternal FFA was associated with the child's fat percentage, BMI and risk for overweight. Maternal ApoB and TC were positively associated with the offspring's fat percentage and maternal TG was positively associated with their children's WHtR.ConclusionsBoth pBMI and maternal lipids during early pregnancy are independently related to offspring adiposity.

Associations of Prenatal Exposure to Ramadan with Small Stature and Thinness in Adulthood: Results From a Large Indonesian Population-Based Study

A growing body of evidence suggests that maternal diet during pregnancy can lead to permanent alterations to the physiology of the fetus. It is unknown whether intermittent maternal fasting during Ramadan has long-term associations with the offspring's body composition. By using data from the third wave of the Indonesian Family Life Survey (2000), we compared the body mass indices (weight (kg)/height (m)(2)) of Muslims who had been in utero during Ramadan with those of Muslims who had not been in utero during Ramadan. Adult Muslims who had been in utero during Ramadan were slightly thinner than Muslims who had not been in utero during Ramadan (adjusted adult body mass index: -0.32, 95% confidence interval: -0.57, -0.06). Those who were conceived during Ramadan also had smaller stature, being on average 0.80 cm shorter than those who were not exposed to Ramadan prenatally. Among non-Muslims, no such associations were found. This study suggests that exposure to Ramadan during pregnancy may have lasting consequences for adult body size of the offspring.

Gestational Weight Gain and Body Mass Index in Children: Results from Three German Cohort Studies

IntroductionPrevious studies suggested potential priming effects of gestational weight gain (GWG) on offspring’s body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.MethodsWe combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring’s mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5–6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.ResultsIn adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m2 of ‘real’ BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.DiscussionIncreased GWG is likely to be associated with overweight in offspring of non-overweight mothers.