JPC SYSTEMIC PATHOLOGY
REPRODUCTIVE SYSTEM
January 2022
R-B06 (NP)

Signalment (JPC #1947395):  A 6-month-gestation Holstein fetus

HISTORY:  A Holstein cow with no previous history of reproductive problems aborted this fetus.  The cow was vaccinated against rabies, leptospirosis, infectious bovine rhinotracheitis, brucellosis, and bovine viral diarrhea.

HISTOPATHOLOGIC DESCRIPTION: 

Chorioallantois, cotyledonary:  Diffusely, the chorioallantoic stroma is moderately thickened by fibrin, edema, numerous degenerate neutrophils, fewer lymphocytes and macrophages, and scant necrotic debris that multifocally extends to the allantoic membrane surface and to a lesser extent multifocally expands the chorionic villi.  Chorionic villi are multifocally characterized by loss of tissue architecture with replacement by karryorhectic and cellular debris (lytic necrosis).  Trophoblasts lining villi are shrunken and often sloughed with hypereosinophilic cytoplasm and pyknotic nuclei (necrosis), and multifocally there are numerous large aggregates of fibrin, sloughed cells, and multiple colonies of 1um coccobacilli along the chorionic surface.  Multifocally, the tunica media and tunica adventitia of arteries and arterioles within the chorioallantoic stroma are expanded and disrupted by variably degenerate neutrophils, fibrin, and karyorrhectic debris (necrotizing vasculitis).  Multifocally within the blood vessel lumina are variably sized aggregates of fibrin adhered to the tunica intima (thrombi).

Amnion:  Diffusely, the amnion is markedly thickened up to 1mm by abundant eosinophilic homogeneous material, dilated vessels, fibrin, numerous degenerate neutrophils, fewer lymphocytes and macrophages, and scattered cellular and karyorrhectic debris (lytic necrosis).  There are multifocal to coalescing areas of lytic necrosis along both surfaces of the membrane characterized by moderate amounts of eosinophilic cellular and karyorrhectic debris admixed with aggregates of basophilic granular material (mineral), scattered hemorrhage, fibrin, edema, and colonies of 1um coccobacilli.

Fetal lung:  Diffusely, alveolar septae are expanded 2-3 times normal by macrophages and fewer lymphocytes, fibrin, congested vessels, and increased clear space (edema).  Occasionally, multifocal alveolar and bronchiolar lumina contain viable and degenerate neutrophils and small amounts of fibrin. Multifocally peribronchiolar lymphoid aggregates mildly compress the adjacent airways. Interlobular septa are diffusely expanded by increased clear space (edema) and dilated lymphatics and are infiltrated by few scattered macrophages and lymphocytes. 

MORPHOLOGIC DIAGNOSIS: 

1. Chorioallantois, cotyledonary; amnion: Placentitis and amnionitis, necrotizing, subacute, diffuse, moderate, with necrotizing vasculitis, fibrin thrombi, and colonies of coccobacilli Holstein, bovine.
2. Lung: Pneumonia, interstitial, histiocytic, subacute, diffuse, moderate, with bronchial-associated lymphoid tissue hyperplasia.

ETIOLOGIC DIAGNOSIS:  Ureaplasmal abortion

CAUSE:  Ureaplasma diversum

GENERAL DISCUSSION: 

• Ureaplasma is an important cause of bovine abortion, is widespread in the US, and more significant in heifers than cows due to lack of acquired immunity
• Ureaplasma are in the family Myco­plasmataceae, lack cell walls, stain poorly with Gram stains, and are smaller than the resolving power of the light microscope (0.2-0.3 um); mycoplasma are the smallest free-living parasites capable of autonomous growth and require complex media and closely controlled growth conditions for culture
• 3 genera in the family Myco­plasmataceae:
  • Mycoplasma: Urease negative, requires sterols
  • Ureaplasma: Hydrolyze urea to ammonia (urease positive), requires sterols
  • Acholeplasma: Does not require sterols, seldom associated with disease
• May cause vulvitis, embryonic death, abortion, or stillborn/weak calves
• Organism may be present for approximately 117 days prior to abortion
• Recent study found 28% prevalence of Ureaplasma diversum in Brazilian cattle herds with poor reproductive performance (Carli, J Vet Diagn Invest. 2022)

PATHOGENESIS:

• Role of Ureaplasma in disease is not fully elucidated
• May cause loss of ciliary activity and epithelial damage
• Present and long-lived in prepuce, vulva, frozen semen, and nasal mucosa
• May adhere to spermatozoa causing sperm abnormalities and decreased sperm motility
• In a study of Brazillian herds with poor reproductive performance, approximately 20% of bulls were carriers for both diversum and Mycoplasma bovis, possible synergistic relationship (Carli, J Vet Diagn Invest. 2022)

TYPICAL CLINICAL FINDINGS:

• Abortion and partially or completely retained placenta
• Vulvitis, infertility

TYPICAL GROSS FINDINGS:

• Embryonic death, mid to late term abortions, birth of dead or weak calves
• Amnion typically most severely affected, chorioallantois may also be affected
  • Early: multifocal to diffuse reddening
  • Chronic: multifocal to diffuse thickening, fibrosis, mineralization, hemorrhage, necrosis, and occasional meconium staining
• Granular vulvitis: Hyperemia, 1-2 mm diameter raised, gray to red nodules most prominent on ventral vulvar mucosa that can persist more than a year
• Mucopurulent discharge of short duration

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Ureaplasma stain poorly with Gram stains and are smaller than the resolving power of the light microscope (0.2-0.3 um)
• Placenta: Necrotizing placentitis; with fibrosis, mineralization, heavy mononuclear cell infiltrate and foci of necrosis and hemorrhage; mild arteritis
• Amnionitis may be present without placentitis (Foster, Pathologic Basis of Veterinary Disease, 1181)
• Fetus: Well preserved, non-suppurative pneumonia; prominent peribronchiolar lymphoid tissue, erosive conjunctivitis
• Lymphoplasmacytic vulvitis and salpingitis

ADDITIONAL DIAGNOSTIC TESTS:

• Culture required for definitive diagnosis
• Culture techniques are stringent because of the fragile nature of the organisms
• PCR

DIFFERENTIAL DIAGNOSIS:

• Bacterial placentitis:
  • Brucella abortus (R-B03): Necrotizing placentitis; fetal bronchopneumonia; necrotizing arteritis, hepatitis, splenitis, and nephritis
  • Coxiella burnetii (R-B07): Acute, diffuse, suppurative placentitis with extensive necrosis of cotyledonary villi and intercotyledonary epithelium
  • Chlamydia abortus (R-B08): Necrotizing placentitis with cotylendonary and intercotylendonary lesions; marked vasculitis; Chlamydophila inclusions
• Mycotic placentitis (R-F01):
  • Aspergillus fumigatus is the most frequent cause of mycotic placentitis in cattle, amnion may appear thickened and white to yellow

COMPARATIVE PATHOLOGY:

1. diversum in other species:

• diversum: Associated with pneumonia, conjunctivitis, mastitis, vulvovaginitis and infertility in cattle, horses, swine, dogs and cats
• Sheep: Transmitted venereally and causes infertility, low birth rates, abortion

Other Ureaplasma spp.

• Mycoplasma dispar (with Ureaplasma): Associated with "cuffing" pneumonia of calves
• gallorale: Infertility in poultry
• urealyticum: Human endometritis, infertility, low birth weights and abortions; frequently isolated from the vaginal flora

REFERENCES:

1. Carli SD, Dias ME, da Silva M, Breyer GM, Siqueira FM. Survey of beef bulls in Brazil to assess their role as source of infectious agents related to cow infertility. J Vet Diagn Invest. 2022;34(1): 54-60.
2. Foster RA. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1179, 1181.
3. Lopez A and Martinson SA. Respiratory System, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:552.
4. Schlafer DH, Foster RA. Female Genital System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:399-402, 411-416.

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