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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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2/6

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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3/6

336 Keller,

Griffith,

and Lang

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3 3 4 4

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-



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.



5/6

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.

References

1 Archibald

LF,

Schultz RH, Fahning

ML,

et al.: Rete

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2 Black VH, Bogart BI: Peroxisomes in inner adrenocor-

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3 Byskov AG: The anatomy and ultrastructure of the rete

system in the fetal mouse ovary. Biol Reprod 19:720-

735, 1978

4 Byskov AG: Does the rete ovarii act as a trigger for the

onset of meiosis? Nature 252:396-397, 1974

5

Byskov AG: The role of the rete ovarii in meiosis and

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6 Byskov AG, Linten-Moore S: Follicle formation in 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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