Reprod Dom Anim 41, 472–476 (2006); doi: 10.1111/j.1439-0531.2006.00674.
x
ISSN 0936-6768
Short Communication
The Effect of Dose and Route of Administration of R-cloprostenol on the Parturient
Response of Sows
K Kaeoket
Faculty of Veterinary Science, Mahidol University, Nakorn-pathom, Thailand
Contents
The aims of the present study were to further examine the
efficacy of different doses and routes of R-cloprostenol
administration on the parturition response in sows. Fifty
crossbred multiparous sows (Landrace · Yorkshire) with an
average parity number of 4.7 ± 2.4 were allocated to induce
farrowing by one of the following treatments: Group I
(control, n ¼ 10) injection with normal saline 2 ml adminis-
tered intramuscularly (i.m.); Group II (n ¼ 10) injection with
75 lg of R-cloprostenol administered i.m. (at 7 AM);Group III
(n ¼ 10) injection with 75 lg of R-cloprostenol (at 7 AM)
together with 10 IU of oxytocin (24 h after injection of
R-cloprostenol) administered i.m.; Group IV (n ¼ 10) injec-
tion with 37.5 lg of R-cloprostenol (at 7 AM) administered into
perivulva region; Group V (n ¼ 10) injection with 37.5 lg of
R-cloprostenol (at 7 AM) administered into perivulva region
together with 10 IU of oxytocin (24 h after injection of R-
cloprostenol) administered i.m. The following parameters: pre-
farrowing maternal behaviour, restless behaviour, R-clopros-
tenol or oxytocin injection to farrowing interval, expulsion
intervals, duration of farrowing, total number of piglets born,
litter birthweight, umbilical cord morphology and the degree
of meconium staining were record. There were no significant
differences among groups for the pre-farrowing maternal
behaviours. In all the sows, the restless behaviour was not
observed. There were no significant effect of oxytocin admin-
istration (10 IU, i.m.) on the percentage of umbilical cord
morphology and the degree of meconium staining in different
groups. There were no significant effect of route and dose of
administration on the number of total piglet born, piglet born
alive, stillbirth, mummy and litter birthweight. No significant
effects of the different groups were found on the R-clopros-
tenol and oxytocin injection to farrowing interval, expulsion
interval and farrowing duration. In conclusion, the present
results demonstrated that a half dose (37.5 lg) of R-clopros-
tenol administered into the perivulva region was effective for
inducing farrowing as the full recommended dose (75 lg)
administered into the neck region (i.m.) and with no restless
behaviour.
Introduction
Pre-weaning piglet mortality rates average 10–15% and
may reached 30% in some herds (Vaillancourt et al.
1992; Straw et al. 1998; Cutler et al. 1999). Most of this
piglet loss occurs during the first 3 days postpartum,
which mainly occur during the first few hours of life
(Straw et al. 1998). Stillbirths remain a primary problem
in intensive pig farming and account for 5–10% (Fraser
et al. 1997; Tantasuparuk et al. 2000; Van der Lende
et al. 2001; Lucia et al. 2002; Leenhouwers et al. 2003;
Tummaruk et al. 2004; Van Dijk et al. 2005). The ability
 2006 The Author. Journal compilation  2006 Blackwell Verlag
to predictably induce parturition in a group of sow may
lead to a reduction in neonatal mortality of the piglets
and puerperal diseases of the sows by allowing farmer to
assist the sows that are having a difficult farrowing, to
supervise colostrums intake, or to do cross fostering
piglets.
It is widely accepted that the available method of
inducing parturition in sows is by injecting prostaglan-
din F2a or one of its analogs (i.e. cloprostenol,
luprostiol and dinoprost) and also injecting these
hormones in combination with oxytocin. Several studies
have been carried out, demonstrating that more than
80% of sows will farrow within 36 h of an intramuscular
injection (i.m.) of PGF2a or its analogs administered at
112–114 days of gestation (Hammond and Matty 1980;
Holtz et al. 1983; Guthrie 1985; Cameron et al. 2000;
Keı̈ta et al. 2002; Balogh and Bilkei 2003). It has also
been shown that inducing parturition in the sow using
PGF2a (full dose ¼ 10 mg) or cloprostenol (Estru-
mate, Essex, Germany; full dose ¼ 175 lg) in combi-
nation with oxytocin (10–20 IU) resulted in increasing
(i.e. more than 85% of sows farrowed within 36 h of an
injection, i.m.) the predictability of parturition (Chan-
taraprateep et al. 1986; Dial et al. 1987; Balogh and
Bilkei 2003). More recently, Mota-Rojas et al. (2002,
2005) and Alonso-Spilsbury et al. (2004) reported that
injecting oxytocin (i.e. 20–50 IU) during parturition not
only had a significant decrease in farrowing time and
expulsion intervals but also had a significant higher
number of stillborn piglets per litter, number of piglets
with ruptured and haemorrhagic umbilical cords. It has
been shown that these pathological conditions resulted
in anoxia and stillborn of the piglets. Anoxia induces
redistribution of fetal blood with expulsion of meconi-
um to the amniotic fluid and its aspiration because of
fetal gasping (Martinez-Burnes et al. 2002). Therefore,
the presence of meconium on skin becomes indicator of
fetal anoxia in the pig (Randall 1972; Mota-Rojas et al.
2002; Alonso-Spilsbury et al. 2004, 2005). Although
using PGF2a and its analogs alone or in combination
with oxytocin to induce farrowing has proven effica-
cious, many farmers refuse to use these products,
because of high cost of PGF2a and Cloprostenols.
It is now established that injecting PGF2a at the half
manufacturer’s recommended dose into the vaginal
mucosa is as effective as an i.m. injection at the full
recommended dose for inducing parturition in sows
(Koh et al. 1986; Perestrelo and Perestrelo 1986;
Friendship et al. 1990). It has also been reported that
Induce Farrowing by Using R-cloprostenol
injection of PGF2a (Lutalyse, Upjohn, ON, Canada;
half dose ¼ 5 mg) or cloprostenol (Planate, Coopers
Agropharm, Ajax, ON, Canada; half dose ¼ 88 lg) into
the perianal region (at about the 4- or 8-o’clock
position) is as effective as a route of administration into
vaginal mucosa (Kirkwood et al. 1996).
Cloprostenol exists as two optically active isomers
(D-cloprostenol and L-cloprostenol) and racemic mix-
ture, DL-cloprostenol (Kral et al. 1989). Recently, it has
been shown that D-cloprostenol (i.e. R-cloprostenol) is
approximately 10 times more potent than DL-cloproste-
nol (Re et al. 1994). Consequently, when D-cloprostenol
is used a lower dosage could be given than that required
for DL-cloprostenol. However, the half dose of
R-cloprostenol (Preloban; Intervet, Unterscheißheim,
Germany; half dose ¼ 37.5 lg) by perivulva region (at
about 3- or-9-o’clock position) of administration and in
combination with or without oxytocin remains to be
elucidated. Therefore, the aims of the present study were
to further examine the efficacy of different doses and
routes of R-cloprostenol administration on the parturi-
tion response in sows.
Materials and Methods
Animals and induction of parturition
Fifty crossbred (Landrace · Yorkshire) multiparous
sows with an average parity number of 4.7 ± 2.4
(means ± SD) were kept in a farrowing house with an
evaporating system of a commercial herd. The sows
were kept in individual farrowing crates and fed twice a
day with commercial diet formulating for pregnant
sows. Water was available ad libitum. They were selected
for induction of parturition at 113 or 114 days of
gestation. The average gestation period for sows on this
herd is 115 days. Parturition was induced by one of the
following treatments.
Group I (control, n ¼ 10) injection with normal
saline 2 ml administered i.m.;
Group II (n ¼ 10) injection with 75 lg of R-
cloprostenol (Preloban) administered i.m. (at 7 AM);
Group III (n ¼ 10) injection with 75 lg of R-
cloprostenol (Preloban, at 7 AM) together with
10 IU of oxytocin (24 h after injection of Preloban)
administered i.m.;
Group IV (n ¼ 10) injection with 37.5 lg of R-
cloprostenol (Preloban, at 7 AM) administered into
perivulva region at about 3- or-9-o’clock position;
Group V (n ¼ 10) injection with 37.5 lg of R-
cloprostenol (Preloban, at 7 AM) administered into
perivulva region together with 10 IU of oxytocin
(24 h after injection of Preloban) administered i.m.;
Seven sows were excluded because of the farrowing
process had completed at night time, and before 7 AM on
the next day (i.e. at a time of oxytocin injection).
Data collections
Sows were observed throughout the day of R-clopros-
tenol injection for mothering behavioural changed,
restless behaviour and reaction on the site of injection
(i.e. redness, swelling and urticaria), commencing from 0
 2006 The Author. Journal compilation  2006 Blackwell Verlag
473
to 12 h after injection. Sows farrowing at night time,
before the day of observation (13–24 h after injection of
R-cloprostenol) were excluded from the study. Sows
farrowing during the day of observation (from 24 to
36 h after injection of R-cloprostenol) were observed for
the behavioural observations as follows (Burne et al.
2000a,b, 2001): posture (i.e. kneel, lie belly, lie side, sit,
stand), nesting behaviour (i.e. grasping behaviour, paw
floor, paw wall, root floor, root wall, step) and others
behaviours (i.e. inactive, defecate, urinate, drink, chew
fixtures, object scratch, rear leg scratch, shake head).
The following parameters were also recorded: time from
treatment (i.e. after injection of R-cloprostenol and
oxytocin) to the onset of farrowing, expulsion intervals,
duration of parturition, presentation of the piglets (i.e.
anterior and posterior presentation), total number of
piglets born (stillborn, mummy and born alive), umbil-
ical cord morphology (i.e. normal, oedema, congestion
and haemorrhage) and bodyweight of each piglet. In
addition, the degree of meconium staining on the skin of
piglets at birth was classified as follows (Mota-Rojas
et al. 2002; Alonso-Spilsbury et al. 2004: unstained,
slightly stained (25% of body surface area), moderately
stained (50% of body surface area), and severely stained
(more than 50% of body surface area).
Statistical analysis
The umbilical cord morphology, the degree of meconium
staining and the presentation of the piglet were analyzed
and results express on a per cent basis. Time from
treatment (i.e. after injection of R-cloprostenol and
oxytocin) to the onset of farrowing (min), expulsion
intervals (min), duration of parturition (min), total
number of piglets born (i.e. stillborn, mummy and born
alive) were analyzed as one-way model with five treat-
ments using the GLM procedure of SAS statistical
package (SAS Institute, 1989). Student’s t-test under the
general linear model was used to compare the differences
between groups only when overall significance was
found. A p £ 0.05 was considered statistically significant.
Results
Altogether 40 sows (groups II-V), 82.5% of the sows
were farrowed between 24 h and 34 h after injection of
R-cloprostenol. There were no significant differences
among groups for the pre-farrowing maternal behaviour
(i.e. posture, nesting behaviour and other behaviours).
In all the sows, the restless behaviour was not observed.
The reaction on the site of injection, e.g. redness,
swelling and urticaria, were not seen.
There were no significant effects of oxytocin admin-
istration (10 IU, i.m.) on the percentage of umbilical
cord morphology (Table 1) and on the degree of
meconium staining in different groups (Table 2). The
percentage of the anterior and posterior presentations of
the piglet is presented in Table 1. There were no
significant effect of route and dose of administration
on the number of total piglet born, piglet born alive,
stillbirth, mummy, litter birthweight and average litter
birthweight (Table 3). No significant effect of the
different groups were found on the R-cloprostenol
474 K Kaeoket

Table 1. Morphology of umbilical

Normal Oedema Congestion Haemorrhage Anterior Posterior cord (designated as normal,
Groups (%) (%) (%) (%) presentation (%) presentation (%) oedema, congestion and haemor-
rhage) and the presentation (i.e.
I (n ¼ 120 piglets) 90.8 0 7.5 1.7 75.4 24.6 anterior and posterior) of the pig-
II (n ¼ 110 piglets) 87.3 0.9 10.9 0.9 64.0 36.0 lets in different groups
III (n ¼ 73 piglets) 87.7 0 12.3 0 67.1 32.9
IV (n ¼ 70 piglets) 87.1 0 12.9 0 67.1 32.9
V (n ¼ 105 piglets) 89.4 0 10.6 0 84.6 15.4

Table 2. Piglet with meconium stainings on the skin in different (2003), the present results showed that more than 80%
groups (percentage)
of the sows farrowed within 36 h of i.m. and perivulva
Slightly Moderately Severely injection of PGF2a analogs administered one or two
Groups Unstained stained stained stained days before expected farrowing date. Nevertheless,
farrowing processes of seven sows had completed at
I (n ¼ 120 piglets) 55.0 35.8 9.2 0
II (n ¼ 110 piglets) 41.8 50.0 6.4 1.8
night time (less than 24 h after R-cloprostenol injec-
III (n ¼ 73 piglets) 35.6 52.1 12.3 0 tion). Therefore, in practice, the time of R-cloprostenol
IV (n ¼ 70 piglets) 42.9 51.4 5.7 0 injection need to be adjusted in order to allow farmer to
V (n ¼ 105 piglets) 27.6 53.4 13.3 5.7 assist the sows that are having a difficult farrowing at
day time, to supervise colostrums intake, or to do cross
fostering piglets.
injection to farrowing interval, oxytocin injection to It has been demonstrated that PGF2 a are responsible
farrowing interval, expulsion interval and farrowing for pre-farrowing maternal behaviour and restlessness
duration (Table 4). behaviour in female pigs (Burne et al. 2000a,b, 2001,
2002). In addition, Walton et al. (2002) reported that
PGF2 a induce nesting behaviour in gilt was associated
Discussion with an increased in hypothalamic immediate early gene
The present data showed that a half dose (37.5 lg) of (IEG) expression (coinduction of c-fos and c-jun),
R-cloprostenol administered into perivulva region was whereas treatment with cloprostenol did not alter nest-
effective for inducing farrowing as the full recommended building behaviour or hypothalamic IEG expression.
dose (75 lg) administered into neck region (i.m.). This Nevertheless, luteolytic doses of both PGF2 a and
might be due to the fact that the lymphatic and venous cloprostenol resulted in increased expression of c-fos
vessels of female reproductive tract is greatly intercon- and c-jun mRNA in corpora luteal tissue of the gilts,
nected, resulting in an increased level of local ovarian suggesting that PGF2 a , and not cloprostenol, crosses
R-cloprostenol concentration (Oxenreider et al. 1965; the blood-brain barrier and acts directly on central
Krzymowski et al. 1990; Stefanczyk-Krzymowska et al. receptors to mediate its effect on nest-building beha-
1998; Stefanczyk-Krzymowska and Krzymowski 2002; viour. These findings support the present results in that
Stefanczyk-Krzymowska et al. 2005). In agreement with the restless behaviour was not seen in R-cloprostenol
Chantaraprateep et al. (1986) and Balogh and Bilkei treated sows.

Table 3. The number of total piglet born, born alive, stillbirth, mummy, litter birthweight and average litter birthweight in different groups
(mean ± SD)

Groups Total piglet born Born alive Stillbirth (%) Mummy (%) Litter birth weight (kg) Average litter birth weight (kg)

I (n ¼ 10 sows) 12.3 ± 2.2 11.4 ± 2.1 0.8 ± 0.9 (6.5) 0.1 ± 0.3 (0.8) 18.4 ± 2.8 1.5 ± 0.3
II (n ¼ 10 sows) 12.6 ± 2.9 12.2 ± 2.7 0.4 ± 0.9 (3.2) 0±0 (0) 19.2 ± 3.9 1.6 ± 0.3
III (n ¼ 8 sows) 9.3 ± 3.4 9.0 ± 3.5 0.1 ± 0.4 (1.1) 0.1 ± 0.4 (1.1) 14.9 ± 5.4 1.6 ± 0.2
IV (n ¼ 7 sows) 10.9 ± 2.4 10.4 ± 2.5 0.4 ± 0.5 (3.4) 0±0 (0) 16.5 ± 3.4 1.5 ± 0.2
V (n ¼ 8 sows) 13.7 ± 2.1 11.9 ± 2.1 1.4 ± 1.6 (10.2) 0.4 ± 0.8 (2.9) 19.3 ± 3.4 1.4 ± 0.1
Overall significance NS NS NS NS NS NS

NS, not significant.

Table 4. R-cloprostenol injection

R-cloprostenol injection Oxytocin injection to Expulsion Farrowing to farrowing interval, oxytocin
Groups to farrowing interval (min) farrowing interval (min) interval (min) duration (min) injection to farrowing interval,
expulsion interval and farrowing
I (n ¼ 10 sows) – – 17.5 ± 7.8 246.3 ± 121.5 duration in different groups
II (n ¼ 10 sows) 1501.0 ± 112.1 – 23.3 ± 12. 0 389.5 ± 203.3 (mean ± SD)
III (n ¼ 8 sows) 1723.4 ± 190.0 283.4 ± 190.0 33.8 ± 17.9 296.8 ± 107.4
IV (n ¼ 7 sows) 1541.8 ± 193.4 – 22.7 ± 11.8 275.0 ± 96.9
V (n ¼ 8 sows) 1512.4 ± 111.4 121.1 ± 97.0 21.7 ± 6.2 300.6 ± 91.2
Overall significance NS NS NS NS

NS, not significant.

 2006 The Author. Journal compilation  2006 Blackwell Verlag

Induce Farrowing by Using R-cloprostenol
It has been earlier reported that injection of PGF2 a
(Lutalyse, half dose ¼ 5 mg) or cloprostenol (Pla-
nate, half dose ¼ 88 lg) into the perianal region (at
about the 4- or 8-o’clock position) is as effective as a
route of administration into vaginal mucosa (Kirkwood
et al. 1996). However, in the present study, we further
demonstrated that induce farrowing by using R-clopr-
ostenol (Preloban) administered into the perivulva
region (at about the 3- or 9-o’clock position) as lower
dose as 37.5 lg is also as effective as an i.m. injection at
the full recommended dose (75 lg). The accomplish-
ment of R-cloprostenol to induce farrowing in the
present study might be explained by the study of Beretta
and Cavalli (2004) in that R-cloprostenol (Preloban)
purely consisted of the active isomer of cloprostenol. In
addition, it has also been shown that D-cloprostenol (i.e.
R-cloprostenol) is approximately 10 times more potent
thanDL-cloprostenol (Re et al. 1994). Consequently,
when D-cloprostenol is used a lower dosage could be
given than that required for DL-cloprostenol.
Mota-Rojas et al. (2002, 2005) and Alonso-Spilsbury
et al. (2004) reported that injecting oxytocin (i.e. 20–
50 IU, administered immediately following the birth of
the first piglet) during parturition resulted in a signifi-
cant decrease in time from injection to farrowing and
expulsion intervals, and also a significant higher number
of stillborn piglets per litter, number of piglets with
ruptured and haemorrhagic umbilical cords. In con-
trast, no significant effects of oxytocin administration
on the similar parameters were found in the present
study. The reason might be that a lower dosage (i.e.
10 IU) was used and the difference in timing of
administration of oxytocin (i.e. 24 h after initial of R-
cloprostenol administration) in the present study. In
addition, it has been reported that farrowing induction
by using of PGF (Lutalyse 5 mg ¼ single dose or
2.5 mg ¼ split dose) and oxytocin (20 IU, 24 h after
initial administration of PGF), particularly the admin-
istration of oxytocin, may have been a factor in the
farrowing complications and the high number of
stillbirths in sows with a closed cervix at the time of
oxytocin treatment (Cassar et al. 2005). Taken this
results and the present results together, there is little to
be gained by routine use of oxytocin as part of an
induce parturition programme.
In conclusion, the present results demonstrated that a
half dose (37.5 lg) of R-cloprostenol administered into
the perivulva region was effective for inducing farrow-
ing as the full recommended dose (75 lg) administered
into the neck region (i.m.) and with no restless
behaviour.
Acknowledgements
The authors are grateful to Panida Chanapiwat, Siriporn Tantawet,
Chawanlak Kongsuk, Faculty of Veterinary Science, Mahidol Uni-
versity, for excellent technical assistance. Assoc. Prof. Dr. Nils
Lundeheim, Department of Animal Breeding and Genetics, Faculty
of Veterinary Medicine and Animal Science, Swedish University of
Agricultural Science, and Assoc. Prof. Dr. Wichai Tantasuparuk,
Department of Obstetrics Gynaecology and Reproduction, Faculty of
Veterinary Science, Chulalongkorn University, are thanked for advice
in statistical analysis. R-cloprostenol (Preloban) for this study was
generously provided by Intervet (Thailand) Ltd.
 2006 The Author. Journal compilation  2006 Blackwell Verlag
475
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Submitted: 12.10.2005
Author’s address (for correspondence): Kampon Kaeoket, Faculty of
Veterinary Science, Mahidol University, Phutthamonthol 4 Rd.,
Salaya, Phutthamonthol, Nakorn-pathom, Thailand 73170. E-mail:
vskkk@mahidol.ac.th