162
The daily production of testicular spermatozoa varies greatly from one species to
another. In animal species used in reproductive toxicology such as the rat and
mouse, the very high production of spermatozoa and the existence of a large epididymal reserve of male gametes may mask the reproductive toxicity of a compound at low doses [36]. In the mouse for example, the production of spermatozoa
should be reduced by 80 to 90% to observe an impairment of fertility.
10.4 Toxicologic Evaluation of Environmental Chemicals
on the Reproductive Sphere
Reproductive toxicity is defined as adverse impacts of chemical substances on sexual function/fertility in adult males and females, as well as developmental toxicity
in the offspring. Such substances which interfere in some way with normal reproduction in humans and other species are called reprotoxic.
The evaluation of reproductive toxicity by exogenous molecules can be subdivided into two main sections. On one hand, we must consider direct effects on fertility that include the harmful effects on the libido, sexual behavior, on different
aspects of gametogenesis in both sexes, hormonal activity or the physiological
response that would disrupt the capacity of fertilization, the fertilization process
itself, or development of the fertilized egg up to and including implantation. On the
other hand, we will consider the toxicity on development in its broadest sense. That
includes any effect disrupting normal development, also well before after birth. Are
considered toxic effects on the embryo and the fetus (e.g., abortion, death, reduction
body weight, stunting and development, organ toxicity, functional, structural, perior post-natal abnormalities) and mental alteration or physical development after
birth, up to and including normal pubertal development.
The embryo corresponds to the first period of life intrauterine fertilization at the
end of organogenesis. The fetus corresponds to the period of intrauterine life including functional maturation and growth until birth. Relevant fertility studies on one or
two generation(s) together with teratogenesis studies allow highlighting the toxic
effects on reproduction and the calculation of different indexes used during the evaluation properties of a substance: (i) a fertility index that is the percentage of mating
resulting in a pregnancy; (ii) a pregnancy index that is the percentage of gestations
ending with the birth of living animals; (iii) a viability index that corresponds to the
percentage of newborns who survive at least 4 days; and (iv) a lactation index that
is the percentage of living animals at 4 days who are still alive at the time of weaning (i.e., about 21 days in the mouse model).
The toxicologic literature is abounding with examples of environmental chemicals, including pharmaceutical drugs, with adverse and/or deleterious effects on the
male reproductive sphere in laboratory animals. Indeed, unless proven otherwise,
one can assume that similar effects (i.e., greater, lesser or equal) are likely to occur
in humans exposed to these molecules.
C. Pineau
The daily production of testicular spermatozoa varies greatly from one species to
another. In animal species used in reproductive toxicology such as the rat and
mouse, the very high production of spermatozoa and the existence of a large epididymal reserve of male gametes may mask the reproductive toxicity of a compound at low doses [36]. In the mouse for example, the production of spermatozoa
should be reduced by 80 to 90% to observe an impairment of fertility.
10.4 Toxicologic Evaluation of Environmental Chemicals
on the Reproductive Sphere
Reproductive toxicity is defined as adverse impacts of chemical substances on sexual function/fertility in adult males and females, as well as developmental toxicity
in the offspring. Such substances which interfere in some way with normal reproduction in humans and other species are called reprotoxic.
The evaluation of reproductive toxicity by exogenous molecules can be subdivided into two main sections. On one hand, we must consider direct effects on fertility that include the harmful effects on the libido, sexual behavior, on different
aspects of gametogenesis in both sexes, hormonal activity or the physiological
response that would disrupt the capacity of fertilization, the fertilization process
itself, or development of the fertilized egg up to and including implantation. On the
other hand, we will consider the toxicity on development in its broadest sense. That
includes any effect disrupting normal development, also well before after birth. Are
considered toxic effects on the embryo and the fetus (e.g., abortion, death, reduction
body weight, stunting and development, organ toxicity, functional, structural, perior post-natal abnormalities) and mental alteration or physical development after
birth, up to and including normal pubertal development.
The embryo corresponds to the first period of life intrauterine fertilization at the
end of organogenesis. The fetus corresponds to the period of intrauterine life including functional maturation and growth until birth. Relevant fertility studies on one or
two generation(s) together with teratogenesis studies allow highlighting the toxic
effects on reproduction and the calculation of different indexes used during the evaluation properties of a substance: (i) a fertility index that is the percentage of mating
resulting in a pregnancy; (ii) a pregnancy index that is the percentage of gestations
ending with the birth of living animals; (iii) a viability index that corresponds to the
percentage of newborns who survive at least 4 days; and (iv) a lactation index that
is the percentage of living animals at 4 days who are still alive at the time of weaning (i.e., about 21 days in the mouse model).
The toxicologic literature is abounding with examples of environmental chemicals, including pharmaceutical drugs, with adverse and/or deleterious effects on the
male reproductive sphere in laboratory animals. Indeed, unless proven otherwise,
one can assume that similar effects (i.e., greater, lesser or equal) are likely to occur
in humans exposed to these molecules.
C. Pineau