common in these species. There are many causes of this reduced fertility; it can result from anything from lack of cyclic activity of the female to perinatal mortality. Insults
that occur during the period of the fetus that result in fetal death and abortion, or teratogenesis, are best understood from the perspective of the normal embryology,
gestational physiology, and the mechanism responsible for induction of parturition in each animal species.
A wide variety of agents, both infectious and non-infectious, are capable of crossing the placenta to cause fetal injury. Most maternal virus infections are not transmitted to
the fetus, however, several viruses that infect domestic animals have the capacity to cross the placenta and to subsequently induce disease andror developmental defects
Ž .
teratogenesis . Teratogenesis is the production of physical defects in offspring in utero. The outcome of virus infection of the fetus depends on the susceptibility of the fetus to
the infecting virus which, in turn, is a reflection of the gestational age of the fetus at exposure as well as the virulence characteristics of the infecting virus. The potential
consequences of fetal viral infections include teratogenesis, fetal disease with or without abortion, growth retardation, persistent postnatal infection, or no obvious abnormality
Ž
. Catalano and Sever, 1971 . This review will describe and compare aspects of blue-
Ž .
Ž .
tongue virus BTV infection of the ruminant fetus and equine arteritis virus EAV infection of the equine fetus.
2. Maintenance of pregnancy and induction of parturition
Parturition normally must be timed so that fetal development and physiological Ž
. preparation ensure optimal survival of progeny Rossdale et al., 1997 , a process that
requires dialogue between the fetus and dam. The fetus either signals readiness for birth Ž
to the uterus, or the placenta signals impending delivery to the fetus Thorburn et al., .
1991 . Whether or not parturition is best viewed as a release from the inhibitory effects of pregnancy on the myometrium rather than an active process mediated by uterine
Ž .
stimulants Lopez-Bernal et al., 1995; Norwitz et al., 1999 , or more simply a change in balance of the two, is moot. Birth of the fetus is immediately preceded by a dramatic
change in uterine reactivity and coordinated contractility that is sustained by oxytocin, Ž
prostanoid and even proinflammatory cytokine secretion Pashen, 1984; Kelly, 1996; .
Nathanielsz et al., 1997; Mitchell et al., 1998 . The specific sequence of events differs between species, and species-specific differences in the mechanisms of pregnancy
maintenance and induction of parturition influence the occurrence of abortion in different animal species. Furthermore, abortigenic viral infections cause premature
expulsion of the fetus by either stimulating the normal delivery process or by inhibiting the maintenance of pregnancy, whereas normal gestation must be sustained for develop-
mental defects to occur in fetuses in infected with teratogenic viruses
Placental steroids are mediators of pregnancy and of the parturition process. All placental mammals appear to require progesterone for the establishment and mainte-
Ž .
nance of pregnancy Geisert and Conley, 1998 . Uterine quiescence is maintained in Ž
large part by the high concentrations of progesterone in uterine tissues Weems et al., .
1989 . Two sources of progesterone are possible, corpora lutea andror the placenta, and
the relative importance of each varies with species. The relative contributions of the corpus luteum and placenta as sources of progesterone can also change as gestation
advances, thus placental production of progesterone can, by itself, sustain pregnancy in Ž
. the ewe and mare late in gestation Casida and Warwick, 1945; Holtan et al., 1979 .
This is important because disruption of placental progesterone production in these species, as occurs with death of the fetus, will quickly lead to fetal expulsion in the latter
half of pregnancy. In contrast, fetal expulsion is delayed in those species, that depend on the corpus luteum as the principal source of progesterone throughout gestation. The
balance between placental production and metabolism of progesterone is of considerable importance to the maintenance of pregnancy and induction of parturition, and this
Ž .
balance may differ between species Conley and Mason, 1990
and so influence occurrence of abortion.
Estrogen is also an important modulator of uterine activity through its influence on Ž
. prostaglandin synthesis and levels of oxytocin receptors Zeeman et al., 1997 . Thus, an
increase in estrogen or a decrease in the ratio of progesterone to estrogen at the level of the myometrium signals maternal preparation for parturition. In contrast, fetal prepara-
tion involves an activation of the pituitary–adrenal axis and an increase in fetal cortisol
Ž .
synthesis Wood and Cudd, 1997 . The fetal cortisol surge precedes birth in both the ovine and equine fetus, and the secretion of cortisol by the sheep fetus appears to initiate
Ž .
the parturition cascade Norwitz et al., 1999 . A sharp rise in the secretion of fetal cortisol induces the expression of placental enzymes in the sheep, both 17a-hydroxylase
Ž .
and aromatase cytochromes P450 France et al., 1988 , which promote a pre-partum Ž
. burst in placental estrogen synthesis Liggins, 1989 . The process of parturition is less
clear in the mare. Like the sheep, the perinatal equine fetus experiences activation of the adrenal cortex with increased secretion of cortisol, and recent evidence indicates that
Ž .
progesterone levels decline immediately prior to birth Silver, 1994 . Fetal administra- Ž
. tion of ACTH can induce parturition in the pregnant mare Ousey et al., 1998 , whereas
maternal dexamethasone administration is relatively ineffective. Much remains to be determined regarding the initiation of parturition in the mare, and the interaction and
metabolism of progesterone and estrogen, but it is clear that there is an increase in
Ž uterine responsiveness to certain agents that precedes fetal expulsion Leadon et al.,
. 1982 . The influence of fetal viral infections on levels of these various modulators is
virtually uncharacterized.
3. Fetal viral infections: predisposing factors
