Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow,Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

Study Overview

The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age.

Conclusion and Significance

Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system.     

Reproductive success and failure: the role of winter body mass in reproductive allocation in Norwegian moose

A life history strategy that favours somatic growth over reproduction is well known for long-lived iteroparous species, especially in unpredictable environments. Risk-sensitive female reproductive allocation can be achieved by a reduced reproductive effort at conception, or the subsequent adjustment of investment during gestation or lactation in response to unexpected environmental conditions or resource availability. We investigated the relative importance of reduced investment at conception compared with later in the reproductive cycle (i.e. prenatal, perinatal or neonatal mortality) in explaining reproductive failure in two high-density moose (Alces alces) populations in southern Norway. We followed 65 multiparous, global positioning system (GPS)-collared females throughout the reproductive cycle and focused on the role of maternal nutrition during gestation in determining reproductive success using a quasi-experimental approach to manipulate winter forage availability. Pregnancy rates in early winter were normal (≥0.8) in all years while spring calving rates ranged from 0.4 to 0.83, with prenatal mortality accounting for most of the difference. Further losses over summer reduced autumn recruitment rates to 0.23–0.69, despite negligible predation. Over-winter mass loss explained variation in both spring calving and autumn recruitment success better than absolute body mass in early or late winter. Although pregnancy was related to body mass in early winter, overall reproductive success was unrelated to pre-winter body condition. We therefore concluded that reproductive success was limited by winter nutritional conditions. However, we could not determine whether the observed reproductive allocation adjustment was a bet-hedging strategy to maximise reproduction without compromising survival or whether females were simply unable to invest more resources in their offspring.     

Antenatal sex determination in blood from pregnant women.

Reported results concern Y-chromatin of lymphocytes and granulocytes in the peripheral blood of pregnant women. In women who later delivered male children, a mean of 3.75% Y-chromatin was found in lymphocytes. Even after investigation of paternal Y-chromatin, the rate of false diagnoses (14%) in prenatal sex diagnosis could be reduced only moderately. In early pregnancy lymphoid cells with a Y-chromatin could be first traced only in the 8th week; granulocytes showing a Y-chromatin did not appear until the 9th week.     

Puberty after prenatal growth restraint

There is increasing evidence for a link between prenatal growth and pubertal development. Here we highlight a selection of pubertal characteristics in children who were born small for gestational age (SGA). Boys born SGA are at risk of high levels of follicle-stimulating hormone (FSH) and low levels of inhibin B and a small testicular volume during adolescence. In girls born SGA, the age at pubertal onset and the age at menarche are advanced by about 5-10 months; prenatal growth restraint may also be associated with higher FSH levels and smaller internal genitalia in adolescence. The ovulation rate was found to be reduced in adolescent girls born SGA, and an insulin-sensitizing therapy was capable of raising this low ovulation rate. Menarche is definitely advanced in girls born SGA with precocious pubarche and in those with an early-normal onset of puberty. Current evidence suggests that insulin resistance is a key mechanism linking a post-SGA state to early menarche; hence, insulin sensitization may become a valid approach to prevent early menarche and early growth arrest in girls born SGA.     

Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4

Ninety nine consecutive insulin dependent and 101 non-diabetic pregnant women were examined by ultrasonograph to assess early fetal growth. In 42 of the diabetic mothers and three of the non-diabetic mothers the scan showed early intrauterine growth delay. At 4-5 years of age all children available for study were evaluated by the Denver developmental screening test. Only 23 of the 34 children of diabetic mothers with early intrauterine growth delay had normal test scores compared with 46 of the 50 children of diabetic mothers with normal intrauterine growth. The children failed in personal-social development, gross motor development, and particularly in language and speech development. Children of diabetic mothers with normal early fetal growth had scores very similar to those of the children of non-diabetic mothers, of whom 76 of the 86 tested had normal scores.This study suggests that children with a history of growth delay in early diabetic pregnancy should be screened for possible developmental impairment.     

Maternal Prenatal Positive Affect,Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study

Background

We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation.

Methods

Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records.

Results

One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04–0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1–0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions.

Conclusions

This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.     

Growth hormone normalises height, prediction of final height and hand length in children with Prader-Willi syndrome after 4 years of therapy

BACKGROUND: Based on the reported favourable effects of growth hormone (GH) treatment on growth and body composition in Prader-Labhart-Willi syndrome, we studied age dependency and the long-term effects on growth dynamics to elucidate the assumed hypothalamic GH deficiency. METHODS: We examined 23 children treated with hGH (24 U/m(2)/week) during a median of 4 (range 1.5-5.5) years; group 1: 10 young underweight (age 0.3-4.1 years), group 2: 8 prepubertal overweight (age 3.7-9.5 years) and group 3: 5 pubertal overweight children (age 9.0-14.6 years). RESULTS: After 4 years of therapy, height gain amounted to 1.8 SD; height (0.0 SD) and hand length (-0.2 SD) were normalised in the 2 prepubertal groups; in children above 6 years, height prediction approached parental target height. Weight for height rose in group 1 (to 0.64 SD) and decreased in group 2 (to 0.71 SD) to normal levels. Bone maturation of the pubertal children was too advanced to show a clear growth response to GH (height gain 0.42 SD). Even in this group, weight for height was reduced, but remained supernormal. CONCLUSION: Under exogenous GH, growth and body proportions are normalised in prepubertal children. With early institution of treatment, final height prediction reaches the parental target height range after 3 years. Such a growth-promoting effect of exogenous GH has so far only been described in children with GH deficiency.     

DNA methylation of IGF2, GNASAS,INSIGF and LEP and being born small for gestational age

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR), and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (&lt;32 weeks) and with a birth weight too low for their gestational age (-1SDS) and a normal postnatal growth (>-1SDS at 3 months post term; “AGA”). The SGA individuals were not only lighter at birth, but also had a smaller length (P=3.3x10^-13) and head circumference at birth (P=4.1x10^-13). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5%, 47.5%, 79.4% and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non epigenetic mechanisms that may lead to similar later health outcomes.     

Long term renal outcome of childhood haemolytic uraemic syndrome.

OBJECTIVE--To evaluate the long term outcome of renal function in infants and children after diarrhoea associated haemolytic uraemic syndrome. SETTING--The Hospital for Sick Children, Great Ormond Street, and the Royal Free Hospital, London. SUBJECTS--103 children with the syndrome who presented between 1966 and 1985; 88 attended for follow up investigations (40 male, 48 female) with a mean age 11.6 (range 5.2-22.6) years and a mean duration of follow up of 8.5 (range 5.1-21.3) years. MAIN OUTCOME MEASURES--Blood pressure, ratio of early morning urine albumin to creatinine concentration, glomerular filtration rate, and plasma renin activity. RESULTS--The mean (SD) systolic blood pressure standard deviation score was 0.38 (0.67) and diastolic blood pressure SD score was 0.10 (0.76). The geometric mean ratio of overnight urine albumin to creatinine concentration was 1.27 (range 0.03-48.2), significantly higher than the value observed in 77 normal children (0.32 (0.05-1.95), p less than 0.0001). Glomerular filtration rate estimated from the plasma clearance of chromium-51 EDTA was 95.1 (22.7) ml/min/1.73 m2 surface area, and 16 children had a rate of less than or equal to 80 ml/min/1.73 m2. Significant negative correlations were found between glomerular filtration rate and urinary albumin to creatinine ratio (r = -0.41, p less than 0.0001) and glomerular filtration rate and systolic blood pressure SD score (r = -0.48, p less than 0.0001). A significant positive correlation was found between urinary albumin to creatinine ratio and systolic blood pressure SD score (r = 0.25, p = 0.02). CONCLUSIONS--After an acute episode of diarrhoea associated haemolytic uraemic syndrome 31% (27/88) of children had an increased albumin excretion, 18% (16/88) had a reduced glomerular filtration rate and 10% (9/88) had both, in association with a higher systolic blood pressure, indicating considerable residual nephropathy in this group.     

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage.Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview.Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States.Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days.Main outcome measures Pregnancy outcomes up to 20 weeks of gestation.Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use.Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.     

Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats

Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations.     

New method for assessing changes in growth and sexual dimorphism in paleoepidemiology

This paper has three goals. First, traditional methods used for analyzing growth disruption (GD) and sexual dimorphism (SD) in prehistoric skeletal populations are critiqued. Second, a new method, using adult vertebrae, is presented which helps overcome these limitations. Third, this new method is then tested in the Dickson Mounds skeletal population. Between A.D. 950 and 1300 this popultion underwent a transition from hunting and gathering (PreMississippian: PreMiss.) to maize horticulture (Mississippian: Miss.). Previous research has found a decrease in long bone length in Miss. children, but no difference in adults, or a change in SD. Could this be due to catch-up growth? In the adult skeleton vertebral neural canals (VNCs) size and vertebral body heights (VBHs) can easily be measured. VNCs generally cease growth by early childhood, whereas VBHs grow through young aduthood. This new method offers inference into prehistoric GD and SD previously thought impossible. For example, if VNCs are reduced, but not VBHs, it implies early GD with subsequent catch-up growth. If both VNCs and VBHs are reduced, GD was presumably chronic. Moreover, within this framework, preadult SD can be examined. Results from Dickson show that early GD was followed by catch-up growth. There was a significant change in SD, with females becoming smaller. They had chronic GD. Miss. males had early GD, followed by catch-up growth. Indeed, Miss. males, compared to PreMiss. males, had significantly larger VBHs. Together, these results suggest females lost, but males gained, social status. Thus, vertebral morphometrics may be an invaluable new tool for paleoepidemiologists.     

Effects of maternal occupational exposure to organic solvents on offspring visual functioning: a prospective controlled study

BACKGROUND: Previous studies in adults and animals with high level exposure to organic solvents suggested impairments in visual functioning. The objective of this pilot study was to examine the effects of maternal occupational exposure to organic solvents during pregnancy on offspring color vision and visual acuity, the development of which may be especially vulnerable to organic solvent exposure. METHODS: We conducted a prospective cohort study of 32 offspring of women who were exposed occupationally to organic solvents during pregnancy compared with 27 nonexposed children. Monocular and binocular color vision and visual acuity were assessed using the Minimalist Test and the Cardiff Cards, respectively. Children with known hereditary color vision loss were excluded. RESULTS: Solvent-exposed children had significantly higher error scores on red-green and blue-yellow color discrimination, as well as poorer visual acuity compared with the control group. Exposure index (an estimated measure of exposure intensity) was not significantly related to color discrimination or visual acuity score. Despite excluding all children with a known family history of color vision loss, clinical red-green color vision loss was found among 3 of the 32 exposed children compared with none of the matched controls. CONCLUSIONS: These preliminary findings suggest that occupational exposure to organic solvents during pregnancy is associated with an increased risk of color vision and visual acuity impairment in offspring. The importance of routine visual function screening in risk assessment after prenatal exposure to chemicals warrants further attention.     

Genetic heterogeneity in neural tube defects.

In 1985-1987, the authors attempted to ascertain all cases of confirmed neural tube defects (NTD) in California and Illinois, not only among live-born infants (postnatal) but also cases ascertained during pregnancy (prenatal). Mothers of both prenatal and postnatal NTD cases were interviewed within 5 months. Among postnatal NTD cases, 14.9% (45/303) had anomalies not ordinarily associated with NTD. The frequency of non-NTD related anomalies was 9.4% (5/53) in anencephaly, 0/3 in craniorachischisis, 22.9% (8/35) in encephalocele, 14.5% (27/186) in spina bifida, 20% (1/5) in multiple NTD cases and 19% (4/21) in other NTDs. However, relatively few postnatal NTD cases had known multiple malformation patterns; Meckel-Gruber syndrome was the most common, with 2 postnatal cases, and 3 additional prenatal cases. Maternal age, paternal age and birth order in postnatal cases were 26.7 +/- 5.4 SD, 28.9 +/- 5.8 and 2.8 +/- 1.8, respectively. These characteristics were similar in prenatal NTD cases (27.9 +/- 6.0, 30.1 +/- 6.3, 2.5 +/- 1.5, respectively). We also found no differences in parental ages among different types of NTD. Frequency of prior spontaneous abortion differed neither between postnatal NTD (9.3%) and postnatal controls (8.1%), nor between prenatal NTD (10.7%) and prenatal control (8.7%). Loss rates in the pregnancy immediately prior to the index NTD cases were not significantly higher than in control subjects. The high frequency of non-NTD associated malformations (14.9%) indicates the caution must be exercised before assuming that a given NTD case is polygenic-multifactorial in etiology, especially cases of encephalocele.     

Stunted at 10 Years. Linear Growth Trajectories and Stunting from Birth to Pre-Adolescence in a Rural Bangladeshi Cohort

Background

Few studies in low-income settings analyse linear growth trajectories from foetal life to pre-adolescence. The aim of this study is to describe linear growth and stunting from birth to 10 years in rural Bangladesh and to analyse whether maternal and environmental determinants at conception are associated with linear growth throughout childhood and stunting at 10 years.

Methods and Findings

Pregnant women participating in the MINIMat trial were identified in early pregnancy and a birth cohort (n = 1054) was followed with 19 growth measurements from birth to 10 years. Analyses of baseline predictors and mean height-for-age Z-scores (HAZ) over time were modelled using GLMM. Logistic regression analysis was used to investigate the associations between baseline predictors and stunting (HAZ<-2) at 10 years. HAZ decreased to 2 years, followed by an increase up to 10 years, while the average height-for-age difference in cm (HAD) to the WHO reference median continued to increase up to 10 years. Prevalence of stunting was highest at 2 years (50%) decreasing to 29% at 10 years. Maternal height, maternal educational level and season of conception were all independent predictors of HAZ from birth to pre-adolescence (p<0.001) and stunting at 10 years. The highest probability to be stunted at 10 years was for children born by short mothers (<147.5 cm) (OR_adj 2.93, 95% CI: 2.06–4.20), mothers with no education (OR_adj 1.74, 95% CI 1.17–2.81) or those conceived in the pre-monsoon season (OR_adj 1.94, 95% CI 1.37–2.77).

Conclusions

Height growth trajectories and prevalence of stunting in pre-adolescence showed strong intergenerational associations, social differentials, and environmental influence from foetal life. Targeting women before and during pregnancy is needed for the prevention of impaired child growth.     

Somatic chromosomal abnormalities in infertile men and women

Infertility--the inability to achieve conception or sustain a pregnancy through to live birth--is very common and affects about 15% of couples. While chromosomal or genetic abnormalities associated with azoospermia, severe oligozoospermia or primary ovarian failure were of no importance for reproduction prior to the era of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), advances in assisted reproductive techniques (ART) now enable many infertile couples to have children. These developments have raised the question of the genetic consequences of ICSI: concerns of the potential harm of the invasive procedure and concerns about the genetic risk. The infertile male and female definitely have an increased risk to carry a chromosomal abnormality. Detection of such an abnormality is of fundamental importance for the diagnosis of infertility, the following treatment, the evaluation of the risk for the future child and the appropriate management of the pregnancy to be obtained. Therefore, cytogenetic screening of both partners is mandatory prior to any type of ART. The present review is based on several surveys on male and female infertility and analyzes the types and frequencies of the different reported chromosome abnormalities according to the type of impairment of spermatogenesis and the type of treatment planned or performed. With regard to assisted reproductive techniques (especially ICSI) the main types of chromosomal abnormalities are discussed and their potential risks for ICSI. If available, reported cases of performed ICSI and its outcome are presented. The detection of an abnormal karyotype should lead to comprehensive genetic counselling, which should include all well-known information about the individual type of anomaly, its clinical relevance, its possible inheritance, the genetic risk of unbalanced offspring, and the possibilities of prenatal diagnosis. Only this proceeding allows at-risk couples to make an informed decision regarding whether or not to proceed with ART. These decisions can be made only when both partners have clearly understood the genetic risks and possible consequences when ART is used.     

Association between postnatal catch-up growth and obesity in childhood: prospective cohort study

ObjectiveTo identify predictors of postnatal catch-up growth from birth to two years and its relation to size and obesity at five years.DesignRegional prospective cohort study.SettingAvon longitudinal study of pregnancy and childhood, United Kingdom.Subjects848 full term singletons from a 10% random sample of the Avon longitudinal study of pregnancy and childhood.ResultsSize at birth was representative of the national reference. Overall, 30.7% (260 of 848) of infants showed a gain in SD score for weight greater than 0.67 SD scores between zero and two years, indicating clinically significant catch-up growth. These children had lower weight, length, and ponderal index at birth than other children, and were more often from primiparous pregnancies. They also had taller fathers than other children, and their mothers had lower birth weights and were more likely to smoke during pregnancy. Children who showed catch-up growth between zero and two years were heavier, taller, and fatter (body mass index, percentage body fat, and waist circumference) at five years than other children.ConclusionsIn this contemporary well nourished cohort, catch-up growth was predicted by factors relating to intrauterine restraint of fetal growth. Children who showed catch-up growth between zero and two years were fatter and had more central fat distribution at five years than other children. Mechanisms that signal and regulate early catch-up growth in the postnatal period may influence associations between small size at birth and risks for disease in adulthood.     

Weight variation by sex and nature of risk factors in high-risk infants: an evolutionary perspective

A retrospective cohort study was conducted to explore growth variation during the intrauterine and early postnatal period by sex and nature of high-risk factors (i.e. physiological and pathological) in 831 Korean infants at a University hospital. The results showed that infants with a physiological risk showed a more congruent intrauterine growth pattern compared to those with a pathological risk. Particularly with a physiological risk, female infants experienced more compatible intrauterine and postnatal growth than males, although male infants were heavier than female infants at a given gestational age. In conclusion bigger may not necessarily be better for prenatal growth in humans. A more confluent intrauterine growth in infants with physiological risk can be beneficial for early postnatal catch-up growth. From an evolutionary perspective, female infants with a physiological risk may keep their advantageous edge over male infants during the early postnatal period although such an advantage may not be present with a pathological condition.     

Effects of nicotine exposure during prenatal or perinatal period on cell numbers in adult rat hippocampus and cerebellum: a stereology study

Smoking during pregnancy poses a potential risk to unborn children. The present study examined the long-term effects of early nicotine exposure on the number of pyramidal and granule cells in the hippocampus, and Purkinje cells in the cerebellar vermis. The loss of neurons is the most severe form of brain injury with significant functional implications. In this study, rats were exposed to nicotine during either the prenatal (PRE) period or both the prenatal and early postnatal (PERI) period. It was hypothesized that nicotine treatment would result in long-term decreases in neuronal numbers, and that PERI treatment would be more detrimental to these cell populations than the PRE treatment. The results showed that neither PRE nor PERI nicotine exposure reduces the numbers of pyramidal, granule or Purkinje cells. Neither the regions where these cells reside, nor the cell densities were affected by nicotine. Although no significant cell loss was observed, the current nicotine exposure regimens may lead to alterations in cellular functions or cytoarchitectures. The present results in conjunction with previous reports showing significant cell loss from nicotine exposure during the brain growth spurt suggest that "patch-like" nicotine exposure during prenatal period may alter the sensitivity or the responsiveness of the developing brain to the injurious effects of nicotine during the most vulnerable stage of brain development - the brain growth spurt. Furthermore, the current stereology cell counting results are not in agreement with some reports in the literature, and this discrepancy may simply be a function of different cell counting techniques used.     

Synergistic effects of prenatal hypoxia and postnatal high-fat diet in the development of cardiovascular pathology in young rats

We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.