Offspring of mothers fed a high fat diet display hepatic cell cycle inhibition and associated changes in gene expression and DNA methylation

The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver∶brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction.     

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis

Background

Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach.

Methods and Findings

We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10⁻⁹), birth weight (p = 2.19 × 10⁻¹⁵), and gestational age (p = 1.51 × 10⁻⁷). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects.

Conclusions

Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.     

IgM-Antibodies against Phosphorylcholine in Mothers and Normal or Low Birth Weight Term Newborn Infants

Objective

To determine levels of athero-protective IgM antibodies against phosphorylcholine in mothers and term-born normal or low birth weight infants.

Approach

Twenty three mother-infant pairs were studied, of whom 16 infants were within the normal weight range for gestational age (NGA; 3652[504] g) and 7 were small for gestational age (SGA; birth weight: 2715[255] g), the latter <2SD below the Swedish reference data mean for normal fetal growth. All infants were born at term (mean±SD 40.5±1.1 weeks). Serum was available from 6 mothers with SGA and 14 with NGA infants. Participating mothers were aged 34.0±3.9 years (no difference between groups). Fourteen neonates were boys and seven were girls. Levels of anti-PC IgM were determined by ELISA.

Results

Neonatal IgM anti-PC levels were low (undetectable in 8 infants out of which 3 were SGA) with a median of 76[range 0–2.51] U/ml. Maternal IgM anti-PC levels were significantly higher (median 7198[range: 25.32–656.0]) U/ml) and the proportion of mothers in highest quartile (>75th percentile) was larger in mothers of NGA-infants (43%) vs. those of SGA-infants (0%, p = 0.032).

Conclusions

IgM anti-PC levels are low at birth, which suggests that these antibodies do not play a “housekeeping” role in immune function during fetal life/development, but arise predominately on exposure to external antigens after birth. Furthermore, low maternal IgM anti-PC levels may play a role in placental insufficiency, contributing to poor fetal growth and a small-for-date baby. This preliminary observation may have implications for the future risk of atherosclerosis/cardiovascular disease development in pregnant women and their offspring.     

Great expectations: dominance,breeding success and offspring sex ratios in red deer

Differences in dominance rank among red deer (Cervus elaphus) females (hinds) on Rhum were related to their breeding success as well as to the comparative success of male and female offspring. Males (stags) born to mothers above median rank were more successful than hinds, while hinds born to subordinate mothers were more successful than stags. The ratio of male to female calves produced by dominant mothers was significantly higher than that produced by subordinates. Since dominance rank among hinds is related to their body weight as adults and to their birth weight, these results suggest that the birth sex ratio may be affected by environmental factors operating during a female's early development.     

Birth weight in an African-American population living under moderate ecologic stress

The African-American population of McNary, Arizona, resides at an altitude of 2200 m. The lengthy winters are typically quite cold; the monthly mean temperature from November to April is 1.8 degrees C. Data from 318 singleton full-term births of African-American babies from 1949 to 1972 show a mean weight of 3095 g (s.d. = 427 g). At birth 1.9% of the babies weighed at least 4 kg; 9.7% weighed less than 2.5 kg. These data suggest that altitude may have influenced birth weight in this sample. Significant patterns in birth weight exist for sex, parity, mother's age, and severity of the winter preceding the year of birth. The birth weight of female babies born following warm winters is significantly lighter than those born during years following cold winters. There are relatively fewer high-birth-weight babies, in comparison to other African-American populations. Birth weight is also significantly lighter than three other African-American samples, even though African-American mothers of McNary had full-term professional care. Birth weight of African-American babies born in McNary is consistent with the overwhelming African ancestry of the African-American population of McNary. Sex differences in birth weight of babies born following cold winters can be ascribed to gender-related hereditary or physiologic factors at the level of the fetus. Maternal inactivity during particularly cold winters may be a contributing factor.     

Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals

The role of genes in normal birth-weight variation is poorly understood, and it has been suggested that the genetic component of fetal growth is small. Type 2 diabetes genes may influence birth weight through maternal genotype, by increasing maternal glycemia in pregnancy, or through fetal genotype, by altering fetal insulin secretion. We aimed to assess the role of the recently described type 2 diabetes gene TCF7L2 in birth weight. We genotyped the polymorphism rs7903146 in 15,709 individuals whose birth weight was available from six studies and in 8,344 mothers from three studies. Each fetal copy of the predisposing allele was associated with an 18-g (95% confidence interval [CI] 7-29 g) increase in birth weight (P=.001) and each maternal copy with a 30-g (95% CI 15-45 g) increase in offspring birth weight (P=2.8x10-5). Stratification by fetal genotype suggested that the association was driven by maternal genotype (31-g [95% CI 9-48 g] increase per allele; corrected P=.003). Analysis of diabetes-related traits in 10,314 nondiabetic individuals suggested the most likely mechanism is that the risk allele reduces maternal insulin secretion (disposition index reduced by ~0.15 standard deviation; P=1x10-4), which results in increased maternal glycemia in pregnancy and hence increased offspring birth weight. We combined information with the other common variant known to alter fetal growth, the -30G-->A polymorphism of glucokinase (rs1799884). The 4% of offspring born to mothers carrying three or four risk alleles were 119 g (95% CI 62-172 g) heavier than were the 32% born to mothers with none (for overall trend, P=2x10-7), comparable to the impact of maternal smoking during pregnancy. In conclusion, we have identified the first type 2 diabetes-susceptibility allele to be reproducibly associated with birth weight. Common gene variants can substantially influence normal birth-weight variation.     

Intergenerational Predictors of Birth Weight in the Philippines: Correlations with Mother's and Father's Birth Weight and Test of Maternal Constraint

Background

Birth weight (BW) predicts many health outcomes, but the relative contributions of genes and environmental factors to BW remain uncertain. Some studies report stronger mother-offspring than father-offspring BW correlations, with attenuated father-offspring BW correlations when the mother is stunted. These findings have been interpreted as evidence that maternal genetic or environmental factors play an important role in determining birth size, with small maternal size constraining paternal genetic contributions to offspring BW. Here we evaluate mother-offspring and father-offspring birth weight (BW) associations and evaluate whether maternal stunting constrains genetic contributions to offspring birth size.

Methods/Principal Findings

Data include BW of offspring (n = 1,101) born to female members (n = 382) and spouses of male members (n = 275) of a birth cohort (born 1983–84) in Metropolitan Cebu, Philippines. Regression was used to relate parental and offspring BW adjusting for confounders. Resampling testing was used to evaluate whether false paternity could explain any evidence for excess matrilineal inheritance. In a pooled model adjusting for maternal height and confounders, parental BW was a borderline-significantly stronger predictor of offspring BW in mothers compared to fathers (sex of parent interaction p = 0.068). In separate multivariate models, each kg in mother’s and father’s BW predicted a 271±53 g (p<0.00001) and 132±55 g (p = 0.017) increase in offspring BW, respectively. Resampling statistics suggested that false paternity rates of >25% and likely 50% would be needed to explain these differences. There was no interaction between maternal stature and maternal BW (interaction p = 0.520) or paternal BW (p = 0.545).

Conclusions/Significance

Each kg change in mother’s BW predicted twice the change in offspring BW as predicted by a change in father’s BW, consistent with an intergenerational maternal effect on offspring BW. Evidence for excess matrilineal BW heritability at all levels of maternal stature points to indirect genetic, mitochondrial, or epigenetic maternal contributions to offspring fetal growth.     

Glycosylated Fibronectin and Inhibin are Lower and Anti-Müllerian Hormone is Higher in Umbilical Cord Blood when Mothers have Preeclampsia

Objective: Preeclampsia is a common disorder of pregnancy, causing significant morbidity and mortality for mothers and infants. Several molecules, including glycosylated fibronectin (GlyFn), the inhibin-related proteins, anti-müllerian hormone (AMH), and the insulin-like growth factor axis, are altered in maternal plasma in the setting of preeclampsia; however, these molecules have not been previously measured in cord blood of infants born to mothers with preeclampsia, which may represent changes in fetal physiology. We evaluated potential biomarkers of preeclampsia in umbilical cord blood to fill the gap in knowledge.Methods: This is a case-control study of 196 neonates born at a tertiary teaching hospital in Boston from 2010–2017. Forty-nine neonates born to mothers with preeclampsia were matched 1:3 by gestational age, sex, and birth weight z-score with 147 controls. Eleven analytes were measured in cord blood by enzyme-linked immunosorbent assay. Binary logistic regression analyses were performed to evaluate associations between preeclampsia and analytes.Results: Mean cord blood levels of GlyFn and total inhibin were significantly lower in neonates born to mothers with preeclampsia compared to controls, and AMH levels were significantly higher in males born to mothers with preeclampsia than male controls. Associations remained significant after controlling for maternal and neonatal characteristics.Conclusion: Cord blood levels of GlyFn and inhibin are decreased and AMH (male) levels are increased in infants of preeclamptic mothers, which is opposite the pattern these biomarkers show in serum of mothers with preeclampsia. These molecules may be important in the pathophysiology and long-term effects of preeclampsia on the developing fetus.Abbreviations: AMH = anti-müllerian hormone; ELISA = enzyme-linked immunosorbent assay; GlyFn = glycosylated fibronectin; IGF = insulin-like growth factor; IGFBP5 = insulin-like growth factor binding protein 5; LOD = limit of detection; PAPP-A = pregnancy-associated plasma protein A; PAPP-A2 = pregnancy-associated plasma protein A2     

The extended Pedersen hypothesis

The Pedersen hypothesis of fetal macrosomia in neonates born to diabetic mothers has been extended. In neonates born to gestational diabetic mothers, it is suggested that an intrinsic fetal pancreatic beta-cell hyperplasia 'pulls' glucose across the placenta, i.e. assists in glycemic control of the mother. The initial increase in fetal size due to fetal hyperinsulinism gives rise to developing hypoxemia, and the limitation in fetal oxygen availability alters differential tissue utilization of glucose, increases alpha-glycerophosphate synthesis in fetal adipocytes, and gives rise to a further increase in fetal adiposity.     

Association of birth weight and length with air temperature, sunlight, humidity and rainfall in the city of Warsaw, Poland

Several studies have shown the month of birth effect on birth weight and height of children. The mechanism of this phenomenon is not fully explained. Using data from Warsaw hospitals, the influence of four climatic factors (temperature, sunlight, humidity and rainfall) on birth outcomes was studied. The sample consisted of 10,631 neonates (5450 boys and 5181 girls) born between May 2004 and April 2005. Individual values for birth weight and length were standardised on the overall mean and standard deviation for all subjects, separately for each sex. Differences in means of Z-score birth outcomes between months, seasons and semi-annual periods of birth were assessed by one-way analysis of variance, separately for each sex. The relation between average values of four atmospheric factors and average neonatal outcomes for each month of birth was assessed by a weighted Spearman rank correlation. The results revealed significant differences in average Z-scores of neonate weight and length between months of birth for boys and girls. Significant seasonal variation in Z-scores means was only found for birth length in boys. The correlation between four atmospheric factors during pregnancy and birth length was the highest for boys and occurred in the second trimester. Second trimester of fetal growth is the period most sensitive to influences of climatic factors.     

Gastroschisis, low maternal age, and fetal morbidity outcomes

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.     

Does lambing season affect mother-young relationships and lamb vigor in D’man sheep reared in oases?

Although sheep are known to be seasonal breeders and give birth in winter, not all of them follow this trend. A few breeds can be mated and give birth all year round, meaning that mothers and neonates will have to face contrasting climatic conditions. The aim of this study was to test whether lambing season affects maternal and neonatal behaviors in D’man sheep. During four different lambing seasons (winter, autumn, summer and spring), periparturient ewes (n = 111) and their lambs (n = 213) were kept under 24-h-video surveillance in order to record postpartum behaviors. Mother-young preference was tested around 48 h after parturition. Lamb vigor was studied by the determination of birth weight, early postnatal behavior and rectal temperature at birth and 48 h later. Litter expulsion time was not affected by lambing season, but birth weight was biased against summer and winter born lambs. Ewes provided a higher intensity of care to their offspring in winter: latency for grooming was shorter and time spent grooming was longer compared to lambing in spring and summer (P = 0.01 in all cases). On the other hand, lambs were the most active in spring as they were faster to extend their hind legs (P = 0.01), stand up (P = 0.04) and reach the udder (P = 0.04). Rectal temperature at 48 h was affected by season of birth (P < 0.001) with higher values observed in summer. Glycemia variation between birth and 48 h was the lowest in spring born lambs and plasma levels increased less in spring born lambs than in winter (P < 0.0001), autumn (P < 0.0001) and summer born lambs (P < 0.0001). In the choice test, mothers clearly preferred their own young and no season effect was detected except that in the first minute of the test they spent less time near their own young in winter than in the other seasons (P = 0.04). Lambs also chose their mother successfully without any major effect of the season however, but winter born lambs were the least vocal (P = 0.01). Overall, this study show that maternal care, lamb behavior and vigor vary lightly according to seasons, albeit not in a consistent manner. In conclusion, a season is no more detrimental than another for the onset of mother-young relationships.     

Reduced weight in mice offspring after in utero exposure to 2450-MHz (CW) microwaves

Time-bred CD-1 mice (100) were sham-irradiated or irradiated with 2450-MHz (CW) microwaves at 28 mW/cm² for 100 minutes daily from the 6th through 17th day of gestation. The offspring were examined either as fetuses after hysterotomy on the 18th day of gestation or as naturally born neonates on the 1st and 7th day of age. Fetuses of half of the dams were examined on the 18th day of gestation. The incidence of pregnancy and the numbers of live, dead, resorbed, and total fetuses were similar in both groups. The mean weight was significantly lower (10%) in live microwave-irradiated fetuses, and ossification of sternal centers was significantly delayed. In the offspring that were born naturally, the mean weight of microwave-irradiated 7-day-old suckling mice was significantly lower (10%) than that of the sham-irradiated group. Survival rates of neonates in these two groups were not different. These data demonstrate that the decreased fetal weight seen in microwave-irradiated mice is retained at least 7 days after birth. Evidence from other published studies is presented to show that the retarded growth is persistent and might be interpreted as permanent stunting.     

Does fetal sex affect pregnancy outcome?

Background: In maternal fetal medicine, gender differences in outcome are often observed.Objective: This article reviews the fetal sex-dependent differences found in many aspects of pregnancy, from conception through birth.Methods: The MEDLINE, EMBASE, and Current Contents databases were searched, for the years 1985 to 2006, using the following Medical Subject Headings and text words: fetal gender, finale, female, sex ratio at birth, pregnancy outcome, preterm birth, and stillbirth. The search was not limited by language. In addition, the bibliographies of known relevant articles were examined to capture any reports not already identified in the electronic search. All reports that provided information on gender differences in pregnancy outcome were included for review.Results: An extremely high male-to-female ratio was found in fetuses born after very short-duration pregnancy; this level declined around the 20th week and stabilized at term. In the absence of manipulation, both the sex ratio at birth and the population sex ratio have been found to remain consistent. A higher incidence of preterm birth and premature preterm rupture of membranes has been observed in different populations among mothers of male newborns compared with mothers of females. It has been speculated that this higher incidence may be linked to the relatively greater weight at lower gestational age of male newborns versus females. Women carrying male fetuses had higher rates of gestational diabetes mellitus, fetal macrosomia, failure to progress during the first and second stages of labor, cord prolapse, nuchal cord, and true umbilical cord knots. Cesarean sections were also more frequently found among male neonates compared with females.Conclusions: Male sex is an independent risk factor for adverse pregnancy outcome. Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period, particularly after preterm birth.Key words: fetal gender, male, female, sex ratio of birth, perinatal outcome.     

Body Mass Index Development from Birth to Early Adolescence; Effect of Perinatal Characteristics and Maternal Migration Background in a Swedish Cohort

Background

Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring.

Objectives

To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics.

Methods

A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data.

Results

We observed a significant BMI change over time in children and time interaction with maternal migration status (P<0.0001). Estimated BMI over time adjusted for maternal and perinatal characteristics of offspring, showed slower BMI growth before age of 5, followed by an earlier plateau and steeper BMI growth after 5 years among children of immigrant mothers compared with children of Swedish mothers. These differences in BMI growth were more prominent among children with mothers from outside Europe.

Conclusion

Beside reinforcing early childhood as a crucial period in development of overweight, the observed slower BMI development at early childhood among children of immigrants followed by a steeper increase in BMI compared with children of Swedish mothers is important for further studies and for planning of preventive public health programs.     

Smoking in pregnancy: associations with skinfold thickness,maternal weight gain,and fetal size at birth.

Skinfold thickness is an index of subcutaneous fat, and certain maternal conditions during pregnancy affect the skinfold thicknesses of the baby. A study was performed to investigate the effect of smoking on skinfold thickness, maternal weight gain, and fetal size at birth. A total of 452 mothers with normal singleton pregnancies were groups as: non-smokers, light-to-moderate smokers, or heavy smokers. Maternal age, height, parity, and duration of pregnancy were similar in the three groups. Heavy smokers gained significantly less weight than non-smokers, but there was no significant difference in skinfold thickness. Babies born to smokers had lower birth weights and smaller head circumferences and were shorter than those born to non-smokers, but skinfold thicknesses were similar. The presence of a normal layer of subcutaneous fat in babies whose mothers smoked suggests that fetal growth retardation is not caused by nutritional deficiencies.     

Effect of altitude on the lung function of high altitude residents of European ancestry

The forced vital capacity (FVC), forced expiratory volume in one second (FEV), and ratio of FEV to FVC (%FEV) of 161 male and 158 female youths of European ancestry who were born at high altitudes and who were residing in La Paz, Bolivia (average altitude of 3,600 m) were examined and compared with those for lowland Europeans and highland Aymara Amerindians. FVC and FEV were significantly larger (p less than .001) in the La Paz Europeans than in two lowland control samples of European ancestry, with the relative differences between samples varying from small (1.5-4.1%) to moderate (7.7-11.9%). It could not be determined whether the enhanced lung volumes of the La Paz European children were acquired through an accelerated development of lung volumes relative to stature during adolescence, as is the case for Amerindian highlanders. After controlling for body and chest size, FVC and FEV were significantly smaller in the La Paz Europeans than in highland Aymara (p less than .001), suggesting that the lung volumes of the Aymara are influenced by factors other than simply growth and development at high altitude. Finally, as found in Amerindians, chest size is an important determinant of intra-individual variation in lung function among highland Europeans.     

Higher arterial oxygen saturation during submaximal exercise in Bolivian Aymara compared to European sojourners and Europeans born and raised at high altitude

Arterial oxygen saturation (SaO(2)) was measured at 3,600-3,850 m by pulse oximetry at rest and during submaximal exercise in three study groups: 1) highland Aymara natives of the Bolivian altiplano (n = 25); 2) lowland European/North American sojourners to the highlands with at least 2 months of acclimatization time to 3,600 m (n = 27); and 3) subjects of European ancestry born and raised at 3,600 m (n = 22). Aymara subjects maintained approximately 1 percentage point higher SaO(2) during submaximal work up to 70% of their maximal work capacity, and showed a smaller rate of decline in SaO(2) with increasing work compared to both European study groups. The higher-exercise SaO(2) of Aymara compared to Europeans born and raised at 3,600 m suggests genetic adaptation. The two European study groups, who differed by exposure to high altitude during their growth and development period, did not show any significant difference in either resting or exercise SaO(2). This suggests that the developmental mode of adaptation is less important than the genetic mode of adaptation in determining exercise SaO(2). A weak correlation was detected (across study groups only) between the residual forced vital capacity (FVC) and the residual SaO(2) measured at the highest level of submaximal work output (P = 0.024, R = 0.26). While firm conclusions based on this correlation are problematic, it is suggested that a part of the higher SaO(2) observed in Aymara natives is due to a larger lung volume and pulmonary diffusion capacity for oxygen. Results from this study are compared to similar studies conducted with Tibetan natives, and are interpreted in light of recent quantitative genetic analyses conducted in both the Andes and Himalayas.     

Transgenerational effects of poor elemental food quality on Daphnia magna

Environmental effects on parents can strongly affect the phenotype of their offspring, which alters the heritability of traits and the offspring’s responses to the environment. We examined whether P limitation of the aquatic invertebrate, Daphnia magna, alters the responses of its offspring to inadequate P nutrition. Mother Daphnia consuming P-poor algal food produced smaller neonates having lower body P content compared to control (P-rich) mothers. These offspring from P-stressed mothers, when fed P-rich food, grew faster and reproduced on the same schedule as those from P-sufficient mothers. In contrast, offspring from P-stressed mothers, when fed P-poor food, grew more slowly and had delayed reproduction compared to their sisters born to control mothers. There was also weak evidence that daughters from P-stressed mothers are more susceptible to infection by the virulent bacterium, Pasteuria ramosa. Our results show that P stress is not only transferred across generations, but also that its effect on the offspring generation varies depending upon the quality of their own environment. Maternal P nutrition can thus determine the nature of offspring responses to food P content and potentially obfuscates relationships between the performance of offspring and their own nutrition. Given that food quality can be highly variable within and among natural environments, our results demonstrate that maternal effects should be included as an additional dimension into studies of how elemental nutrition affects the physiology, ecology, and evolution of animal consumers.