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C.L.Davis Foundation
Gross Morbid Anatomy of Diseases of Animals
DISEASES OF THE FEMALE REPRODUCTIVE TRACT
C.D.Buergelt, University of Florida
Female Tract Anomalies
Female hypogonadism may be acquired or congenital. Inflammation, chemotherapy
with cyclophosphamides or radiation may destroy the function of a cyclic ovary.
Congenital ovarian hypoplasia 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 (Muellerian)
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 didelphys
Failure of proper fusion of the caudal portions of the paramesonephric (Muellerian)
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 patter. 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
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 becomes
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
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.
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 exraluminal 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.
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.
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.
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.
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 Camylobacteriosis
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.
Cystic Endometrial Hyperplasia-Pyometra Complex in the Bitch
This condition is one of the most important endocrine disorders in the bitch. It is a
complex polysystemic disease that occurs in nulliparous animals after prolonged
priming of the endometrium by estrogens that upregulate isoreceptors for progesterone.
The genital lesions are the result of prolonged hormonal dysfunction followed by
bacterial infection. The disease initially develops during the luteal phase of the ovarian
cycle and is precipitated by repeated estrous cycles that are not interrupted by
pregnancy. In the initial phase of the complex, hyperplastic endometrial glands are
distended as cysts . Later on the hyperplastic glands and the lumen of the uterus fill up
with neutrophils.
Subinvolution of Placental Sites.
The condition occurs in young bitches postpartum and leads to persistent hemorrhagic
vaginal discharge. It can be confused with pyometra. It is the result of retention of
trophoblasts within the endometrium, myometrium and perimetrium. Recovery may be
spontaneous, though peritonitis sometimes results as complication.
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
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 amd may interfere with breeding practices. The condition
has to be differentiated from IPV.
Venereal Spirochetosis
This venereal disease of rabbits is caused by Treponema cuniculi, a spirochete. It
causes clinical signs in both female and male rabbits. The prepuce and vulva near the
mucocutaneous junction are the most comon sites of lesions. These vary from
erythematous macules, papules or nodules to erosions,ulcers and crusts.
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.
Polyp. The vaginal polyp or fibroid in the bitch is a benign tumor which is dependent
upon estrogenic stimulation for its formation. The tumor is often pedunculated.
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.