Page 319 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

286 SECTION | II Organ Toxicity

VetBooks.ir of which are essential for spermatogenesis to occur contin- to be primarily androgen dependent, and the secretions of
these glands, as well as those of the epididymidis, are
uously in the seminiferous tubules (Senger, 2003; Genuth,
important components of seminal fluid. Conversion of tes-
2004b; Evans and Ganjam, 2017). In some species, FSH is
primarily required for the onset of puberty and the initia- tosterone to DHT can generally occur in the epididymidis,
tion of spermatogenesis, with many of the functions of prostate and seminal vesicles. Hormonally active xenobio-
FSH in the immature male being taken over by testoster- tics which alter the normal endocrine events associated
one in the sexually mature animal (Haschek et al., 2010). with epididymal and accessory gland development and
Testosterone stimulates Sertoli cells to produce several function can have adverse effects on male fertility.
androgen-regulated proteins (including androgen-binding
protein), which are required for spermatogenesis Sexual Behavior, Erection, Emission and Ejaculation
(Senger, 2003; Haschek et al., 2010). Interference with
Sexual behavior is mediated by estradiol in postnatal
this testosterone-mediated effect by antiandrogens (e.g.,
males and females. The conversion of the steadily pro-
vinclozolin) which prevent interactions between testoster-
duced testosterone in the male to estradiol in the brain
one and the androgen receptor or by the inhibition of
(plus the effects of estrogens of testicular origin) results
testosterone synthesis by excessive glucocorticoids
in the male being sexually receptive most of the time
(e.g., chronic stress, alterations in endogenous glucocorti-
(Senger, 2003). Adequate libido and sexual receptivity, as
coid metabolism or the administration of xenobiotics
well as adequate concentrations of testosterone, are neces-
with glucocorticoid-like activities) has the potential to
sary for erection of the penis, which is required for intro-
adversely affect Sertoli cell function, and, therefore, sper-
mission during copulation (Sikka et al., 2005). Olfactory
matogenesis. Estrogens are required for various aspects of
(detection of pheromones), auditory and visual stimuli play
the normal development and function of Sertoli cells and
roles in facilitating cholinergic and NANC (non-adrener-
germ cells within the seminiferous tubules (O’Donnell
gic/non-cholinergic) parasympathetic neuron-mediated
et al., 2001; Hess, 2003; Evans and Ganjam, 2017).
penile erection, which, depending on the species, involves
Xenobiotics which mimic or inhibit the actions of estra-
various degrees of nitric oxide-associated vasodilation and
diol within the testis can disrupt normal spermatogenesis.
vascular engorgement (Senger, 2005; Sikka et al., 2005).
During copulation, the events which lead to emission of
Positive and Negative Feedback Loops Involved the secretions of the accessory sex glands and the ejacula-
in Male Reproduction tion of spermatozoa generally involve tactile stimuli to
Positive and negative feedback mechanisms help maintain the glans penis and stimulation by sympathetic neurons
an endocrine environment which is conducive to normal (Sikka et al., 2005).
male reproductive function (Figure 17.2). The Sertoli cell
can produce activin and inhibin which respectively
Normal Female Reproductive Anatomy
increase and decrease the secretion of FSH by gonado-
and Physiology
tropes and, in some species, GnRH release from the hypo-
thalamus (Haschek et al., 2010). Testosterone, DHT and Reproductive Anatomy of the Female
estradiol all provide negative feedback to the hypothala-
Although there are some distinct morphological differ-
mus with respect to GnRH release, and testosterone can
ences between species (e.g., simplex uterus in primates,
also directly inhibit LH secretion by gonadotropes
duplex cervices in rabbits), the female reproductive tract
(Senger, 2003; Haschek et al., 2010; Evans and Ganjam,
generally consists of paired ovaries and the “tubular
2017). Xenoestrogens and xenoandrogens have the poten-
genitalia,” which include the paired oviducts (uterine
tial to disturb the hypothalamic pituitary gonadal axis
tubes) and uterine horns contiguous with a uterine body
(O’Donnell et al., 2001). It is currently thought that anti-
and cervix, vagina, vestibule and vulva (Senger, 2003;
androgens and a variety of other xenobiotics can interfere
Evans et al., 2007; Evans and Ganjam, 2017). The
with these feedback loops and possibly other endocrine
organs involved in female reproductive function are
pathways, resulting in Leydig or interstitial cell hyperpla-
physiologically and morphologically dynamic and func-
sia (Thomas and Thomas, 2001; O’Connor et al., 2002;
tion to produce the oocyte, facilitate its fertilization,
Evans, 2017).
provide an environment for embryonic and fetal devel-
opment, and transport the fetus from the maternal to the
Epididymal and Accessory Sex Gland Function external environment. Variations in size, appearance,
Epididymal development and function are dependent on location and function of the female reproductive organs
the proper balance of androgenic and estrogenic stimula- depend on the endocrine milieu dictated by the effects
tion and are required for normal male reproductive func- of sexual maturation, stage of the estrous or menstrual
tion and fertility. The accessory sex glands are considered cycle, gestational hormone production of maternal, fetal