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10.4.1 Endocrine Disruptors
Among the various environmental agents, chemical agents are the focus of attention,
and among these, a particular class of agents, the endocrine disruptors (EDs). The
most widely accepted definition of an ED is the one provided by the World Health
Organization in 2002, according to which “An endocrine disruptor is a substance or
mixture of substances that alters the function of the endocrine system and thereby
induces adverse effects in an intact organism, its offspring or within (sub) populations”. However, only very few substances fully meet this definition. As a result,
WHO has further work on the definition of potential ED: “A potential endocrine disruptor is a substance or mixture of substances whose properties could result in endocrine disruption in an intact organism, in its offspring, or within (sub) populations”.
Naturally occurring but also synthetic (e.g., DBCP, PCBs, dioxin and organochlorine pesticides), xenohormones are found in the food chain where it could
behave like sex steroid hormones. The first xenohormones studied were xenooestrogens, which can mimic the action of estradiol. These hormones exert effects
via cellular receptors that can interact with other estrogens, but also with xenohormonal substances, because of the common characteristics of their structure. The
xeno-estrogens may have been deliberately administered as drugs (e.g., diethylstilbestrol in pregnant women). Xeno-estrogens can also be integrated by food, pollute
the air or water or be present on professional sites. There are therefore of synthetic
origin (drugs, chemicals and household, cosmetics) or biological, such as phytoestrogens or estrogens present in human waste (urinary estrogen).
In order for a xeno-estrogen to act on a receptor, its binding capacity to this
receptor must be sufficient, that the quantity of molecules reaching the target tissue
is much greater than that of estradiol, that it does not bind, or misbehave, to the
steroid binding proteins present in the biological fluids that might trap it, and finally,
that the target cells are exposed to specific moments of development or for a period
of sufficient duration.
Of the tens of thousands of man-made chemicals, only a few agents have been
tested for their xeno-hormonal activities; that its activities are estrogenic (or anti-),
or androgenic (or anti-). But xeno-estrogens present in food and of synthetic origin
constitute only a small part of the totality of xeno-estrogens; the rest consists of
natural phytoestrogens, especially of plant origin.
In fact, there is very little data available on the possible effects of xeno-hormones
on the male and female reproductive sphere in a so-called “normal” environment.
On the other hand, experimentally, it was demonstrated yet twenty-five years ago
that the administration of several xeno-estrogens at high concentrations, such as
organochlorine pesticides (lindane, methoxychlore, polychlorobyphenyls (PCBs))
or alkylphenols (surfactants present in detergents or shampoos), induced alterations
of reproductive function in vertebrates. The mechanisms of action of xeno- hormones
can be diverse. Indeed, certain xeno-hormonal agents may interfere with the action
of estrogens but by pathways not directly involving their binding to the estradiol
receptor.
10 An Overview of Male Reproductive Toxicants: Facts and Opinions
10.4.1 Endocrine Disruptors
Among the various environmental agents, chemical agents are the focus of attention,
and among these, a particular class of agents, the endocrine disruptors (EDs). The
most widely accepted definition of an ED is the one provided by the World Health
Organization in 2002, according to which “An endocrine disruptor is a substance or
mixture of substances that alters the function of the endocrine system and thereby
induces adverse effects in an intact organism, its offspring or within (sub) populations”. However, only very few substances fully meet this definition. As a result,
WHO has further work on the definition of potential ED: “A potential endocrine disruptor is a substance or mixture of substances whose properties could result in endocrine disruption in an intact organism, in its offspring, or within (sub) populations”.
Naturally occurring but also synthetic (e.g., DBCP, PCBs, dioxin and organochlorine pesticides), xenohormones are found in the food chain where it could
behave like sex steroid hormones. The first xenohormones studied were xenooestrogens, which can mimic the action of estradiol. These hormones exert effects
via cellular receptors that can interact with other estrogens, but also with xenohormonal substances, because of the common characteristics of their structure. The
xeno-estrogens may have been deliberately administered as drugs (e.g., diethylstilbestrol in pregnant women). Xeno-estrogens can also be integrated by food, pollute
the air or water or be present on professional sites. There are therefore of synthetic
origin (drugs, chemicals and household, cosmetics) or biological, such as phytoestrogens or estrogens present in human waste (urinary estrogen).
In order for a xeno-estrogen to act on a receptor, its binding capacity to this
receptor must be sufficient, that the quantity of molecules reaching the target tissue
is much greater than that of estradiol, that it does not bind, or misbehave, to the
steroid binding proteins present in the biological fluids that might trap it, and finally,
that the target cells are exposed to specific moments of development or for a period
of sufficient duration.
Of the tens of thousands of man-made chemicals, only a few agents have been
tested for their xeno-hormonal activities; that its activities are estrogenic (or anti-),
or androgenic (or anti-). But xeno-estrogens present in food and of synthetic origin
constitute only a small part of the totality of xeno-estrogens; the rest consists of
natural phytoestrogens, especially of plant origin.
In fact, there is very little data available on the possible effects of xeno-hormones
on the male and female reproductive sphere in a so-called “normal” environment.
On the other hand, experimentally, it was demonstrated yet twenty-five years ago
that the administration of several xeno-estrogens at high concentrations, such as
organochlorine pesticides (lindane, methoxychlore, polychlorobyphenyls (PCBs))
or alkylphenols (surfactants present in detergents or shampoos), induced alterations
of reproductive function in vertebrates. The mechanisms of action of xeno- hormones
can be diverse. Indeed, certain xeno-hormonal agents may interfere with the action
of estrogens but by pathways not directly involving their binding to the estradiol
receptor.
10 An Overview of Male Reproductive Toxicants: Facts and Opinions