Toxicology 09 – Developmental origins of health and disease (DOHaD)
DOHaD
Teratogen; agent that can disturbe the development of the embryo or fetus and
producing malformations such as birth defects
Effects depend on organism (for example not in animal), genetic,
susceptibility, timing
Effect may be unique to some organs
Likelihood of damage increases with usage
Adverse (nadelige) fetal environmental lead to functional change resulting in
increased susceptibility to disease later in life.
Maternal nutritition
Stress during pregnancy
Smoking
Maternal health
Exposure to chemicals
Reduced fetal growth is related to impaired glucose tolerance, metabolic syndrome
and higher rate of cardiovascular diseases, they will get diabetes later in life.
Epigenetics; how genotypes give rise to phenotype. It controls what part of DNA are
expressed, when and how.
DNA methylation; methyl marks added to DNA bases
repress gene activity.
o Methylated DNA; there will be no gene expression
o Methylation is dynamic during development
Histone modification; molecules can attach to the ‘talls’ of
proteins histones. These alter the activity of the DNA
wrapped around them.
Due to epigenetic; a lifelong change resulting from changes in gene expression
during development
The effect depends on the timing of exposure;
Early; heart development
Mid; doubling lungs
Late; islands of Langerhans
Chemicals that modify the epigenome;
Vinclozolin
DES; change in DNA methylation of promotor of oestorgen-responsive gene
(irregulatiry of mestrucal cycle, no milk production etc.)
Methozychlor
Bispenol A (BPA); Bisphenol A (BPA); reduces gene methylation and induces
obesity
Dioxin
Phytoestrogens
Heavy metals
Tributyltin
Cigarette smoke
DOHaD
Teratogen; agent that can disturbe the development of the embryo or fetus and
producing malformations such as birth defects
Effects depend on organism (for example not in animal), genetic,
susceptibility, timing
Effect may be unique to some organs
Likelihood of damage increases with usage
Adverse (nadelige) fetal environmental lead to functional change resulting in
increased susceptibility to disease later in life.
Maternal nutritition
Stress during pregnancy
Smoking
Maternal health
Exposure to chemicals
Reduced fetal growth is related to impaired glucose tolerance, metabolic syndrome
and higher rate of cardiovascular diseases, they will get diabetes later in life.
Epigenetics; how genotypes give rise to phenotype. It controls what part of DNA are
expressed, when and how.
DNA methylation; methyl marks added to DNA bases
repress gene activity.
o Methylated DNA; there will be no gene expression
o Methylation is dynamic during development
Histone modification; molecules can attach to the ‘talls’ of
proteins histones. These alter the activity of the DNA
wrapped around them.
Due to epigenetic; a lifelong change resulting from changes in gene expression
during development
The effect depends on the timing of exposure;
Early; heart development
Mid; doubling lungs
Late; islands of Langerhans
Chemicals that modify the epigenome;
Vinclozolin
DES; change in DNA methylation of promotor of oestorgen-responsive gene
(irregulatiry of mestrucal cycle, no milk production etc.)
Methozychlor
Bispenol A (BPA); Bisphenol A (BPA); reduces gene methylation and induces
obesity
Dioxin
Phytoestrogens
Heavy metals
Tributyltin
Cigarette smoke
