THE REPRODUCTIVE

SYSTEMPATHOLOGY
 Female
reproductive
system pathology
• The reproductive system in veterinary medicine is
fairly complicated.

• The differences in the reproductive system between

the sexes and among species are complex.

• The temporal and physiologic features of the

reproductive cycle vary greatly among species.
•
• And, with pregnancy, there are SO MANY changes.
• The reproductive system consists of
 the gonads (testes or ovaries),
produce the gametes (sperm or ova),
and
duct system to the external
environment.
Associated accessary glands
 Sexual differentiation:
• Chromosomal sex (genetic sex) is normally determined at fertilization
by the formation of either an XY or XX zygote. XX are genetic females and
XY are genetic males.

• Gonadal sex means – development of testes or ovaries? Well, if there is a

Y chromosome, the gonads become testes.
– The Y chromosome has an SRY (Sex-Determining Region on the Y
chromosome) gene that codes for Testis-Determining Factor (TDF) and
that is what urges the primordial genderless less gonad to become a
testis. Without TDF that primordial sex-less gonad eventually goes
female (ovary).

• Phenotypic sex - does it LOOK like a male or a female? Phenotypic sex is

determined by the male gonad (or absence thereof).
– Testicular tissue secretes Müllerian duct inhibitory substance (MIS) that
causes the Müllerian ducts to regress and the Wolffian ducts to
continue development, into the vas deferens and epididymis.
– Then testosterone from the Leydig cells of the testis helps with all the
other features of being male.
– Without testes producing MIS or testosterone, the Müllerian ducts
continue to develop into uterus and oviducts and the Wolffian ducts
regress.
Intersex/ Hermaphrodite
• It is any combination of two sexes in one individual due
to genetic problems, chromosomal abnormalities, or
inappropriate hormone exposure or unknown reaso.
• Hermaphrodite and intersex are more or less
synonymous.

• Hermaphrodites represents a broad grouping and general

term just means animals that have some of the
characteristics (genetic, gonadal, phenotypic) of both
sexes.

• A true hermaphrodite has both ovarian and testicular

tissue - at least one gonad containing ovarian and testicular
tissue (i.e. an ovotestis) or has one male and one female
gonad and exhibits anomalies of the external genitalia.
RARE condition
 Freemartin

• It is intersex condition seen in cows. A freemartin is a sterile

female with underdeveloped ovaries born co-twin to a male.

• In cattle with multiple conceptions, the placental blood vessels

usually fuse so that a common circulation develops between the
fetuses.

• There is “sharing” of cells due to these anastomoses resulting in

permanent colonization of the female with cells from the male that
express small amounts of TDF (testis determining factor), inhibiting
ovarian development.

• In addition, MIS and testosterone secreted by the male inhibit

development of the female tract.

• This condition has been documented in dogs, pigs, goats, and mice.
 Ovary disorders
• Once an animal starts
cycling, the size and
form of the ovaries are
altered by secretion of
hormones from the ovary
itself as well as the
pituitary and
hypothalamus.
 DISEASES OF THE OVARY
Disorders of development:
• Ovarian agenesis (no ovaries): This condition is
most often seen in ruminants, pigs, and dogs.
Ovarian agenesis can affect one or both ovaries
and the associated tubular genitalia may be
absent or underdeveloped.

• Ovarian hypoplasia and ovarian dysgenesis:

Small, misshapen ovaries and usually the tubular
tract is also a underdeveloped and weird. This
condition is seen most often in horses, it is
Turner’s syndrome. Animals genetically are XO.

• Ovarian remnants (misplaced bits): Sometimes

 Inflammation and Ovarian Cysts

• Oophoritis is ovarian inflammation. This condition is rare in most

species and is usually due to a systemic bacterial infection.

Ovarian Cysts
• Many types of cysts occur in or around the ovary. These include cysts of
the ovary itself, of the fimbria, and mesonephric duct cysts
(developmental remnants).

• Cystic ovarian disease comes in two types – cysts composed of

follicles or cysts that are corpora lutea. The presentation and
clinical problems are very different. In one case, there is way too much
estrogen (follicular cysts) and in the other case there is too much
progesterone (cystic CL). Clinical signs vary – with the former there can
be prolonged estrus-like behavior OR anestrus, and with the latter, it is
usually anestrus.

• Paraovarian (Cysts around the ovary)are pretty common in horses.

They arise from embryonal remnants of other stuff. They usually do not
 Ovarian neoplasia
• What are the kinds of cells that can become neoplastic
in the ovary?
– Surface epithelium – these are adenoma/carcinoma;
– follicular lining cells - these are granulosa/theca cell
tumors; and germ cells

• Ovarian adenoma/ adenocarcinoma: These can

occur in all species, but are most common in the dog.
Adenocarcinomas can implant on the peritoneum

• Granulosa cell tumors: These occur in the horse,

the dog and the cow. The tumors can get really
LARGE! In mares, sometimes these tumors produce
testosterone and the mare acts like a stallion. Because
almost all these tumors are benign, surgical
removal of the affected ovary is generally curative.
 Teratoma: These tumors
originate from germ cell
tumors that come from a
single germ cell that has
completed its first meiotic
division. As a result, they can
act as stem cells and have
tissue of more than one
embryonic germ layer.

These tumors can be really

wild, containing hair, bits
of bone, teeth, etc. They
are usually benign but rarely
can be malignant.
 Uterus and cervix
• The uterus of domestic mammals is composed of
two horns, a body and a cervix.
– Histologically it is divided into the endometrium,
containing endometrial glands, and the myometrium
(whichis the muscle) and perimetrium
– The main function to produce a protective environment
for the conceptus in cases of pregnancy.
– 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.
 Noninfectious diseases of the uterus:
• Müllerian duct development arrest (segmental
aplasia) leads to a variety of deformities:
• Imperforate hymen. The hymen forms where the
paramesonephric duct merges with the urogenital sinus.
There is a slight ridge or extra flap of tissue here as a
result. For those animals with the least perfect fusion, the
hymen is a flap of tissue that stretches to cover the caudal
vaginal lumen. With complete obstruction by the hymen,
secretions accumulate anterior to the obstruction and may
result in development of a fluctuating swelling.

• Segmental aplasia of the cervix may result in

mucometra (uterus fills with mucus) or cystic enlargement
of the cervix.

• Double external os of the cervix occurs when Müllerian

ducts don’t fuse. There may be a band of tissue caudal to,
or in, the external os of the cervix.
 Uterine placement problems
• Uterine torsion: Twisting of uterus
• This condition is seen in all species, but is most common in cattle.
– Cattle have a well developed intercornual (between the two horns) ligament so
when one horn twists, the whole uterus twists.
– secondary to pregnancy, hydrometra, or pyometra, i.e., something making
the uterus HEAVY.
– Multiparous species without an intercornual ligament (dog, cat) may have only
one horn or part of a horn twist.
– Twists over 180 degrees result in obstruction of veins, uterine infarction
and fetal death

Uterine prolapse: expulsion of uterus to the external environment

• most common in dairy cows and ewes which occurs immediately after or within
several hours of parturition
• contributory causes:
– Recumbency with the hindquarters lower than the forequarters,
– excessive traction to relieve dystocia or retained placenta, uterine atony or
hypotony, postparturient hypocalcemia, and
– consumption of legumes with high estrogen content, have all been incriminated
Prolapse of the uterus almost invariably
• Occlusion of the vasculature as a result of the heavy uterus dangling out the hind
end leads to infarction, necrosis and in some cases even gangrene.
 Fluid and glandular problems

• Cystic endometrial hyperplasia (CEH): This

condition is most important in the dog. It is part of a
continuum - cystic endometrial
hyperplasia/pyometra.

• In the dog the luteal phase is quite long, so there can

be lots and lots of progesterone for quite a while after
an estrogen surge and this might be what makes
dogs so particularly susceptible to this problem.

• The uterus makes abundant mucus and if bacteria

get in, they can grow very well and create pus.
• Hydrometra/ mucometra: The uterus is filled with thin or
viscous fluid. This condition is often associated with cystic
endometrial hyperplasia. The other main cause is aplasia of
some part of the caudal tubular tract resulting in trapped
secretions.

• Hydrosalpinx: Distention of the uterine tube with fluid, usually

due to obstruction, such as with segmental aplasia, or following
uterine irrigation in cattle causing inflammation and adhesion
formation.

• Subinvolution of placental sites (SIPS): This condition is

seen almost exclusively in dogs. Normally uterine bleeding
should stop 7 to 10 days after whelping. With SIPS, dogs may
bleed for weeks or months, and develop severe anemia and
sometimes fatal blood loss. After parturition, the trophoblasts
just keep tunneling through the endometrium, and eventually
erode through to cause hemoperitoneum.
Inflammation of the uterus/ uterine tube
Salpingitis
• Inflammation of the uterine tube (Fallopian tube/ oviduct).
• Usually an extension of endometritis and/or metritis.
– The poor oviduct - it is small and fragile and any kind of
inflammation is likely to lead to scarring and obstruction. When
this happens, the eggs cannot get to where they need to go to
get fertilized.
• Pyosalpinx: Oviduct filled with pus. NOT common.
• The majority of inflammatory lesions of the uterus begin
in the endometrium as endometritis

• Endometritis: Inflammation of the endometrium only

(doesn’t go through to the muscle wall). Animals are not
SICK, just can’t support a pregnancy.
– Chronic endometritis gets fibrotic, and glands are often
atrophied. Periglandular fibrosis may result in cystic glands.
Can result in infertility. This is a big problem in MARES
• Pyometra: Pus filled uterusis. Seen in the dog,
cat, and cow and rarely sheep.
– The uterus can be mildly to severely distended and
filled with pus or foul smelling fluid.
– The endometrium is thickened, necrotic, and
ulcerated, in addition to being hyperplastic and
cystic.
– The serosa is congested.
– The wall is friable and may rupture.
– Animals are very sick.

• Metritis: Inflammation of the ENTIRE uterine

wall (endometrium and myometrium)
– It might START OUT as endometritis
– Uterus is FLACCID and Animal is SICK.
 Neoplasia of the Uterus/
Oviduct
Leiomyoma/Leiomyosarcomas
• This is a benign and malignant smooth muscle tumor of uterus, cervix,
or vagina that occurs in all animal species but is most common in the dog.
• The malignant form is less common than their benign counterpart.
Fibropapilloma
This tumor affects the vulva of young cows. They are caused by infection with
bovine papillomavirus. The masses are sessile and round to cauliflower like,
basically “warts”.

Uterine adenocarcinoma
• These tumors can occur in all species, but are particularly common in old
domestic rabbits and chickens.
Lymphosarcoma
• This is the most common uterine neoplasm in the cow. Probably also the
most common neoplasm in cows, period. It can be part of multicentric
bovine lymphosarcoma or of primary uterine origin.
Vulvar squamous cell carcinoma
• most often seen in cows, horses, and ewes. They are typically locally
aggressive, but are slow to metastasize to regional lymph nodes.
Transmissible venereal
tumor
• This is a transmissible tumor that can be seen in
all canidae including dogs, jackals, foxes, and
coyotes

• TVTs are macrophage origin tumors with an

abnormal chromosome number, i.e., different
from the regular dog number of chromosomes.
• It is transmitted by close contact including
sexual, from one host to another.

• Clinically, there are one or more expansive, and

often ulcerated and friable masses.

• The neoplasm normally regresses over several

months and this regression is associated with T
lymphocyte infiltrates so presumably the
immune system eventually recognizes the cells
as foreign and kicks them out
 Diseases of the Pregnant
Uterus
• Loss of embryos or Early Embryonic Death
(EED)
• Death can be before you even know there is a
pregnancy (30-35 days in large animals) or early
embryo life

• 30% of pregnancies in all species are terminated by

EED, and that the cause of MOST of these are
chromosomal abnormalities.

• There is delayed return to estrus and large animals

may be “open” at pregnancy palpation
 Fetal death
• Fetuses that die a little bit later may be mummified, macerated, or
aborted.

Mummification -
• In mummification, the dead fetus just slowly desiccates and shrinks
and can look like a big very dry glob at parturition. It is sterile.
• usually happens in multiparous species - one of the fetuses dies but
the others maintain the pregnancy.
• There is no bacterial infection.
Maceration
• the fetus would be macerated consisting only of fluid and fetal
bones (wet and gooey due to the action of the bacterial enzymes).
• Similar to mummification, except that there is a bacterial infection
Abortion
• Defined as the expulsion of a fetus prior to the time of expected
viability.

Stillbirth
• dead fetus delivered within the period of expected viability.
• Retained placenta: If the placenta
is not expelled with 12 hours in the
cow, and 2 hours in the mare, it is
considered retained. All that
nutritious material AND an open
cervix – what bacteria could possibly
resist? A retained placenta can
predispose to infection and systemic
complications.
 Infectious causes of abortion,
by species
 Brucella abortus
 Bovine herpesvirus 1
 Tritrichomonas foetus:
 Bovine virus diarrhea
 Toxoplasmosis
 Coxiella burnetiiis
 Brucella melitensis

• Check out in different species: bovine,

caprine, ovine and equine
 Quiz
1. What is freemartinism?
2. What is uterine prolapse?
3. What is teratoma?
4. What is maceration
5. ____________ is tumor of smooth muscle
cells of uterus
Male reproductive
pathology
• The male reproductive system consists of the testes,
duct system and associated glands.

• The testes perform two major functions: the

production of sperm the secretion of steroid hormones
(like testosterone).

• The temperature within the scrotum is approximately

2-4°C lower than that of the abdomen.

• Elevated temperature affects spermatogenesis

because it impairs enzyme systems of the mammalian
testes
• The pampiniform plexus is a thermoregulator for
testicular function
• Tunica vaginalis: This is an extension of the
peritoneum into the scrotal sac
– so anything that affects the peritoneum can affect the
tunic vaginalis. Peritonitis, fills with fluid, hydrocoele,
herniation of abdominal viscera, especially intestines

Testicular hypoplasia:
• occurs in all species, but is most common in cattle,
sheep, and goats.
• The hypoplastic testis may be unilateral or bilateral
and 25% normal size and is freely movable in the
scrotum.

• Histologically, the seminiferous tubules are small

and lined by Sertoli cells alone or Sertoli cells and
stem cells/ spermatogonia showing little to no
mitotic activity.
• Cryptorchids is retain one or both testes somewhere
along the path of descent.
– The undescended, retained within the abdomen, testicle may
be located anywhere from just caudal to the kidney to within
the inguinal canal.
– Such a testis suffer thermal suppression of spermatognesis

Sperm granulomas
• Sperm are NOT recognized by the body as self so if they
escape from the tubular structures to which they are
supposed to be confined, there WILL BE a foreign body
reaction!

• The causes of sperm getting out - obstruction,

inflammation with rupture, and congenital
malformations.

• The body’s response to sperm outside of the seminiferous

tubules is a granulomatous reaction which can in turn
 Testicular degeneration
• Testicular degeneration and atrophy are the most
common cause for infertility in males (unilateral or
bilateral)

• There are a large number of causes including:

– ionizing radiation
– temperature extremes
– trauma/inflammation/ infection (local or systemic disease)
– vitamin A deficiency
– zinc deficiency
– occlusion of spermatic vessels (spermatic cord torsion)
– blockage of epididymis and increased pressure or formation of
sperm granulomas
– toxins (chlorinated naphthalenes, amphotericin B, gentamicin,
carbamates, cyclophosphamide, locoweed, some mycotoxins)
– hormonal problems (neoplasms of the hypothalamus and pituitary,
hypothyroidism, diabetes mellitus, Sertoli cell tumors that produce
estrogen)
– Advancing age
 Infectious diseases of the testis/
epididymis
Bacterial orchitis/epididymitis
– Orchitis is rare in all domestic species. Epididymitis is slightly more
common.
– In domestic animals, Brucella is often the most common cause of
orchitis/epididymitis (Brucella canis, Brucella abortus, Brucella
melitensis).
Neoplasm of testis
• Cells of testis include:
– Sertoli cells (these are the cells that line the tubules)- secrete small
amounts of estrogen,
– Interstitial cells (Leydig cells), these secrete testosterone), and
– Germ cells: Spermatogenic cells
What kind of tumors do they make?
– Interstitial cell tumors, Sertoli cell tumors, and seminomas.
– All are very common in dogs, especially old dogs and all three equal
frequency
– incredibly common in retained (cryptorchid) testicles
– They are all mostly BENIGN
 Accessory sex glands

• Accessory sex glands include: prostate gland,

bulbourethral gland, and seminal vesicles

• All function for the same reason - to supply the

fluid part of the semen.

• There are very few diseases associated with

the accessory sex glands.

• Seminal vesicles are most important in

ruminants and stallions; and prostate in the
dog and cat
Conditions affecting the accessory sex glands:
Seminal vesiculitis:
• Rare, seen most commonly in bulls and stallions.

Prostatic hyperplasia:
– PROSTATE gets many problems, mostly in DOGS
– Usually occurs due to too many androgens. So, there might be a
Leydig cell tumor in the testes!
– It causes constipation, and can interfere with urination.
– The gland is diffusely enlarged up to 4X normal size and may be
nodular or have cystic areas.

• Prostatitis : occurs when bacteria from the urinary tract move in

• Prostatic cysts: Big fluid-filled cavities in the prostate happen in
association with hyperplasia, neoplasia or prostatitis. Can
interfere with defecation.
• Prostatic carcinoma: Carcinomas of the prostate gland occur in older
dogs. Grossly, an asymmetrically enlarged prostate is the most common
finding.
 Noninfectious conditions ofthe
penis/ prepuce
• Congenital hypoplasia: An underdeveloped prepuce and penis
may be associated with hermaphroditism, associated with
shortening of retractor penis muscle or by early castration.

• Directional “deviations” of the penis: Persistent penile

frenulumis a common cause of penile deviation in bulls.
– This condition can also be seen in boars, dogs, and rarely other species.
– Congenital curvature of the os penis can cause deviations in dogs.

• Hematomas: These can be from rupture of the corpus

cavernosum or external trauma. It happens in young bulls and
stallions.

• Paraphimosis: This is the inability to retract the penis in to

the prepuce.
– It is seen most commonly in stallions associated with trauma, but any
other cause of inflammation, neoplasia, or paralysis of the penis can
cause paraphimosis.
– Phenothiazine tranquilizers (chlorpromazine especially) can also cause
paraphimosis.
 Infectious diseases of the penis/
prepuce
• Balanoposthitis is inflammation ofthe glans penis and
prepuce. (Balanitis is inflammation of the penis and posthitis is
inflammation of the prepuce.) The following are some causes:

 Equine coital exanthema, infectious balanoposthitis

(BHV-1), and dourine were already covered under
venereal diseases in the female. Each can cause
lesions on the penis and prepuce.

 Ulcerative posthitis: This is seen in sheep, rarely in

bulls. it may be due to incomplete development of the
penis and prepuce, and tendency for wethers to
accumulate urine in the sheath. Also called “sheath rot”,
it is caused by corynebacteria.
 Neoplasia of the penis/ prepuce
• Fibropapilloma:
– These benign tumors are seen in young bulls, 1 to 2
years of age.
– They are caused by bovine papillomavirus type 2 and
are usually located on the glans penis. They can
interfere with the movement of the penis - both
retraction and protrusion.
• Squamous papilloma: These benign tumors are
most common in the horse. There is also a
transmissible genital papilloma of swine caused
by papillomaviruses.
• Squamous cell carcinoma (SCC): Genital SCC
is most common in the horse, but also occurs in
dogs, and in cattle.
– Ulcerative and proliferative lesions extensive and cover
most of the glans.
 Mammary Gland

• Developmental disorders -
• Supernumerary teats or nipples are fairly
common in many species. In cattle, as many as
30% of
• animals may have additional teats! Horses are
the only species in which the male does not
develop teats at all.
Bovine mastitis
• The normal skin of the mammary gland and
teathave regular population sof bacteria which
probably help to maintain an ecologic balance.
Mammary tumors (Reading assignment)

• Mammary masses are very common

in dogs and to a lesser extent, cats,
but are rare in all other species.
THANK YOU!!!