Page 324 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Reproductive Toxicity and Endocrine Disruption Chapter | 17 291

VetBooks.ir which includes the following in their respective order: (1) secreted in sufficient quantities and at the appropriate
time during pregnancy. The proper reproductive devel-
sperm binding to the zona pellucida of the oocyte involv-
ing interactions between species-specific sperm and
opment of the female fetus is primarily dependent on
oocyte proteins; (2) the sperm acrosomal reaction, which exposure to estrogens at specific times during gestation.
results in the release of acrosomal enzymes and exposure However, the male fetus must have appropriately timed
of the equatorial segment of the sperm plasma membrane; exposure to normal amounts of both androgens and
(3) acrosomal enzyme-associated penetration of zona pel- estrogens for normal development of the reproductive
lucida by a single spermatozoon; (4) fusion of the plasma tract and optimal adult reproductive performance (Hess,
membrane of the sperm at its equatorial segment with the 2003). Depending on the timing of exposure, EDCs,
plasma membrane of the oocyte; (5) membrane fusion- especially those which function as gonadal steroid
associated sperm engulfment and the oocyte cortical receptor agonists and antagonists, can potentially inter-
reaction, which prevents additional oocyte zona binding fere with normal gestational signaling and sexual
and membrane fusion (i.e., polyspermy prevention); differentiation.
female pronucleus formation and completion of meiosis;
decondensation within the sperm nucleus and male pronu-
cleus formation and, finally, the fusion of male and female Maternal Recognition of Pregnancy
pronuclei or syngamy which produces a zygote ready to The embryo generally enters the uterus several days after fer-
undergo embryogenesis (Senger, 2003; Genuth, 2004b; tilization. One of the first endocrine events which must occur
Evans and Ganjam, 2017). From the complexity of the in most mammalian species, other than those for which the
fertilization process, it is apparent that toxicants which timing of luteolysis and duration of pregnancy are very simi-
result in subtle aberrations in sperm and oocyte formation lar to one another (i.e., dogs and cats), is the prevention of
and maturation can have profound effects on gamete luteolysis (i.e., entry into the next estrus or period of sexual
function. receptivity) and the maintenance of luteal phase progesterone
concentrations (Senger, 2003; Evans et al., 2007). The mech-
anism for this embryo endometrium interaction in subpri-
The Endocrinology of Pregnancy mates (intraovarian event in primates), also referred to as
and Placentation “maternal recognition of pregnancy,” has been elucidated in
several species and involves embryonic production of
Gestational Hormones species-specific interferon-τ in ovine and bovine species
Pregnancy begins with fertilization of the oocyte within (o-IFN-τ and b-IFN-τ, respectively), estradiol secretion by
the oviduct, followed by the first cleavage of the zygote, porcine embryos, intrauterine embryonic migration in equids
and terminates with parturition. Although the endocrine and placental chorionic gonadotropin (hCG) in humans
physiology and duration of mammalian pregnancy are (Senger, 2003; Genuth, 2004b). The timing of “maternal rec-
very species specific and are characterized by a great deal ognition of pregnancy” is species specific and in subprimates
of interspecies variation, the overall goals during the generally corresponds to the time period spanning the normal
entire gestation for all pregnant mammals, their embryo(s) oxytocin-mediated synthesis and release of PGF 2α the endo-
and, eventually, the maternal fetal placental unit are metrium, as well as transport of the luteolysin to the ovary.
the same. A uterine environment conducive to embryonic Xenobiotics which interfere with embryonic and, in the case
and fetal development must be facilitated and the preg- of humans, placental development or those toxicants which
nancy (pregnancies in multitocous animals) must be mimic the actions of the luteolysin (e.g., endotoxin) can ter-
maintained for the entire normal gestational length. The minate early pregnancies. Some species of mammals, such
primary hormones involved in establishing the proper as dogs, cats, camelids, goats, swine and rabbits, depend
uterine environment and maintaining pregnancy are pro- solely on luteal progesterone secretion for the maintenance
gesterone secreted by the maternal ovary and/or the pla- of pregnancy (Senger, 2003). The placenta takes over
centa, as well as, in some species, a variety of placental progesterone-associated pregnancy maintenance in sheep at
progestagens. In addition, a variety of other endogenous approximately 50 days post-conception and between the 6th
hormones of maternal, fetal and/or placental origin and 8th month of gestation in cattle (Senger, 2003). The
(depending on the species and gender of the offspring), uterofetoplacental unit of the mare begins to produce a
including androgens, estrogens, prolactin, placental lacto- unique assortment of progestagens classified as 5α-preg-
gen, equine and human chorionic gonadotropins (eCG nanes, beginning at about day 70 of pregnancy (Ginther,
and hCG, respectively) and relaxin, also have important 1992; Evans et al., 2007; Evans, 2011b). A number of toxi-
gestational functions. Normal embryonic and fetal devel- cants (e.g., ergopeptine alkaloids) have been found to inter-
opment require that gestational hormones, especially fere with normal progestagen metabolism in the mare
endogenous androgens and estrogens, be synthesized and (Evans, 2011b).