Uterine environment-periglandular fibrosis and endometritisUterine secretions are critical to the survival and the development of the embryo. Proteins and phosphatase, responsible for
acidity of the uterus, are dependent on progesterone secretion to help maintain pregnancy.
More important to early embryonic loss are histopathologic changes of the endometrium. Studies have indicated reduced fertility
and higher incidence of embryonic and early fetal loss in mares with periglandular fibrosis or endometritis.
Periglandular fibrosis or scarring of the endometrium is a common cause of early fetal loss in mares between 40 and 90 days
of gestation, with a relationship to early foal losses prior to 40 days. Fibrosis, essentially chokes-off the endometrial
glands, preventing adequate nutritional support of the embryo and decreases the likelihood that a particular mare can carry
a foal to term.
The severity of fibrosis is a function of the mare's age, the number foals she has produced over her lifetime, and the level
of uterine infection she has been exposed to. Older mares are more likely to have scarring and other uterine changes due to
previous pregnancies, though the uterine scarring, per se, may not be a primary underlying cause of early embryonic death,
though severe fibrosis has been shown to increase embryonic mortality.
Endometritis may result in the loss of the embryo in three possible ways.
First, an increased number of inflammatory cells in the uterus, initiated by infection, may cause destruction of the embryo.
Second, the organism causing the infection (usually a bacteria) may have a direct effect on the embryo.
Third, uterine irritation-caused infection may cause the mare to return to heat, through the release of prostaglandin, which
affects progesterone secretion and therefore maintenance of pregnancy.
Endometritis or uterine inflammation often follows breeding. Mares are somewhat unique among domestic species in that semen
is deposited directly into the uterus during natural or artificial insemination. Breeding therefore introduces contamination
into the uterus. Mares undergo a natural period (36-48 hours) that allows the uterus to clear itself of excess sperm and
contaminants, restoring sterility prior to the arrival of the embryo from the oviduct, four to five days later.
The sperm and contaminants trigger the immune system, which initiates a cascade of events, drawing white blood cells into
the uterus, beginning the clearing process. Therefore, in the normal, healthy mare the clearing process will negate the effects
of endometritis, and allow for a healthy uterus prior to the arrival of the embryo.
"We know a lot more today about the cascade response of the endometrium and its contamination in terms of the underlying causes
of residual or post-breeding endometritis," says Barry Ball, DVM, Ph.D., University of California, Davis. "Older mares that
have degenerative changes in the uterus seem to have reduced ability to clear, which otherwise is the normal inflammatory
response that we see post-breeding. If that lack of clearing persists for several days, then there becomes a concern of its
effect on the conceptus or the embryo when it arrives in the uterus."
The question is the relative importance, suggests Ball.
"My feeling is that there is not much data from the standpoint of causation regarding endometritis. Defects in the oocyte
may have a bigger impact, particularly in older mares, though older mares also have a higher incidence in post-breeding endometritis
as well. Sometimes it is hard to separate those factors."
Progesterone deficiencyProgesterone is required for survival of the equine embryo. Progesterone released by the healthy corpus luteum of the ovary
maintains the calm state of the uterus during pregnancy.
Low levels of progesterone have been associated with embryonic loss.
"Although reduced progesterone concentrations have been implicated in spontaneous embryonic loss in mares, the cause-and-effect
relationship between reduced progesterone and embryonic loss is not well understood," says Ball.
Before the maternal recognition of pregnancy, which occurs from days 14 to 16 in mares, three mechanisms that may lead to
reduced progesterone levels and corresponding embryonic loss have been proposed: (1) uterine-induced, premature luteolysis;
(2) primary luteal insufficiency; and (3) failure of the conceptus to block luteolysis. Premature luteolysis, the early
dissolution of the corpus luteum, can be induced by endometrial irritants, such as endometritis. Primary luteal insufficiency,
which results from decreased progesterone production by the mid-cycle corpus luteum, has been associated with short interovulatory
intervals and decreased progesterone levels at day 12. The presence of the conceptus in the uterus prevents luteolysis and
maintains progesterone secretion from the corpus luteum by blocking or reducing prostaglandin F2a secretion by the endometrium.
The early equine conceptus is mobile within the uterus from the time of first detection with ultrasonography until day 15
or 16. This mobility has been proposed to be necessary for luteal maintenance and the recognition of pregnancy. As the embryo
moves within the uterus it touches the walls of the endometrium, likely sending a receptor trigger blocking prostaglandin
release. Failure of the conceptus to block luteolysis because of poor embryo mobility or underdevelopment has been proposed
as a cause of embryonic loss.
Maternal ageThere is a decline in fertility with increased mare age.
Some of this decrease is due to a proportion of aged mares not detected pregnant after breeding, although much of the increase
is due to a higher incidence of pregnancy loss with increased maternal age. Though no critical age for increased pregnancy
loss has been identified, increased loss has been noted in mares greater than 13 years of age.
"Increased pregnancy loss is also paradoxically seen in very young mares (11-16 months of age)," says Ball. "Mares appear
to be most susceptible to pregnancy loss when they are very young or very old."
"Embryonic loss rates are much higher in aged mares," adds Vanderwall.
Ball also notes, "Clearly, as the mare gets older, the rate of embryo losses goes up."
Early embryonic loss needs to be differentiated from fertilization failure, which is essentially the same for young and older
mares. 'The cumulative incidence of embryonic loss between fertilization and day 40 may be as low as 20 percent in young mares
to more than 70 percent in aged mares. Under field conditions, the detected incidence of embryonic loss between days 14 and
40 is about 10-15 percent in young mares, and 25-30 percent for aged mares, greater than 18 years of age.