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DOI: 10.1177/030098588702400408
1987 24: 335Vet PatholL. S. F. Keller, J. W. Griffith and C. M. LangReproductive Failure Associated with Cystic Rete Ovarii in Guinea Pigs
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Vet. Pathol.
24335-339 (1987)
Reproductive Failure Associated with
Cystic Rete Ovarii in Guinea Pigs
L.
S
F.
Keller,
J.
W .
Griffith,
and
C.
M.
Lang
The Pennsylvania State University, The Milton
S.
Hershey Medical Center, and
Department of Com parative Medicine, Hershey,
PA
Abstract Cystic ovaries were found at necropsy in 54 of
7
1 (76 ) female guinea pigs between 18 and 60
months
of
age. Histologic appearance and loca tion of the cysts within the ovary were consis tent with cystic rete
ovarii. Microscopic appearance of the large ovarian cysts suggested reprodu ctive performance in these guinea
pigs shou ld be comprom ised. Breeding records indicated that fertility was marked ly reduced in affected fem ales
over fifteen months of age. Cystic endome trial hyperplasia, mucom etra, endom etritis in ap propria te placental
tissue, or fibroleiomyomas were seen in
21
of 54 (39 ) guinea pigs with cystic ovaries, but in only one of 17
(6 )
guinea pigs without cystic ovaries.
Ov arian cysts are co mm on in aged rats ,22 guinea
pigs,24.26.33 ca ttle ,27 an d wo men .25
The se cysts are usually
derived
from ovar ian follicles,
corpora lutea, ova rian surface epi thel ium, remn ants of
the mesonephr ic and paramesonephr ic duc ts ,
or rete
ovarii.9.17.22.24-27.31.33h e
rete
ovari i is a homologue of
the rete testis an d has been described as a norm al s truc-
ture in numerous species of
mammal^.^^.^^
The rete
system in most mammals consists of three parts : 1)
the extraovarian rete ,
2)
the connecting rete,
and 3)
t he
in tra ov aria n ~ e t e . ~he intraovarian rete tubules
are
l ined by cuboidal epi thel ium while the connect ing a nd
extraovarian rete o vari i are l ined by ci l ia ted colum nar
epithelium.8 All rete cells contain dense rete bodies
t h a t r e s e m b l e m i c r o p e r o x i s o m e s ' 8 ~ ' 9 n d p e r o x i-
somes.'
Cystic changes in the m am ma lian ova ry need to be
studied since they may cause infertility in aging lab-
ora tory and domest ic an imals and in Cys-
tic ovarie s were diagnosed
at
necropsy in female guinea
pigs from a single breeding colony with low rep rodu c-
t ive performance. T he pu rpose of this report is to de-
scribe the ova rian gross and microscopic app earance,
the incidence, age distr ibut ion, an d reprod uctive per-
form ance of guinea pigs with cystic ovaries.
Materials and Methods
All
of
the an imals were from a closed colony established
in 1969 with 5 Abyssinian guinea pigs to study spontaneous
diabetes mellitus. Due to declining reproduction , some H art-
ley guinea pigs were introduced into the colony to increase
reproductive vigor from crossbreeding. These guinea pigs
were housed in s tainless steel cages at 72 t 2 F, 50 20
relative humidity with a
12
hour light :dark cycle without
twilight. They were fed commercial guinea pig chow, sup-
plemented with kale twice per week, and provided with water
ad libitum.
Guinea pigs of this study died of various causes or were
euthanized because of severe health problems. At necropsy
all organs were completely and systematically examined ac-
cording to a written protocol. The cystic ovaries were sec-
tioned through the cyst wall and thickest part of the paren-
chyma in an attempt to identify functional ovarian tissue.
Tissues were collected from each organ , fixed in 10 neutra l
buffered formalin, and processed by standard histological
methods. s Written necropsy reports of female guinea pigs
were reviewed to de termin e the incidence of cystic ovaries.
Reproduction records were maintained on females in the
colony who were bred at least once. Inbreeding was practiced
whenever possible within certain family lines, and in many
cases breeding was accomplished by placing one male and
one female together until 4 hours postpartum so the female
would be rebred as soon as possible. In some cases one male
and one female or one male and two females were paired for
30
days. Oral glucose tolerance test values and blood and
urine glucose values were recorded for the guinea pigs at
specified intervals. The clinical diabetic status was deter-
mined using previously published methods.
Results
Cystic ovaries were diagnosed in
54
of 71 (76 )
fem ale guinea pigs a t necropsy. Sm aller ovar ian cysts
were a n incid ental finding; however, larger cysts could
be identif ied as an ab dom inal mass by palpat ion. M ost
guinea pigs with cystic ov aries were between 2 a n d 4
years old (Fig. 1). Both ova ries were cystic in
44
of 54
(81.5 ) guinea pigs. In guinea pigs wh ere only one
ovar y contain ed cysts, the right ovar y was affected in
eight of
ten
(80 ) cases. Cysts ranged from 0.5
cm to
7 c m in diameter . T he sizes of the cysts vaned among
animals wi th in the same age group an d be tween age
335
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336 Keller,
Griffith,
and Lang
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Age (years)
Guinea Pigs with Cystic Ovaries
Fig. 1. Age distribution and
incidence
ofguinea pigswith
cystic ovaries.
groups. The average size of the cysts increased with
advancing age (Table 1).
Forty-eight of 54 (85 ) of the affected animals had
cystic ovaries visible by both gross and microscopic
examination. The ovarian cysts observed in most of
the guinea pigs were multilocular, clear, fluid-filled di-
lated structures (Fig. 2). The diameter and number of
cysts per ovary varied. Sectioning and histologic ex-
amination revealed that
80
to 90 of the ovarian
parenchyma was replaced by epithelial lined cysts (Fig.
3). The cysts were centered in the hilar region of the
ovary and were lined with flattened, cuboidal, or co-
lumnar epithelial cells, some of which contained cilia
(Fig. 4). Focal papillary hyperplasia was noted in cysts
from 13 of 54 (24 ) animals. Twelve of the 13 (92.3 )
guinea pigs with papillary hyperplasia were more than
18 months old. Eight of the 13 (61.5 ) guinea pigs
with papillary hyperplasia in the cysts and 21 of 54
(39 ) guinea pigs with cystic ovaries had extraovarian
reproduction-related lesions (Table 2). One ovary con-
tained a large teratoma. A detailed description of these
lesions is beyond the scope of this paper. The average
age of guinea pigs with cystic ovaries and other con-
current reproductive lesions was 38.9 months while
guinea pigs with no cystic ovaries averaged 30.4 months
old.
Analysis of reproductive records revealed that fer-
tility was similar between guinea pigs with and without
cystic ovaries up to 15 months of age. However, after
15 months of age there was a marked decrease in the
proportion of affected guinea pigs delivering as com-
pared to guinea pigs without cystic ovaries (Table 3).
Litter size did not differ significantly between the groups
nor did diabetic status. Approximately 50 of guinea
Table
1. Approximateage and
average
cyst size in guinea
pigs
with cystic ovaries.
Number of
Age Average Cyst Size Affected
Animals*
_ _ _ _ _ ~ ~
18 months
Microscopic
8
24
months 1.08 cm 3
30
months
2.29
cm
7
36 months 2.50 cm
5
42
months 2.90 cm
5
48 months 3.38 cm 13
60
months 3.58 cm 6
*
Cyst size was not recorded in seven guinea pigs.
pigs in each group were classified as diabetic.
No
cor-
relation could be found between the reproductive le-
sions described and lesions seen in any of the endocrine
organs.
Discussion
Five types of cysts can be found in the ovaries of
various laboratory animal species and are classified
according to tissue of origin within the ovary, and in-
clude: 1) follicular cysts, 2) luteal cysts, 3) inclusion
cysts,
4
parovarian cysts, and
5)
cysts of rete ovarii.
Follicular cysts are derived from secondary follicles
that fail to ovulate or undergo atresia and are the most
common. The follicular cysts seen in cattle, swine, and
aged rats frequently secrete estrogen in normal or ex-
cessive amounts leading to irregular estrous cycles, per-
sistent estrus, and infertility.
3 22 23
Although the patho-
genesis of follicular cysts is uncertain, investigators
believe that luteinking hormone levels are not suffi-
ciently elevated to luteinize the follicle, thus creating
a mature follicle that becomes cystic. Histologically,
follicular cysts are large with a thin wall made up of
several layers of granulosa cells, have an increased
amount of fluid, and do not contain an oocyte.
Luteal cysts are corpora lutea that develop a central
cavity and fail to regress. These cysts persist and serve
as a progesterone source. The pathogenesis of luteal
cysts is unknown but may involve an abnormality in
hypothalamic-hypophysealfunction or a failure of the
endometrium to produce a luteolytic substance.13Mi-
croscopically, the cystic corpus luteum has a wall made
up of large, polyhedral granuloluteal cells with abun-
dant eosinophilic, foamy cytoplasm. These cells are
surrounded by smaller thecal-luteal cells that are de-
rived from the ovarian stroma.
Inclusion cysts arise from segments of the ovarian
surface epithelium. They are variable in size and con-
sist of a unilocular, fluid-filled space which is usually
lined by a single layer of flattened epithelial cells. In-
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4/6
Cystic Ovaries
in
Guinea Pigs
33
Fig. 2. Urogenital tract from guinea pig with cystic ovaries. The right ovary (arrowheads) is enlarged and cystic.
Fig. 3 Rete cysts. Remaining ovarian parenchyma (p) compressed laterally. Bar
= 225
pm.
clusion cysts cause pressure atrophy
of
adjacent ovar-
ian parenchyma, do not routinely secrete any hor-
mones, and are commonly found in the mare.11.31
Parovarian cysts are vestigial remnants of the me-
sonephric and paramesonephric ducts that give rise to
vesicular structures located in the mesosalpinx or me-
sovarium. During ovarian development, cords of ep-
ithelial and primordial germ cells develop and grow in
the stroma of the ovarian blastema. In the hilar region
of the ovary the cords that are derived from the me-
sonephric tubules are devoid of germ cells and are
known as rete ovarii.I6 Cystic rete ovarii have been
Table 2. Extraovarian lesions associated with cystic ova-
ries in guinea pigs.
Guinea
pigs
Guinea Pigs
Without
Extraovarian Lesion with Cystic
Cystic
Ovaries
Ovaries
Uterine or cervical leiomyoma
6/54
0/17
Cystic endometrial hyperplasia 7/54 0/17
Endometritis 3/54 1/17
Mucometra
2/54 0/17
Inappropriate placental tissue
3/54
0/17
previously reported in guinea heifers, cats,8
sheep,Io swine,32 rairie deer mice,24 camel,28 ogs,30
and women.25Hyperplasia and metaplasia of the rete
ovarii have also been described in aging women.25Cysts
of the rete ovarii in guinea pigs are usually concentrated
in the hilar region of the ovary and are in continuity
with one another. The rete ovarii of young animals
may contain dilated regions lined by epithelium sim-
ilar to that in larger cysts of older animals.24
A
previous study found no evidence to indicate that
Fig.
4.
Ciliated epithelium which lines portions of rete
cysts. Bar = 20 pm.
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338 Keller,
Griffil
Table
3
Age range and fertility of guinea pigs with and
without cystic ovaries (C.O.).
Num- Percent
Num-
ber Deliv-
Deliv-
Bred ered
ered
Under 15 months age with C.O. 50 24 48
Under 15 months age without C.O. 13 6 46
Over 15 months age with C.O. 30 4 13
Over 15 months age without C.O. 6 3 50
guinea pigs with cystic ovaries had altered estrous cycles
or reprod~ction.~~owever, in this study a reduction
in fertility was seen in guinea pigs with ovarian cysts
as compared to unaffected animals over
15
months
of
age, suggesting that cystic ovaries may be a cause of
infertility
in
older guinea pigs. From this, one may
speculate that the cysts progressively enlarge with age
and eventually destroy normal ovarian function.
The pathogenesis of rete ovarii cysts has been pos-
tulated to be related to the secretory activity of the cells
lining the rete tubules. The tubules apparently have no
outlet for the fluid accumulation and expand into cysts
which cause pressure atrophy of the adjacent ovarian
parenchyma.8 A hormone may activate these cells to
and excessive secretions may result in the
cyst development. Secretory activity in the rete tubules
has been reported in the cat,8 heifer, ferret,5 mink,5
and dog. Periodic acid-Schiff (PAS)-positive cyto-
plasmic granules have been described in the connecting
and extraovarian rete, and PAS-positive secretions have
been seen in the tubule lumens when meiosis
begin^.^
Investigators have suggested that estrogens in the feed
may cause ovarian cysts and infertility in guinea pigs
but no cause-effect relationship has been proved.26
Similarly, endometrial gland hyperplasia has been re-
ported in swine and laboratory rodents that acciden-
tally received an excessive amount of estrogens in their
feed.
One investigator considered the rete ovarii an on-
togenic male remnant with no functional importance
in the female.25However, various studies have sug-
gested that the rete ovarii system is essential for the
onset of meiosis and ovarian development in many
species. Researchers do not know if the rete ovarii
influence germ cells by direct cellular contact or by
means of a secretory component.6 Some authors have
suggested that the dense rete bodies present in rete cells
may influence the regulation of steroid synthesis2 or
may be involved in lipid metabolism.20
Cystic dilatation of the rete ovarii in guinea pigs
appears to be a function of aging in this study, but very
small rete ovarian cysts have been reported in guinea
pigs as young as a few months of age.24More work is
necessary to investigate the pathogenesis of rete ovarii
:h and ang
cysts,
to
determine the fluid composition within the
cysts, and to determine if there is a relationship be-
tween these cysts and other reproductive tract lesions
observed in these guinea pigs.
Acknowledgement
Supported in part by grants RR00469 and RR07006 from
the Division of Research Resources, National Institutes of
Health, Bethesda, Maryland.
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4 Byskov AG: Does the rete ovarii act as a trigger for the
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Request reprints from Dr. Lynn
S F.
Keller, Department of Comparative Medicine, The M.
S.
Hershey Medical Center,
Pennsylvania State University, PO Box 850, Hershey, PA 17033 (USA).
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