PARTURITION IN THE GOAT: PLASMA CONCENTRATIONS OF PROSTAGLANDIN F AND STEROID HORMONES AND UTERINE ACTIVITY DURING LATE PREGNANCY AND PARTURITION
I. UMO, R. J. FITZPATRICK AND W. R. WARD Department of Veterinary Clinical Studies, University ofLiverpool,
'Leahurst', Neston, Merseyside, L64 7TE
(Received 14 April 1975) SUMMARY
in plasma concentrations of hormones and uterine activity associated with sponparturition in the goat were examined. No change in oestradiol-17\g=b\ concentration was detected during the experimental period, but oestradiol-17\g=a\ consistently increased in concentration 3\p=n-\4days before parturition. This was followed by an increase in prostaglandin F two days later, while a pre-partum decline in progesterone concentration occurred 18\p=n-\20 h after the significant increase in prostaglandin F. The onset of uterine contractions coincided with a significant decline in progesterone concentration and a period of continually rising prostaglandin F and oestradiol-17\g=a\ concentrations. Uterine activity expressed in Montevideo units did not change until 10\p=n-\8h before foetal expulsion. These results support the hypothesis that in the goat the elevated prepartum concentration of prostaglandin F brings about luteolysis and a subsequent decline in progesterone
Changes taneous
concentration.
INTRODUCTION
Recent studies have suggested that prostaglandins (PG's) may be important in the control of parturition in several species (Liggins, Fairclough, Grieves, Kendall & Knox, 1973). In goats, blood concentrations of PGF are elevated before delivery (Thorburn, Nicol, Bassett, Shutt & Cox, 1972; Currie, Wong, Cox & Thorburn, 1973). Administration of PGF2a to goats in late pregnancy causes a fall in plasma progesterone concentration and premature parturition (Currie & Thorburn, 1973). It might be expected that PGF2ci, a potent luteolysin in several species (Inskeep, 1973) would be responsible for the pre-partum decline in progesterone in goats (Irving, Jones & Knifton, 1972; Thorburn & Schneider, 1972), since this species depends on the corpus luteum for the progesterone requirements of pregnancy (Linzell & Heap, 1968). Thorburn et al. (1972) and Currie et al. (1973) have presented preliminary evidence of an association between the prepartum decline in progesterone and the increase in PGF. The present study has examined the precise temporal relationships between PGF, oestrogens and progesterone in serial blood samples obtained from eight goats during late pregnancy and spontaneous parturition.
MATERIALS AND METHODS
Animals and surgical techniques Four goats with single foetuses (determined by radiography) were starved for 24 h before surgery 138 days after mating. Anaesthesia was induced with intravenous thiopentone and maintained with halothane and oxygen. At laparotomy a polythene catheter (o.d. 1-57 mm) was advanced 10 cm into the main uterine vein via one of its branches. Air-filled balloons (4-5 ml capacity) attached to polyvinyl catheters (o.d. 2-1 mm) were inserted between the uterine wall and the foetal membranes through a small incision in the uterine wall. In four other goats (with twin pregnancies), similar polythene catheters were inserted, under local anaesthesia, via the lateral saphenous vein into the vena cava to sample the uterine venous effluent. The tips of the catheters were localized according to the method of Coudert, Phillips, Palmer & Faiman (1972).
Sampling
Heparinized blood samples were obtained every 4 h from 1 day after surgery until about 1 day post partum. The catheters were flushed with 3-4 ml heparinized saline (200 i.u./ml) after each blood collection. Samples were centrifuged within 20 min of collection and the plasma stored deep frozen until required for assays. Intra-uterine pressure was recorded via polythene tubing connected to a Statham pressure transducer and a 2-channel recorder (Devices Ltd). The recorder was calibrated between 0-30 mmHg. Tracings were obtained every 3 h for 30 min until regular contractions were observed. Thereafter continuous recording was made until about 6 h post partum. Re¬ cordings were made in two goats at 12 h and at 24 h post partum. The recording system was sensitive to respiratory and abdominal movements but these did not exceed an amplitude of 5 mmHg. Uterine contractions with an amplitude of less than 5 mmHg are not regarded as indicative of parturition. Hormone assays
All hormones were estimated by specific radioimmunoassays; PGF according to the method of Sharma (1972) and progesterone, oestradiol-17a and oestradiol-17/? according to the method of Hotchkiss, Atkinson & Knobil (1971). The specificities and cross-reactions of the antisera used have been reported (Sharma, 1972; Dobson & Dean, 1974). Results are presented without correction for recovery which was 81-8 ± 15-3 (s.d.) % (n 6) for pro¬ gesterone; 67-9 ±4-5 % (n 6) for oestradiol-17a; 83-8 + 3-4 % for oestradiol-17/? (« 10) and 82-6+ 12-6 % (n 24) for prostaglandin F. Data were analysed by Student's '/' test. =
=
=
=
results
The mean gestation length in this group of goats was 146-8 ± 2-3 (s.e.m.) days (n 8). This did not differ from the length of gestation of unoperated goats from the same group 147-8 ±3-5 days (n 10). Parturition was normal and all the kids were born alive. Data are presented relative to foetal expulsion (time 0). =
=
Prepartum hormonal changes
Prostaglandin F concentrations in the uterine venous plasma of four goats are shown in Fig. 1. It can be seen that the increase in concentration occurred in two stages. There was a primary increase from 0-25-0-3 ng/ml 8-3 days pre partum to 0-8-1-2 ng/ml at about 48 h prepartum. This primary increase was significant in three goats (G7, G8 and G84). A second¬ ary and more rapid increase occurred at 12-8 h pre partum. Maximal PGF concentrations of varying magnitude from 2-8 to 62-5 ng/ml were recorded just before or at foetal expulsion.
6
48
Days
32 16 Hours
O
8
48
6
Days Time before delivery
32 Hours
16
Fig. 1. Plasma prostaglandin F concentrations in the uterine vein of four goats before delivery (arrow). Each point before 48 h pre partum is the average concentration (5-6 daily samples) while points after 48 h represent duplicate estimations of single samples collected at the times shown.
6
4
2
Days before and after delivery
Fig. 2. Changes in the uterine venous plasma of oestradiol-17a (O), progesterone (D), prosta¬ glandin F ( ), before and after delivery (arrow). The values are the means of 5-6 daily observations in four goats (n 20 or 24). =
There was a post-partum fall in concentration to 0-3 + 0-1 ng/ml at 12 h. A similar pattern of PGF concentration was observed in the vena cavai plasma of four other goats. The mean progesterone concentration in the uterine venous blood is shown in temporal relationship with the concentrations of PGF and oestradiol-17a in Fig. 2. The uterine venous plasma concentrations of progesterone remained fairly stable until a sudden and significant (P < 0-01) decline at 24 h pre partum. The progesterone concentration at 24 h pre partum was 0-8 ±0-1 (n 8) and the post-partum concentration was about 0-5 ng/ml. Oestradiol- ß concentrations did not show any change during the experimental period. The mean of four or five daily determinations is shown in Table 1. On the other hand, oestradiol-17a showed a consistent rise beginning about 4-3 days before delivery with maxima of 1-5-7-5 ng/ml during the 24 h before foetal expulsion. The mean of five or six daily determinations is shown in temporal relationship with PGF and progesterone in Fig. 2. Post-partum oestradiol-17a concentrations ranged from 0-2 to 0-5 ng/ml. =
Table 1.
Oestradiol-17ß concentrations in the uterine venous blood of two goats before parturition (means ± s.e.m.) Oestradiol- ß (Pg/ml)
Days pre partum
240 ±23-0 175 + 19-2 175 ±4-2 165+ 10-5
8 7 6 5 4 3 2 1
(«)
168+16-5 205+17-25 260 ±12-2 245 ±8-29
48 hours pre partum
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I. UMO, R. J. FITZPATRICK AND W. R. WARD Department of Veterinary Clinical Studies, University ofLiverpool,
'Leahurst', Neston, Merseyside, L64 7TE
(Received 14 April 1975) SUMMARY
in plasma concentrations of hormones and uterine activity associated with sponparturition in the goat were examined. No change in oestradiol-17\g=b\ concentration was detected during the experimental period, but oestradiol-17\g=a\ consistently increased in concentration 3\p=n-\4days before parturition. This was followed by an increase in prostaglandin F two days later, while a pre-partum decline in progesterone concentration occurred 18\p=n-\20 h after the significant increase in prostaglandin F. The onset of uterine contractions coincided with a significant decline in progesterone concentration and a period of continually rising prostaglandin F and oestradiol-17\g=a\ concentrations. Uterine activity expressed in Montevideo units did not change until 10\p=n-\8h before foetal expulsion. These results support the hypothesis that in the goat the elevated prepartum concentration of prostaglandin F brings about luteolysis and a subsequent decline in progesterone
Changes taneous
concentration.
INTRODUCTION
Recent studies have suggested that prostaglandins (PG's) may be important in the control of parturition in several species (Liggins, Fairclough, Grieves, Kendall & Knox, 1973). In goats, blood concentrations of PGF are elevated before delivery (Thorburn, Nicol, Bassett, Shutt & Cox, 1972; Currie, Wong, Cox & Thorburn, 1973). Administration of PGF2a to goats in late pregnancy causes a fall in plasma progesterone concentration and premature parturition (Currie & Thorburn, 1973). It might be expected that PGF2ci, a potent luteolysin in several species (Inskeep, 1973) would be responsible for the pre-partum decline in progesterone in goats (Irving, Jones & Knifton, 1972; Thorburn & Schneider, 1972), since this species depends on the corpus luteum for the progesterone requirements of pregnancy (Linzell & Heap, 1968). Thorburn et al. (1972) and Currie et al. (1973) have presented preliminary evidence of an association between the prepartum decline in progesterone and the increase in PGF. The present study has examined the precise temporal relationships between PGF, oestrogens and progesterone in serial blood samples obtained from eight goats during late pregnancy and spontaneous parturition.
MATERIALS AND METHODS
Animals and surgical techniques Four goats with single foetuses (determined by radiography) were starved for 24 h before surgery 138 days after mating. Anaesthesia was induced with intravenous thiopentone and maintained with halothane and oxygen. At laparotomy a polythene catheter (o.d. 1-57 mm) was advanced 10 cm into the main uterine vein via one of its branches. Air-filled balloons (4-5 ml capacity) attached to polyvinyl catheters (o.d. 2-1 mm) were inserted between the uterine wall and the foetal membranes through a small incision in the uterine wall. In four other goats (with twin pregnancies), similar polythene catheters were inserted, under local anaesthesia, via the lateral saphenous vein into the vena cava to sample the uterine venous effluent. The tips of the catheters were localized according to the method of Coudert, Phillips, Palmer & Faiman (1972).
Sampling
Heparinized blood samples were obtained every 4 h from 1 day after surgery until about 1 day post partum. The catheters were flushed with 3-4 ml heparinized saline (200 i.u./ml) after each blood collection. Samples were centrifuged within 20 min of collection and the plasma stored deep frozen until required for assays. Intra-uterine pressure was recorded via polythene tubing connected to a Statham pressure transducer and a 2-channel recorder (Devices Ltd). The recorder was calibrated between 0-30 mmHg. Tracings were obtained every 3 h for 30 min until regular contractions were observed. Thereafter continuous recording was made until about 6 h post partum. Re¬ cordings were made in two goats at 12 h and at 24 h post partum. The recording system was sensitive to respiratory and abdominal movements but these did not exceed an amplitude of 5 mmHg. Uterine contractions with an amplitude of less than 5 mmHg are not regarded as indicative of parturition. Hormone assays
All hormones were estimated by specific radioimmunoassays; PGF according to the method of Sharma (1972) and progesterone, oestradiol-17a and oestradiol-17/? according to the method of Hotchkiss, Atkinson & Knobil (1971). The specificities and cross-reactions of the antisera used have been reported (Sharma, 1972; Dobson & Dean, 1974). Results are presented without correction for recovery which was 81-8 ± 15-3 (s.d.) % (n 6) for pro¬ gesterone; 67-9 ±4-5 % (n 6) for oestradiol-17a; 83-8 + 3-4 % for oestradiol-17/? (« 10) and 82-6+ 12-6 % (n 24) for prostaglandin F. Data were analysed by Student's '/' test. =
=
=
=
results
The mean gestation length in this group of goats was 146-8 ± 2-3 (s.e.m.) days (n 8). This did not differ from the length of gestation of unoperated goats from the same group 147-8 ±3-5 days (n 10). Parturition was normal and all the kids were born alive. Data are presented relative to foetal expulsion (time 0). =
=
Prepartum hormonal changes
Prostaglandin F concentrations in the uterine venous plasma of four goats are shown in Fig. 1. It can be seen that the increase in concentration occurred in two stages. There was a primary increase from 0-25-0-3 ng/ml 8-3 days pre partum to 0-8-1-2 ng/ml at about 48 h prepartum. This primary increase was significant in three goats (G7, G8 and G84). A second¬ ary and more rapid increase occurred at 12-8 h pre partum. Maximal PGF concentrations of varying magnitude from 2-8 to 62-5 ng/ml were recorded just before or at foetal expulsion.
6
48
Days
32 16 Hours
O
8
48
6
Days Time before delivery
32 Hours
16
Fig. 1. Plasma prostaglandin F concentrations in the uterine vein of four goats before delivery (arrow). Each point before 48 h pre partum is the average concentration (5-6 daily samples) while points after 48 h represent duplicate estimations of single samples collected at the times shown.
6
4
2
Days before and after delivery
Fig. 2. Changes in the uterine venous plasma of oestradiol-17a (O), progesterone (D), prosta¬ glandin F ( ), before and after delivery (arrow). The values are the means of 5-6 daily observations in four goats (n 20 or 24). =
There was a post-partum fall in concentration to 0-3 + 0-1 ng/ml at 12 h. A similar pattern of PGF concentration was observed in the vena cavai plasma of four other goats. The mean progesterone concentration in the uterine venous blood is shown in temporal relationship with the concentrations of PGF and oestradiol-17a in Fig. 2. The uterine venous plasma concentrations of progesterone remained fairly stable until a sudden and significant (P < 0-01) decline at 24 h pre partum. The progesterone concentration at 24 h pre partum was 0-8 ±0-1 (n 8) and the post-partum concentration was about 0-5 ng/ml. Oestradiol- ß concentrations did not show any change during the experimental period. The mean of four or five daily determinations is shown in Table 1. On the other hand, oestradiol-17a showed a consistent rise beginning about 4-3 days before delivery with maxima of 1-5-7-5 ng/ml during the 24 h before foetal expulsion. The mean of five or six daily determinations is shown in temporal relationship with PGF and progesterone in Fig. 2. Post-partum oestradiol-17a concentrations ranged from 0-2 to 0-5 ng/ml. =
Table 1.
Oestradiol-17ß concentrations in the uterine venous blood of two goats before parturition (means ± s.e.m.) Oestradiol- ß (Pg/ml)
Days pre partum
240 ±23-0 175 + 19-2 175 ±4-2 165+ 10-5
8 7 6 5 4 3 2 1
(«)
168+16-5 205+17-25 260 ±12-2 245 ±8-29
48 hours pre partum
>^.jK»i
