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2005
Development and Cell Biology.
Environmental constraints during
early life result in phenotypic changes that can be associated
with increased disease risk in later life. This suggests
persistent alteration of gene transcription. DNA methylation,
which is largely established in utero, provides a causal
mechanism by which unbalanced prenatal nutrition results
in such altered gene expression. We investigated the effect
of unbalanced maternal nutrition on the methylation status
and expression of the glucocorticoid receptor (GR) and
peroxisomal proliferator-activated receptor (PPAR) genes
in rat offspring after weaning. Dams were fed a control
protein (C; 180 g/kg protein plus 1 mg/kg folic acid),
restricted protein (R; 90 g/kg casein plus 1 mg/kg folic
acid), or restricted protein plus 5 mg/kg folic acid (RF)
diet throughout pregnancy. Pups were killed 6 d after
weaning (n = 10 per group). Gene methylation was determined
by methylation-sensitive PCR and mRNA expression by semiquantitative
RT-PCR. PPARalpha gene methylation was 20.6% lower (P
< 0.001) and expression 10.5-fold higher in R compared
with C pups. GR gene methylation was 22.8% lower (P <
0.05) and expression 200% higher (P < 0.01) in R pups
than in C pups. The RF diet prevented these changes. PPARgamma
methylation status and expression did not differ among
the groups. Acyl-CoA oxidase expression followed that
of PPARalpha. These results show that unbalanced prenatal
nutrition induces persistent, gene-specific epigenetic
changes that alter mRNA expression. Epigenetic regulation
of gene transcription provides a strong candidate mechanism
for fetal programming.
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Center for Nutrition and Pregnancy,
Department of Animal and Range Sciences, North Dakota State
University, Fargo 58105, USA.
The objectives of this study were
to evaluate intestinal cellularity and vascularity in mature
ewes in response to dietary restriction and pregnancy status
and to quantify the response of these variables to increased
nutrient demand of fetal growth. In Exp. 1, 28 mature Dorset
x crossbred white-faced ewes (61.6+/-1.8 kg initial BW)
were fed a pelleted, forage-based diet. Treatments were
arranged in a 2 x 3 factorial, with dietary restriction
(60% restriction vs. 100% maintenance for respective states
of pregnancy) and pregnancy status (nonpregnant, NP; d 90
and 130) as main effects. Dietary treatments were initiated
on d 50 of gestation and remained at 60 or 100% maintenance
throughout the experiment. Nonpregnant ewes were fed dietary
treatments for 40 d. In Exp. 2, four Romanov ewes were naturally
serviced (Romanov fetus and Romanov dam; R/R); two Romanov
embryos per recipient were transferred to four Columbia
recipients (Romanov fetus and Columbia recipient; R/C),
and three Columbia ewes were naturally serviced (Columbia
fetus and Columbia dam; C/C). In Exp. 1, dietary restriction
and pregnancy status interacted with regard to maternal
jejunal DNA concentration (P < 0.01), with restricted
ewes having a greater DNA concentration (mg/g; fresh basis)
at d 130. Vascularity (percentage of total tissue area)
in the jejunum was increased (P < 0.06) as a result of
dietary restriction and pregnancy status. Total microvascular
volume ofjejunal tissue was not altered by dietary restriction
and increased (P < 0.01) at d 130 of pregnancy. In Exp.
2, R/R ewes had less (P < 0.09) DNA (g) in the jejunum
compared with R/C and C/C ewes. Jejunal vascularity (%)
was increased (P < 0.05) in R/R ewes compared with R/C
or C/C ewes, whereas total jejunal microvascular volume
remained unchanged. These data demonstrate intestinal vascular
density responds to changes in diet and physiological state.
In addition, pregnancy increased total jejunal microvascular
volume.
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Department of Family Medicine, Aga
Khan University, Karachi, Pakistan.
BACKGROUND: Maternal diet is an important
determinant of outcomes of pregnancy. Malnutrition during
pregnancy and its consequences maximally affect the health
and long-term outcomes of the population. Low birth weight
accounts for almost 30% of all births; with maternal malnutrition
as a dominant risk factor. This study aims to investigate
the existing beliefs and practices regarding food restrictions
during pregnancy and lactation and also to assess whether
there is any relationship with education level of the respondent
and their beliefs and practices. METHODS: A cross-sectional
survey was conducted at Community Health Center (CHC) of
The Aga Khan University Hospital, Karachi from July-September
2000. Four hundred adult female respondents, who came to
the outpatient services as a patient or as an attendant,
were interviewed after taking verbal consent. A self administered
pre-coded and pre-tested questionnaire was filled by the
respondent. RESULTS: More than three fourths of respondents
were literate. Twelve percent believed in restricting some
food item during pregnancy and about 25% believed the same
during lactation. No statistically significant association
was found between belief about food restriction during pregnancy
or during lactation and education level of the respondent.
CONCLUSION: Undue food restrictions during pregnancy and
lactation do exist in our culture. To assess the true picture
we need to conduct larger studies in the community. The
information obtained from the studies will help us in addressing
these issues for improvement of nutritional knowledge and
dietary practices and to avoid undue food restrictions.
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2000
Third Department of Internal Medicine,
Mie University School of Medicine, Tsu, Japan.
The patient was a 32-year-old obese
woman with a history of type 2 diabetes and hypertension
for 6 years. Although she was treated with antihypertensive
agents and intensive insulin therapy, her hyperglycemia
was difficult to control. She wanted to have a baby but
pregnancy was not recommended because her diabetes was
under poor control and the use of antihypertensive medication.
To achieve good control of obesity, diabetes and hypertension,
she was admitted to our clinical department for weight
reduction using very low calorie diet (VLCD). During VLCD
she had a 19.8 kg reduction in body weight and her blood
glucose and blood pressure were in good control without
the use of drugs. Five months later, she became pregnant
after the fourth trial of intrauterine insemination (IUI)
and gave birth to a female baby under insulin therapy.
This is the first report that showed the usefulness of
VLCD for prepregnant control of glucose metabolism and
blood pressure in an obese hypertensive patient with type
2 diabetes mellitus.
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1987
The effects of providing 50% of
normal feed intake for 10 weeks followed by 16 weeks of
ad lib feeding on estrous cycles and mammary tumor incidence
were studied in female rats initially 4 months and 15-16
months old. Initially all young rats exhibited regular
or irregular estrous cycles and only about 41% of the
older rats cycled regularly or irregularly; the remainder
of the older rats did not cycle. During underfeeding,
both the young and older rats lost body weight and ceased
to cycle. After refeeding 100% of both young and old rats
resumed cycling, the young rats for a much longer period
than the old rats, and more of both groups continued to
cycle than their ad lib-fed controls. Upon refeeding,
the young and old rats reached the body weights of the
ad lib-fed controls in about 3 weeks. Mammary tumors were
initially present only in old rats and regressed during
underfeeding; they rapidly reached control size upon refeeding.
Plasma PRL levels declined during underfeeding but rebounded
to higher than control values upon refeeding in both young
and old rats. In young but not in old rats, plasma LH
levels fell during underfeeding but returned to control
values upon refeeding. These results demonstrate that
a relatively short period of underfeeding, followed by
refeeding, can delay the decline in reproductive cycles
in young rats and reinitiate estrous cycles in older rats.
These effects appear to be mediated via the neuroendocrine
system.
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