- Email: [email protected]
Estrogen-induced delay of farrowing in swine
Theriogenology
37: 1205-I
212,
1992
ESTROGEN-INDUCEDDELAY OF FARROWINGIN SWINE B T. Eckerle,’ L. A. Edgerton? A. L. Jacobs3 and G. Ft. Newton4 Department of Animal Sciences University of Kentucky Lexington, KY 40546-0215 Received for publication: JuZy 11, 1991 Accepted: March 28, 1992 ABSTRACT Eighty-four sows and gilts were assigned to 4 treatment groups to assess the effects of estrogen upon normal and prostaglandin-induced farrowing. Sows in Group 1 were injected with saline and corn oil vehicles at 800 hours on Day 112 of gestation and served as controls. Sows in Group 2 received saline and 3 mg of estradiol benzoate. Sows in Group 3 received 10 mg of prostaglandin F2a (PGF2a) and corn oil, and sows in Group 4 received both the PGF2a and estradiol benzoate. The control sows farrowed at 74.5 + 6.8 hours after vehicle injections. Surprisingly, the average time from treatment to onset of parturition was significantly increased (P < 0.05) by the injection of estrogen alone (Group 2 = 100 r 9 hours). Closer examination showed that the interval was dichotomous with 6 of the 21 sows in Group 2 farrowing in less than 54 hours and 14 of 21 sows farrowing only after 100 hours. Prostaglandin injections shortened (P < 0.05) the interval to 41 + 8 hours. Litter size averaged 10.9 pigs and was similar for all treatments. As used in this study, there was no advantage to combining estrogen with prostaglandin-induced farrowing. Induced farrowing did not significantly reduce incidence of livebirths, but birthweights were lower (P c 0.05) in prostaglandin-treated gilts (Groups 3 and 4). Weaning weights remained lower for pigs from prostaglandin-treated sows, but treatment-related differences were not significant (P > 0.1). Performance characteristics of estrogen-treated sows and their litters were equal to those of the control sows. Key words: swine, estradiol benzoate, prostaglandin,
farrowing
Acknowledgments The investigation reported in this paper (No. 91-5-121) is in connection with a project of the Kentucky Agricultural Experiment Station and is published with the approval of the director. The authors thank Dr. R. G. Loy of the University of Kentucky for the anti-progesterone sera. 1 Present Address: 7984 Jaymes Street, Dublin Ohio 43017. 2 To whom reprint requests should be sent. 3 Present Address: Departmen! of Biochemistry and Molecular Blvd. 4
University
of Texas
M.D.
Anderson
Present Address: Center,
Copyright
Prairie
Cancer
Center,
Biology, 1575 Holcombe Houston, TX 77030.
International Dairy Goat Research Center, Coop Agriculture View A&M University, Prairie View, TX 77446-2886.
0 1992 Butterworth-Heinemann
Research
Theriogenolog
1206
y
INTRODUCTION Parturition in many species, including swine, involves a prepartum decrease in circulating concentrations of progesterone and an increase in estrogen, which peaks within 48 hours of parturition. If progesterone concentrations are maintained via exogenous administration, gestation is maintained. If parturition is delayed more than 2 days by exogenous progesterone, it is accompanied by reduced concentrations of estrogen and a high incidence of stillbirths (1). Conversely, if progesterone concentrations are reduced prematurely by administration of prostaglandins, parturition occurs prematurely. Induction of parturition before Day 112 (prior to peak estrogen concentrations) is associated with reduced birth weights and poor survival rates in pigs (2). Thus either delaying or hastening farrowing is often detrimental to the survival and growth of pigs. Although administration of estrogen results in premature delivery of sheep (3), goats (4), and cattle (5), it has been reported to have no effect on the time of delivery in pigs (6). However, Wilson et al. (7) demonstrated with gilts that if farrowing was delayed by progesterone, subsequent administration of estrogen (3 mg estradiol benzoate) dramatically reduced the incidence of stillbirths associated with such a delay. We designed the present study to determine whether similar administration of estrogen might also improve the survival rate as well as other performance characteristics of offspring from sows induced to farrow early. MATERIALSAND METHODS Eighty-four sows (n=68) and gilts (n=16), hereafter referred to collectively as sows, were used in the study. Most of the sows (n = 76) were Yorkshire X Hampshire crosses; the remainder were purebred Yorkshire (n = 7) and Hampshire (n = 1). The sows farrowed from November through the following April and were then assigned to one of four treatment groups (n = 21 per group). All injections were given subcutaneously in the neck at 0800 hours on Day 112 of gestation (Day 0 = first day of estrus). Group 1 served as controls and received saline ( 2 ml) and corn oil (1 ml). Group 2 received saline and 3 mg of estradiol benzoatea in corn oil. Group 3 received corn oil and 10 mg PGF2a.b Group 4 received both estradiol benzoate and PGF2a. The sows were observed every 2 hours and thzn more frequently when farrowing was imminent or in progress. The data recorded included the time from treatment to onset of parturition, the duration of farrowing, the number of pigs born live and the total number born, and the interval from weaning to estrus. Also recorded were the birth weights of the pigs (taken the morning after birth), the weaning weights (taken at 28 days of age) and the percentage of pigs surviving at weaning. In addition, blood samples (5 ml) were collected from the vena cava of sows (8) immediately before treatment and again 12 hours later. Samples were allowed to coagulate for 24 hours at 4” C and then serum was separated by centrifugation. Serum was decanted and stored at -15” C until assayed for progesterone by radioimmunoassay (9). Data were analyzed by analysis of variance using orthogonal contrasts to compare treatments (10). Contrasts for birth weights and weaning weights were analyzed using litter size (for birth weights) and the number of offspring born live (for weaning a Steraloids, Wilton, N.H. b Lutalyse, The Upjohn Company, Kalamazoo, Ml.
1: 0.5
10.5
Mean live births
+ 0.5
+ 1.5
f 0.5
f 0.6
i 0.2
+ 0.9
+ 8.9
7.12 + 0.12
1.25 + 0.02
7.7
95.0
10.0
10.6
4.7
4.3
100.6
+ 0.6
+ 1.5
+ 0.6
f 0.6
f 0.3
* 0.9
f 8.4
6.80 + 0.13
1.16 + 0.02
7.1
95.8
10.1
10.6
5.0
4.5
41 .l
Treatment groupb 2 = Estrogen 3 = Prostaglandin
f 0.4
+ 4.4
+ 0.6
z!?0.4
* 0.3
-t 1.5
+ 8.0
7.04 + 0.13
1.07 + 0.02
7.2
89.0
10.2
11.4
5.0
5.7
41.2
4 = Estrogen + Prostaglandin
eLS means adjusted for number of live births.
Qows in Group 1 received saline and corn oil on Day 112 of gestation. Sows in Group 2 received 3 mg estradiol benzoate in oil plus saline. Sows in Group 3 received 10 mg prostaglandin F2a in saline plus oil. Sows in Group 4 received both estradiol benzoate and prostaglandin F2a. CMean f standard error. dLS means adjusted for litter size.
aTreatment contrasts were: 1+2 vs 3+4, 1 vs 2, and 3 vs 4. Contrasts not listed for each characteristic indicate P > 0.1, contrasts with no asterisk indicate P < 0.1, one asterisk indicates P c 0.05 and two asterisks indicate P < 0.01.
Weaning weights (kg)*
(kg)d 7.08 + 0.12
1.20 It 0.02
Birth weights
vs 4
It- 0.5
7.9
No. of pigs weaned per sow
1+2 vs 3+4’,3
+ 2.3
Percentage of live births
94.5
3 vs 4’
+ 0.5
11.2
(hours) of farrowing
Days from weaning to estrus
Duration
Mean litter size
i 6.8C
+ 0.3
74.5
4.3
1 vs 2’
3+4**
1 = Control
+Y0.8
(hours)
1+2 vs
Significant Orthogonal Contrastsa
4.5
to onset of parturition
Period from treatment
Characteristic
Table 1. Farrowing and performance characteristics of treated sows and pigs
9
% 2 B
2 (b 2.
1208
Theriogenology
weights) as covariates. The survival rate of pigs at birth and at weaning and the time from treatment to the onset of parturition were compared among treatment groups by Chi-square analysis via the FunCat Procedure (10). Normality of the farrowing distribution was compared with the Chi-square distribution (11). RESULTSAND DISCUSSION Gestation length in the control sows averaged 115 days, which was consistent with the herd average. Thus, injections of the vehicle on Day 112 had no apparent effect on the time to parturition. However, PGF2a, with or without estrogen, reduced the time between administration of treatments and the onset of parturition (Table 1). The interval from treatment to the onset of parturition was about 41 hours. One sow in Group 3 and 2 sows in Group 4 had intervals to parturition exceeding 100 hours. Excluding the data on those 3 sows resulted in mean intervals to parturition of 29.3 and 30.5 hours for Groups 3 and 4, respectively. These intervals are consistent with other estimates (12), which included only sows that farrowed within a restricted period. Luteal production of progesterone is generally regarded to be essential for the maintenance of pregnancy in swine. The reduction (P c 0.05) in concentration of progesterone in the serum of prostaglandin-treated sows (Groups 3 and 4) 12 hours after the treatment indicates that luteolysis was the mechanism by which farrowing was induced in this study (Table 2). Therefore, our results are consistent with other reports (as reviewed in reference 6) with respect to the effects of prostaglandins upon the induction of parturition in swine. Table 2. Progesterone concentrations in the serum before and 12 hours after treatment Characteristic Control
Treatment Groupa E PG
E+PG
Concentration of P4 at time of treatment
9.2 + 0.6b
ng/ml 8.8 + 0.4 9.4 + 0.8
9.7 k 0.9
Concentration of P4 12 hours after treatment
8.7 + 0.6
8.3 Z!Z0.6
5.1 I!I 0.6C
5.0 Ik 0.5c
a Controls sows (Group 1) received saline and corn oil at 800 hours on Day 112 of gestation; sows in Group 2 (E) received 3 mg estradiol benzoate in oil plus saline; sows in Group 3 (PG) received 10 mg PGF2a in saline plus oil; sows in Group 4 (E + PG) received 3 mg estradiol benzoate and 10 mg PGF2a. bMean + standard error. cconcentration of P4 in prostaglandin-treated groups was less (P < 0.05) than the pretreatment values and less (P < 0.05) than the post-treatment values of control and estradiol benzoate-treated groups. Administration of estrogen alone to sows on Day 112 (Group 2, Table 1) resulted in a delay of parturition. In the control sows, the times from the administration of vehicle
Theriogen olog y
1209
to the onset of farrowing were distributed normally, with a mean of 74.5 ? 6.8 hours. In contrast, the average time to the onset of parturition in sows receiving estrogen only was 100.6 k 8.9 hours. Closer examination of the data shows that the response to estrogen on Day 112 was dichotomous. Fourteen of the sows in Group 2 farrowed 2 1 SD after the mean interval of the control group. However, 6 sows began to farrow within a time interval shorter than that of the control animals. This dichotomous response to estrogen treatment is shown in Figure 1. The overall delay of parturition due to estrogen treatment and the dichotomous effect of estrogen upon the time of parturition was unexpected. The administration of estrogen induces parturition prematurely in ruminants (3-5). First et al. (6) reported that the administration of estrogen late in gestation to sows or to the fetuses did not alter the length of gestation. However, they used a different analogue (estradiol cypionate) administered over a period of days beginning as early as Day 80 of gestation, at doses from 5 to l&fold greater than those in our present study. Any or a combination of these factors may account for the difference is response between the earlier study and our present one.
40
60
80
100
120
>130
Hours Figure 1.
Intervals from treatment to the onset of farrowing for sows treated with estradiol benzoate on Day 112 (Group 2).
Observations from the present study do not explain the split in time to the onset of parturition. Dukes et al. (13) reported that administration of estradiol to rats on Day 20 of gestation delayed the time of parturition while the injection of estradiol at noon on Day 21 caused early delivery. When estradiol was given at 9:30 a.m. on Day 21, it caused a split between early and late parturition, similar to the results we observed for Group 2. Thus, a slight shift in the stage of gestation at which estrogen is administered may also modify the time to parturition in swine. Control sows farrowed from Day 113 to Day 116. This suggests that injections on Day 112 were given at different times relative to the normal length of gestation for each sow. Therefore, the dichotomous
1210
Theriogenology
interval to parturition observed in swine may reflect mechanisms similar to those in rats (13). Estrogen causes the formation of uterine receptors for relaxin (14) and oxytocin (15), actions which can account for hastening the process of parturition(l6,17). In contrast, estrogen treatment can also stimulate or maintain luteal function during gestation in both rats (18) and swine (14), although the mechanisms likely differ for each species (18, 19). Progesterone concentrations in samples taken every 6 hours from 2 cannulated sows which received estrogen on Day 112 did not decline until, or after, the onset of parturition, suggesting that prolonged gestation was associated with luteal maintenance(20). The modification of time to farrowing with estrogen treatment is intriguing because it offers the potential to synchronize farrowing over a broader range of days than is possible with prostaglandin alone. Of course, this would be of economic value only if the ensuing parturition and neonatal survival rate were normal or enhanced. Other observations made in this study indicated that estrogen treatment had few, if any, negative side effects (Table 1). No treatment modified the duration of farrowing. One sow in Group 4 required 31 hours to farrow, which accounts for the rise in time for that group. Mean litter size, ranged from 10.6 to 11.4 among the four groups, and, as expected, was not altered by the treatments administered on Day 112 of gestation. The percentage of livebirths also was not affected markedly by treatment, although it was slightly lower (P c 0.1) for Group 4 than that for Group 3. However, the lower number in Group 4 reflects the high incidence of stillborn pigs (90%) in the sow with the 31-hour farrowing period. The remaining 20 sows in Group 4 averaged a rate of 93% livebirths. An early induction of farrowing may reduce the birth weights of offspring since the pigs born in the two prostaglandin-treated groups (Groups 3 and 4) were lighter (P c 0.02) than those born in the control and the estrogen-treated groups. The birth weights of pigs receiving both prostaglandin and estradiol benzoate tended to be lower (P < 0.1) than those of pigs receiving prostaglandin alone. Because reduced birth weight is a predictor of a reduced rate of survival, it is of concern that estrogen treatment may have contributed to the lower birth weights in Group 4. However, the number of pigs weaned and the pig weights at weaning were not altered significantly by any of the treatments. In summary, we were not able to demonstrate that combining estrogen treatment with the administration of prostaglandin to induce farrowing improved the performance of either sows or their litters. This appears to be consistent with studies in which estradiol benzoate was given 6 to 20 hours after prostaglandin treatment (21). However, the present study demonstrated that estrogen can delay farrowing in sows. Furthermore, such a delay had no apparent negative effect on the subsequent parturition, offspring survival rate or growth. This may have practical implications for the synchronization of farrowing, because it offers the potential to delay farrowing in sows as well as to induce farrowing with prostaglandins. The fact that estrogen administration did not delay the onset of farrowing in sows that also received prostaglandin indicates that the degree of delay could be controlled by a sequential administration of estrogen and prostaglandin. However, estrogen had a dichotomous action resulting in both early and late farrowing. A consistent response is obviously essential for any compound to be used for the synchronization of farrowing. Thus, the
1211
Theriogenology
factor(s) which determine(s) whether estrogen delays or hastens farrowing must be identified before estrogen can be utilized as part of a management program to extend the range of days over which farrowing can be synchronized. REFERENCES 1.
Wilson, M.E., Edgerton, L.A., Cromwell, G.L. and Stably, T.S. Progesterone and estrogen concentrations in gilts with delayed parturition. J. Anim. Sci. =:323329 (1981).
2.
Holtz, W., Diallo, T., Spangenberg, B., Rockel, P., Bogner, H. Smidt, D. and Leidl, W. Induction of parturition in sows with a prostaglandin F2a-analog. J. Anim. Sci. &:367-373 (1979).
3.
Currie, W.B. Endocrinology of pregnancy and parturition in sheep and goats. In: Proceedings of the Symposium, Management of Reproduction in Sheep and Goals. (University of Wisconsin, Madison). pp. 72-78 (1977).
4.
Currie, W.B. and Thorburn, G.D. Release of prostaglandin F, regression of corpora lutea and induction of premature parturition in goats treated with estradiol-170. Prostaglandins 11:i 093-l 103 (1973). GrBnberg-Pedersen, H. Partus provacatus hos koen. Nord. Ved. Med. ?l_:591597 (1969).
5.
6.
First, N.L., Lohse, J.K. and Nara, B.S. The endocrine control of parturition. 1: Butterworth Cole, D.J.A. and Foxcroft, G.R. (eds), Control of Pig Reproduction. Scientific, London, 1982. pp. 31 l-342.
7.
Wilson, M.E., Edgerton, L.A., Cromwell, G.L. and Stahly, T.S. Effects of estrogen and prostaglandin on progesterone-delayed farrowing. Theriogenology x:577583 (1989).
8.
Carle, B.N. and Dewhirst, W.H. A method for bleeding swine. J. Am. Vet. Med. Assoc. =:495-496 (1942).
9.
Saunders, M.J., Edgerton, L.A., Kagan, J.M., Stahly, T.S. and Cromwell, G.L. Comparison of intrauterine and subcutaneous sites of estrogen injection for luteal maintenance in swine. J. Anim. Sci. =:146-149 (1983).
10.
SAS User’s Guide: Statistics.
11.
Steele, R.G.D. and Torrie, J.H. Principles and Procedures of Statistics. Hill, New York, 1960, pp. 349-350.
12.
Diehl, J.R., Godke, R.A., Killian, D.B. and Day, B.N. Induction of parturition in swine with prostaglandin F2a. J. Anim. Sci. &3:1229-1234 (1974).
13.
Dukes, M., Chester, R. and Atkinson, P. Effects of oestradiol and prostaglandin F2n on the timing of parturition in the rat. J. Reprod. Fertil. ;F8:325-334 (1974)
SAS Institute, Inc., Cary, NC. 1985. McGraw-
1212
Theriogenology
14.
Mercado-Simmen, R.C., Goodwin, B., Ueno, M.S.,Yamamoto, S.Y. and BryantGreenwood, G.D. Relaxin receptors in the myometrium and cervix of the pig. Biol. Reprod. =:120-l 28 (1982).
15.
Fuchs, A.R., Periyasamy, S., Alexandrova, M. and Soloff, M.S. Correlation between oxytocin receptor concentration and responsiveness to oxytocin in pregnant rat Endocrinology m:742-749 (1983). myometrium: effects of ovarian steroids.
16.
Butler, W.R. and Boyd, R.D. Relaxin enhances synchronization of parturition induced with prostaglandin F2a in swine Biol Reprod. a:1 061-l 065 (1983).
17.
Welp, C., Jochle, W. and Holtz, W. Induction of parturition in swine with a prostaglandin analog and oxytocin: a trial involving dose of oxytocin and parity. Theriogenology =:509-520 (1984).
18.
Khan, I., Glaser, L.A. and Gibori, G. Reactivation of regressing corpora lutea by estradiol in the pregnant rat: dependence on placental lactogen. Biol. Reprod. =:I 083-l 088 (1987).
19.
Bazer, F.W. and W.W. Thatcher. Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2a by the uterine endometrium. Prostaglandins u:397-401 (1977).
20.
Eckerle, B.T. The Actions of Estradiol Benzoate and Prostaglandin F2a on Parturition in Swine. M.S. Thesis. University of Kentucky, Lexington, 1988.
21 . Guthrie, H.D. Control of time of parturition in pigs. uSuppl.):229-244 (1985).
J. Reprod. Fertil.
37: 1205-I
212,
1992
ESTROGEN-INDUCEDDELAY OF FARROWINGIN SWINE B T. Eckerle,’ L. A. Edgerton? A. L. Jacobs3 and G. Ft. Newton4 Department of Animal Sciences University of Kentucky Lexington, KY 40546-0215 Received for publication: JuZy 11, 1991 Accepted: March 28, 1992 ABSTRACT Eighty-four sows and gilts were assigned to 4 treatment groups to assess the effects of estrogen upon normal and prostaglandin-induced farrowing. Sows in Group 1 were injected with saline and corn oil vehicles at 800 hours on Day 112 of gestation and served as controls. Sows in Group 2 received saline and 3 mg of estradiol benzoate. Sows in Group 3 received 10 mg of prostaglandin F2a (PGF2a) and corn oil, and sows in Group 4 received both the PGF2a and estradiol benzoate. The control sows farrowed at 74.5 + 6.8 hours after vehicle injections. Surprisingly, the average time from treatment to onset of parturition was significantly increased (P < 0.05) by the injection of estrogen alone (Group 2 = 100 r 9 hours). Closer examination showed that the interval was dichotomous with 6 of the 21 sows in Group 2 farrowing in less than 54 hours and 14 of 21 sows farrowing only after 100 hours. Prostaglandin injections shortened (P < 0.05) the interval to 41 + 8 hours. Litter size averaged 10.9 pigs and was similar for all treatments. As used in this study, there was no advantage to combining estrogen with prostaglandin-induced farrowing. Induced farrowing did not significantly reduce incidence of livebirths, but birthweights were lower (P c 0.05) in prostaglandin-treated gilts (Groups 3 and 4). Weaning weights remained lower for pigs from prostaglandin-treated sows, but treatment-related differences were not significant (P > 0.1). Performance characteristics of estrogen-treated sows and their litters were equal to those of the control sows. Key words: swine, estradiol benzoate, prostaglandin,
farrowing
Acknowledgments The investigation reported in this paper (No. 91-5-121) is in connection with a project of the Kentucky Agricultural Experiment Station and is published with the approval of the director. The authors thank Dr. R. G. Loy of the University of Kentucky for the anti-progesterone sera. 1 Present Address: 7984 Jaymes Street, Dublin Ohio 43017. 2 To whom reprint requests should be sent. 3 Present Address: Departmen! of Biochemistry and Molecular Blvd. 4
University
of Texas
M.D.
Anderson
Present Address: Center,
Copyright
Prairie
Cancer
Center,
Biology, 1575 Holcombe Houston, TX 77030.
International Dairy Goat Research Center, Coop Agriculture View A&M University, Prairie View, TX 77446-2886.
0 1992 Butterworth-Heinemann
Research
Theriogenolog
1206
y
INTRODUCTION Parturition in many species, including swine, involves a prepartum decrease in circulating concentrations of progesterone and an increase in estrogen, which peaks within 48 hours of parturition. If progesterone concentrations are maintained via exogenous administration, gestation is maintained. If parturition is delayed more than 2 days by exogenous progesterone, it is accompanied by reduced concentrations of estrogen and a high incidence of stillbirths (1). Conversely, if progesterone concentrations are reduced prematurely by administration of prostaglandins, parturition occurs prematurely. Induction of parturition before Day 112 (prior to peak estrogen concentrations) is associated with reduced birth weights and poor survival rates in pigs (2). Thus either delaying or hastening farrowing is often detrimental to the survival and growth of pigs. Although administration of estrogen results in premature delivery of sheep (3), goats (4), and cattle (5), it has been reported to have no effect on the time of delivery in pigs (6). However, Wilson et al. (7) demonstrated with gilts that if farrowing was delayed by progesterone, subsequent administration of estrogen (3 mg estradiol benzoate) dramatically reduced the incidence of stillbirths associated with such a delay. We designed the present study to determine whether similar administration of estrogen might also improve the survival rate as well as other performance characteristics of offspring from sows induced to farrow early. MATERIALSAND METHODS Eighty-four sows (n=68) and gilts (n=16), hereafter referred to collectively as sows, were used in the study. Most of the sows (n = 76) were Yorkshire X Hampshire crosses; the remainder were purebred Yorkshire (n = 7) and Hampshire (n = 1). The sows farrowed from November through the following April and were then assigned to one of four treatment groups (n = 21 per group). All injections were given subcutaneously in the neck at 0800 hours on Day 112 of gestation (Day 0 = first day of estrus). Group 1 served as controls and received saline ( 2 ml) and corn oil (1 ml). Group 2 received saline and 3 mg of estradiol benzoatea in corn oil. Group 3 received corn oil and 10 mg PGF2a.b Group 4 received both estradiol benzoate and PGF2a. The sows were observed every 2 hours and thzn more frequently when farrowing was imminent or in progress. The data recorded included the time from treatment to onset of parturition, the duration of farrowing, the number of pigs born live and the total number born, and the interval from weaning to estrus. Also recorded were the birth weights of the pigs (taken the morning after birth), the weaning weights (taken at 28 days of age) and the percentage of pigs surviving at weaning. In addition, blood samples (5 ml) were collected from the vena cava of sows (8) immediately before treatment and again 12 hours later. Samples were allowed to coagulate for 24 hours at 4” C and then serum was separated by centrifugation. Serum was decanted and stored at -15” C until assayed for progesterone by radioimmunoassay (9). Data were analyzed by analysis of variance using orthogonal contrasts to compare treatments (10). Contrasts for birth weights and weaning weights were analyzed using litter size (for birth weights) and the number of offspring born live (for weaning a Steraloids, Wilton, N.H. b Lutalyse, The Upjohn Company, Kalamazoo, Ml.
1: 0.5
10.5
Mean live births
+ 0.5
+ 1.5
f 0.5
f 0.6
i 0.2
+ 0.9
+ 8.9
7.12 + 0.12
1.25 + 0.02
7.7
95.0
10.0
10.6
4.7
4.3
100.6
+ 0.6
+ 1.5
+ 0.6
f 0.6
f 0.3
* 0.9
f 8.4
6.80 + 0.13
1.16 + 0.02
7.1
95.8
10.1
10.6
5.0
4.5
41 .l
Treatment groupb 2 = Estrogen 3 = Prostaglandin
f 0.4
+ 4.4
+ 0.6
z!?0.4
* 0.3
-t 1.5
+ 8.0
7.04 + 0.13
1.07 + 0.02
7.2
89.0
10.2
11.4
5.0
5.7
41.2
4 = Estrogen + Prostaglandin
eLS means adjusted for number of live births.
Qows in Group 1 received saline and corn oil on Day 112 of gestation. Sows in Group 2 received 3 mg estradiol benzoate in oil plus saline. Sows in Group 3 received 10 mg prostaglandin F2a in saline plus oil. Sows in Group 4 received both estradiol benzoate and prostaglandin F2a. CMean f standard error. dLS means adjusted for litter size.
aTreatment contrasts were: 1+2 vs 3+4, 1 vs 2, and 3 vs 4. Contrasts not listed for each characteristic indicate P > 0.1, contrasts with no asterisk indicate P < 0.1, one asterisk indicates P c 0.05 and two asterisks indicate P < 0.01.
Weaning weights (kg)*
(kg)d 7.08 + 0.12
1.20 It 0.02
Birth weights
vs 4
It- 0.5
7.9
No. of pigs weaned per sow
1+2 vs 3+4’,3
+ 2.3
Percentage of live births
94.5
3 vs 4’
+ 0.5
11.2
(hours) of farrowing
Days from weaning to estrus
Duration
Mean litter size
i 6.8C
+ 0.3
74.5
4.3
1 vs 2’
3+4**
1 = Control
+Y0.8
(hours)
1+2 vs
Significant Orthogonal Contrastsa
4.5
to onset of parturition
Period from treatment
Characteristic
Table 1. Farrowing and performance characteristics of treated sows and pigs
9
% 2 B
2 (b 2.
1208
Theriogenology
weights) as covariates. The survival rate of pigs at birth and at weaning and the time from treatment to the onset of parturition were compared among treatment groups by Chi-square analysis via the FunCat Procedure (10). Normality of the farrowing distribution was compared with the Chi-square distribution (11). RESULTSAND DISCUSSION Gestation length in the control sows averaged 115 days, which was consistent with the herd average. Thus, injections of the vehicle on Day 112 had no apparent effect on the time to parturition. However, PGF2a, with or without estrogen, reduced the time between administration of treatments and the onset of parturition (Table 1). The interval from treatment to the onset of parturition was about 41 hours. One sow in Group 3 and 2 sows in Group 4 had intervals to parturition exceeding 100 hours. Excluding the data on those 3 sows resulted in mean intervals to parturition of 29.3 and 30.5 hours for Groups 3 and 4, respectively. These intervals are consistent with other estimates (12), which included only sows that farrowed within a restricted period. Luteal production of progesterone is generally regarded to be essential for the maintenance of pregnancy in swine. The reduction (P c 0.05) in concentration of progesterone in the serum of prostaglandin-treated sows (Groups 3 and 4) 12 hours after the treatment indicates that luteolysis was the mechanism by which farrowing was induced in this study (Table 2). Therefore, our results are consistent with other reports (as reviewed in reference 6) with respect to the effects of prostaglandins upon the induction of parturition in swine. Table 2. Progesterone concentrations in the serum before and 12 hours after treatment Characteristic Control
Treatment Groupa E PG
E+PG
Concentration of P4 at time of treatment
9.2 + 0.6b
ng/ml 8.8 + 0.4 9.4 + 0.8
9.7 k 0.9
Concentration of P4 12 hours after treatment
8.7 + 0.6
8.3 Z!Z0.6
5.1 I!I 0.6C
5.0 Ik 0.5c
a Controls sows (Group 1) received saline and corn oil at 800 hours on Day 112 of gestation; sows in Group 2 (E) received 3 mg estradiol benzoate in oil plus saline; sows in Group 3 (PG) received 10 mg PGF2a in saline plus oil; sows in Group 4 (E + PG) received 3 mg estradiol benzoate and 10 mg PGF2a. bMean + standard error. cconcentration of P4 in prostaglandin-treated groups was less (P < 0.05) than the pretreatment values and less (P < 0.05) than the post-treatment values of control and estradiol benzoate-treated groups. Administration of estrogen alone to sows on Day 112 (Group 2, Table 1) resulted in a delay of parturition. In the control sows, the times from the administration of vehicle
Theriogen olog y
1209
to the onset of farrowing were distributed normally, with a mean of 74.5 ? 6.8 hours. In contrast, the average time to the onset of parturition in sows receiving estrogen only was 100.6 k 8.9 hours. Closer examination of the data shows that the response to estrogen on Day 112 was dichotomous. Fourteen of the sows in Group 2 farrowed 2 1 SD after the mean interval of the control group. However, 6 sows began to farrow within a time interval shorter than that of the control animals. This dichotomous response to estrogen treatment is shown in Figure 1. The overall delay of parturition due to estrogen treatment and the dichotomous effect of estrogen upon the time of parturition was unexpected. The administration of estrogen induces parturition prematurely in ruminants (3-5). First et al. (6) reported that the administration of estrogen late in gestation to sows or to the fetuses did not alter the length of gestation. However, they used a different analogue (estradiol cypionate) administered over a period of days beginning as early as Day 80 of gestation, at doses from 5 to l&fold greater than those in our present study. Any or a combination of these factors may account for the difference is response between the earlier study and our present one.
40
60
80
100
120
>130
Hours Figure 1.
Intervals from treatment to the onset of farrowing for sows treated with estradiol benzoate on Day 112 (Group 2).
Observations from the present study do not explain the split in time to the onset of parturition. Dukes et al. (13) reported that administration of estradiol to rats on Day 20 of gestation delayed the time of parturition while the injection of estradiol at noon on Day 21 caused early delivery. When estradiol was given at 9:30 a.m. on Day 21, it caused a split between early and late parturition, similar to the results we observed for Group 2. Thus, a slight shift in the stage of gestation at which estrogen is administered may also modify the time to parturition in swine. Control sows farrowed from Day 113 to Day 116. This suggests that injections on Day 112 were given at different times relative to the normal length of gestation for each sow. Therefore, the dichotomous
1210
Theriogenology
interval to parturition observed in swine may reflect mechanisms similar to those in rats (13). Estrogen causes the formation of uterine receptors for relaxin (14) and oxytocin (15), actions which can account for hastening the process of parturition(l6,17). In contrast, estrogen treatment can also stimulate or maintain luteal function during gestation in both rats (18) and swine (14), although the mechanisms likely differ for each species (18, 19). Progesterone concentrations in samples taken every 6 hours from 2 cannulated sows which received estrogen on Day 112 did not decline until, or after, the onset of parturition, suggesting that prolonged gestation was associated with luteal maintenance(20). The modification of time to farrowing with estrogen treatment is intriguing because it offers the potential to synchronize farrowing over a broader range of days than is possible with prostaglandin alone. Of course, this would be of economic value only if the ensuing parturition and neonatal survival rate were normal or enhanced. Other observations made in this study indicated that estrogen treatment had few, if any, negative side effects (Table 1). No treatment modified the duration of farrowing. One sow in Group 4 required 31 hours to farrow, which accounts for the rise in time for that group. Mean litter size, ranged from 10.6 to 11.4 among the four groups, and, as expected, was not altered by the treatments administered on Day 112 of gestation. The percentage of livebirths also was not affected markedly by treatment, although it was slightly lower (P c 0.1) for Group 4 than that for Group 3. However, the lower number in Group 4 reflects the high incidence of stillborn pigs (90%) in the sow with the 31-hour farrowing period. The remaining 20 sows in Group 4 averaged a rate of 93% livebirths. An early induction of farrowing may reduce the birth weights of offspring since the pigs born in the two prostaglandin-treated groups (Groups 3 and 4) were lighter (P c 0.02) than those born in the control and the estrogen-treated groups. The birth weights of pigs receiving both prostaglandin and estradiol benzoate tended to be lower (P < 0.1) than those of pigs receiving prostaglandin alone. Because reduced birth weight is a predictor of a reduced rate of survival, it is of concern that estrogen treatment may have contributed to the lower birth weights in Group 4. However, the number of pigs weaned and the pig weights at weaning were not altered significantly by any of the treatments. In summary, we were not able to demonstrate that combining estrogen treatment with the administration of prostaglandin to induce farrowing improved the performance of either sows or their litters. This appears to be consistent with studies in which estradiol benzoate was given 6 to 20 hours after prostaglandin treatment (21). However, the present study demonstrated that estrogen can delay farrowing in sows. Furthermore, such a delay had no apparent negative effect on the subsequent parturition, offspring survival rate or growth. This may have practical implications for the synchronization of farrowing, because it offers the potential to delay farrowing in sows as well as to induce farrowing with prostaglandins. The fact that estrogen administration did not delay the onset of farrowing in sows that also received prostaglandin indicates that the degree of delay could be controlled by a sequential administration of estrogen and prostaglandin. However, estrogen had a dichotomous action resulting in both early and late farrowing. A consistent response is obviously essential for any compound to be used for the synchronization of farrowing. Thus, the
1211
Theriogenology
factor(s) which determine(s) whether estrogen delays or hastens farrowing must be identified before estrogen can be utilized as part of a management program to extend the range of days over which farrowing can be synchronized. REFERENCES 1.
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Holtz, W., Diallo, T., Spangenberg, B., Rockel, P., Bogner, H. Smidt, D. and Leidl, W. Induction of parturition in sows with a prostaglandin F2a-analog. J. Anim. Sci. &:367-373 (1979).
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Dukes, M., Chester, R. and Atkinson, P. Effects of oestradiol and prostaglandin F2n on the timing of parturition in the rat. J. Reprod. Fertil. ;F8:325-334 (1974)
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Fuchs, A.R., Periyasamy, S., Alexandrova, M. and Soloff, M.S. Correlation between oxytocin receptor concentration and responsiveness to oxytocin in pregnant rat Endocrinology m:742-749 (1983). myometrium: effects of ovarian steroids.
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Butler, W.R. and Boyd, R.D. Relaxin enhances synchronization of parturition induced with prostaglandin F2a in swine Biol Reprod. a:1 061-l 065 (1983).
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Welp, C., Jochle, W. and Holtz, W. Induction of parturition in swine with a prostaglandin analog and oxytocin: a trial involving dose of oxytocin and parity. Theriogenology =:509-520 (1984).
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Khan, I., Glaser, L.A. and Gibori, G. Reactivation of regressing corpora lutea by estradiol in the pregnant rat: dependence on placental lactogen. Biol. Reprod. =:I 083-l 088 (1987).
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Bazer, F.W. and W.W. Thatcher. Theory of maternal recognition of pregnancy in swine based on estrogen controlled endocrine versus exocrine secretion of prostaglandin F2a by the uterine endometrium. Prostaglandins u:397-401 (1977).
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Eckerle, B.T. The Actions of Estradiol Benzoate and Prostaglandin F2a on Parturition in Swine. M.S. Thesis. University of Kentucky, Lexington, 1988.
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