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C.L.Davis Foundation Gross and Morbid Pathology C.D.Buergelt, DVM DISEASES OF THE FEMALE REPRODUCTIVE TRACT Female Tract Anomalies Inflammation, chemotherapy with cyclophosphamides or radiation may destroy the function of a cyclic ovary. Congenital ovarian hypoplasia Female hypogonadism may be acquired or congenital. The condition may affect one or both ovaries and there may be partial or complete ovarian dysfunction. The condition of ovarian hypoplasia is also described as “streak hypogonadism”. Segmental aplasia The condition may affect various portions of the paramesonephric duct (Mullerian) system. Segmental aplasia has been most extensively studied in White Shorthorn cattle in which the defect is caused by a recessive gene linked to the one which is referred to as “White Heifer Disease”. Uterus didelphis Failure of proper fusion of the caudal portions of the paramesonephric (Mullerian) ducts may result in double vagina, double cervix or a divided uterine fundus. If only the caudal portion of the cervix is involved, there will be evidence of duplication of the external os and the cervical canal may be bifurcated to varying degrees. Ovary and Oviduct Basic Function and Response of the Ovary to Injury Ovarian function is twofold: (I) to produce mature eggs and (ii) to provide hormones that regulate the reproductive tract and secondary sex changes and that allow mating to occur. Neither the gametogenic nor the endocrine functions are continuous; they occur in a cyclic pattern. Cyclic variations are regulated by the pituitary gland, ovaries and uterus. The intervals are called estrous cycles in subprimate species and menstrual cycles in man and other primates. The hormones produced by the cycling ovary are estrogens, progesterones, androgens, oxytocin and relaxin. Each of these hormones has a specific effect on specific target organs. Unlike the testis, the ovary appears relatively resistant to injury whether from infectious agents, toxins, nutrient deficiencies or immune over reactivity. On occasion, viruses such as that of African Swine Fever, or compounds such as zearalenone, may exert 1 some destructive or prolonging effects, respectively, on ovarian corpuscles such as porcine corpora lutea. The mammalian ovary is vulnerable to sex chromosomal abnormalities, endocrinopathies, radiation and chemotherapeutic agents. Ovary; mare. Cut section. In contrast to those of other domestic animal species, the mare’s ovary has different morphological and functional features. The medulla lies external to the cortex. The mare ovulates from the ovulation fossa. The follicles grow toward the ovulation fossa at the time of ovulation approaches. The Graafian follicles of the mare’s ovary become quite large prior to ovulation. They may be as large as 3-6 cm in diameter and should not be confused with cystic follicles which apparently do not occur in this species. The texture of the equine ovary is firm due to a very fibroblastic stroma. Several corpora lutea may develop during certain phases of gestation in the ovary of a pregnant mare. Ovarian Cysts Approximately 16 types of ovarian cysts occur in or around the ovary. These include congenital cysts derived from mesonephric duct remnants. Knowledge of the size of the normal mature follicle is needed in order to make the diagnosis of a pathologic cystic condition. Histologic examination and special staining of the wall lining cells of the cystic structures is mandatory for appropriate classification. Some controversy exists in the literature relative to the histologic structures of the cyst walls. Parovarian Cysts These arise from remnants of the mesonephric tubules and ducts. The anterior mesonephric tubules give rise to cysts referred to as epoophoron. The cysts may vary in size from a few millimeters to several centimeters in diameter. They are filled with a clear fluid. They frequently occur in horses and may be already present in the neonate. Bursal Cysts This type of cyst develops from adhesions of the fimbria to the ovary and contains fluid from the tube that flows into the bursa to cause distension. Tubo-ovarian Cyst In cases of salpingitis, clear fluid accumulates in the proximal parts to reflux into the bursa. The cranial portion of the uterine tube distends cystically. Cystic Graafian Follicle This is the most frequently recognized form of intraovarian cystic degeneration. The condition commences during estrus and is associated with a failure of release of luteinizing hormones. The mature follicle is not stimulated to rupture and instead increases via fluid accumulation. In the cow, chronic cysts may lead to the development of uterine hydrometra or mucometra. Affected cows may show anestrus, irregular estrus or signs of nymphomania. Intraovarian Cysts 2 In the sow, follicular cysts may be a cause of infertility. There may be single cysts. If there are multiple cysts, these usually persist. Multiple cysts are a distinctive feature of cystic ovarian disease of swine. Ovarian Tumors Primary ovarian tumors are frequently classified on the basis of morphology, clinical behavior and malignant potential rather than histogenesis. They are described in all domestic animal species, but appear most commonly in the cow, mare and bitch. Granulosa Cell Tumor Eighty percent of the mare’s ovarian tumors are granulosa cell tumors. They are usually unilateral, polycystic, larger than a grapefruit when detected and benign. Many granulosa cell tumors are hormonally active, and most are estrogenic. They produce hormones which result in behavioral abnormalities and changes in the estrous cycle. Surgical removal of the affected ovary is generally curative. Metastases have been reported on occasion. In cattle, these are usually benign and unilateral. They can be solid or cystic. Nymphomania is observed in many of the cases; others lead to bull-like behavior. Cystic endometrial hyperplasia of the uterus is another sequel to the presence of a granulosa cell tumor. Solid and cystic variants of granulosa cell tumors may arise in the ovaries of cows. These tumors also occur in dogs. Serous Cystadenoma These are rare, unilateral tumors that do not metastasize. They apparently do not secrete sufficient amounts of hormones to interfere with reproductive behavior. As in the granulosa cell tumor, the affected ovary is composed of polycystic structures which contain clear fluid. Benign Teratoma These have been reported to occur with some frequency in zebu cattle (Bos indicus). Otherwise they are rare and usually present in young animals. Again, the tumor is composed of multiple tissues foreign to the organ in which they arise. Dysgerminoma This tumor is the counterpart of the testicular seminoma. It is of germ cell origin and can be quite large, solid and lobulated. Metastasis may occur in 10% of the cases. The tumors have been found in canine and caprine ovaries. Epithelial Tumors Papillary adenocarcinomas are considered to be of epithelial (coelomic) origin and arise from the surface epithelium of the ovary. They constitute 45% of all canine ovarian tumors. This type of tumor is frequently bilateral and invades the ovarian bursa to implant onto the abdominal peritoneum. It leads to ascites from blockage of lymphatics. 3 Secondary Tumors Lymphosarcomas may be diagnosed in enlarged ovaries of cows and cats. Uterine Tube The uterine tube (oviduct, fallopian tube) is the site of fertilization. The embryo remains for 3 to 4 days in the uterine tube to be transported into the uterus. The structure is divided into infundibulum, ampulla and isthmus. The epithelial lining produces and secretes the uterine tube fluid. Lesions associated with uterine tube include congenital malformations, fluid distention and occlusions due to inflammation. Hydrosalpinx Intraluminal occlusions from inflammation or extraluminal adhesions may lead to blockage and fluid accumulation. Concurrent oophoritis and endometritis may exist. Pathogens to induce hydrosalpinx and salpingitis in cattle include Ureaplasma spp., Mycoplasma spp., Campylobacter spp., Tritrichomonas spp. and others. Function and Response of the Uterus to Injury The uterus of domestic animal species is composed of two horns, a body and a cervix. Histologically it is divided into the endometrium, containing endometrial glands, the myometrium and perimetrium. The main function of the uterus is to produce a protective environment for the conceptus in cases of pregnancy and to function as a target organ in response to hormones released by the ovary. The uterus itself is capable of interacting with the ovary via luteolytic substances, mainly prostaglandins produced by the endometrial glands. The non-gravid uterus is relatively resistant to infection while under the influence of estrogen. The cervix provides an efficient protective barrier for the uterus. The normal cervix is closed during the luteal phase of the cycle and is patent during estrus. Local antibody production and phagocytosis via opsonins are important defense mechanisms in limiting the duration of uterine infections. Cytokines play important roles as autocrine and paracrine regulators. In ruminants, the best described such example is the role of interferon-gamma in the reproductive tract. The normal endometrium is capable of mounting a local response to invading pathogens, thereby maintaining a sterile environment. To initiate immune response, it is necessary to have cells present for antigen recognition and presentation to immunoregulatory lymphocytes and macrophages. Endometrial lymphocytes are intraepithelial lymphocytes with functional characteristics similar to those in the gut. Females treated with progesterones are more likely to develop infections after intrauterine installation of bacteria. Progesterone inhibits endometrial lymphocyte proliferation and myometrial contractility. 4 Inflammation The majority of inflammatory lesions of the uterus commences in the endometrium as endometritis and is associated with either parturition or mating. Infectious agents may enter the uterus as ascending infection from the caudal parts of the reproductive tract, or hematogenously. Ascending infection occurs especially in the mare. Postpartum Endometritis Postpartum endometritis is more common than postcoital endometritis/metritis. There is usually severe destruction of the endometrium allowing for sepsis to occur. Venereal Campylobacteriosis Postcoital infection with Campylobacter fetus venerealis is relatively rare and leads to a rather inconspicuous endometritis macroscopically. The organisms interfere with conception, and cause embryonic death as well as abortion. Trichomoniasis This venereal infection on occasion may lead to pyometra. Tritrichomonas foetus occurs more frequently as a venereal infection in cattle. The organism is also responsible for early embryonic death, abortion, and postcoital pyometra. Contagious Equine Metritis (CEM) This venereal infection of horses is caused by Taylorella equigenitalis. The lesions in the cervix and vestibule are characterized by hyperemia and edema. The disease is manifested by a copious mucopurulent vaginal discharge. Periuterine Abscess Fairly large abscesses (arrow) can be found in, and close to, the uterus of cattle. Actinomyces pyogenes is a common pathogen involved. Cystic Endometrial Hyperplasia This condition may develop endogenously secondary to follicular ovarian cysts or granulosa cell tumors. Pastures with estrogen-containing plants are an exogenous source for cystic endometrial hyperplasia to develop in ruminants, especially in ewes. Canine Cystic Endometrial - Hyperplasia Complex. This disorder is a complex, polysystemic disease occurring in nulliparous dogs after prolonged priming of the endometrium by estrogens that upregulate the isoreceptors for progesterone. The initial phase is characterized by cystic endometrial gland hyperplasia, followed by the development of pus in the uterine lumen and by complication of bacterial infection as the cervix remains closed. Extragenital disorders associated with pyometra are the result of toxemia and bacteremia and include immune-mediated glomerulitis, bone marrow depression, anemia and leukocytosis. 5 Tumors of the Uterus Primary tumors of the female tubular genitalia are comparatively rare in domestic animal species as compared to humans. Both epithelial and mesenchymal tumors have been reported in domestic animals. Endometrial Biopsy In the mare, the procurement of endometrial tissue for a biopsy specimen is a procedure recommended to assess fertility. Endometrial biopsy techniques have been reported to be of diagnostic and prognostic value in assessing the mare’s ability to conceive, and in carrying a conceptus to term. The endometrial biopsy should be evaluated in conjunction with the mare’s history, clinical examination and other diagnostic tests, including ultrasound and microbiology. Adequate tissue samples and experience by the individual reading the biopsy are prerequisites for a meaningful interpretation of the endometrial biopsy. Several classification schemes have been developed. The most widely used is the grading system established by Kenney in which category I endometrium is essentially healthy tissue; category II includes either inflammation or fibrosis; category III is associated with widespread pathologic changes that drastically reduce the chances of foaling. Grading systems have also been established for bovine endometrial biopsies, but clear criteria predicting reproductive performance have not been established. For the interpretation of any endometrial biopsy in the mare, various factors have to be taken into consideration; these include stage of estrous cycle, ovulatory and anovulatory season, age of the animal, sites of the biopsy, changes associated with the procurement of the tissue samples and fixation. Pathologic changes that determine grading categories for the mare generally are inflammation, periglandular fibrosis, nonseasonal atrophy and lymphatic lacunae. EXTERNAL GENITALIA Vulvular Tumefaction This condition in swine is due to feeding moldy grain contaminated with Fusarium sp. The fungi apparently produce estrogenic metabolites that are responsible for the swelling of the vulva in young gilts. Vaginal prolapse may occur in some cases. Infectious Pustular vulvovaginitis (IPV) This highly contagious venereal disease of cattle is caused by the bovine herpesvirus-1 , the same virus that causes infectious bovine rhinotracheitis. The virus can produce 6 similar lesions on the surface of the penis in bulls. Granular Vulvovaginitis The infection with Ureaplasma diversum can induce diffuse hyperemia and granularity of the vaginal mucosal membranes. It is a painful condition that is associated with a purulent vaginal discharge and may interfere with breeding practices. The condition has to be differentiated from IPV. . Neoplasia Fibropapilloma. This genital wart is caused by the bovine fibropapilloma virus and is the counterpart of the penile lesion in the bull. It affects young animals primarily. Squamous Cell Carcinoma. This growth is the female counterpart of the penile or preputial squamous cell carcinoma seen in the male. It is locally invasive and can be encountered in dogs and horses. Transmissible venereal tumor. Behaves as in male dogs. 7