Volume 6, Issue 8 March 2009
Reproduction management bulletin
In the Spotlight• Cystic Ovarian Disease/Cystic Ovarian
Follicle in cattle– definition of the
condition
• Incidence and clinical signs
• Pathogenesis of Cystic Ovarian Follicles
formation:
- Hypothalamic-pituitary dysfunction
- Ovarian/follicular dysfunction
• Factors predisposing to COF
• Leading directions for the treatment
of COF/COD in cattle
CYSTIC OVARIAN FOLLICLES IN DAIRY CATTLE
Prof. Dr. Geert OpsomerDepartment of Reproduction, obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Salisbury-laan 133, 9820 Merelbeke, Belgium [email protected]
Department of Reproduction, Obstetrics
and Herd Health Faculty of Veterinary
Medicine, Ghent University, Belgium
IntroductionCystic ovarian follicles (COF) are an im-
portant cause of subfertility in modern
dairy cattle. Prolongation of the calving
interval and treatment costs of COF result
in economic losses for the farmer. In the
past COF was mainly associated with clini-
cal symptoms such as nymphomania, and
was therefore usually called Cystic Ovar-
ian Disease (COD). Nowadays it is mainly
seen as a cause of anoestrus leading to
an increased interval parturition-first in-
semination without any obvious clinical
symptoms. Therefore, we currently pre-
fer to use the term COF instead of COD.
DefinitionCystic ovarian follicles develop when one
or more follicles fail to ovulate and subse-
quently do not regress but maintain their
growth. They commonly are defined as
follicle-like structures, present on one
or both ovaries, with a diameter of at
least 2.5 cm for a minimum of ten days
in the absence of a corpus luteum. It has
become clear though that this definition
needs to be revised.
First, the diameter limit is rather artifi-
cial since follicles might already become
cystic at a smaller size. Moreover, many
researchers demonstrated that COF are
actually dynamic structures which can re-
gress and be replaced by new cysts. The
factors that determine whether a cyst will
regress or not remain unknown, although
changes in the mean LH concentrations
seem to be involved. The required persis-
tency of ten days is also questionable. In
addition, in practice, veterinarians gener-
ally do not have the opportunity to per-
form a second examination of an animal
ten days after the initial diagnosis.
The absence of a corpus luteum is anoth-
er requirement to fulfill the definition.
It is however shown that some hormon-
ally inactive cysts do not influence the
oestrous cycle and hence can be found
in the presence of a corpus luteum. This
kind of cysts not influencing the oestrous
cycle and hence not being pathological is
therefore called ‘indifferent cysts’.
As a conclusion, it is clear that due to the
heterogeneity of the cysts it is very dif-
ficult to come to a generally acceptable
definition. Based on our current knowl-
edge and recent literature, COF can be
defined as follicles with a diameter of
at least 2 cm that are present on one or
both ovaries in the absence of a corpus
luteum and that clearly interfere with
normal ovarian cyclicity.
Macroscopically, cysts can be subdivided
into follicular and luteal cysts, which are
considered to be different forms of the
same disorder. Luteal cysts are by some
authors believed to be follicular cysts in
later stages. As follicular cysts secrete
very little or no progesterone while luteal
cysts clearly do, determination of proges-
terone in plasma or milk(fat) is the main
method to make a distinction between
the two types of cysts.
Reproduction management bulletin
Also ultrasound can be useful to differ-
entiate these two types of cystic struc-
tures. Follicular cysts have a thin wall
(≤3mm), and the follicular fluid is usu-
ally uniformly anechogenic, while luteal
cysts have a thicker wall (≥3mm) which
is visible as an echogenic rim. Also, the
latter often have echogenic spots and
web-like luteal structures in the follicu-
lar fluid.
Luteal cysts should however not be con-
fused with hollow ‘cystic’ corpora lutea
which are not pathological as they do
not disrupt the normal cyclicity at all.
Some authors however neglect the im-
portance of making the differential di-
agnosis between a luteal and a follicular
cyst, as the response of both types of
cysts to a standard GnRH treatment is
similar.
Incidence and clinical singsCystic ovarian follicles can occur at dif-
ferent times throughout lactation. Re-
ports on their incidence vary between 6
and 30%. Diagnosis of COF is most often
made during the first 60 days of lactation,
mainly because of the close monitoring
of the postpartum cows. The cysts occur-
ring during the early postpartum period
do however have a self recovery percent-
age of 60% or even higher. As the treat-
ment of COF is reported to be very suc-
cessful and rather cheap, authors usually
advice to treat the affected animals in
stead of waiting for self recovery as the
latter may in some cases lead to signifi-
cantly increased intercalving intervals.
The incidence of COF also depends on
parity. As described by several indepen-
dent authors, the lactational incidence
rate was significantly higher in multipa-
rous cows (±15%) in comparison with
heifers (±7%).
A genetic predisposition exists for COF
but the heritability is rather low (0.07 to
0.12). Authors mentioned that although
the heritability is low, genetic selec-
tion against COF has been successful.
Clinical signs that accompany ovar-
ian cysts are variable. Anoestrus is most
common, especially during the postpar-
tum period. Irregular oestrous intervals,
nymphomania, relaxation of the broad
pelvic ligaments and development of
masculine physical traits are other signs
which may be present, especially later in
lactation.
Pathogenesis of COFOvarian dysfunction, such as cysts occur
most often during the early postpartum
period when the transition from the
noncycling condition during pregnancy
to the resumption of regular cyclicity
after calving takes place. It is generally
accepted that cystic follicles develop due
to a dysfunction of the hypothalamic-
pituitary-ovarian axis. This dysfunction
has a multifactorial etiology in which
genetic, phenotypic and environmental
factors are involved. When discussing
the pathogenesis of COF, a distinction
should be made between a primary de-
fect in hypothalamus-pituitary function
from the problems at the level of the
ovary.
Hypothalamic-pituitary dysfunction
The most widely accepted hypothesis
explaining the formation of a cyst is the
one stating that the LH release from the
hypothalamus-pituitary axis is altered:
the pre-ovulatory LH-surge is either ab-
sent, insufficient in magnitude or occurs
at the wrong time during dominant fol-
licle maturation, finally resulting in cyst
formation. The aberrant LH release does
not seem to be caused by a lower GnRH
content of the hypothalamus, nor by re-
duced GnRH receptor numbers or LH con-
tent in the pituitary.
It is believed that an altered feedback
mechanism of oestrogens on the hypo-
thalamus-pituitary can result in an aber-
rant GnRH/LH release and hence in cyst
formation. A GnRH/LH surge occurring
prematurely during follicular growth, i.e.
when no follicle able to ovulate is pres-
ent, can render the hypothalamus unre-
sponsive to the feedback effect of oes-
tradiol which results in the formation of
ovarian cysts.
An altered feedback mechanism and
GnRH/LH release may be attributed to
factors interfering at the hypothalamic-
pituitary level. Progesterone at supra-
basal levels blocks the LH-surge, thereby
inhibiting ovulation but increasing the
LH pulse frequency. This results in an
anovulatory, persistent follicle with a
larger diameter and a longer lifespan
than normal, very similar to COF. In early
postpartum cows, the suprabasal periph-
eral progesterone levels may originate
from the release of progesterone by the
breakdown of fat during the negative en-
ergy balance (NEB). During late gestation
when cows are in the anabolic phase and
are building their fat depots as energy
reserves for the next lactation, they also
have high progesterone levels to sustain
pregnancy. As progesterone is lipophil-
ic, it will be deposited in the fat at that
time of lactation. In the early postpar-
tum phase however, cows enter NEB and
break down their fat reserves as a source
of energy. In this way released progester-
one may cause suprabasal progesterone
levels and lead to COF formation.
Reproductive tract of a cow with follicular
ovarian cyst
Bovine ovary with thick walled luteal cysts
Reproduction management bulletin
Other factors known to (in)directly
inhibit GnRH/LH pulse secretion at
the exact moment in relation to the
growth and maturation of the domi-
nant follicle, and in this way elicit
cysts are stress, intrauterine infec-
tions and seasonality.
In conclusion, an aberrant LH surge is
likely to be the trigger for the devel-
opment of COF. Abnormal LH release
seems to be caused by an altered
feedback mechanism of oestrogens
on the hypothalamus-pituitary axis.
Ovarian/follicular dysfunction
Also a primary dysfunction at the
level of the follicle may disrupt the
hypothalamic-pituitary-ovarian axis
and through this cause the formation
of COF. First of all, alterations in LH
receptors expression and content in
the follicle may cause anovulation.
Besides the changes in receptors ex-
pression and content, alterations in
steroidogenesis by the dominant fol-
licle may also be involved in cystic de-
generation. After all, the dominant
follicle has to stimulate an LH surge
at the right time in its development
by producing sufficient amounts of
oestrogens. Aberrations in mRNA
expression of steroidogenic enzymes
have been demonstrated in cystic fol-
licles.
Apart from the changes in mRNA
expression for certain receptors and
steriodogenic enzymes, cell prolif-
eration and apoptosis in the granu-
losa and theca interna cell layers also
seem to be altered in some cystic fol -
licles. In our lab we recently demon-
strated that elevated NEFA levels as
occurring in dominant follicles early
after calving have a significant nega-
tive effect on the proliferation of
granulosa and theca interna cells in
vitro. Especially the saturated fatty
acids like stearic acid (18:0) and pal-
mitic acid (16:0) caused a diminished
proliferation and a higher apoptosis
of the oestrogen producing follicular
cells. The latter may be an important
factor in the pathogenesis of COF
since a reduced viability of these fol-
licular cells may be accompanied with
oestrogen levels that are too low to
cause an LH surge at the exact mo-
ment.
As insulin has been shown to be an
important factor that stimulates fol-
licular cells to proliferate and produce
oestrogens, the remarkably steep de-
crease of peripheral insulin levels in
high yielding dairy cows early after
calving can also be seen as an attrib-
utable factor in the pathogenesis of
COF. Indeed, in a field study recently
published by our group we were able
to demonstrate that in some cows
suffering from COF, the peripheral in-
sulin levels near the moment of cyst
formation were significantly lower
than in control cows which did ovu-
late. Earlier, we had demonstrated
using intravenous glucose tolerance
tests (IVGT) that in some cows suf-
fering from COF there was no insulin
response at all after the cows were
given a glucose bolus.
As a conclusion, factors that have a
negative effect on the production of
oestrogens by the follicular granu-
losa and/or theca interna cells can
be seen as significant contributors to
the establishment of COF. High NEFA
levels (especially of saturated fatty
acids) and low insulin levels seem to
act in this way and seem to be impor-
tant risk factors to elicit COF.
Predisposing factors for COFAs mentioned earlier, COF are mainly
observed in high yielding dairy cows
during the first months post partum
and high milk yield is generally con-
sidered as a risk factor, although not
all authors agree in this. Moreover,
besides the fact that a genetic pre-
disposition for COF exists, a genetic
correlation between cysts and the
level of milk production has been es-
tablished, indicating that an ongoing
selection for production will increase
the incidence of COF.
What the genetic factors are and how
they promote the formation of cysts is
however not known. However, the fact
that cows do not develop a cyst during
each lactation and during each ovarian
cycle indicates that gene expression may
be promoted by certain stressors like for
example high milk yield and the herewith
associated NEB. A lot of studies have
been done in order to find a correlation
between the level of milk production, the
herewith associated NEB and the occur-
rence of COF. Although a strict consensus
is lacking, we conclude from the litera-
ture that a link seems to exist between
COF and the magnitude and/or duration
of the NEB accompanying the current lev-
el of milk production. Etiologic factors in-
volved may be lowered levels of glucose,
insulin and IGF1 or elevated NEFA levels
as explained in more detail earlier.
Other significant risk factors are parity,
puerperal diseases like metritis and clini-
cal mastitis and (extreme) stress factors.
In conclusion, it can be stated that factors
influencing the development of COF are
still not fully understood. A major prob-
lem is that most studies measure hor-
mone levels only after the condition had
been diagnosed. Moreover, significant
correlations do not necessarily indicate a
causative relationship.
Treatment of COFOnce the diagnosis of COF is made, the cli-
nician has to take the decision either to do
nothing and hope for spontaneous recovery,
to administer a general hormonal treatment,
or to try to differentiate the type of cyst and
administer a more specific treatment. Re-
COF are mainly observed in high yielding dairy
cows during the first months post partum
Reproduction management bulletin
gardless of the treatment decision, the aim
of the therapy is to re-establish normal oes-
trous cycles as soon as possible by choosing
the most economical treatment. It has been
demonstrated that it usually is more econom-
ical to treat ovarian cysts than to hope for a
spontaneous recovery.
On the basis of the hypothesis that an ab-
sence of the LH pulse is the primary cause
of COF, general treatment of cows affected
by COF is directed to stimulate luteinization
of the cyst which is usually followed by the
re-establishment of a normal oestrous cycle.
Biological preparations high in LH-like activity
(e.g. human chorionic gonadotrophin) and
exogenous GnRH, which acts on the pituitary
gland to cause the release of endogenous LH,
have been widely and effectively used for the
treatment of both follicular and luteal cysts.
Results of both treatments are comparable.
Around 80% of the treated cows exhibit a
fertile oestrus within 16 to 30 days, although
pregnancy rates are slightly lower in compari-
son with those of normal cows. Since both
types (luteal and follicular) of cysts respond
similarly to this kind of treatment, differentia-
tion is not necessary and authors agree that
this approach remains the best initial therapy
for the majority of cows with COF regardless
of their type.
Prostaglandin therapy is also used to treat
cows with luteal cysts. The response of ovar-
ian cysts to this kind of treatment depends
on the presence of luteal tissue and the
veterinarian’s ability to recognize it. Because
palpation per rectum has been reported to
be an inaccurate method for differentiation,
the diagnosis has to be based on the deter-
mination of progesterone in plasma or milk,
or on the use of ultrasonography. Although
the treatment with luteolytic drugs results in
a shorter interval to a fertile oestrus the cost-
benefit evaluation of this kind of treatment
has to incorporate the surplus costs of the im-
mediate cyst differentiation. In this regard, it
has been demonstrated that the practice of
identifying all cysts as either follicular of luteal
prior to treatment is questionable from an
economic point of view. It has also been sug-
gested that the use of prostaglandins given 9
to 14 days after GnRH may shorten the inter-
val from treatment to the first fertile oestrus
by about 12 days, yielding shorter intervals to
conception than when GnRH is used alone.
While doing the latter, one should take into
account the cost of the double treatment
which is another economical drawback.
Cows not responding to GnRH treatment
can be treated with progesterone with fairly
good results. Although the mechanism by
which progesterone causes regression of the
ovarian cyst is not well established, it has been
suggested that this treatment suppresses the
release of LH, resulting in an accumulation
in the pituitary and leading to an enhanced
surge of LH when the progesterone treat-
ment is withdrawn.
As the treatment results by simply injecting
affected cows with GnRH or LH-agonists are
reported to be relatively high, treatments
based on (manual) rupture of the cyst are
currently seen as outdated. Rupturing the
cyst may lead to excessive bleeding especially
in luteal cysts, and/or in the excessive forma-
tion of fibrin leading to the establishment of
adhesions involving the ovary. The latter may
negatively affect pregnancy rates once the
cows are inseminated.
Reproduction management bulletin
ReferencesBartlett PC, Ngategize PK, Kaneene JB,
Kirk JH, Anderson SM, Mather EC, 1986.
Cystic follicular disease in Michigan Hol-
stein-Friesian cattle: incidence, descrip-
tive epidemiology and economic impact.
Prev Vet Med 4, 15-33
Beam SW, 1995. Follicular development
in postpartum cattle: effects of energy
balance and dietary lipid. Ph.D Disserta-
tion, Cornell University, pp 124-136
Beam SW, Butler WR, 1999. Effects of en-
ergy balance on follicular development
and first ovulation in postpartum dairy
cows. J Reprod Fertil, Supplement 54,
411-424.
Butler WR, 2003. Energy balance relation-
ships with follicular development, ovu-
lation and fertility in postpartum dairy
cows. Livest Prod Sci 83, 211-218
Butler ST, Pelton SH, Butler WR, 2004.
Insulin increases 17β-estradiol produc-
tion by the dominant follicle of the first
postpartum follicle wave in dairy cows.
Reproduction 127, 537-545.
Cole WJ, Bierschwal CJ, Youngquist RS,
Braun WF, 1986. Cystic ovarian disease in
a herd of Holstein cows: a hereditary cor-
relation. Theriogenology 25, 813-820
Cook DL, Smith CA, Parfet JR, Youngquist
RS, Brown EM, Garverick HA, 1990. Fate
and turnover rate of ovarian follicular
cysts in dairy cows. J Reprod Fertil 89,
155-66
Day N, 1991a. The diagnosis, differentia-
tion, and pathogenesis of cystic ovarian
disease. Vet Med 86, 753-760
Day N, 1991b. The treatment and preven-
tion of cystic ovarian disease. Vet Med
86, 761-766
Ding C, Cantor CR, 2004. Quantitative
analysis of nucleic acids - the last few
years of progress. J Biochem Mol Biol 37,
1-10
Diskin MG, Mackey DR, Roche JF, Sreenan
JM, 2003. Effects of nutrition and meta-
bolic status on circulating hormones and
ovarian follicle development in cattle.
Anim Reprod Sci 78, 345-370
Dijkhuizen AA, Huirne RBM, Jalvingh
AW, Stelwagen J, 1997. Economic impact
of common health and fertility problems.
In: Dijkhuizen AA, Morris RS (editors).
Animal health economics, principles and
applications. University of Sydney, pp 41-
58
Erb HN, White ME, 1981. Incidence rates
of cystic follicles in Holstein cows accord-
ing to 15-day and 30-day intervals. Cor-
nell Vet 71, 326-331
Franks S, Gharani N, Waterworth D, Bat-
ty S, White D, Williamson R, McCarthy M,
1997. The genetic basis of polycystic ovary
syndrome. Hum Reprod 12, 2641-2648
Hamilton SA, Garverick HA, Keisler DH,
Xu Z.Z., Loos K, Youngquist RS, Salfen
BE, 1995. Characterization of ovarian
follicular cysts and associated endocrine
profiles in dairy cows. Biol Reprod 53,
890-898
Hooijer GA, Lubbers RBF, Ducro BJ, van
Arendonk JAM, Kaal-Lansbergen LMTE,
van der Lende T, 2001. Genetic param-
eters for cystic ovarian disease in Dutch
black and white dairy cattle. J Dairy Sci
84, 286-91
Hooijer GA, van Oijen MAAJ, Frankena
K, Noordhuizen JPTM, 2003. Milk pro-
duction parameters in early lactation:
potential risk factors of cystic ovarian dis-
ease in Dutch dairy cows. Livest Prod Sci
81, 25-33
Huirne RBM, Saatkamp HW, Bergevoet
RHM, 2002. Economic analysis of com-
mon health problems in dairy cattle. In:
Kaske M, Scholz H, Höltershinken M. Re-
cent developments and perspectives in
bovine medicine. Proceedings of the XXII
World Buiatrics Congress, Hannover, Ger-
many, 18-23 August
Huszenicza G, Haraszti J, Molnar L, Solti
L, Fekete S, Ekes K, Yaro AC, 1988. Some
metabolic characteristics of dairy cows
with different post partum ovarian func-
tion. J Vet Med A 35, 506-515
Kesler DJ, Garverick HA, 1982. Ovarian
cysts in dairy cattle: a review. J Anim Sci
55, 1147-1159
Kirk JH, Huffman EM, Lane M, 1982. Bo-
vine cystic ovarian disease: hereditary
relationships and case study. J Am Vet
Med Assoc 181, 474-476
Laporte HM, Hogeveen H, Schukken YH,
Noordhuizen JPTM, 1994. Cystic ovarian
disease in Dutch dairy cattle I. Incidence,
risk factors and consequences. Livest
Prod Sci 38, 191-197
Leathem JH, 1958. Hormonal influences
on the gonadotropin-sensitive hypothy-
roid rat ovary. Anat Rec 131, 487-497
Lopez-Diaz MC, Bosu WTK, 1992. A re-
view of cystic ovarian degeneration in
ruminants. Theriogenology 37, 1163-
1183
Lucy MC, 2001. Reproductive loss in
high-producing dairy cattle: where will
it end? J Dairy Sci 84, 1277-1293
Lucy MC, 2003. Mechanisms linking nu-
trition and reproduction in postpartum
cows. Reproduction, Supplement 61,
415-127
Opsomer G, Coryn M, Deluyker H, de
Kruif A, 1998. An analysis of ovarian dys-
function in high yielding dairy cows after
calving based on progesterone profiles.
Reprod Domest Anim 33, 193-204
Opsomer G, Wensing T, Laevens H, Coryn
M, de Kruif A, 1999.Insulin resistance:
the link between metabolic problems
and cystic ovarian disease in high-yield-
ing dairy cows? Animal Reproduction
Science 56. 211-222.
R00
55_0
9
Intervet International bv, P.O. Box 31, 5830 AA Boxmeer, The Netherlands, Phone +31 (0)485 587600, Fax +31 (0)485 577333, E-mail [email protected], www.intervet.com
Opsomer G, Grohn YT, Hertl J, Coryn M,
Deluyker H, de Kruif A, 2000. Risk factors
for post partum ovarian dysfunction in high
producing dairy cows in Belgium: a field
study. Theriogenology 53, 841-857
Peter AT, 2004. An update on cystic ovar-
ian degeneration in cattle. Reprod Domest
Anim 39, 1-7
Rajala PJ, Gröhn YT, 1998. Disease occur-
rence and risk factor analysis in Finnish Ayr-
shire cows. Acta Vet Scan 39, 1-13
Rajala-Schultz PJ, Gröhn YT, 2001. Compari-
son of economically optimized culling rec-
ommendations and actual culling decisions
of Finnish Ayrshire cows. Prev Vet Med 49,
29-39
Refsdal AO, 1982. Ovariecyster hos melke-
kyr. Norsk Veterinærtidsskrift 94, 789-796
Robker RL, Russell DL, Yoshioka S, Chidanada
Sharma S, Lydon JP, O’Malley BW, Espey LL,
Richards JS, 2000. Ovulation: a multi-gene,
multi-step process. Steroids 65, 559-570
Ryan PL, Raeside JI, 1991. Cystic ovarian de-
generation in pigs: a review. Irish Vet J 44,
22-25
Shresta HK, Nakao T, Higaki T, Suzuki T,
Akita M, 2004. Effects of abnormal ovarian
cycles during pre-service period postpartum
on subsequent reproductive performance
of high-producing Holstein cows. Therio-
genology 61, 1559-1571
Sovani S, Heuer C, Straalen WM van, Noord-
huizen JPTM, 2000. Disease in high produc-
ing dairy cows following post parturient
negative energy balance. Soc Vet Epid Prev
Med, Annual Conference, Edinburgh, 29-31
March.
Staples CR, Thatcher WW, Clark JH,
1990. Relationship between ovarian ac-
tivity and energy status during the early
postpartum period of high-producing
dairy cows. J Dairy Sci 73, 938-947
Thatcher WW, Wilcox CJ, 1973. Post par-
tum estrus as an indicator of reproduc-
tive status in the dairy cow. J Dairy Sci
56, 608-610
Thorsoe H, 1962. Development of poly-
cystic ovaries following thyroidectomy.
Acta Endrocrinol 40, 161-174
Urbanek M, Legro RS, Driscoll DA, Azziz
R, Ehrmann DA, Norman RJ, Strauss JF,
Spielman RS, Dunaif A, 1999. Thirty-sev-
en candidate genes for polycystic ovary
syndrome: strongest evidence for link-
age is with follistatin. Proc Natl Acad Sci
96, 8573-8578
Vanholder T, Leroy JLMR, Van Soom A,
Opsomer G, Maes D, Coryn M, de Kruif
A, 2005. Effect of non esterified fatty
acids on bovine granulosa cell steroido-
genesis and proliferation in vitro. Animal
Reproduction Science 87. 33-44.
Vanholder T, Leroy JLMR, Dewulf J, Du-
chateau L, Coryn M, de Kruif A, Opsomer
G, 2005. Hormonal and metabolic pro-
files of high yielding dairy cows prior to
ovarian cyst formation of first ovulation
post partum. Reproduction in Domestic
Animals 40. 460-467.
Vanholder T, Leroy JLMR, Opsomer G,
Van Soom A, 2005. Β-Hydroxybutyrate
modulates bovine granulosa cell func-
tion in vitro at physiological glucose con-
centrations. Reproduction in Domestic
Animals 40, 362.
Vanholder T, Leroy JLMR, Van Soom A,
Maes D, Coryn M, Fiers T, de Kruif A, Op-
somer G, 2006. Effect of non-esterified
fatty acids on bovine theca cell steroido-
genesis and proliferation in vitro. Animal
Reproduction Science 92. 51-63.
Vanholder T, Leroy JLMR, Van Soom A, Maes
D, Coryn M, de Kruif A, Opsomer G, 2006.
Effect of β-OH butyrate on bovine granulo-
sa and theca cell function in vitro. Reproduc-
tion in Domestic Animals 41. 39-40.
Vanholder T, Opsomer G, de Kruif, 2006.
Aetiology and pathogenesis of cystic ovar-
ian follicles in dairy cattle: a review. Repro-
duction, Nutrition and Development 46.
105-119.
Vanholder T, Leroy JLRM, Opsomer G, de
Kruif A, 2006. Interactions between energy
balance and ovarian activity in high yielding
dairy cows early post partum. Vlaams Dier-
geneeskundig Tijdschrift 75, Special Issue:
‘Fertility in high producing dairy cows’, 79-
85.
Yen SSC, 1999. Polycystic Ovary Syndrome
(Hyperandrogenic Chronic Anovulation).
In: Reproductive endocrinology: physiology,
pathophysiology and clinical management.
Philadelphia (Pa.): Saunders, pp 436-478
Youngquist RS, 1986. Cystic follicular degen-
eration in the cow. In: Morrow D. (editor).
Current therapy in Theriogenology. 2nd ed.,
Philadelphia: WB Saunders Co., pp 243-246
Zulu VC, Sawamukai Y, Nakada K, Kida K,
Moriyoshi M, 2002. Relationship among
Insulin-Like Growth Factor-I, Blood metabo-
lites and Post Partum Ovarian Function in
Dairy cows. J Vet Med Sci 64, 879-885