Page 8 - GPD-1-2

Gene & Protein in Disease DNA methylation and gene expression on rats with protein malnutrition

the quality of health. Numerous studies have shown factor, leading to the subsequent chronic diseases, and the
that the occurrence of chronic diseases is related to a permanent change of the offspring phenotype suggests that
variety of factors, such as genetic , environmental, and intrauterine growth retardation may be related to some
[19]
[2]
behavioral factors. In recent years, epigenetic inheritance stable gene expression changes.
has been postulated as a bridge between gene expression In this study, we used the digital gene expression
and the environment and is an important mechanism profile to investigate the gene expression of adult offspring
[3]
for the development of complex diseases [4,5] . Barker et al. of malnourished rats at different times of life and to
[20]
found the association between fetal growth restriction [6,7] explore the differences in DNA methylation in early
and adult disease through large-scale epidemiological life . Therefore, it is of great significance to identify the
[21]
investigations [8,9] and proposed the “fetal origin hypothesis” functional genes of malnutrition in early life to explore
in 1993. The “fetal origin hypothesis” holds that the fetus is the pathogenesis of related diseases. Studying the DNA
highly sensitive to nutrient supply . Adaptive changes , methylation in the early-life malnutrition environment
[11]
[10]
including reduced blood flow to visceral tissues such will provide a reference for exploring the mechanism of
as kidneys to ensure sufficient blood supply to the heart early-life malnutrition environment and adult diseases as
and brain and reduced hormone secretion to reduce the well as the genetic factors of disease development .
[22]
body’s sensitivity to hormones , occur to the fetus if the
[12]
pregnant mother is unable to absorb adequate nutrients or 2. Materials and methods
the uterus is underdeveloped. These adaptive changes affect
the development and metabolic types of peripheral tissues 2.1. Experimental animals
(liver, fat, skeletal muscle, etc.), resulting in “programmed” In this study, 12 SD rats were purchased from the Medical
changes, which can affect the differentiation, proliferation, Experimental Center of Zhengzhou University, including
and/or function of fetal cells, thereby resulting in diseases nine female rats and three male rats. Each rat weighed
later in life . 200–250 g. Adaptive feeding was performed before mating.
[13]
Epigenetics regulates gene promoter regions and The female and male mice were put in the same cage for
maintains their action throughout the life of the organism, mating at around 5 pm every day. Vaginal swab smear was
ensuring their transcriptional expression and termination. taken the next morning. The day when sperm was found by
st
In recent years, a large number of studies have confirmed microscopic examination was determined as the 1 day of
that epigenetic inheritance is assumed to be a bridge pregnancy. Female rats were kept in a cage (three pregnant
between gene expression and the environment, and an rats per cage) from 1 to 15 days of gestation, and then were
important mechanism underlying the occurrence of kept in a protective cage after 15 days of gestation until they
complex diseases . As a heritable epigenetic mark, DNA gave birth. Until the young rats grew to 21 days old, they
[14]
methylation is particularly sensitive to environmental were separated from the cages after weaning. During the
factors, and is the most important form of epigenetic whole experiment, all rats were fed in the laboratory animal
modification studied thus far. feeding room of Medical College of Henan University in
a quiet environment, with the temperature ranging from
Boubred et al. constructed a rat model of intrauterine 21°C to 22°C and the relative humidity ranging from 50%
nutrition restriction using a 9% low-protein diet , and to 70%. The environment was well-ventilated and clean,
[15]
compared with the normal group, they found that damaged and the animals were given fixed portions of food and free
kidney, reduced glomerular filtration rate, and increased drinking water during the experiment.
glomerular sclerosis in intrauterine undernourished
offspring may lead to renal disease in adulthood. Pond 2.2. Animal grouping
et al. found that the body weight of rats born with energy The newborn mice were classified as IUGR newborn mice
restriction and free feeding during the first two trimesters if their average weight were less than 2 times the standard
of pregnancy were 10 – 20% higher than that of the control deviation, and if there were more than 10 pups per litter.
group . However, studies by Tomi et al. showed that the Some pups were randomly excluded. The specific grouping
[16]
catch-up growth of intrauterine growth restriction (IUGR) of the pregnant rats is as follows.
infants after birth may destroy the blood–brain barrier,
resulting in metabolic dysfunction, reduced glucose Using the random number table method, nine pregnant
content in cerebrospinal fluid and reduced secretion of rats were randomly and evenly allocated to three groups,
brain-derived neurotrophic factor, and may lead to an with three rats in each group:
increased risk of Alzheimer’s disease in adulthood [17,18] . i. Normal control (CON) group. The mother rats were
Many studies have shown that early fetal malnutrition given normal protein diet (20% protein) during the
acquired from the mother is the earliest environmental course of pregnancy, lactation, and after cage separation.

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/gpd.v1i2.169