Introduction to Endocrine Disrupting Chemicals

BOX 1: THE DEVELOPMENTAL ORIGINS OF HEALTH AND
DISEASE (DOHAD)
DOHaD, also referred to as the “Fetal basis of adult disease” (FeBAD), is based on scientific
evidence that the roots of many diseases and dysfunctions occur very early in life,
especially the embryo, fetus, infant, and child. For example, under- or over-nutrition of
a pregnant woman has an influence on the fetus’s propensity to develop metabolic disorders
including obesity, diabetes, and others, later in life. This research has since been
extended to environmental influences such as cigarette smoking, pollution, and environmental
chemicals. Other evidence has shown that the developing germ cells – precursors
to the sperm and egg cells of the fetus – are quite vulnerable to disruptions from
even low doses of EDCs. More recently, the nervous system, the development of which
begins in early gestation and continues well into childhood, has been found to be very
sensitive to EDC exposures. Certain cancers, especially reproductive cancers, seem to
have their origins in early life. While the manifestation of disease or disorder may not
be apparent at birth, following a latent period the results of these exposures become
evident, often in adolescence, adulthood or aging. Thus, DOHaD is a key concept in
understanding the influence of EDC exposures during these vulnerable periods.
latent consequences. The timing of exposure is key to understanding which organ
or tissue may be affected, as the development of different parts of the body occurs
at different rates. Thus, an organ that is developing during the time of the harmful
exposure is more likely to be affected than an organ that has already completed
development.
The outcomes of exposures during vulnerable periods may be physical malformations,
functional defects, or both. Consider again the example of DES given to
pregnant women, whose female fetuses often had structural malformations of the
reproductive tract, together with an increased propensity for rare vaginocervical
carcinomas later in life. Another very real and complex aspect of the windows of
vulnerability concept is that the same exposure can have different effects depending
on when in development the exposure occurred. For instance, in rodents, first
trimester exposure of a fetus to the pesticide chlorpyrifos, a known EDC, can alter
thyroid structure and function in the offspring when they become adults, while
second trimester exposure to chlorpyrifos can increase insulin levels in the adult
offspring.
Some disturbances in hormone levels may not cause obvious structural changes,
but may still lead to functional changes, disease, or dysfunction, later in life. This
concept of windows of vulnerability is referred to variously as the “Fetal basis of
adult disease (FeBAD)” or the “Developmental origins of health and disease (Do-
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