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Regulation of whole-body flux rates and in vivo tissue metabolism of specific nutrients is discussed in relation to three developmental stages: prenatal, birth to weaning and postweaning. The marked decline in relative growth rate and weight-specific uptake of oxygen, glucose and amino acids of the fetus between mid and late gestation may be due in part to recently demonstrated limitations in placental transport capacity during late pregnancy. In fetal, as in neonatal and weaned, animals, insulin is an important regulator of metabolic homeostasis, but evidence for its role in chronic regulation of nutrient partitioning and growth at any stage of development is equivocal. Somatotropin-dependent regulation of skeletal growth, mediated by insulin-like growth factor I, does not develop until soon after birth, but in fetal and postnatal animals somatotropin depresses lipid deposition in adipose tissue by antagonizing stimulation of lipogenesis by insulin, thereby sparing utilization of lipogenic nutrients and promoting net mobilization of nonesterified fatty acids. These and other long-term actions, including effects on mineral metabolism, are consistent with the postulated role of somatotropin as an important homeorhetic regulator of postnatal metabolism and growth of key tissues. The complex integration of tissue metabolism and its regulation in vivo must be studied systematically in meat animals at different stages of development, grown at optimal and suboptimal rates. Existing concepts and methodology provide a foundation for beginning this task; further progress will be impossible without significant conceptual and technical innovation.

In vitro produced, 2-cell bovine embryos were cultured in serum-free medium supplemented with various combinations of growth factors to test the hypothesis that these polypeptide factors are able to signal preimplantation development. The developmental arrest that occurs during the 8-cell stage with typical culture methods might be relieved by a growth factor-dependent mechanism that would stimulate expression of the embryonic genome, thereby mimicking events that occur in vivo in the oviduct during the fourth cell cycle (8- to 16-cell stage). Subsequently, other growth factors might promote compaction and blastulation, processes which normally occur in the uterus. The effects of growth factors on early embryos were evaluated using phase contrast microscopy to monitor progression to the 8-cell stage, completion and duration of the fourth cell cycle, and blastocyst formation. Platelet derived growth factor (PDGF) promoted development beyond the 16-cell stage in 39.1% of the 2-cell embryos examined in all experiments. The duration of the fourth cell cycle among these embryos was approximately 26 hours. During development after the 16-cell stage, PDGF reduced the proportion of embryos bastulating from 12.7% to 5.8%; in contrast, transforming growth factor alpha (TGF alpha), acting during the same developmental time period, increased the proportion of embryos blastulating from 8.6% to 40.6%. These results, using serum-free medium, indicated that PDGF signalled completion of the fourth cell cycle. TGF alpha, and perhaps basic fibroblast growth factor (bFGF), promoted blastulation of 16-cell embryos during subsequent culture.

Summary.Progesterone concentrations measured in plasma samples from 280 bats captured during pregnancy or early lactation were related to fetal attributes indicative of stage of pregnancy. Fetal weight increased exponentially from 40 mg at crown–rump length of 6 mm to 2000 mg at 23 mm (term). Fetal weights at term accounted for up to 35% of the weight of intact pregnant animals. Progesterone concentrations increased from < 5 ng/ml at 2 mm estimated crown–rump length to plateau values of ∼ 65 ng/ml (geometric means) from 16 mm crown–rump length until the most advanced stages of pregnancy. Mean concentration in 8 post-partum bats, most of which were actively lactating, was 8·4 ng/ml; 11 ·6 ng/ml was measured in one animal that was carrying a wet neonate when sampled yet was still pregnant when captured 5 h earlier. Placental concentrations of progesterone ranged from 43 to 964 ng/g wet weight of tissue and mean values increased in a similar fashion though were about 4-fold greater than changes in plasma concentrations of the steroid. The concentrations in placental tissue were at least 15- to 20-fold higher than could be expected from blood contamination, indicating that placental steroidogenesis is likely to occur in this species.Keywords:Myotis; pregnancy; progesterone; bats; placenta

Pregnant ewes were chronically exposed to thermoneutral (TN; 20°C, 30% relative humidity) or hot (H; 40°C 9 h/d, 30°C 15 h/d, 40% relative humidity) environments between d 64 and 136 to 141 of pregnancy. They were sampled for blood at 14-d intervals during this period for measurement of plasma metabolites and hormones, then slaughtered and dissected to measure conceptus weights, dimensions and fetal organ weights. Rectal temperatures of H ewes were elevated .3 to 1.0 C° above those of TN ewes throughout the experiment. Voluntary feed intakes were not altered by heat exposure except after 120 d of pregnancy, when feed intake was about 25% lower (P< .10) by H than by TN ewes. Blood 3-hydroxybutyrate concentrations were not affected by heat, but plasma glucose concentrations were greater in H than in TN animals after 120 d (P< .05). Placental weight, reduced by 54% (P< .001) by heat exposure of ewes, was correlated positively with fetal weight and correlated negatively with fetal/placental weight ratio, fetal brain/liver weight ratio and fetal relative heart weight Late in pregnancy, plasma concentrations of progesterone, cortisol and placental lactogen were reduced (P< .01) in H ewes, whereas triiodothyronine levels were markedly lower (P< .03) at all stages of pregnancy. Plasma concentrations of prolactin were elevated dramatically (P< .01) and a modest increase (P< .03) in somatotropin levels was recorded in H ewes. These results are consistent with our hypothesis that heat-induced fetal growth retardation is secondary to a primary reduction in placental growth; this could be mediated partly by reduced peripheral activity of thyroid hormones. Heat-induced reductions in secretion of progesterone and ovine placental lactogen more likely were a consequence than a cause of placental stunting.

The objective was to study control of mature size by characterizing metacarpal growth plate closure in relation to relevant bone growth-regulating hormones in two breeds exhibiting distinct differences in mature frame size. Thirty-four Suffolk and 34 Dorset ram lambs were slaughtered in pairs within breed at birth, weaning and monthly intervals until 420 d and then bimonthly to 600 d. Plasma growth hormone was depressed to undetectable levels due to the high-energy, ad libitum-fed diet. Plasma insulin-like growth factor-I (IGF-I) rose over the growth period from 116 ng/ml (newborn Suffolk) to a high of 451 ng/ml (420-d Dorset); it appeared to peak at approximately 400 d and then declined to a stable level. Dorsets consistently exhibited higher IGF-I levels. The thyroid hormones exhibited no apparent age association. An age-associated rise was detected for testosterone, but not for estradiol. Mature metacarpal lengths were estimated to be 147.2 and 127.4 mm for Suffolks and Dorsets, respectively. Ninety-five percent of mature length was attained in Suffolks by 226 d and in Dorsets by 165 d. Growth plates, however, did not begin to appear closed until 390 d and closure was not complete in all animals until 480 d, suggesting that metacarpal growth rate was dissociated temporally from growth plate closure. Although growth plate closure likely is controlled by the endocrine system, there were no apparent relationships between circulating hormones and growth plate width, age at closure or zonal divisions within the growth plate, suggesting that the growth plate experiences a very different hormonal environment than what can be measured in the circulating blood.

Radioreceptor assays for prolactin-like (lactogenic) activity and growth hormone (GH)-like activity have been used to study concentrations of caprine placental lactogen (PL) in the circulation during pregnancy. Both lactogenic and GH-like activities increased from less than 100 ng/ml (ovine prolactin- and human GH-equivalents) about 60 days after mating to reach peak levels (400–1600 ng/ml) between days 110 and 130 of pregnancy. The levels of both activities increased in essentially the same fashion but during the last 15 days of pregnancy, lactogenic activity declined less than GH-like activity. This divergence was most pronounced at parturition when levels of lactogenic activity increased (∼ 700 ng/ml) despite very low (< 200 ng/ml) levels of GH-like activity being measured and this probably reflected increased secretion of pituitary prolactin near parturition. When serum from a pregnant goat or a simple alkaline extract of placental cotyledons was fractionated on a column packed with Sephadex G-100, lactogenic and GH-like activities eluted together with distribution coefficients of approximately 0·5–0·6. The possibility that caprine PL serves physiologically as a luteotrophin and/or mammotrophin during pregnancy in goats is discussed.

Summary.Jugular plasma concentrations of oestradiol-17β, prolactin, progesterone and 13,14-dihydro-15-keto-prostaglandin F-2α (PGFM) were measured at 2-h intervals during the last 4 days of pregnancy in 6 goats. During advanced labour and delivery, samples were obtained more frequently and assayed for oxytocin. The animals were housed in a barn with continuous dim lighting. A distinct pattern of oscillation in prolactin concentrations, with peaks during the late afternoon, was apparent during the last 3 days. Geometric means of peak concentrations doubled each day and became of longer duration; night-time nadir values remained low except during the last night before parturition. A progressive increase in oestradiol-17β, with mean levels doubling every 36 h, was apparent during the last 3 days. There was no sharp pre-partum increase in oestradiol-17β. Correlated (r= 0·83) with the increase in oestradiol-17β was a gradual increase in PGFM and when the latter reached ∼ 1000 pg/ml, the non-reversible decline in progesterone reflecting pre-partum luteolysis occurred. Subsequent changes in PGFM related closely to an approximately 20-fold increase in the ratio of oestradiol-17β to progesterone until maximal PGFM levels of 26·5 ± 4·2 ng/ml were reached at delivery. Basal concentrations of oxytocin (8–15 μU/ml) were measured before the last 60 min and markedly higher, though erratic, concentrations were detected at various times before appearance of the allantochorion. Maximal oxytocin values (range 180–1570 μU/ml) occurred within minutes before or after delivery of the first fetus. The results suggest that increased pre-partum production of oestradiol-17β, in addition to provoking sufficient release of prostaglandins to cause luteolysis, may modulate either the sensitivity or set-points for an endogenous rhythm in prolactin secretion at the end of pregnancy. The nature of the oxytocin changes suggests that, after labour has evolved sufficiently, delivery is precipitated by an abrupt increase in oxytocin secretion.Keywords:goat; hormones; luteolysis; labour; parturition

Summary.Concentrations of plasma progesterone were similar to values reported in the literature except that a significant decrease in progesterone during the last day, but before parturition, was detected by systematic, high-intensity blood sampling. Mean concentrations of oestradiol-17β increased sharply and significantly, plateaued for 132·8 ± 1·5 days (mean ± s.e.m., N = 9), then declined sharply in each mare. There was obvious variation between the mares in when these increases and decreases in oestradiol-17β occurred, with the events being related closely to ambient photoperiod conditions rather than to the stage of pregnancy. Concentration of 13,14-dihydro-15-keto-prostaglandin F-2α (PGFM) remained at low levels (< 400 pg/ml) until Day 200 then increased to peak pregnancy levels (> 2000 pg/ml) by Day 300 and remained at this value until parturition. The concentrations of oxytocin remained basal (< 15 μU/ml) throughout pregnancy and increased only at the beginning of the expulsive stage of labour. There was an increase, although not statistically significant, in the relative concentrations of oestradiol-17β to progesterone beginning 3 days before parturtion, with the highest value of the ratio occurring at fetal delivery. Far more striking were acute changes in PGFM and oxytocin during parturition. Maximal concentrations of PGFM (∼30 ng/ml) and oxytocin (> 200 μU/ml) were measured between rupture of the chorioallantois and the completion of delivery. Closely timed samples from one animal showed that oxytocin increased (more than 10 standard deviations of the mean levels during late pregnancy for this animal) before any change in PGFM. In another dystocic mare, both oxytocin and PGFM peaked in the initial stages of delivery but only oxytocin remained elevated until the dystocia was remedied. The results suggest that an abrupt increase in oxytocin secretion precipitates the expulsive phase of parturition in mares.Keywords:oestradiol-17β; progesterone; PGFM; oxytocin, pregnancy; parturition; mare

Summary.Concentrations of progesterone and of 13,14-dihydro-15-keto-prostaglandin F-2α (PGFM) were measured in plasma collected from 6 bitches every 3 h starting 2·8–4·6 days before parturition (birth of first pup) and continuing until 0·4–0·8 days post partum, and in additional samples collected less frequently. Progesterone concentrations at 48, 24, 12 and 3 h pre partumaveraged 2·8 ± 0·3, 2·2 ± 0·4, 1·0 ± 0·3 and 0·7 ± 0·2 ng/ml. At those times PGFM values averaged 380 ± 80, 800 ± 220, 1450 + 450 and 1930 ± 580 pg/ml, respectively. Mean concentrations of PGFM increased about 2·5-fold between 48 and 15 h pre partumin association with the onset of luteolysis, and then increased another 2·5 times before parturition as progesterone fell to nadir values. Peak levels of PGFM ranged from 1060 to 7150 pg/ml (2100 ± 600 pg/ml) and occurred within 1–9 h after the birth of the first pup and before the birth of the last pup. These results suggest that prepartum luteolysis in dogs is initiated by increases in maternal concentrations of PGF, and that progesterone withdrawal causes a further increase in PGF which completes luteolysis and provides a major portion of the uterotonic activity causing expulsion of pups.Keywords:pregnancy; parturition; luteolysis; prostaglandin; dog

Summary.Recordings of uterine electrical activity were made from 5 pregnant pony mares from Day 141 to 320 of pregnancy. Three types of activity were identified. Short, medium and long bursts were quantified as the percentage of time each occurred during the hour analysed and further categorized according to frequency, amplitude and duration. The uterus was most active during the early stages recorded and became increasingly quiescent after Day 240. Short-burst activity was greatest when the uterus was most quiescent. Long bursts showed the greatest percentage of activity until Day 220 and then decreased. Medium-burst activity was present throughout the period studied and high amplitude synchronous medium bursts peaked at Day 221-240.

Relationships between foetal corticosteroid concentrations, utero-ovarian prostaglandin F (PGF) and maternal peripheral progesterone have been examined in detail in goats shortly before spontaneous parturition at term. Foetal corticosteroids increased during the last 13-11 days of gestation and particularly sharply during the last 3 days and even during advanced labour. About 24 h before parturition, acute releases of PGF were evident in the vein draining the pregnant uterine horn, and these corresponded closely to the time of luteal regression. Further release of PGF occurred when progesterone declined to low levels, probably reflecting the course of labour.The changes observed before premature parturition, induced by infusing ACTH into foetal goats, were similar except for the more rapid increase in foetal corticosteroid concentrations. Immature neonates born after ACTH treatment were viable, placental delivery was normal and lactogenesis occurred in the mothers indicating that the treatment promoted full expression of the critical perinatal events. The early, acute releases of PGF were ipsilateral to the ACTH-infused foetus and were luteolytic provided the corpora lutea were also on that side. Luteolysis failed or was abnormally delayed if the corpora lutea were contralateral and prolonged ACTH treatment of the foetuses in such cases caused foetal death probably because of premature failure of the placenta. Similar findings were noted if ACTH infusion of the foetus was accompanied by simultaneous progesterone treatment of the mothers in order to block the induction of labour. It was suggested that placental changes occurring during foetal hypercortisolism might be caused by increased placental oestrogen synthesis and the effect of this on the foeto-maternal junction along with a stimulatory action on PG synthesis in the maternal placenta. Experimental disruption of the normal sequence of events, when labour was blocked by progesterone, proved to be lethal to the foetus if the loss of placental integrity progressed sufficiently.The chain of regulatory signals linking increased activity of the foetal adrenal with parturition thus appears to involve stimulation of oestrogen biosynthesis, PGF release from the maternal placenta and the start of physical changes at the placental junction. Provided the foetus and corpora lutea are ipsilateral, the early releases of PGF effect luteolysis and a withdrawal of progesterone from the maternal circulation. When progesterone concentrations are sufficiently low, labour is initiated and its progress reflected by further release of PGF. The control mechanisms, which also provide for the final maturation of the foetus, clearly enable a close synchronization of the various perinatal events which are essential for the transition from foetal to postnatal life.

Summary.Imidazole, at concentrations between 10−3and 10−2m, exerts a profound stimulatory effect on rabbit uterine strips obtained during pregnancy and studied isometrically in vitro. The action is not duplicated by N-alkylimidazoles which have greater potency as inhibitors of thromboxane synthetase but the effect of imidazole was antagonized by isoproterenol or theophylline. Biochemical analysis indicated that imidazole at concentrations greater than 5 × 10−4mstimulated both high and low affinity forms of cyclic AMP phosphodiesterase. The uterus of pregnant rabbits is profoundly refractory to any kind of pharmacological stimulation and the effects of imidazole, acting to stimulate phosphodiesterase, suggest that the integrity of the adenyl cyclase–cyclic AMP–protein kinase system is a necessary requirement for this organ to remain quiescent during pregnancy.

C.S.I.R.O., Division of Animal Physiology, Ian Clunies Ross Animal Research Laboratory, P.O. Box 239, Blacktown, N.S.W. 2148, Australia(Received 20th June 1974)There is an obligatory requirement for continued secretory activity of the goat CL throughout pregnancy because the placenta does not secrete progesterone in this species (Linzell & Heap, 1968; van Rensburg, 1971; Thorburn & Schneider, 1972; Irving, Jones & Knifton, 1972a). Ovariectomy or ablation of the CL during pregnancy inevitably causes abortion, the effects being due solely to the withdrawal of progesterone (Meites, Webster, Young, Thorp & Hatch, 1951; Irving et al., 1972a). Regression of the CL, as indicated by an abrupt decline in circulating progesterone concentrations, occurs on the day before parturition at term (gestation length 150±3 days) and also before pathological abortion (van Rensburg, 1971). Van Rensburg (1971) has suggested that the decrease in progesterone may reflect a withdrawal of maternal pituitary luteotrophin as a result