The impact of prenatal circadian rhythm disruption on pregnancy outcomes and long-term metabolic health of mice progeny

Animal studies demonstrate that circadian rhythm disruption during pregnancy can be deleterious to reproductive capacity and the long-term health of the progeny. Our previous studies in rats have shown that exposure of pregnant dams to an environment that significantly disrupts maternal circadian rhythms programs increased adiposity and poor glucose metabolism in offspring. In this study, we used mice with a ClockΔ19 mutation to determine whether foetal development within a genetically disrupted circadian environment affects pregnancy outcomes and alters the metabolic health of offspring. Ten female ClockΔ19+MEL mutant mice were mated with 10 wildtype males, and 10 wildtype females were mated with 10 ClockΔ19+MEL mutant males. While genetically identical, the heterozygote foetuses were exposed to either a normal (wildtype dams) or disrupted (ClockΔ19+MEL mutant dams) circadian environment during gestation. Pregnancy outcomes including time to mate, gestation length, litter size and birth weight were assessed. One male and one female offspring from each litter were assessed for postnatal growth, body composition, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test at 3 and 12 months of age. There was no effect of maternal genotype on pregnancy outcomes, with days to plug, gestation length, litter size and perinatal mortality not significantly different between wildtype and ClockΔ19+MEL mutant dams. Similarly, there was no effect of maternal genotype on weight of the offspring at birth or at any stage of postnatal growth. While there was an effect of sex on various tissue weights at 3 and 12 months of age, there were minimal effects of maternal genotype. Relative adrenal weight was significantly reduced (?32%) in offspring from ClockΔ19+MEL mutant dams, whereas gastrocnemius muscle was significantly increased (+16%) at 3 months of age only. Intraperitoneal glucose tolerance tests at 3 months of age revealed female offspring from ClockΔ19+MEL mutant dams had significantly reduced area under the curve following glucose administration (?25%), although no differences were found at 12 months of age. There was no effect of maternal genotype on intraperitoneal insulin tolerance at 3 or 12 months of age for either sex. These results demonstrate that foetal growth within a genetically disrupted circadian environment during gestation has no effect on pregnancy success, and only marginal impacts upon the long-term metabolic health of offspring. These results do not support the hypothesis that circadian rhythm disruption during pregnancy programs poor metabolic homeostasis in offspring. However, when maintained on a 12L:12D photoperiod, the ClockΔ19+MEL mutant dams display relatively normal patterns of activity and melatonin secretion, which may have reduced the impact of the mutation upon foetal metabolic programming.     

Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig

Maternal nutrient restriction and impaired fetal growth are associated with postnatal insulin resistance, hyperinsulinemia, and glucose intolerance in humans but not consistently in other species, such as the rat or sheep. We therefore determined the effect of mild (85% ad libitum intake/kg body wt) or moderate (70% ad libitum intake/kg body wt) maternal feed restriction throughout pregnancy on glucose and insulin responses to an intravenous glucose tolerance test (IVGTT) in the young adult guinea pig. Maternal feed restriction reduced birth weight (mild and moderate: both P < 0.02) in male offspring. Moderate restriction increased plasma glucose area under the curve (P < 0.04) and decreased the glucose tolerance index (K(G)) (P < 0.02) during the IVGTT in male offspring compared with those of mildly restricted but not of ad libitum-fed mothers. Moderate restriction increased fasting plasma insulin (P < 0.04, adjusted for litter size) and the insulin response to IVGTT (P < 0.001), and both moderate and mild restriction increased the insulin-to-glucose ratio during the IVGTT (P < 0.003 and P < 0.02) in male offspring. When offspring were classed into tertiles according to birth weight, glucose tolerance was not altered, but fasting insulin concentrations were increased in low compared with medium birth weight males (P < 0.03). The insulin-to-glucose ratio throughout the IVGTT was increased in low compared with medium (P < 0.01) or high (P < 0.05) birth weight males. Thus maternal feed restriction in the guinea pig restricts fetal growth and causes hyperinsulinemia in young adult male offspring, suggestive of insulin resistance. These findings suggest that mild to moderate prenatal perturbation programs postnatal glucose homeostasis adversely in the guinea pig, as in the human.     

Genetic parameters for early piglet weight,litter traits and number of functional teats in organic pigs

Knowledge remains limited on genetic variation and genetic correlations for traits in sows and piglets that are reared in an organic or outdoor setting. Here, we estimated genetic variance components for individual piglet weight, litter weight, litter size traits, and number of functional teats in a pig population raised under outdoor organic conditions. Data were collected from the largest organic multiplier farm in Denmark. Individual piglet weight was recorded at birth and on day 10. Number of live and dead piglets were recorded at birth, day 4, and day 11. Mean and total litter weight were calculated based on the individual weight of living piglets at birth and on day 10. The estimated heritability was highest for the number of functional teats (0.49), mean weight of a litter at birth (0.33) and on day 10 (0.25). In contrast, heritability was lowest for litter size traits (0.04–0.08) and piglet weight (0.06–0.07). Maternal heritability was much higher for individual piglet weight than direct heritability. The results showed that selection for higher mean weight results in smaller litters. Also, selection for individual birth weight of piglets results in heavier piglets at 10 days. In conclusion, this study confirmed that there is genetic variation in individual piglet weight, litter traits, and number of functional teats in organically and outdoor-reared pigs.     

Estimation of genetic trends from 1977 to 1998 for farrowing characteristics in the French Large White breed using frozen semen

The objective of the study was to estimate genetic trends from 1977 to 1998 in the French Large White (LW) breed for stillbirth and associated traits measured at farrowing using frozen semen. Two groups of pigs (G77 and G98) were obtained by inseminating LW sows with semen from LW boars born either in 1977 or in 1998. A second generation was produced by inter se mating in each group. Farrowing was thoroughly supervised through both direct observations and video recording all long farrowing on a total of 137 first- and second-parity litters produced by sows from this second generation (68 G77 and 69 G98 litters, respectively). Measurements included birth time, weight and birth characteristics (including orientation, presence of cyanosis or oedema, membrane obstruction, umbilical cord length/content) of each piglet, as well as sow traits (weight and backfat thickness, farrowing duration, litter size and within-litter variation of weights at birth). The data were analysed using linear or generalised linear mixed models, according to the definition of the trait (continuous or binary data). The importance of several effects to piglet probability of stillbirth was then quantified by computing the reduction of variance associated with the addition of each effect in the model. Litter size did not significantly differ in first parity, but was higher in G98 second-parity sows: the differences for global (including pre partum dead piglets) and total numbers of piglets born per litter were +2.3 ± 1.1 and +1.3 ± 0.6, respectively. G98 sows also had a higher number of stillbirths in both parities (+0.7 ± 0.3 stillborn per litter). Piglets from G98 litters were heavier at birth (+130 ± 40 g for birth weight adjusted for litter size), without any increase in within-litter heterogeneity of birth weight. No significant difference was detected between G77 and G88 groups for farrowing length and the distribution of time interval between piglet births. G98 stillborn piglets had longer and more often empty umbilical cords at birth. G98 piglets born alive also had more often umbilical nodes than G77 piglets. These characteristics were considered as indicators of increased farrowing difficulties and risk of hypoxia at birth in G98 pigs. Time of birth of each piglet, sow fatness at farrowing and time of first placenta expulsion were the main factors of variation of the piglet's probability of stillbirth.     

Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats

Epidemiological studies linking low birth weight and subsequent cardiometabolic disease have given rise to the hypothesis that events in fetal life permanently program subsequent cardiovascular risk. The effects of fetal programming may not be limited to the first-generation offspring. We have explored intergenerational effects in the dexamethasone-programmed rat, a model in which fetal exposure to excess glucocorticoid results in low birth weight with subsequent adult hyperinsulinemia and hyperglycemia underpinned by increased activity of the key hepatic gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK). We found that the male offspring of female rats that had been exposed prenatally to dexamethasone, but were not manipulated in their own pregnancy, also had reduced birth weight (5.66 +/- 0.06 vs. 6.12 +/- 0.06 g, P < 0.001), glucose intolerance, and elevated hepatic PEPCK activity (5.7 +/- 0.6 vs. 3.3 +/- 0.2 nmol.min(-1).mg protein(-1), P < 0.001). These effects resolved in a third generation. Similar intergenerational programming was observed in offspring of male rats exposed prenatally to dexamethasone mated with control females. The persistence of such programming effects through several generations, transmitted by either maternal or paternal lines, indicates the potential importance of epigenetic factors in the intergenerational inheritance of the "programming phenotype" and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.     

Low birth weight for gestational age associates with reduced glucose concentrations at birth, infancy and childhood

BACKGROUND/AIMS: Our aim was to investigate glucose homeostasis, insulin sensitivity and insulin-like growth factor (IGF) system status in children born small for gestational age (SGA). METHODS: A case-control study was carried out at birth, infancy and childhood, comparing SGA with children appropriate for gestational age strictly matched for age, gender, pubertal status and body mass index. Ninety newborns, 52 infants, and 68 children were studied. Fasting insulin (I(F)), fasting glucose (G(F)) to I(F) ratio (G(F)/I(F)), the homeostasis model assessment of insulin sensitivity, the quantitative insulin sensitivity check index, insulinogenic index and the triglyceride/high-density lipoprotein-cholesterol ratio were measured. IGF-I, IGF-binding protein-3 and the IGF-I/IGF-binding protein-3 molar ratio were assessed. RESULTS: Glucose concentrations were lower in SGA newborns (p < 0.0001), infants (p = 0.01), and children (p = 0.001). Birth weight correlated with glucose levels at birth (r = 0.59, p < 0.0001), 12 months (r = 0.29, p = 0.04) and childhood (r = 0.44, p < 0.0001). CONCLUSION: Our results provide evidence for a developmental adaptation of glucose metabolism in SGA children leading to reduced glucose concentrations.     

Influence of colostrum intake on piglet survival and immunity

Colostrum intake from birth to 24 h after the onset of parturition (T24) was estimated for 526 piglets from 40 litters. Plasma concentrations of immunoglobulin G (IgG), lactate, glucose and cortisol were determined at T24 for six piglets per litter. Plasma IgG concentration was also assayed at weaning (28 days) on the same piglets. Rectal temperature was measured at T24 on all piglets. Mortality was recorded until weaning and comparisons were made between piglets that died before weaning and those that were still alive at weaning. The piglets that died before weaning had lower birth weight, lower colostrum intake, lower weight gain between birth and T24, and had a lower rectal temperature, higher plasma cortisol concentration and lower plasma IgG and glucose concentrations at T24 than piglets still alive at weaning. In addition, a higher proportion of piglets that died before weaning had difficulty taking their first breath after birth and were affected by splayleg. Considering all piglets, colostrum intake was positively related to rectal temperature and plasma glucose concentration and negatively related to plasma cortisol concentration at T24. Plasma IgG concentration at T24 was explained by colostrum intake, IgG concentration in the ingested colostrum, birth weight and birth rank (P<0.0001). Plasma IgG concentration at weaning was related to plasma IgG concentration at T24 (r=0.54; P<0.0001) and to colostrum intake (r=0.32; P<0.0001). Finally, body weight was explained by colostrum intake, birth weight and age until 6 weeks of age (P<0.0001). These results show that colostrum intake is the main determinant of piglet survival through provision of energy and immune protection and has potential long-term effects on piglet growth and immunity.     

A reproductive study of Weiser-Maples guinea pigs]

The Weiser-Maples (WE) guinea pig strain was introduced by Backshire Co., Ltd. (USA) in 1977. We have been breeding WE strain guinea pigs for skin melanization research. The WE guinea pig colony produced 1271 pups in 417 litters from May 1978 through December 1983. Breeding date are shown below. The mean litter size was 3.05, the stillborn rate was 15.2%, the weaning rate for live-born pups was 93.5% and the sex ratio was 1.01. The average age at first vaginal membrane rupture was 31.4 days at which time body weight was 290.5g. The mean length of the first 7 estrous cycles was about 17 days, with no cyclical variation in length. The mean duration of gestation was 67.9 days. Duration of pregnancy varied with litter size. There was an inverse relationship between litter size and duration of pregnancy. Most of the pups were delivered alive in mid-pregnancy with a parturition range of 56 to 76 days. The probability of pup death depends on gestational length: the lowest incidence of mortality was seen in litters born at 70 days. The mortalities were related to litter size but not to parity. There was an inverse relationship between birth weight and litter size. In WE guinea pigs, the mean weight for a litter of 1 was 120 g; for a litter of 5, the mean body weight was 58g. Male body weights were slightly heavier than female at birth and at weaning age. The mean body weights are shown below, date of birth: female 88.3g, male 93.3g, weaning age (2 weeks): female 181.1g, male 198.8g and 30 weeks: female 758.7g, male 1018.0g. These date for WE guinea pigs are comparable to those of other strains.     

Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence

Background

Low birth weight followed by accelerated weight gain during early childhood has been associated with adverse metabolic and cardiovascular outcomes later in life. The aim of this study was to examine the impact of early infant weight gain on glucose metabolism and cardiovascular risk factors in adolescence and to study if the effect differed between adolescents born small for gestational age (SGA) vs. appropriate for gestational age (AGA).

Methodology/Principal Findings

Data from 30 SGA and 57 AGA healthy young Danish adolescents were analysed. They had a mean age of 17.6 years and all were born at term. Data on early infant weight gain from birth to three months as well as from birth to one year were available in the majority of subjects. In adolescence, glucose metabolism was assessed by a simplified intravenous glucose tolerance test and body composition was assessed by dual-energy X-ray absorptiometry. Blood pressures as well as plasma concentrations of triglycerides and cholesterol were measured. Early infant weight gain from birth to three months was positively associated with the fasting insulin concentration, HOMA-IR, basal lipid levels and systolic blood pressure at 17 years. There was a differential effect of postnatal weight gain on HOMA-IR in AGA and SGA participants (P for interaction = 0.03). No significant associations were seen between postnatal weight gain and body composition or parameters of glucose metabolism assessed by the simplified intravenous glucose tolerance test. In subgroup analysis, all associations with early infant weight gain were absent in the AGA group, but the associations with basal insulin and HOMA-IR were still present in the SGA group.

Conclusion

This study suggests that accelerated growth during the first three months of life may confer an increased risk of later metabolic disturbances – particularly of glucose metabolism – in individuals born SGA.     

Maternal age does not affect tetrahydrocannabinol's in utero actions in rats

The potential contribution of maternal age to tetrahydrocannabinol's (THC) in utero effects in rats was studied. Pregnant animals were intubated with 25, 10 or 0 mg/kg of THC from gestation day six to parturition. Animals in the 10 and 0 mg/kg groups were pair fed to those given the 25 mg/kg dose. Each series of doses was administered to females three, four or six months of age. THC lowered maternal weight gain and weights of offspring at birth and at 21 days of age, but did not affect litter size, spontaneous alternation or passive avoidance learning in offspring. Increased maternal age was associated with smaller litter size and lower birth weight and weight at 21 days, but did not interact significantly with THC.     

Body weight loss during lactation and its influence on weaning-to-service interval and ovulation rate in Landrace and Yorkshire sows in the tropical environment of Thailand

The aim of this study was to investigate the ovulation rate and the weaning-to-service interval (WSI) of sows in relation to their body weight loss during lactation in tropical climatic conditions. Effect of lactation length (LL), number of total born piglets, number of live born piglets, litter birth weight, average piglet birth weight, number of pigs weaned, litter weaning weight and average pig weaned weight on sow weight loss during lactation were also studied. This study was conducted in two commercial purebred sow herds (A, B) in the central part of Thailand from August to December 1997. The herds had both Landrace (L) and Yorkshire (Y) sows. The 123 sows (55 L and 68 Y) in herd A and 153 sows (95 L and 58 Y) in herd B, parity 1-4, were weighed within 4 days after farrowing and at weaning. Lactation length, litter size at birth and at weaning, litter weight at birth and at weaning, and WSI were recorded for each of these sows. In herd A, 52 sows (20 L and 32 Y) were examined once by laparoscopy between days 8 and 14 after AI-service. These sows had farrowed at least seven piglets in the previous parturition. The numbers of corpora lutea (CL) in both ovaries were counted, and were assumed to equal the ovulation rate. L-sows had significantly (P < 0.05) higher relative weight loss during lactation (RWL) than Y-sows. The RWL increased by 0.7% for each extra pig weaned. When LL increased by 1 day, within the interval of 17-34 days, RWL decreased by 0.6%. Sows with a high weight loss had significantly (P < 0.05) longer WSI than sows with medium or low weight loss. Weight loss had a significant (P < 0.05) effect on WSI in parity 1 and 2 sows. Y-sows had more CL than L-sows (15.7 versus 14.0) (P < 0.05). RWL, parity and regression on lactation length had no significant effect on number of CL. In conclusion, sows with higher number of pigs weaned lose more weight. Under the restricted feeding regime applied, high weight loss during lactation prolongs WSI in parity 1 and 2 sows, but has no influence on the ovulation rate at first oestrus after weaning. The ovulation rate is higher in Yorkshire than in Landrace sows. The ovulation rate is independent of parity.     

Visfatin levels in prepubertal children born small or large for gestational age

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6?ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3?ng/ml vs. 12.5±6.7?ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.     

Influence of some sow characteristics on within-litter variation of piglet birth weight

Within-litter variation of piglet birth weight (BW0) is associated with an increased piglet mortality and a high variability in pig weight at weaning and weight or age at slaughter. Data collected in two experimental herds were used to quantify within-litter variability in BW0 and to assess the influence of factors mainly related to the sow. Within 24 h after birth, piglets born alive were individually weighed and stillborn piglets were collectively (first data set) or individually (second data set) weighed. The first data set was restricted to litters with no or only one stillborn piglet (3338 litters). It was used to assess the influence of genetic selection on BW0 variation by comparing litter characteristics before (1994 to 1996) and after (2001 to 2004) the development of hyperprolific sows in this herd. The second data set included all litters (n = 1596) from sows born between 2000 and 2004. For each litter, mean BW0 (mBW0) and its coefficient of variation (CVBW0) were calculated. Then, variance analyses were performed to test the influence of litter size, parity, year of sow birth and season at conception. Prolificacy improvement was associated with an increased CVBW0 in litters from pure Large White (LW) and Landrace × Large White (LR × LW) crossbred sows. The CVBW0 averaged 21% and was significantly influenced by litter size and parity. It increased from 15% to 24% when litter size varied from less than 10 piglets to more than 15 piglets. The proportion of small piglets (i.e. weighing less than 1 kg) increased concomitantly. The CVBW0 was not repeatable from a parity to the following. It was lowest for first and second parities (20%) and thereafter increased progressively. The CVBW0 was positively related to sow's backfat thickness gain during gestation. Taking into account litter size, parity, year of sow birth and season at conception explained 20% of BW0 variation. Thus, major part of heterogeneity is due to other factors, presumably including embryo genotype, on the one hand, and factors that influence embryo and foetus development, such as epigenetic factors, on the other hand.     

Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention

Zidovudine (AZT) lowers the perinatal transmission of HIV but can impair mitochondrial function by depleting mitochondrial DNA (mtDNA). AZT therapy and perinatal nutritional deprivation affect the body fat distribution, which influences glucose tolerance. We sought to model intrauterine exposure to AZT in humans to determine whether it interacts with low-protein diet (LPD) to impact on birth weight and glucose homeostasis in the offspring. Pregnant dams and their offspring were given AZT, an LPD, or AZT and an LPD (LPD + AZT). AZT reduced mtDNA copy number in liver and birth weight in the offspring and increased their fasting glucose and insulin (P = 0.021, 0.03, 0.001, and 0.011 respectively) at 6-8 wk of age. LPD decreased litter size and birth weight (P = 0.01 and 0.012). In the LPD + AZT group, birth weight and litter size were reduced compared with untreated controls, and fasting blood glucose and insulin were raised. There was a significant interaction between LPD and AZT on fasting insulin levels (P = 0.025). Islet size was not significantly affected, but the mean beta-cell area/islet was reduced in the LPD + AZT group compared with controls (P < 0.05). Early exposure to AZT interacts with LPD to impair fetal development in this model. This combination appeared to impair the supply of insulin and, hence, glucose homeostasis, perhaps as a result of impaired mitochondrial function. Although it is not certain that this can be extrapolated to humans, maternal nutritional deprivation combined with AIDS therapy could influence both birth weight and onset of diabetes.     

High multivitamin intake by Wistar rats during pregnancy results in increased food intake and components of the metabolic syndrome in male offspring

The effect of high multivitamin intake during pregnancy on the metabolic phenotype of rat offspring was investigated. Pregnant Wistar rats (n=10 per group) were fed the AIN-93G diet with the recommended vitamin (RV) content or a 10-fold increase [high vitamin (HV) content]. In experiment 1, male and female offspring were followed for 12 wk after weaning; in experiment 2, only males were followed for 28 wk. Body weight (BW) was measured weekly. Every 4 wk, after an overnight fast, food intake over 1 h was measured 30 min after a gavage of glucose or water. An oral glucose tolerance test was performed every 3-5 wk. Postweaning fasting glucose, insulin, ghrelin, glucagon-like peptide-1, and systolic blood pressure were measured. No difference in BW at birth or litter size was observed. Food intake was greater in males born to HV dams (P<0.05), and at 28 wk after weaning, BW was 8% higher (P<0.05) and fat pad mass was 27% higher (P<0.05). Food intake reduction after the glucose preload was nearly twofold less in males born to HV dams at 12 wk after weaning (P<0.05). Fasting glucose, insulin, and ghrelin were 11%, 62%, and 41% higher in males from HV dams at 14 wk after weaning (P<0.05). Blood glucose response was 46% higher at 23 wk after weaning (P<0.01), and systolic blood pressure was 16% higher at 28 wk after weaning (P<0.05). In conclusion, high multivitamin intake during pregnancy programmed the male offspring for the development of the components of metabolic syndrome in adulthood, possibly by its effects on central mechanisms of food intake control.     

Effect of dietary supplementation of different oils during the first or second half of pregnancy on the glucose tolerance of the sow

Poor glucose tolerance may be an under-researched contributory factor in the high (10% to 20%) pre-weaning mortality rate observed in pigs. Insulin resistance commences at around week 12 of gestation in the sow, although there are conflicting reports in the literature about the extent to which insulin resistance is modulated by maternal diet. The aim of the study was to determine the effects of supplementing the maternal diet with different dietary oils during either the first half or the second half of gestation on the glucose tolerance of the sow. Sows were offered the control (C: n = 5) diet as pellets or the C diet plus 10% extra energy (n = 16 per group) derived from either: (i) extra pellets; (ii) palm oil; (iii) olive oil; (iv) sunflower oil; or (v) fish oil. Experimental diets were fed during either the first (G1) or second (G2) half of gestation. A glucose tolerance test (GTT) was conducted on day 108 of gestation by administering 0.5 g/kg glucose i.v. Blood samples were taken every 5 to 10 min for 90 min post administration. The change in body weight and backfat thickness during gestation was similar but both type and timing of dietary supplementation influenced litter size and weight. With the exception of the sunflower oil group, supplementing the maternal diet in G1 resulted in larger and heavier litters, particularly in mothers offered palm oil. Basal blood glucose concentrations tended to be more elevated in G1 than G2 groups, whilst plasma insulin concentrations were similar. Following a GTT, the adjusted area under the curve was greater in G1 compared to G2 sows, despite no differences in glucose clearance. Maternal diet appeared to influence the relationship between glucose curve characteristics following a GTT and litter outcome. In conclusion, the degree of insulin sensitivity can be altered by both the period during which maternal nutritional supplementation is offered and the fatty acid profile of the diet.     

Maternally transmitted foetal <Emphasis Type="Italic">H19</Emphasis> variants and associations with birth weight

This study was designed to test the hypothesis that polymorphic variation in maternally transmitted foetal H19 alleles is associated with offspring size at birth and alterations in maternal glucose concentrations in pregnancy. Inferred parent of origins of transmitted alleles from 13 haplotype tag SNPs in the H19 gene region from 845 family (mother, partner, offspring) trios from the prospective Cambridge Baby Growth Study and 315 trios from the retrospective Cambridge Wellbeing Study cohorts were tested for association with offspring size at birth measures, as well as maternal glucose concentrations 1 h after a glucose load at week 28 of pregnancy. The foetal rs2071094 allele inherited from the mother was associated with increased birth weight (p = 0.0015) adjusted for gestational age, parity and sex. In the Cambridge Baby Growth Study it was also associated with increased head circumference (p = 0.004), length (p = 0.017) and sum of skinfold thicknesses (p = 0.017) at birth. In contrast to these results there was no association between offspring birth weight and either the maternal rs2071094 genotype or the foetal allele from the father. None of the foetal alleles or maternal genotypes were associated with maternal glucose concentrations, neither were there any other associations with offspring birth weight. In conclusion, consistent with imprinting, common polymorphic variation in foetal H19 alleles transmitted only from the mother are associated with birth weight and other markers of size at birth. Polymorphic variation in H19 is not associated with significant changes in maternal glucose tolerance in the third trimester of pregnancy.     

Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension

Previously, we demonstrated that adult blood pressure was increased in offspring of rabbit mothers with chronic secondary renal hypertension. Our study identified sex-specific differences in the programming of hypertension, with female, not male, offspring, having increased blood pressure at 30 wk of age. The aim of this study was to characterize the maternal hypertension during pregnancy to determine potential programming stimuli. Further, we examined the impact of chronic maternal hypertension on offspring birth weight, nephron number, and renal noradrenaline content (as an index of renal innervation density). Three groups of mothers and their offspring were studied: two-kidney, one-wrap (2K-1W, n = 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n = 8) hypertensive, and a sham-operated group (n = 9). Mean arterial blood pressure was increased by approximately 20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (P(G) < 0.001). Plasma renin activity (PRA; P(G) < 0.05) and aldosterone (P(G) < 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by approximately 20% in offspring of both groups of hypertensive mothers (P(T) < 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased ( approximately 40%, P < 0.05) at 5 wk of age in female 2K-1W offspring compared with sham offspring. Glomerular number was not reduced in female offspring of either group of hypertensive mothers; however, glomerular tuft volume was reduced in female 2K-2W offspring (P < 0.05), indicative of a reduction in glomerular filtration surface area. In conclusion, the two models of renal hypertension produced differential effects on the offspring. The impact of a stimulated maternal renin-angiotensin system in the 2K-1W model of hypertension may influence development of the renal sympathetic nerves and contribute to programming of adult hypertension.     

Association of Diabetes in Pregnancy with Child Weight at Birth,Age 12 Months and 5 Years – A Population-Based Electronic Cohort Study

Background

This study examines the effect of diabetes in pregnancy on offspring weight at birth and ages 1 and 5 years.

Methods

A population-based electronic cohort study using routinely collected linked healthcare data. Electronic medical records provided maternal diabetes status and offspring weight at birth and ages 1 and 5 years (n = 147,773 mother child pairs). Logistic regression models were used to obtain odds ratios to describe the association between maternal diabetes status and offspring size, adjusted for maternal pre-pregnancy weight, age and smoking status.

Findings

We identified 1,250 (0.9%) pregnancies with existing diabetes (27.8% with type 1 diabetes), 1,358 with gestational diabetes (0.9%) and 635 (0.4%) who developed diabetes post-pregnancy. Children whose mothers had existing diabetes were less likely to be large at 12 months (OR: 0.7 (95%CI: 0.6, 0.8)) than those without diabetes. Maternal diabetes was associated with high weight at age 5 years in children whose mothers had a high pre-pregnancy weight tertile (gestational diabetes, (OR:2.1 (95%CI:1.25–3.6)), existing diabetes (OR:1.3 (95%CI:1.0 to 1.6)).

Conclusion

The prevention of childhood obesity should focus on mothers with diabetes with a high maternal pre-pregnancy weight. We found little evidence that diabetes in pregnancy leads to long term obesity ‘programming’.     

Long-term effects of postovulatory aging of mouse oocytes on offspring: a two-generational study.

Aims of this study were to analyze the long-term effects of postovulatory aging of mouse oocytes on 1) reproductive traits of parental (F(0)) and first (F(1))-generation females (pregnancy rate, gestation length, litter size, perinatal death, and sex ratio of offspring) and 2) developmental and behavioral variables of F(1) and second-generation (F(2)) offspring (birth weight and weight gain during preweaning development, postnatal day of attainment of immediate righting, spontaneous motor activity, and passive and active conditioned learning ability). Hybrid (C57BL/6JIco x CBA/JIco) females were artificially inseminated at 13 h (control group) or 22 h (oocyte-aged group) after GnRH injection. Experimental (oocyte-aged group) F(0) females exhibited lower pregnancy rate, shortened gestation length, decreased litter size, higher perinatal death of their pups, and increased percentage of male offspring compared to control F(0) females. Postovulatory aging of oocytes was also associated with increased number of growth-retarded pups, delayed development of the righting reflex, and higher spontaneous motor activity and emotionality of F(1) offspring. Postovulatory aging of F(0) oocytes did not affect birth weight, weight gain during preweaning development, passive and active conditioned learning ability of F(1) offspring, or reproductive traits of F(1) females or developmental and behavior variables of F(2) offspring.