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In vitro steroid production by adrenals and kidney-gonads from embryonic southern snow skinks (Niveoscincus microlepidotus): implications for the control of the timing of parturition?

In some mammalian species, hormones produced by the embryo(s) at the completion of development are involved in the cascade of events that result in parturition. Our overall aim was to determine whether a similar mechanism exists in viviparous reptiles. The alpine skink Niveoscincus microlepidotus provides a useful model for studies of gestation and parturition in viviparous reptiles as the completion of embryonic development and parturition are temporally separated; ovulation occurs in spring, embryonic development is completed by autumn, but parturition does not occur until the following spring. In this study, we determined how in vitro steroid hormone production by embryonic adrenals (progesterone, corticosterone, and testosterone) and mesonephric kidney-gonads (oestradiol and testosterone) varied during the later stages of gestation. We hypothesised that embryonic adrenals and kidney-gonads were capable of producing steroid hormones in vitro, and that the pattern of production would change as parturition approached, would be influenced by temperature, and would increase in the presence of corticotropin (ACTH) or pregnenolone, respectively. Embryonic adrenals and kidney-gonads were incubated with or without ACTH or the steroid precursor pregnenolone, respectively. Tissues were incubated for 3 h at either 16 or 24 degrees C (preferred body temperature of pregnant N. microlepidotus). Incubation medium was analysed for steroid hormones using radioimmunoassay. Low levels of progesterone were produced in vitro during the later stages of gestation when embryonic adrenals were incubated with ACTH. In vitro corticosterone production by embryonic adrenals also occurred, with greater production occurring when tissues were incubated at 24 degrees C. Testosterone was produced in vitro by both adrenals and kidney-gonads in March (late autumn when embryonic development was complete, but prior to parturition the following spring), with greater production at 16 degrees C. This peak in testosterone production coincided with differentiation and continuing growth of the hemipenes. Low levels of oestradiol were produced in vitro by embryonic kidney-gonads in March. These results provide some support for the hypothesis that corticosterone production by the embryonic adrenal may have a role in determining the timing of parturition in a viviparous reptilian species. Further research is needed to differentiate the activity of various tissues and steroid hormones in control of embryonic development, sexual differentiation, and the potential regulation of gestation and parturition in N. microlepidotus and other viviparous reptiles.

Adrenal Glands↗

The timing of parturition in the pig is altered by intravenous naloxone.

This experiment tested the hypothesis that opioid antagonists could influence the timing of the onset and progress of parturition in the pig. Primiparous pigs (gilts) received a jugular catheter on Days 104 to 106 of pregnancy. At 1400 h on Day 112 the gilts received 10 mg PGF2alpha, i.m. to induce parturition. At 1000 h on Day 113 (i.e., 20 h later) gilts received either saline (n=6), 1 mg/kg, i.v. naltrexone (n=4) or 1 mg/kg, i.v. naloxone (n=5). Blood samples were taken daily from Days 108 to 116. On Day 113, blood samples were taken hourly from 0500 to 0900 h and then every 30 min until 2400 h, or until the birth of the last piglet (BLP) (whichever was sooner) and assayed for progesterone, oxytocin (OT), cortisol and PRL. Additional blood samples for OT and cortisol assay were taken every minute from 0930 to 1100 h on Day 113 and for 30 min during parturition. Naloxone, but not naltrexone, delayed the onset of parturition relative to saline controls (by 14 h 21 min; P<0.05). Duration of parturition and rate of births were not significantly affected by treatment. Mean plasma OT increased in the 4 h following naloxone but not saline treatment, during which time OT plasma pulse amplitude was reduced in naloxone and naltrexone-treated animals relative to saline treated controls. The PRL secretion rose following treatment in saline treated animals, consistent with approaching parturition, but failed to rise in opioid antagonist treated animals. Progesterone concentrations remained elevated in naloxone-treated animals for longer than in the other groups. These data suggest that a rapid change in overall effect of parenteral administration of naloxone to parturient pigs occurs from delaying its onset when administered as in these experiments, to facilitating its progress when given during parturition (earlier experiments). The delay of onset of parturition may be mediated by interference with hypothalamic control of OT or PRL release.

Animals↗

Direct pathways to the supraoptic nucleus from the brainstem and the main olfactory bulb are activated at parturition in the rat.

Sensory input from female reproductive structures is paramount for the co-ordination of neuroendocrine changes at parturition. Using a retrograde tracer (fluorescent latex microspheres) in combination with Fos (as an indicator of neuronal activation) and tyrosine hydroxylase (to identify catecholaminergic neurons) immunocytochemistry we identified cells within the brainstem and main olfactory bulb that project to the supraoptic nucleus, and which become significantly activated at parturition (compared to virgin rats and rats on the day of expected parturition). Within the A2/C2 region in the nucleus tractus solitarii, 60% of the projecting activated cells were catecholaminergic, as were 59% of such cells in the A1/C1 region of the ventrolateral medulla. This suggests that oxytocin and vasopressin neurons within the supraoptic nucleus are stimulated at parturition via afferent inputs from the brainstem, but the input is not exclusively noradrenergic. Within the mitral layer of the main olfactory bulb, cells that projected to the supraoptic nucleus were significantly activated, suggesting that the olfactory system may regulate supraoptic nucleus cell firing at parturition. The preoptic area, organum vasculosum of the lamina terminalis and medial amygdala contained cells that projected to the supraoptic nucleus but these projections were not significantly activated at parturition, although non-projecting cells in these regions were. On the expected day of parturition, but before birth, projections from the organum vasculosum of the lamina terminalis to the supraoptic nucleus became significantly activated. These findings provide evidence of direct afferent pathways to the supraoptic nucleus from the brain stem and olfactory bulbs that are activated at parturition.

Afferent Pathways↗

Clinical signs and hormonal changes in dairy heifers after induction of parturition with prostaglandin F2 alpha.

Parturition was induced in 12 dairy heifers with prostaglandin (PG) F2 alpha about 2 weeks before the expected time of calving. Eight animals gave birth after two injections (group 1), three animals needed more than two injections (group 2) and one animal (cow no. 740) required one injection. All animals in groups 1 and 2 had retained foetal membranes and the time needed to induce parturition was 59 +/- 7 and 149 +/- 10 h, respectively. As cow no. 740 did not have retained foetal membranes and calved 24 h after one PGF2 alpha injection, it was excluded from the results. Udder distension and relaxation of the pelvic ligaments could predict the calving to within 12 h. Furthermore, the pre-calving drop of body temperature could predict the time of parturition to within 16 h. The total white blood cells and polymorphonuclear cells were at their highest values on the day preceding parturition whereas mononuclear cells had a tendency to increase 3 days after calving. Increased levels of haemoglobin were found at the time of parturition, whereas, plasma-calcium levels significantly decreased after parturition (P < 0.001). Progesterone levels markedly decreased after the first PGF2 alpha injection and reached 2 nmol/l at the time of parturition. Plasma levels of oestradiol-17 beta reached the peak at the time of parturition, whereas, the highest levels of the PGF2 alpha metabolite and cortisol were recorded 16 h after calving.

Animals↗

Influence of fetal death and fetectomy on gestation and the initiation of parturition in the ewe.

Depressed function of the fetal hypothalamic-pituitary-adrenal axis results in prolonged gestation, and fetal death causes premature parturition. The objective of this experiment was to determine effects of death in utero of a sibling, or its removal, on the duration of gestation and concomitant changes in maternal serum concentrations of oestradiol (E) and progesterone (P). Ovine placental lactogen (oPL) was also determined as an index of placental viability. Blood samples were collected in the morning, beginning 3 days prior to surgery on Day 115 +/- 3 of gestation and continuing daily until 3 days post partum. Surgeries were performed via mid-ventral laparotomy to induce fetal death or to remove the fetus. Fetal death was induced by ligating the umbilicus. Duration of gestation was similar (P > 0.05) in control (C, n = 6) and sham-operated (S, n = 3) ewes (148 +/- 1.0 and 148.6 +/- 0.7 days, respectively). On the day of parturition, concentrations of P, E and oPL were 5.2 +/- 1.9 ng mL-1, 135 +/- 22 pg mL-1 and 153 +/- 54 ng mL-1, respectively, in ewes from combined C and S groups. Total fetectomy (n = 3) resulted in a rapid decrease (P < 0.05) in maternal serum concentrations of P, E, and oPL. Ligation of the umbilicus of both fetus(es) in utero (n = 4) induced fetal death, decreased (P < 0.05) length of gestation to 118.8 +/- 1.8 days and decreased (P < 0.05) serum concentrations of P and oPL prior to parturition and oPL on the day of parturition. In addition, maternal serum concentrations of E failed (P > 0.05) to increase at parturition. Length of gestation and concentrations of P, E and oPL at parturition were not affected (P > 0.05) by removal of one fetus when its sibling was undisturbed (n = 4) compared to control ewes. In contrast, death of one fetus with its sibling undisturbed (n = 5) decreased (P < 0.01) length of gestation (139.2 +/- 2.8 days), but did not affect P, E and oPL (P > 0.05) on all days tested. In conclusion, death of one fetus reduced the duration of gestation, but changes prepartum in maternal serum concentrations of P and oPL were similar to ewes delivering only live fetuses. The increase in maternal concentrations of E that normally occur at parturition was absent in ewes giving birth to only dead fetuses and, therefore, was not a prerequisite to parturition.

Abortion, Veterinary↗

Effects of low and high calcium intake prepartum on calcium mobilization rate around parturition in dairy cows.

Forty-one dairy cows were fed a low (LCa-13 g/d) and a high (HCa-83.5 g/d) calcium ration in the 8 weeks prior to parturition and the effect on the Ca mobilization rate around parturition was studied. Plasma Ca values were stable in the LCa group around parturition. In the older cows of the HCa group a very slight decrease in the mean plasma Ca was observed: 2.58 mmol/l at 12-36 h ante partum decreased to 2.38 mmol/l at parturition. Hypocalcaemia, which commonly occurs around parturition, did not occur in 40 of the cows. A subclinical hypocalcaemia (1.8 mmol/l) occurred in one cow (parity 10) from the HCa group. To assess the efficiency of Ca mobilization, a severe hypocalcaemia (1.0 mmol/l) with clinical signs was induced by means of Na2EDTA infusion (0.90 mmol/min), starting at 10 h post-partum. The older cows in the LCa group required more Na2EDTA than those in the HCa group. Higher urinary hydroxyproline excretion in the week before parturition in the LCa than in the HCa group suggested a higher bone turnover. Plasma PTH levels around parturition were not significantly different between the groups. The amount of colostrum milked out in the first 10 h post-partum did not influence Ca homeostasis around parturition. The results contradict those of many other experiments in which hypocalcaemia was observed in cows ingesting high levels of Ca. It is concluded that the restricted feed intake prepartum possibly had a favourable effect on Ca homeostasis.

Animals↗

Differential regulation of the progesterone receptor A and B in the human uterine cervix at parturition.

The concept of a blockade of progesterone during human pregnancy and withdrawal of this blockade at parturition remains controversial There is no sharp fall in serum progesterone before parturition, but treatment with an antiprogestin is successful for labor induction at term pregnancy. The human progesterone receptor (PR) exists in two isoforms (PR-A and PR-B), mediating different biological responses. Here, the hypothesis of a progesterone withdrawal at parturition in terms of a change in PR isoforms was tested. Cervical biopsies were obtained at term before the onset of labor, immediately after parturition and from non-pregnant women. Solution hybridization showed a tendency for the PR mRNA level to be decreased at parturition. Immunohistochemistry displayed decreased PR(A + B) and PR-B levels (p < 0.05) immediately after parturition. The relative importance of PR-A seemed higher immediately after parturition as compared to its importance in non-pregnant and term pregnant women. Our results are consistent with the concept of a functional progesterone blockade at the receptor level at term pregnancy, and withdrawal of this blockade at parturition. These observations may have important clinical and therapeutic implications.

Case-Control Studies↗

Relaxin enhances synchronization of parturition induced with prostaglandin F2 alpha in swine.

To investigate the effects of relaxin on induction of parturition in swine, 59 sows and gilts were randomly allotted within parity to 4 treatment groups. Control animals were injected with saline while the other 3 groups received prostaglandin F2 alpha (PGF, 10 mg i.m.) at 0800 h on Day 112 of gestation to induce luteolysis and parturition. Relaxin (600 U i.m.) was administered either on Day 111 or on both Days 110 and 111 to 2 groups of sows receiving PGF. All farrowings were attended and the time of delivery of each piglet was recorded. PGF injection on Day 112 of gestation induced parturition in 43 of 44 treated animals. The interval (mean +/- SD) from Day 112 to parturition in control animals was 70 +/- 30 h and this was decreased to 30 +/- 9 h with PGF alone. When relaxin was administered prior to PGF on Day 111 or on both Days 110 and 111, parturition occurred after 26 +/- 4 or 27 +/- 3 h, respectively. Thus, relaxin treatment had little effect on reducing the interval to parturition, but improved the synchrony of onset of farrowing as indicated by a decrease (P less than 0.01) in variation. Relaxin pretreatment prevented any instances of delayed parturition (after 35 h) which occurred in 1/3 of the cases in response to PGF alone. This variation in response appeared unrelated to parity of sow. The mechanism by which relaxin enhanced the synchronous onset of parturition after PGF treatment in swine is unknown, but the most likely suggestions are through sensitization of the uterus to the withdrawal of progesterone and the well-known effects of relaxin on cervical dilatation.

Animals↗

Effects of the kappa-opioid agonist U50,488 on parturition in rats.

1. The effects of the kappa-opioid agonist U50,488 on parturition were studied in the rat. 2. Given directly after the birth of the second pup U50,488 (5 mg or 10 mg kg-1, i.p.) delayed the birth of the subsequent 4 pups by ca. 100 min, acting like morphine (10 mg kg-1, i.p.). In controls given the vehicle i.p., the birth of the 4 pups after treatment took 45.4 +/- 4.6 min. The effects of U50,488 could be prevented by simultaneous naloxone injection (10 mg kg-1). Injection of either U50,488 or morphine at 1 mg kg-1, i.v. also significantly delayed parturition. The effects of U50,488 but not of morphine were fully prevented by preinjection with nor-binaltorphimine (0.5 mg kg-1, i.v.) showing selective kappa-opioid receptor-mediated inhibition by U50,488 of established parturition. 3. In rats with an indwelling jugular venous cannula, i.v. injection of U50,488 (5 mg kg-1) after the birth of the second pup slowed parturition in a similar way to i.p. injection and significantly reduced blood plasma oxytocin concentration measured by radioimmunoassay compared with vehicle-injected controls. 4. Bolus i.v. injections of oxytocin (4 mu once per 5 min) significantly reduced the delay in parturition caused by i.v. U50,488, but continuous i.v. infusion of oxytocin (4 mu 5 min-1) was less effective. 5. Since i.v. oxytocin did not immediately reverse the effects of U50,488 on parturition, direct effects of U50,488 on isometric uterine contractions in vitro were sought. U50,488 inhibited spontaneous or oxytocin-stimulated contractions of uteri from rats within 24 h after parturition in a dose-related manner; the inhibitory effect was not naloxone-reversible.6. Thus U50,488 inhibited established parturition in the rat in a Kappa-opioid selective manner by reducing oxytocin secretion. The inhibitory effect may well have been potentiated by a direct non-opioid depressant action on contractile activity of the uterus.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Relationships among sex steroids, oxytocin, and their receptors in the rat uterus during late gestation and at parturition.

Sex steroids and oxytocin (OT) produced within intrauterine tissues have been implicated in the regulation of parturition. The purpose of these studies was 1) to determine the relationships among estradiol (E2), progesterone (P4), OT, and their receptors in uterine tissues during late gestation and parturition in the rat; 2) to observe the effects of the estrogen antagonist tamoxifen (TAM) on these factors; and 3) to evaluate the rat as a potential model for events at human parturition. Concentrations of E2, P4, PGE2, and OT were measured by RIA. E2 receptor (ER) was measured by enzyme immunoassay, and P4 receptor (PR) and OT receptor (OTR) were measured by binding assays. OT messenger RNA (mRNA) was measured by ribonuclease protection assay. Groups (n = 5) of pregnant rats (normal gestation = 22 days) were treated with TAM (200 mg/day) or vehicle and killed on gestation day 19, 21, 21.5, or 22 or after delivery of the first pup. Serum E2 increased throughout late gestation accompanied by an increase in uterine OT mRNA and ER. Serum P4 declined after day 19, and uterine PR did not change significantly. Uterine PGE2 increased progressively, reaching peak levels the evening before delivery. Uterine OTR did not increase until the morning of delivery, and uterine OT peptide concentrations increased only during parturition. Parturition was significantly delayed by 24 h in the TAM-treated group. TAM inhibited the increase in serum E2, uterine ER, and OT mRNA and peptide, but had no effect on serum P4 or uterine PR levels. With TAM, the responses of uterine OTR and PGE2 were significantly delayed, but still underwent a significant increase before the delayed parturition. These results support the hypothesis that E2 stimulates the synthesis of ER, OT, and OTR within the rat uterus and is essential for normal parturition. P4 withdrawal may be more important to the increases in OTR and PGE2, but these are delayed in the absence of estrogen. These data also suggest that the rat may be a relevant model for human parturition.

Animals↗

Endogenous opioid actions and effects of environmental disturbance on parturition and oxytocin secretion in rats.

Blood samples were taken from conscious, chronically-catheterized rats during parturition for measurement of oxytocin by specific radioimmunoassay. After the birth of the 3rd pup, rats were allowed to remain in their nesting cage (undisturbed rats) or were transferred for 45 min to a glass bowl (disturbed rats); at the time of transfer, rats were given an i.v. injection of the opioid antagonist naloxone or saline vehicle. Subsequent parturition was prolonged in saline-treated disturbed rats, but not in naloxone-treated disturbed rats. Parturition was significantly hastened in naloxone-treated undisturbed rats. Naloxone injections were followed by a large rise in plasma oxytocin concentrations in disturbed and undisturbed rats. We conclude, from a statistical analysis of the relationship within experimental groups between plasma oxytocin concentration and speed of parturition, that the effects of disturbance and of naloxone upon parturition may be accounted for, at least in part, by their effects upon oxytocin release. However, the effects of disturbance on parturition may not be mediated entirely by activation of opioid pathways. Naloxone did not potentiate oxytocin release in non-pregnant rats, or on Day 1 post partum, but did potentiate oxytocin release on Day 22 of pregnancy even in rats before the onset of parturition. Endogenous opioid pathways regulating oxytocin release therefore appear to be active during late pregnancy and during parturition itself.

Animals↗

Protein and fat metabolism in cows given somavubove before parturition.

Forty-one Holstein cows were injected with 0, 5, or 14 mg/d of bST for the last 46 +/- 6 d before parturition. Compared with data for controls, the 5- and 14-mg doses of bST increased apparent protein synthesis about 16% before parturition. Exogenous bST before parturition increased apparent protein degradation 30% during wk 1 after parturition. During wk 1 of lactation, 14 mg of bST also increased milk protein yield 33%. No treatment differences were present in concentration of serum NEFA, body condition score, or thickness of subcutaneous fat. Therefore, administration of bST before parturition did not alter metabolism of subcutaneous fat. Prepartum treatment with 5 and 14 mg of bST increased and maintained serum somatotropin at 6.5 and 22.7 ng/ml, respectively, compared with 1.6 ng/ml in controls. Concentrations of serum IGF-I were initially increased but were not maintained as parturition approached. On d -23, IGF binding protein 3 was increased 65% but was not different among groups by d -7. For groups administered the 5 and 14 mg/d of bST, IGF binding protein 2 was decreased 40%. Administration of bST before parturition increased protein reserves and stimulated milk protein yield for 1 wk but did not alter metabolism of subcutaneous fat. Furthermore, energy balance appeared to be a major regulator of concentrations of IGF binding protein 3 and responsiveness of IGF-I to exogenous somatotropin before parturition.

Adipose Tissue↗

Control of parturition in ruminants.

Parturition is a process which, when set into motion, occurs to completion. This review concerns the control of parturition in ruminants. Parturition is an endocrine event, dependent upon the activation of the fetal hypothalamus-pituitary-adrenal (HPA) axis. In sheep and other ruminants, increases in plasma concentrations of cortisol induce the activity of 17-hydroxylase and 17,20 lyase in the placenta, increasing the biosynthesis of oestrogen relative to progesterone. The increase in the so-called E:P ratio increases myometrial activity and culminates in labour and delivery. Much work has been done to identify the mechanism of the endogenous activation of the fetal HPA axis. Recent work suggests that production of prostanoids within the fetal brain influences fetal ACTH secretion, and that induction of prostanoid biosynthesis at the end of gestation might be important in the process of parturition. Oestrogen and androgens, secreted by the placenta at the end of gestation, augment activity of the fetal HPA axis by increasing fetal ACTH secretion and by decreasing negative feedback sensitivity to cortisol. Although significant progress has been made concerning the neuroendocrinology of parturition, many significant questions remain. Is parturition regulated or simply programmed? Is parturition the ultimate result of neuronal maturation within the fetal hypothalamus, or is there a complex interplay between the placenta and fetal hypothalamus? Answers to these and other important questions await further research, but may provide key information which will prove useful in understanding general principles of parturition in many mammalian species.

Adrenocorticotropic Hormone↗

[Biochemical changes in the peripheral blood in cows 45 days after parturition].

Blood samples were collected from v. jugularis in five-day intervals from parturition to postpartum day 45 in the rearing conditions of a dairy cow production herd, consisting of 10 groups with 10 pluriparous cows each (crossbreds of Bohemian Pied cattle with Holstein-Friesian cattle). In blood serum the following activities were determined photometrically: aspartate aminotransferase--AST (0.36-0.47 mukat.l-1), gamma-glutamyl transferase--GMT (0.50-0.83 mukat.l-1) and lactate dehydrogenase--LD (7.22-9.10 mukat.l-1); their average values were at an almost constant level. Only did AST and GMT values decrease slightly from day 25 after parturition. The glucose average content on the day of parturition (4.07 mmol.l-1) steeply decreased to postpartum day 5 (2.79 mmol.l-1), and later on, it increased irregularly. The average values of total protein (66.7-73.2 g per 1) slightly increased from postpartum day 20. The values of urea (2.33-2.37 mmol.l-1) and bilirubin (3.49-5.15 mmol.l-1) did not show any larger changes in dependence on the time elapsing from parturition. The average content of creatinine (124-162 mmol.l-1) increased irregularly from postpartum day 15 and then it decreased. Cholesterol concentrations were gradually increasing from 2.58 mmol.l-1 on the day of parturition to 4.99 mmol.l-1 on day 45 after parturition. The average contents of calcium (2.20-2.66 mmol.l-1) and phosphorus (1.75-2.27 mmol.l-1) were irregularly increasing until day 20 after parturition. Also the average content of magnesium (0.86-1.15 mmol.l-1) rose from day 25 after parturition.

Animals↗

[Dynamics of clinico-biochemical indicators in cattle with ketonuria during the dry period and after parturition].

The study was performed in eight high-pregnant cows in which medium to high ketonuria was repeatedly detected. The control group consisted of six cows free from ketonuria before parturition. Blood and urine were sampled from the cows two to eight weeks before parturition, on the day of parturition, 24 hours, three to five days and two to six weeks after parturition. The concentrations of oxidated ketone bodies and beta-hydroxybutyrate were determined by the distilling method. Further, the values of clinico-biochemical parameters in the urine and blood were determined within the range of the preventive diagnosis system. No marked changes in the health condition were found by the current clinical examination. The average concentration of total ketone bodies in the blood of the cows two to eight weeks before parturition was 29.2 mg per litre; the respective values recorded in the control cows were lower by about a half. The concentration of ketone bodies in the blood of the cows in the experimental group decreased on the day of parturition. The decrease was followed by a gradual rise of the total ketone bodies content in the blood up to 50.6 mg per litre two to six weeks after parturition. Alterations testifying to a disorder in the function of liver were observed in the cows of both groups throughout the period under study. The disorder was due to excessive administration of crude protein to the high-pregnant cows combined with the use of low-quality silage. After parturition the feed ration was not differentiated according to performance and was deficient in the basic nutrients and vitamins. Ketonuria was obviously due to the simultaneous intensification of hepatal and alimentary ketogenesis, caused by hepatopathy in combination with the intake of large amounts of poor-quality silage containing butyric acid.

Animal Feed↗

Endocrine regulation of the onset of parturition in rats.

The endocrine regulation of parturition exhibits several interspecies differences. Among the endocrine parameters considered to be the most important ones from the point of view of the regulation of parturition the concentration of oestrogens (oestradiol, oestriol and oestrone), progesterone, PGF2 alfa and its degradation product PGFM, was determined in both peripheral and uterine venous blood by RIA method in rats starting from the 15th day of pregnancy to the 3rd or 4th day following parturition. In the pregnant rat oestriol could only be detected on the day of parturition (21th day). Concentrations of oestriol and oestradiol were the highest on the day of parturition. An opposite tendency could be observed as far as progesterone concentration was concerned, i.e., the concentration decreased gradually from the 15th day of pregnancy onwards and the lowest value was reached on the day of parturition both in peripheral and uterine venous blood. PGF2 alfa and PGFM concentrations in the uterine vein increased gradually from the 15th day of pregnancy and the highest value could be detected peri partum. Our data, in accordance with those of others support the idea that the hormones investigated are involved in the process of parturition, i.e., characteristic changes of oestrogens, progesterone and prostaglandin levels ensue in the rat prior to parturition.

Animals↗

Myometrial progesterone responsiveness and the control of human parturition.

OBJECTIVE: The goal of this review is to assess the body of literature addressing the mechanism of progesterone withdrawal in the control of human parturition and in particular the recent advances in testing the hypothesis that human parturition is initiated by decreased myometrial responsiveness to progesterone, ie, functional progesterone withdrawal. METHODS: Published studies of progesterone responsiveness of the pregnant human myometrium in the context of parturition control were reviewed. RESULTS: Advances in understanding the molecular basis for progesterone receptor (PR)-mediated control of progesterone responsiveness has led to the hypothesis that functional progesterone withdrawal in human parturition is mediated by specific changes in myometrial PR expression, function, or both. The human PR exists as two major subtypes, PR-A and PR-B. As PR-A represses progesterone actions mediated by PR-B, the extent of progesterone responsiveness is inversely related to the PR-A/PR-B expression ratio. In women, the onset of term labor is associated with a significant increase in the myometrial PR-A/PR-B expression ratio that may facilitate functional progesterone withdrawal. Interestingly, expression of the estrogen receptor-alpha (ERalpha) increases concordantly with the PR-A/PR-B expression ratio in nonlaboring myometrium. This finding indicates that functional estrogen activation and functional progesterone withdrawal are linked. CONCLUSION: Functional progesterone withdrawal in human parturition is likely mediated by an increase in the myometrial PR-A/PR-B expression ratio and possibly by modulation of coactivator and corepressor proteins. Functional progesterone withdrawal appears to induce functional estrogen activation. Thus, for most of pregnancy, progesterone may decrease myometrial estrogen responsiveness by inhibiting ERalpha expression. Such an interaction would explain why the human myometrium is refractory to the high levels of circulating estrogens for most of pregnancy. At term, functional progesterone withdrawal removes the suppression of ERalpha expression leading to an increase in ERalpha and a concomitant increase in myometrial estrogen responsiveness. Estrogen can then act to transform the myometrium to a contractile phenotype. This model explains why disruption of progesterone action alone triggers the full parturition cascade. The link between functional progesterone withdrawal and functional estrogen activation may be a critical mechanism for the endocrine control of human parturition.

Estrogens↗

Accuracy of canine parturition date prediction from the initial rise in preovulatory progesterone concentration.

Accurate prediction of parturition date is useful for clinical management of canine parturition. For nearly all normal canine pregnancies, parturition occurs 64-66 days from the LH peak, the timing of which cannot be differentiated from the initial sharp rise in serum progesterone (P4) concentrations. We sought to determine by retrospective analysis if prebreeding serum progesterone concentrations could accurately predict parturition date. Serum progesterone concentrations recorded as serial samples from 63 bitches (19 breeds) were analyzed. Progesterone concentrations were measured by radioimmunoassay (RIA) or chemiluminescent immunoassay (CLIA). The CLIA method was validated for use in determining P4 concentrations in canine serum and results were comparable to those obtained with RIA. Bitches were grouped by nonpregnant body weight (BW) and litter size (LS). Day 0 (D0), the day of preovulatory rise in serum P4, was defined as the day that P4 concentration rose to > or =l.5 ng/ml and was at least twice the baseline concentration. The predicted parturition date, 65 days following the day of preovulatory rise in serum P4 (D65), was compared to actual parturition date, the day the first pup was delivered. We determined that mean P4 concentration at D0 for all BW groups was 2.02+/-0.18 ng/ml and there was significant variation in P4 concentrations between BW groups after D1. In addition, we determined that the accuracy of parturition date prediction within a +/-1, +/-2, and +/-3 day interval using prebreeding serum progesterone concentrations was 67, 90, and 100%, respectively, and that the accuracy was not affected by body weight or litter size.

Animals↗