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Reproductive Failure Associated with Cystic Rete Ovarii in Guinea Pigs

L. S. F. Keller, J. W. Griffith and C. M. Lang
Vet Pathol 1987 24: 335
DOI: 10.1177/030098588702400408
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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 Comparative 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 location of the cysts within the ovary were consistent with cystic rete
ovarii. Microscopic appearance of the large ovarian cysts suggested reproductive performance in these guinea
pigs should be compromised. Breeding records indicated that fertility was markedly reduced in affected females
over fifteen months of age. Cystic endometrial hyperplasia, mucometra, endometritis in appropriate 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.

Ovarian cysts are common in aged rats,22 guinea

pigs,24.26.33 cattle,27
and women.25
These cysts are usually derived from ovarian follicles,
corpora lutea, ovarian surface epithelium, remnants of
the mesonephric and paramesonephric ducts, or rete
ovarii.9.17.22.24-27.31.33
The rete ovarii is a homologue of
the rete testis and has been described as a normal structure 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) the
intraovarian ~ e t e The
. ~ intraovarian rete tubules are
lined by cuboidal epithelium while the connecting and
extraovarian rete ovarii are lined by ciliated columnar
epithelium.8 All rete cells contain dense rete bodies
that resemble microperoxisomes'8~'9and peroxisomes.'
Cystic changes in the mammalian ovary need to be
studied since they may cause infertility in aging laboratory and domestic animals and in
Cystic ovaries were diagnosed at necropsy in female guinea
pigs from a single breeding colony with low reproductive performance. The purpose of this report is to describe the ovarian gross and microscopic appearance,
the incidence, age distribution, and reproductive performance of guinea pigs with cystic ovaries.

Materials and Methods

All of the animals were from a closed colony established
in 1969 with 25 Abyssinian guinea pigs to study spontaneous
diabetes mellitus. Due to declining reproduction, some Hartley guinea pigs were introduced into the colony to increase
reproductive vigor from crossbreeding. These guinea pigs
were housed in stainless steel cages at 72 -t 2 F, 50% f 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 according to a written protocol. The cystic ovaries were sectioned through the cyst wall and thickest part of the parenchyma in an attempt to identify functional ovarian tissue.
Tissues were collected from each organ, fixed in 10% neutral
buffered formalin, and processed by standard histological
methods.I s Written necropsy reports of female guinea pigs
were reviewed to determine 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 24 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 determined using previously published methods. l4

Results
Cystic ovaries were diagnosed in 54 of 71 (76%)
female guinea pigs at necropsy. Smaller ovarian cysts
were an incidental finding; however, larger cysts could
be identified as an abdominal mass by palpation. Most
guinea pigs with cystic ovaries were between 2 and 4
years old (Fig. 1). Both ovaries were cystic in 44 of 54
(81.5%) guinea pigs. In guinea pigs where only one
ovary contained cysts, the right ovary was affected in
eight of ten (80%) cases. Cysts ranged from 0.5 cm to
7 cm in diameter. The sizes of the cysts vaned among
animals within the same age group and between age

335

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336

Keller, Griffith, and Lang

Table 1. Approximateage and average cyst size in guinea

pigs with cystic ovaries.

16
14

Age

12
UI

.P
n

18 months
24 months
30 months
36 months
42 months
48 months
60 months

f
2

Number of
Affected
Animals*

Microscopic
1.08 cm
2.29 cm
2.50 cm
2.90 cm
3.38 cm
3.58 cm

8
3
7
5
5
13
6

_ _ _ _ _ ~ ~

10

.-g

Average Cyst Size

* Cyst size was not recorded in seven guinea pigs.

F
x
\
\
s
I
x
\
\
\
\
\
\
\
\
\
\
\
\
\
\
N
\
\
\
N
\
\
\
\
\
W
14

2%

3%

4%

Age (years)
Guinea Pigs with Cystic Ovaries

Fig. 1. Age distribution and incidence ofguinea pigs with

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 dilated structures (Fig. 2). The diameter and number of
cysts per ovary varied. Sectioning and histologic examination 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 columnar 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 contained 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 concurrent reproductive lesions was 38.9 months while
guinea pigs with no cystic ovaries averaged 30.4 months
old.
Analysis of reproductive records revealed that fertility 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 compared to guinea pigs without cystic ovaries (Table 3).
Litter size did not differ significantlybetween the groups
nor did diabetic status. Approximately 50% of guinea

pigs in each group were classified as diabetic. No correlation could be found between the reproductive lesions 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 include: 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 excessive amounts leading to irregular estrous cycles, persistent estrus, and infertility.13,22,23Although the pathogenesis of follicular cysts is uncertain, investigators
believe that luteinking hormone levels are not sufficiently 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-hypophyseal function or a failure of the
endometrium to produce a luteolytic substance.13Microscopically, the cystic corpus luteum has a wall made
up of large, polyhedral granuloluteal cells with abundant eosinophilic, foamy cytoplasm. These cells are
surrounded by smaller thecal-luteal cells that are derived from the ovarian stroma.
Inclusion cysts arise from segments of the ovarian
surface epithelium. They are variable in size and consist of a unilocular, fluid-filled space which is usually
lined by a single layer of flattened epithelial cells. In-

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Cystic Ovaries in Guinea Pigs

331

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 ovarian parenchyma, do not routinely secrete any hormones, and are commonly found in the mare.11.31
Parovarian cysts are vestigial remnants of the mesonephric and paramesonephric ducts that give rise to
vesicular structures located in the mesosalpinx or mesovarium. During ovarian development, cords of epithelial 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 mesonephric tubules are devoid of germ cells and are
known as rete ovarii.I6 Cystic rete ovarii have been

previously reported in guinea

heifers, I cats,8
sheep,Ioswine,32prairie deer mice,24a camel,28dogs,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 similar to that in larger cysts of older animals.24
A previous study found no evidence to indicate that

Table 2. Extraovarian lesions associated with cystic ovaries in guinea pigs.

Extraovarian Lesion

Uterine or cervical leiomyoma

Cystic endometrial hyperplasia
Endometritis
Mucometra
Inappropriate placental tissue

Guinea pigs Guinea Pigs

Without
with Cystic
Cystic
Ovaries
Ovaries

6/54
7/54
3/54
2/54
3/54

0/17
0/17
1/17
0/17
0/17

Fig. 4. Ciliated epithelium which lines portions of rete

cysts. Bar = 20 pm.

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Keller, Griffil:h, and Lang

338

Table 3. Age range and fertility of guinea pigs with and

without cystic ovaries (C.O.).
Percent
Num-Number DelivDeliv- ered
Bred ered
Under 15 months age with C.O.
Under 15 months age without C.O.
Over 15 months age with C.O.
Over 15 months age without C.O.

50
13
30
6

24
6
4
3

48%
46%
13%
50%

cysts, to determine the fluid composition within the

cysts, and to determine if there is a relationship between 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.

References

guinea pigs with cystic ovaries had altered estrous cycles

or reprod~ction.~~
However, 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 postulated 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 cytoplasmic granuleshave 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
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Similarly, endometrial gland hyperplasia has been reported in swine and laboratory rodents that accidentally received an excessive amount of estrogens in their
feed. I I
One investigator considered the rete ovarii an ontogenic male remnant with no functional importance
in the female.25However, various studies have suggested that the rete ovarii system is essential for the
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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

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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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