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Effect of sow vitamin D status at parturition on the vitamin D status of neonatal piglets.

The plasma concentrations of calcium, phosphorus, vitamin D, and vitamin D metabolites were determined in cholecalciferol-treated sows and untreated sows at parturition and their piglets (at birth and at 10 days of age) to determine the relationship between sow vitamin D status and neonatal piglet vitamin D status. At birth, there was a high degree of correlation between sow and piglet plasma concentrations of 25-hydroxycholecalciferol (r = 0.944), 24,25-dihydroxycholecalciferol (r = 0.895), and 25,26-dihydroxycholecalciferol (r = 0.737). Neonatal piglet plasma 1,25-dihydroxyvitamin D was low (42.0 +/- 10.2 pg/ml) and was not correlated with maternal plasma 1,25-dihydroxyvitamin D (r = 0.022). Neonatal plasma calcium and phosphorus were significantly correlated (P less than 0.05) with maternal plasma 1,25-dihydroxyvitamin D (r = 0.515 and 0.581, respectively). Parenteral cholecalciferol treatment of sows before parturition proved an effective means of supplementing young piglets with cholecalciferol (via the sow's milk) and its more polar metabolites via placental transport. However, it had no significant effect on either the plasma mineral or 1,25-dihydroxyvitamin D status of the sow or young piglet.

Aging↗

Effect of low carbohydrate diets during pregnancy on parturition and postnatal survival of the newborn rat pup.

To test the hypothesis that maternal dietary carbohydrate is essential for the postnatal survival of the newborn rat pup, two experiments were designed. Pregnant dams were fed one of two basal carbohydrate-free diets. In experiment 1, the primary energy source was edible oleic acid; in experiment 2, it was soybean oil. Supplemental glucose was substituted for lipid. In experiment 1, pregnant dams were fed 4% dietary glucose for d 0-8 to allow successful implantation, as shown previously. Beginning on d 9 the dams were fed 0, 2, 4, 8, 12 or 62% glucose. Control dams (62% glucose) normally delivered pups weighing 5.6 g on d 21. Dams fed zero glucose delivered pups, weighing 3.1 g, 2 d late. The survivability of the litters increased with maternal dietary carbohydrate. All pups from dams fed 0-4% glucose died within 48 h. Pup survival to d 7 was 10% at 8% glucose, 23% at 12% glucose and 82% at 62% glucose. In experiment 2 soybean oil-based diets (basal supplied ca. 4% glycerol) with 0, 4, 12 and 62% glucose were fed from d 0. At zero glucose, fewer dams delivered late and birth weights were greater than in experiment 1. However, all pups born to zero-glucose dams died by d 4. Pup survival to d 7 was 48% at 4% glucose and 84% at 12% glucose. The data demonstrate that maternal dietary carbohydrate is required for fetal growth, normal parturition and postnatal survival of rat pups. The results indicate that late gestation, parturition and the neonatal period may be especially vulnerable to maternal carbohydrate deprivation.

Animals↗

Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition.

Adult↗

Progesterone control of interleukin-8 production in endometrium and chorio-decidual cells underlines the role of the neutrophil in menstruation and parturition.

Interleukin-8 (IL-8) attracts neutrophils into tissues and causes them to degranulate. Both menstruation and parturition involve neutrophil migration into uterine tissues and therefore IL-8 is a likely mediator of the tissue re-arrangements that accompany these events. We have examined the ability of endometrium explants and chorion cells in culture to synthesize and release IL-8 and the ability of progesterone, a synthetic progestin [medroxyprogesterone acetate (MPA)] and dexamethasone to inhibit this production. In endometrium, the stage of the menstrual cycle did not affect IL-8 production but a 10(-6) M concentration of progesterone or dexamethasone significantly reduced the concentration of IL-8 in medium after 24 h. After a further 24 h with lipopolysaccharide (LPS) stimulation, only MPA and dexamethasone inhibited production significantly. In chorion cells, IL-8 production was significantly decreased by both MPA and dexamethasone in the LPS stimulated cells but the reduction in the first 24 h was not significant. The IL-8 produced in uterine tissues might act synergistically with prostaglandin E (PGE), a likely site for this interaction being blood vessels where PGE production is also repressed by progesterone. Such a cooperative action would maintain low leukocyte entry into uterine tissues in the presence of progesterone and falling steroid levels would induce leukocyte immigration and activation with consequent tissue destruction. Such steroid-dependent interactions are important in our understanding of the mechanisms of menstruation and parturition and could allow new approaches to the treatment of uterine pathology.

Cells, Cultured↗

Induction of parturition, progesterone secretion, and delivery of placenta in beef heifers given relaxin with cloprostenol or dexamethasone.

Sixty primiparous beef heifers from a crossbreeding study were used to examine the effects of inducing parturition with relaxin (3,000 U/mg) combined with cloprostenol (500 micrograms, i.m., n = 30) or dexamethasone (20 mg, i.m., n = 30) at Day 273, 10 +/- 1 days before expected parturition (Day 283). Heifers were assigned at random within cloprostenol and dexamethasone groups to receive relaxin (1 mg, n = 5/treatment), i.m. or in the cervical os (OS), at 0 h (the same time as cloprostenol and dexamethasone) or 24 h later. Eleven and six first-calving heifers and sixteen and nine second-calving cows also received cloprostenol + relaxin and cloprostenol + phosphate-buffered saline, respectively. Radioimmunoassay of daily plasma samples indicated an abrupt decrease in progesterone with time (p less than 0.001), from 7.5 +/- 0.50 to 1.0 +/- 0.30 ng/ml (mean +/- SE) within 48 h for all groups. The mean rate of progesterone decrease (ng/ml in 24 h) was accelerated (p less than 0.01) in relaxin-treated heifers (5.3 +/- 0.36), in contrast to dexamethasone- and cloprostenol-treated control heifers (2.8 +/- 0.40). Relaxin combined with cloprostenol or dexamethasone shortened the calving period in these heifers by reducing the interval between treatment and calving (33 vs. 56 h; p less than 0.01). The incidence and duration of retained placenta were reduced by 22 vs. 75% and 14 vs. 34 h for relaxin combined with cloprostenol or dexamethasone as compared with cloprostenol- or dexamethasone-treated controls, respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biological activity of luteinizing hormone in the peripartum cow: least activity at parturition with an increase throughout the postpartum interval.

The biological (B) and immunological (I) activities of luteinizing hormone (LH) were determined during four peripartum periods in the cow. The sampling periods were PRE-5 (approximately 5 days prior to parturition), POST-3 (Day 2 or 3 postpartum), POST-12 (Day 11 or 12 postpartum) and LUTEAL (Day 11 or 12 following the first observed postpartum estrus). Blood samples were collected at 10-min intervals for either 8 h (PRE-5, POST-3, and POST-12) or 6 h (LUTEAL). Four hours prior to the end of each sampling period, 100 micrograms of luteinizing hormone-releasing hormone (LHRH) was injected i.v. Plasma concentrations of LH were analyzed by a validated bioassay (rat interstitial cell testosterone) and a radioimmunoassay. Area under the LHRH-induced LH release curve was calculated by the trapezoidal rule, and endogenous LH was determined by averaging the pre-LHRH treatment values. Paired t-analyses were used to compare LH release between periods. The periods of lowest (p less than 0.05) bioactive LH (BLH) were PRE-5 and POST-3. During POST-12, BLH was maximal. Endogenous immunoactive LH (ILH) was maximal during the POST-12 period, with PRE-5, POST-3, and LUTEAL being the least (p less than 0.05). The B:I ratio was lowest (p less than 0.05) around the time of parturition (PRE-5 and POST-3), then increased (p less than 0.05) by Day 12 postpartum. The ratio then increased (p less than 0.05) again by the LUTEAL period. These data suggest that the biological quality of LH changes throughout the puerperium. We infer from these data that the low biological activity of LH (subquality LH) may contribute to the postpartum infertility in the cow.

Animals↗

Diethylstilbestrol-induced perinatal lethality in the rat. II. Perturbation of parturition.

Evidence is presented suggesting that the fetolethal properties of diethylstilbestrol (DES) are indirect, mediated maternally through a perturbation of the normal mechanisms of parturition. Oral administration of the compound to Sprague-Dawley rats near Day 18 of pregnancy was shown to delay the onset of parturition, prolong labor, and induce dystocia, with a concomitant large increase in perinatal mortality. Exposure during Days 8-16 was without effect, whereas treatment in the Day 18-20 interval resulted in preterm delivery. Inability to initiate labor at term, accompanied by fetal death, also resulted from the administration of hCG on Days 16-18. The relative incidence of stillbirths in DES-exposed pups was markedly decreased by Caesarean delivery. The average weight of the maternal pituitary gland was not affected by treatment, whereas maternal adrenal glands were 30% larger. Maternal blood levels of corticosterone were not significantly elevated, however. The average number of follicles on Day 21 was significantly reduced by DES, and a histological analysis failed to demonstrate a luteotropic effect of the compound. In dams treated on Days 8-18, serum progesterone was reduced by as much as 60%, and total estrogens were 32% lower than in controls. We conclude that DES acts in the rat to depress the preterm levels of steroid hormones, which leads to a failure of uterine contraction accompanied by placental detachment and fetal death.

Animals↗

Parturition in the rabbit is compromised by daytime nursing: the role of oxytocin.

Rabbits nurse briefly only once each night and are frequently both pregnant and lactating. To investigate the influence of the daily timing of nursing on parturition, does (n = 10 per group) were remated after giving birth and were allowed to nurse under one of three schedules: group 1 every 24 h in the light, group 2 every 24 h in the dark, and group 3 at any time. Whereas does from groups 2 and 3 nursed and gave birth normally, does of group 1, forced to nurse out of phase with the normal schedule, showed disturbed nursing behavior and prolonged gestation followed by many stillbirths. In a second experiment, pregnant does (n = 10 per group) were treated daily either with oxytocin (OT) in the light (group 4), with OT in the dark (group 5), or with progesterone (P; group 6) or saline (group 7) in the light. All does gave birth normally except those of group 4, which responded similarly to group 1 does. These findings demonstrate that in the rabbit, parturition may be seriously compromised if does nurse out of phase with the normal schedule and suggest that a shift in the daily timing of OT release may underlie this.

Animals↗

Effect of estrogens on plasma platelet-activating factor acetylhydrolase and the timing of parturition in the rat.

In the present study we examined the effects of estrogens on plasma platelet-activating factor acetylhydrolase (PAF-AH) activity in pregnant rats in an attempt to further define the role of platelet-activating factor (PAF) in parturition. The plasma PAF-AH activity decreased starting on Day 13 of pregnancy and reached its lowest level by Day 19 (36.5 +/- 5.7 nmol.min-1.ml-1 plasma, mean +/- SD). The maternal plasma PAF-AH activity rapidly increased to 67.3 +/- 3.5 nmol.min-1.ml-1 plasma by Day 2 postpartum, to 88.8 +/- 14.4 by Day 7, and to 109.1 +/- 4.4 by Day 21, returning to nonpregnant levels by Day 35 in the dams that were allowed to nurse through Day 21. The PAF-AH activity did not increase in dams from which the pups were removed 2 days after delivery. When 17 alpha-ethynylestradiol (0.25 mg/kg) was administered s.c. to pregnant rats for 3 days starting at Day 17 of pregnancy, the plasma PAF-AH activity in the animals decreased by 80% on Day 19, and the rats delivered prematurely on Day 21. When a similar dose of 17 alpha-ethynylestradiol was injected into the pregnant rats for 3 days starting on Day 15, the enzyme activity again decreased by approximately 80% on Day 17 and Day 19 of pregnancy; however, it returned to a value similar to that seen in the controls by Day 21, and the time at which the treated rats delivered was similar to that for the control animals. These observations provide further support for a role of PAF and PAF-AH and their possible regulation by estrogens in the initiation and maintenance of parturition.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

A role for glucocorticoids in parturition in a marsupial, Macropus eugenii.

Dexamethasone treatment induces premature birth in tammar wallabies. Treatment was administered at one of three times between 1200 h on Day 24 and 0930 on Day 25, and birth occurred 22.8 +/- 0.5 h later, significantly earlier than the time of birth for controls, which was 47.7 +/- 2.3 h after treatment. The neonates from treated females were significantly lighter than control neonates (360 +/- 9 vs. 413 +/- 5 mg), and 60% of these died within 12 h of birth, suggesting that premature birth can lead to neonatal mortality. None of the control neonates died. The patterns of secretion of prolactin, prostaglandin F2 alpha-metabolite (PGFM), and progesterone of control and treated animals around the time of birth were similar. A transient pulse of PGFM was coincident with birth while prolactin levels in plasma increased before, and progesterone concentrations fell steeply immediately after, parturition in both groups of animals. The only difference between control and treated animals was in the timing of the hormonal events, which, along with birth, was significantly advanced by the treatment. We conclude that cortisol may play a role in triggering parturition in this marsupial species.

Animals↗

Role of carboxy-extended forms of oxytocin in the rat uterus in the process of parturition.

The hypothalamic synthetic pathway of oxytocin (OT) involves the synthesis of carboxy-extended forms that serve as intermediate prohormones. We hypothesized that extended forms of OT are synthesized in the late-gestational rat uterus and that they compete for OT receptor binding. Parturition occurs only when the ratio of OT to its extended forms reaches a critical level. We have measured OT and its extended forms using two antisera, one recognizing OT and its extended forms, the other recognizing only mature amidated OT. Uterine tissue concentrations of extended forms of OT were 5- to 30-fold greater than those of OT, and both increased progressively and significantly through late gestation. The ratio of OT to its extended forms did not change significantly. Antagonists of estrogen or progesterone receptors reduced concentrations of extended forms by > 90% and of OT by 50%, though the estrogen antagonist significantly prolonged gestation and the progesterone antagonist induced preterm delivery. Using a muscle bath preparation, extended forms of OT were weak uterine stimulants and did not alter the OT concentration-response curves. Extended forms of OT were two to three orders of magnitude less able than OT to displace radiolabeled OT from late-gestational uterine binding sites. We conclude that uterine carboxy-extended OT prohormones are regulated in part by estrogen and progesterone. However, these extended forms of OT have little direct biological activity and do not compete with OT for receptor binding. Their role in the process of parturition may be confined to acting as substrates for OT synthesis.

Animals↗

Cortisol in fetal fluids and the fetal adrenal at parturition in the tammar wallaby (Macropus eugenii).

Glucocorticoid hormones may play a critical role in initiating parturition in tammar wallabies. In this study, we investigated the concentration of cortisol in fetal fluids and cortisol production by fetal adrenals over the last 3 days of the 26-day pregnancy and within 24 h postpartum. The fetal adrenals almost doubled in size between Days 24 and 26 of pregnancy, and their cortisol content increased over 10-fold during this period, from 10 pg to over 100 pg per adrenal pair. After birth, neonatal adrenals continued to grow, but cortisol content fell dramatically to 20 pg. The prepartum increase in adrenal cortisol was reflected by a substantial rise in cortisol concentrations in yolk sac fluid, allantoic fluid, and fetal blood, which were below 10 ng/ml on Day 24 and rose to over 40 ng/ml by Day 26. Cortisol concentrations in neonatal blood decreased postpartum, mirroring decreased cortisol content in neonatal adrenals. Cortisol production by the fetal adrenal was stimulated in vitro by ACTH and prostaglandin E2, suggesting that the in vivo increase may be stimulated by release of ACTH from the fetal hypothalamic-pituitary axis and prostaglandin E2 from the placenta. These results indicate that increasing cortisol production by the fetal adrenal is a characteristic of late pregnancy in the tammar wallaby and support the suggestion that fetal cortisol may trigger the initiation of parturition in this marsupial species.

Adrenal Glands↗

Macrophage trafficking in the uterus and cervix precedes parturition in the mouse.

Immune activation is implicated in the etiology of preterm labor, but little is known about macrophage number or distribution in the uterus or cervix at term. This study tested the hypothesis that macrophages migrate into the reproductive tract before the onset of parturition. Paraffin-embedded sections from the mid-uterine horn and cervix of C3/HeN mice on Days 15 and 18 of pregnancy, the day of birth (Day 19), and 1 day postpartum were stained with a pan-macrophage marker to analyze cell numbers and distribution. During pregnancy, uterine macrophages were dispersed in endometrium, usually associated with vasculature and subluminal epithelium. In myometrium, macrophages were clustered in stromal connective tissue; near term and postpartum, cells appeared to surround the muscle bundles. Total macrophage numbers were increased on Day 15 relative to those in nonpregnant controls, declined before birth, and increased postpartum. In the cervix, macrophages congregated in subepithelium, often perivascular or near ganglia. Macrophage numbers in the cervix peaked on Day 18, then declined to nonpregnant levels by the day after birth. Thus, macrophage numbers in the uterus were inversely related to those in the cervix. These findings raise the possibility that macrophages and their products may be involved in uterine contractility and cervical remodeling during the processes of parturition.

Animals↗

Glucocorticoid regulation of human and ovine parturition: the relationship between fetal hypothalamic-pituitary-adrenal axis activation and intrauterine prostaglandin production.

Birth in many animal species and in humans is associated with activation of hypothalamic-pituitary-adrenal function in the fetus and the increased influence of glucocorticoids on trophoblast cells of the placenta and fetal membranes. We suggest that in ovine pregnancy glucocorticoids directly increase fetal placental prostaglandin production, and indirectly increase prostaglandin production by maternal uterine tissues through the stimulation of placental estradiol synthesis. The events of ovine parturition are compared with those of human parturition. In the latter, we suggest similar direct effects of glucocorticoids on prostaglandin synthesis and metabolism in fetal membranes and similar indirect effects mediated by glucocorticoid-stimulated increases in intrauterine corticotropin-releasing hormone expression.

Adrenal Glands↗

Occurrence of estrogen receptor alpha in bovine placentomes throughout mid and late gestation and at parturition.

The bovine placenta produces estrogens from the first trimester until the end of its life span. However, with the exception of the immediate prepartal and intrapartal phases, in which an involvement of placental estrogens has been suggested for the preparation of parturition, their function has not been elucidated yet. To test for a role of placental estrogens as local factors regulating placental growth and differentiation, placentomes from cows that were pregnant for 150, 220, 240, and 270 days, and parturient cows (3 animals per group) were screened immunohistochemically for the expression of estrogen receptor alpha (ERalpha). Indirect immunoperoxidase staining methods were applied using primary monoclonal antibodies (pmAbs) directed against the C-terminus (AER311, HT277) or the N-terminus (AER314, 1D5) of the ERalpha molecule. Both types of pmAbs identified ERalpha in stromal cells and capillary pericytes of the maternal caruncular septae. Using pmAb 1D5, the mean percentage of ERalpha-positive caruncular stromal cells decreased from 39.0% +/- 5.9% in pregnant cows to 17.5% +/- 8.3% at parturition (P = 0.011). Only pmAb recognizing the C-terminus identified ERalpha in the caruncular epithelium, in which positive reactions were found in all cells, with the exception of areas adjacent to the chorionic plate and to major chorionic villi, where the specific signal gradually faded and occasionally disappeared. No positive reactions were observed in the fetal part of the placentomes. The expression of ERalpha in bovine placentomes was further confirmed by the detection of ERalpha-specific mRNA by reverse transcriptase-polymerase chain reaction and by Western blot analysis. The results suggest a role for placental estrogens as paracrine factors involved in the regulation of placental growth and differentiation.

Animals↗

A case of sarcoidosis which relapsed twice after successive parturitions.

A 30-year-old Japanese woman relapsed into sarcoidosis after two successive parturitions. The cutaneous lesions consisted of scar sarcoidosis, papular type, nodular type, and subcutaneous nodules with histologically typical "naked tubercles". Hypergammaglobulinemia, elevation of both serum angiotensin converting enzyme and lysozyme levels, and bilateral hilar lymphadenopathy were found in the acute and subacute stages, and spontaneously returned to normal levels 16 months after the onset. Our case suggests that parturition may trigger the onset of sarcoidosis.

Acute Disease↗

Effect of late hypothalamo-pituitary disconnection on the development of the HPA axis in the ovine fetus and the initiation of parturition.

The studies of Liggins et al. (1) in which fetuses stalk-sectioned from day 116 onwards delivered at or near term, suggested that a connection between the fetal hypothalamus and pituitary is not essential for parturition to occur. The objective of this study was to repeat these experiments on the effects of pituitary stalk sections at different gestational ages and include information on the plasma concentrations of key fetal hormones. We have used the more sophisticated technique of hypothalamo-pituitary disconnection (HPD) at either of two gestational age ranges (123-127 days or 133-135 days). Completeness of the procedure was assessed by demonstrating an attenuated prolactin response to chlorpromazine challenge. Following HPD, gestation was prolonged for at least eight days beyond term (146.2 +/- 1.5 days) in 9 of the 10 fetuses operated. Fetal plasma ACTH1-39 concentrations were not different between the HPD and control fetuses, increasing in all groups with increasing gestation. Fetal plasma cortisol concentrations increased (P < 0.01) in control fetuses over gestation. Cortisol concentrations did not change significantly in the day 125 HPD group following HPD but increased in the day 135 HPD group (P < 0.05) with advancing gestation. These latter concentrations, however were markedly less (P < 0.001) than those for control fetuses prior to parturition. Fetal and maternal plasma PGE2 concentrations increased (P < 0.01) in the control group over gestation but did not change following HPD. Maternal plasma progesterone concentrations decreased (P < 0.05) after day 143 in the control group but did not change in the HPD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Effects of subacute opioid administration during late pregnancy in the rat on the initiation, duration and outcome of parturition and maternal levels of oxytocin and arginine vasopressin.

1. The effects, on parturition in the rat, of subacute and acute opioid administration were studied. Further experiments investigated the role of modulation of maternal plasma and pituitary oxytocin (OXY) and arginine vasopressin (AVP) levels in these effects. 2. Subacute opioid (M320, buprenorphine or bremazocine) administration prolonged the gestation of rats. This was accompanied by toxic effects on the offspring. Acute subcutaneous (s.c.) M320 (10 micrograms/kg) administration was accompanied by prolonged gestation without toxic effects. 3. Subacute M320 (10 micrograms/kg, s.c., twice daily) treatment was accompanied by increased interbirth intervals in parturient rats. 4. Maternal OXY but not AVP release, as assessed by measurement of plasma and pituitary immunoreactivity, was elevated during and up to 1 h after the completion of parturition. Subacute M320 treatment did not inhibit this elevated OXY release.

Animals↗