Page 322 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Reproductive Toxicity and Endocrine Disruption Chapter | 17 289

VetBooks.ir testosterone (Evans et al., 2007; Evans and Ganjam, sexual contact in these species can interfere with the ovu-
latory process.
2017). In granulosa cells (reportedly theca interna cells in
some species), the release of FSH from the anterior pitui-
tary induces aromatase-mediated conversion of testoster- Formation and Function of a CL
one produced in the theca cells into estradiol (Senger,
Following ovulation, a cascade of endocrine changes
2003; Evans et al., 2007; Evans and Ganjam, 2017).
takes place in the female subprimate which facilitates the
Stimulation of aromatase activity by xenobiotics can have
transition from sexual receptivity to non-receptivity. Once
an overall estrogenic effect on exposed animals (increased
an ovulation occurs, blood concentrations of follicular
production of estradiol).
estradiol and inhibin return to their basal levels, and gran-
ulosa cells continue their growth, differentiation and
The Effects of Estrogenic Feedback increased production and release of progesterone (luteini-
on the Hypothalamic Pituitary Gonadal Axis zation) under the influence of LH (Evans et al., 2007).
The functional ovarian structure which eventually devel-
Increasing concentrations of estrogens associated with
ops from each ovulated follicle is a CL, which is com-
estrus alter the hypothalamic GnRH secretory pattern and
prised of large and small luteal cells derived from the
decrease pituitary secretion of FSH, while greatly increas-
granulosa and theca interna cells (granulosa cells in
ing the amount of LH produced and released by the ante-
horses), respectively (Senger, 2003; Evans et al., 2007).
rior pituitary gland (preovulatory LH surge) (Senger,
In most species, luteal cells are responsive to LH and pro-
2003; Evans et al., 2007; Evans and Ganjam, 2017).
duce progesterone until, shortly before the usual end dies-
Although inhibin produced by granulosa cells further
trus in non-pregnant animals, the CL undergoes luteolysis
decreases FSH secretion, dominant follicles surviving to
mediated by oxytocin-stimulated production of prosta-
estrus do not undergo atresia because of an enhanced sen-
glandins F 2α (PGF 2α )(Ginther, 1992; Senger, 2003;
sitivity to basal FSH levels (Senger, 2003; Wilker and
Evans et al., 2007). While luteolysis is an intraovarian
Ellington, 2006). Xenoestrogens have the potential to
event in primates, oxytocin-stimulated endometrium pro-
either imitate or inhibit these estradiol feedback mechan-
duces the luteolysin (PGF 2α ) in subprimates (Senger,
isms in sexually mature females, depending on the
2003; Evans and Ganjam, 2017). Xenobiotics, which can
amount of estrogenic xenobiotic, the endocrine milieu at
cause endometritis or mimic the actions of oxytocin or
the time of the exposure and the relative binding affinity
PGF 2α (e.g., endotoxin or lipopolysaccharide (LPS)) can
of the xenobiotic for ERs.
be associated with premature luteolysis. Conversely, toxi-
cants with the opposite oxytocin/PGF 2α -related effects
Ovulation would be expected to disrupt normal reproductive cyclic-
ity by prolonging the lifespan of the CL and causing a
The granulosa cells in the one or more dominant estrous
prolonged diestrus or pseudo-pregnancy (e.g., xenoestro-
follicles (Graafian follicles) cease to divide shortly prior
gens in swine).
to ovulation and undergo further differentiation, with
Species of animals can vary in the number of fertile
increased numbers (up-regulation) of LH receptors which
ovulations and, therefore, CLs, which are characteristi-
will be responsive to the estrogen-induced preovulatory
cally associated with each estrous cycle. Monotocous
LH surge (Senger, 2003; Evans et al., 2007; Evans and
mammalian species usually only ovulate a single second-
Ganjam, 2017). As LH increases, granulosa cells (theca
ary oocyte each estrous cycle. The ovaries of litter-
interna cells in some species) continue to convert preg-
bearing (polytocous) mammals generally develop multiple
nenolone to progesterone, but estradiol production
follicles which mature, ovulate and form functional CLs.
decreases, resulting in a slight preovulatory decline in
estradiol (Evans et al., 2007; Evans and Ganjam, 2017).
The preovulatory LH surge is associated with increased Summary of the Effects of Estrogens and
follicular pressure, degeneration of theca cells and weak- Progesterone During the Female Reproductive Cycle
ening of the follicular wall, completion of the first meiotic The endocrine changes which occur during the estrous
division within the oocyte (end of meiotic inhibition cycle are reflected in behavior and the size, morphology,
except in dogs and foxes) and, finally, ovulation of a sec- position and function of the tubular genitalia. Estrogens
ondary oocyte arrested in metaphase II (Senger, 2003; have multiple effects on the female reproductive tract
Evans et al., 2007; Evans and Ganjam, 2017). In felids, which include: the previously discussed interactions with
ferrets, mink, camelids and rabbits, the preovulatory LH the hypothalamus and anterior pituitary to alter the pat-
surge is induced by copulation (intromission or vaginal terns GnRH and gonadotropin secretion, which govern
stimulation in most induced ovulators; seminal fluid in follicular development and ovulation; facilitation of sex-
camelids). Toxicants which interfere with copulation or ual receptivity; increased blood flow, genital swelling,