Genetic abnormalities
Most cases of congenital deformities of the pituitary and/or adrenal glands that lead to prolonged gestation are associated with pituitary gland abnormalities.
Pituitary Gland Abnormalities Prolonging Gestation in Cattle and Sheep
Pituitary gland abnormalities are thought to be caused by a recessive gene that results in a nonfunctional or aplastic pituitary gland. These abnormalities have been described in Holstein-Friesian, Ayrshire, Guernsey, and Jersey breeds of cattle. Affected fetuses cease to grow at 6–7 months gestation and are small-for-gestational-age at birth. There is no spontaneous parturition in affected cattle because of the pituitary gland abnormalities. Calves are usually dead when delivered. Some may show evidence of severe craniofacial defects.
With prolonged gestation associated with multiple skeletal abnormalities, affected calves show evidence of pituitary aplasia or hypoplasia. These conditions have been reported in Hereford cattle. Arthrogryposis, torticollis, kyphosis, and scoliosis are present, and some calves also have a cleft palate.
Adrenal Gland Abnormalities and Prolonged Gestation in Cattle and Sheep
An autosomal recessive gene causes prolonged gestation in Holstein-Friesian cows due to fetal adrenal malfunction. The fetal adrenal glands fail to produce corticosteroids at term in response to fetal ACTH. As a result, the fetus continues to grow until it outgrows its blood supply, resulting in fetal gigantism.
Induction of parturition with dexamethasone does not induce normal calving because of insufficient preparation of the birth canal. A cesarean section will save the dam, but the fetus often dies due to adrenal insufficiency.
Prolonged gestation (465 days) has been reported in the Swedish Red breed with fetal gigantism (100 kg) and unilateral adrenal gland dysgenesis.
Combined Pituitary and Adrenal Gland Abnormalities in Cattle and Sheep
Courtesy of Professor Arnaud Sartelet, Clinique Veterinaire Universitaire, University of Liège, Belgium.
This condition is caused by hypoplasia of both the pituitary and adrenal glands. It has been reported in Holstein-Friesian, Ayrshire, and Swedish breeds of cattle. Gestation is prolonged by 21–150 days. Pronounced abdominal enlargement is seen in some cases. There is no attempted parturition unless the fetus dies first after having outgrown its blood supply. Cervical relaxation is poor, and dystocia invariably results. The calf can weigh 48–80 kg at birth (fetal gigantism) and shows signs of postmaturity. The coat and hooves are longer than normal, and the teeth are prominent and loose. If the calf survives birth, dyspnea results from failure of surfactant release, and the calf may die. At necropsy, hypoplasia of the cranial pituitary and adrenal glands is evident.
Inherited adenohypophyseal and adrenal cortical hypoplasia occurs in Belgian Blue. Except for some hirsutism, affected calves are of normal appearance. Live but nonviable fetuses can be born more than 30 days after insemination. An inherited genetic recessive disorder is responsible.
Prolonged Gestation Associated with Cloning
A unique, iatrogenic cause of prolonged gestation is somatic cell nuclear cloning in fetal calves and lambs. Early placental abnormalities have been detected in a high proportion of such animals, and placentomegaly may be seen in later pregnancy. The abnormality may result in fetal death or, if the fetus survives, in the large offspring syndrome. The prolonged gestation in some clones is due to a lack of ACTH release from the fetal pituitary or to failure of the abnormal placenta to respond to fetal cortisol near term (the fetal adrenals are normal). Spontaneous birth may not occur, and prolonged gestation results. Fetal lung and maternal mammary development is retarded and can compromise fetal survival, hence, prepartum corticosteroid therapy with or without cesarean section delivery is recommended.
Fetopathogenic Infection
Prolonged gestation has been associated with materno-fetal infection with both pestiviruses (bovine viral diarrhea virus, border disease virus) and arboviruses (Akabane virus, bluetongue virus, Rift Valley fever virus, Schmallenberg virus).
Although bovine viral diarrhea virus can cause abortion in cattle, it can also produce congenital defects in the fetus. These include cerebellar hypoplasia, anencephaly, and hydrocephaly. Affected calves may be born with severe CNS defects, and prolonged gestation occasionally occurs if pituitary function is compromised. The related pestivirus border disease virus can produce severe brain and coat abnormalities in fetal lambs. Pituitary compromise in such lambs can lead to prolonged gestation.
Akabane virus, found in Africa, Australia, the Middle East, and the Far East, can be transmitted by insects to both pregnant cattle and sheep. Bovine fetuses exposed to the virus during a gestation-susceptible period (76–104 days) may develop hydranencephaly (fluid-filled cavitation of the brain). Exposure to the virus at 105–174 days of pregnancy may cause both hydranencephaly and arthrogryposis. Affected fetuses may have severe brain damage. The cerebral cortex may be absent and the cranial cavity filled with fluid. Cerebellar hypoplasia may be present, and the brain stem is smaller than normal. Compromise of pituitary function in the affected fetus can lead to prolonged gestation.
Bluetongue virus, found in Africa, Australia, North and South America, and Europe, is also transmitted by insects; infection can occasionally cause prolonged gestation. The fetuses of cows exposed to the virus at 60–120 days of pregnancy developed hydranencephaly, whereas fetuses exposed later in pregnancy developed less severe CNS defects.
Gestation lengths >200 days have been recorded in ewes vaccinated during pregnancy with Rift Valley fever attenuated viral vaccine. Affected lambs developed severe brain defects and skeletal abnormalities. Some ewes developed hydrops amnion by the fourth month of gestation. Ewes in which pregnancy is not terminated developed ketosis.
Toxic Plants as a Cause of Prolonged Gestation in Cattle and Sheep
Plant toxins may cause fetal deformity and prolonged gestation when eaten accidentally or fed experimentally.
When ingested by sheep in early pregnancy, Veratrum californicum (skunk cabbage) produces fetal deformities, gigantism, and prolonged gestation. Cranial defects and brain and eye abnormalities has been reported in fetuses of ewes fed this plant at 14 days of gestation; pregnancy length in some cases was >230 days. The plant contains the amine cyclopamine, which is believed to be responsible for fetal abnormalities. This plant also contains a number of toxic alkaloids that cause GI disturbances, dyspnea and convulsions in sheep. V album has similarly caused prolonged gestation and fetal abnormalities in Holstein-Friesian cows in Japan.
An unidentified toxin in the plant Salsola tuberculatiformis (cauliflower saltwort) is thought to cause prolonged gestation in sheep. Pregnancy has reported to be extended >220 days, and affected lambs show atrophy of the pituitary, adrenal, and thyroid glands. Fetuses appear to be most susceptible to the toxin in the first and third trimesters of pregnancy. Amniotic fluid continues to increase in volume in cases of prolonged gestation associated with this plant. Physical abnormalities such as cleft palate prevent normal swallowing of amniotic fluid in affected fetuses. Excessive fetal weight and the weight of accumulated fetal fluids may lead to rupture of the prepubic tendon in ewes.
