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Tissue concentrations of endothelial cell adhesion molecules in the lower uterine segment during term parturition.

OBJECTIVE: To determine the concentration of endothelial cell adhesion molecules in the lower uterine segment during parturition at term. METHODS: We analyzed protein extracts from the lower uterine segments of 38 women who had nonelective cesareans at term. We measured concentrations of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1 by enzyme-linked immunosorbent assay. Subjects were grouped according to cervical dilatation (less than 2 cm, n = 10; 2 to less than 4 cm, n = 9; 4-6 cm, n = 9; more than 6 cm, n = 10) and duration of labor (up to 6 hours, n = 14; 6-12 hours, n = 10; 12-24 hours, n = 9; longer than 24 hours, n = 5) at the time of cesarean. RESULTS: The median concentration of intercellular adhesion molecule-1 increased significantly with increasing dilatation (from 2.24 ng/mg total protein at less than 2 cm to 6.73 ng/mg at 4-6 cm) and increasing duration of labor (from 2.53 ng/mg up to 6 hours to 5.90 ng/mg at 12-24 hours). However, this study did not have adequate statistical power to identify differences in concentrations of the other endothelial adhesion molecules. CONCLUSION: The results indicate that parturition at term is associated with expression of intercellular adhesion molecule-1.

Adult↗

Induction of parturition in pigs by intravaginal application of the prostaglandin analog cloprostenol.

Cloprostenol was deposited in the vaginal lumen of sows on Day 111 of pregnancy at dosages of 100, 125 or 175 g and volumes of 1, 2 or 5 ml, respectively. A control group was treated with physiological saline. In 92 out of 93 prostaglandin-treated sows, parturition commenced approximately 22 h after application, with no significant differences between dose levels or volumes. There were also no differences in the average size and weight of litters born, weaning weight, frequency of postpartum complications or post-weaning fertility. Intravaginal application of cloprostenol is thus a simple and efficient means of inducing parturition in sows.

Journal Article↗

Induction of parturition in goats with fenprostalene.

Eleven dairy goats of several breeds were administered 0.5 mg of the prostaglandin analogue fenprostalene (0.5 mg s.c.) on Days 146 to 148 of pregnancy. Parturition was successfully induced in all does, with a mean interval to first kid of 31.6 h +/- 0.83 (SEM). The course and duration of labor were normal. All kids were delivered alive. The incidence of dystocia due to fetal posture was 1/11; the incidence of fetal membranes retained for longer than 6 h was 1/11. These data indicate fenprostalene is safe and efficacious for induction of parturition with an interval to effect not significantly different from that reported for dinoprost or cloprostenol.

Journal Article↗

Hippocampal electrical activity in the female rat: the estrous cycle, copulation, parturition, and pup retrieval.

Hippocampal electrical activity was examined in female rats across the four phases of the estrous cycle, as well as during copulation, parturition, and pup retrieval. Possible hormonal effects on hippocampal activity were examined by recording daily during struggling and immobility throughout five estrous cycles. No differences in the characteristics of rhythmical slow activity (RSA), large-amplitude irregular activity (LIA), or their relation to behavior were found between the phases of the estrous cycle. Behaviors examined during copulation were lordosis, hopping, and ear wiggling. Lordosis and ear wiggling were both accompanied by irregular waves, with some low frequency RSA also present during lordosis. Hopping was accompanied by RSA which was greater in amplitude and frequency than RSA during walking. Parturition behaviors examined included body extensions, genital or pup licking, and 'body flattening'. Body extensions were found to be associated with irregular hippocampal activity, and appeared to be a Type 2 behavior. Interestingly, sudden suppressions of the hippocampal record lasting 1-5 s often preceded body extensions. Irregular hippocampal activity was present at all times during genital and pup licking. Body flattening was typically accompanied by very high amplitude irregular waves which, although the rats were awake, resembled a sleeping hippocampal pattern. Pup retrieval involved walking and was thus always accompanied by RSA.

Animals↗

Continuous infusion of relaxin on periparturient progesterone, oxytocin and relaxin plasma concentrations and time of parturition in beef heifers.

These studies were designed to determine whether continuous i.v. infusion of increasing dosages of porcine relaxin during late pregnancy in beef heifers would influence circulating blood concentrations of relaxin, progesterone and oxytocin, and time of onset of parturition. Beef heifers were bred by artificial insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone infusion and blood sampling from Day 277 to Day 286. Intravenous infusion of purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280, 500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283-286). Phosphate-buffered saline (PBS, 10 ml h-1) was infused during these same times to control animals (n = 6). Relaxin treatment steadily increased the circulating plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared with less than 0.5 ng ml-1 in PBS-treated controls. Relaxin infusion in increasing dosages over the treatment time was associated with a significant decrease (P < 0.01) in plasma progesterone concentration compared with the PBS controls. The rate of change in progesterone levels between pRLX and PBS groups differed (P < 0.05) at 300 U h-1, 600 U h-1 and 700 Uh-1 dosage intervals, respectively. Plasma levels of oxytocin at 4 h intervals remained similar (P > 0.05) during the pretreatment period and throughout continuous infusion of pRLX and PBS. Mean concentrations of oxytocin in PBS control heifers peaked at 0.95 pgml-1 during the corresponding infusion of 700 Uh-1 pRLX, which peaked at 0.77 pgml-1. Although continuous i.v. infusion of relaxin resulted in a decrease in circulating blood levels of progesterone, it did not significantly reduce the interval between the beginning of pRLX treatment and parturition compared with the PBS-infused control heifers. These results indicate that continuous i.v. infusion of high levels of porcine relaxin resulted in a decrease in progesterone secretion in late pregnant beef heifers.

Animals↗

Plasma beta-endorphin around parturition and its relationship to cortisol level and resumption of pituitary and ovarian functions in dairy cows.

The objectives were to evaluate the concentrations of beta-endorphin in peripheral circulation around parturition and to investigate their relationship to the concentrations of cortisol and postpartum resumption of pituitary and ovarian functions in dairy cows. Subjects were 21 Holstein-Friesian cows in late pregnancy. Blood samples were collected from these animals from day 270 in pregnancy until the first ovulation after calving. Average immunoreactive (IR) beta-endorphin concentrations in cows with dystocia (n = 8) in periparturient period (from day 270 of pregnancy until 24 h after calving) were slightly higher than those in cows with normal calving (n = 13) in the same period although the difference was not significant. During the periparturient period, the peak level of IR beta-endorphin was seen at the time of rupture in cows with normal calving and it was observed at the time of parturition in cows with dystocia. The trend of IR beta-endorphin secretion appeared to be concomitant with cortisol secretion in the periparturient period but not in postpartum period (from 24 h after calving until the first ovulation). Average IR beta-endorphin concentrations in cows with dystocia in the postpartum period were not significantly different from those in cows with normal calving. There was no significant association between average IR beta-endorphin concentrations in early postpartum period (from 24 h until 7 days after calving) and the responsiveness of luteinising hormone (LH) to exogenous GnRH administered on day 7 postpartum. However, a negative correlation (r = -0.593; n = 21; P = 0.004) was observed between average IR beta-endorphin concentrations and LH concentrations during the period from day 1 until the first ovulation in the 21 cows. In addition, a positive correlation (r = 0.498; n = 21; P = 0.020) was seen between the beta-endorphin concentrations and time to the first ovulation after calving. The results from this study suggest that beta-endorphin may release into peripheral blood differently from cortisol and that it may be involved in regulating LH secretion and thus the resumption of ovarian cyclicity in postpartum dairy cows.

Animals↗

Plasma progesterone in alpaca (Lama pacos) during pregnancy, parturition and early postpartum.

Plasma progesterone concentration during pregnancy and the early postpartum period was measured by radioimmunoassay in five alpacas (Lama pacos), of the Huacaya breed, whose pregnancy length had a mean of 344.8 +/- 4.4 days. Concentration of progesterone increased (P < 0.001) from low premating values (0.11 +/- 0.06 nmol/l) to greater values at 30 days of pregnancy (8.05 +/- 1.13 nmol/l) and remained high up to 2 months of pregnancy. A slight transitory decline was observed between 3 to 7 months. Concentration of plasma progesterone dropped markedly during the 72 h before parturition especially, at the day of parturition.

Animals↗

Cross-sectional study of the effects of parturition and lactation on bone mineral density later in life.

OBJECTIVE: The present cross-sectional study investigated the effects of parturition and lactation on bone mineral density (BMD) later in life. METHODS: The subjects were 456 premenopausal and 713 postmenopausal Japanese women aged 40-69 years old. They were classified into six subgroups at 5-year increments. Age, height, weight, menopausal status, age at menopause (in postmenopausal women), years since menopause (in postmenopausal women), parity, and total lactation period were recorded. Lumbar spine BMD (L2-4) was measured by dual-energy X-ray absorptiometry (DEXA). In each subgroup, correlations of parturition and lactation with BMD were investigated using Pearson's correlation test and multiple regression analyses. RESULTS: In premenopausal women aged 40-44 years old (n=143), total lactation period was inversely correlated with BMD (r= -0.293, P<0.01). This relationship remained significant after adjusting for age, height, weight, and parity (P<0.05). Although the total lactation period was inversely correlated with BMD in the group aged 60-64 years old (r= -0.194, P<0.05, n=218), this relationship disappeared after adjusting for age, YSM, height, weight, and parity. However, in the other subgroups, there were no significant correlations between total lactation period and BMD. There were no significant correlations observed between parity and BMD in any groups. CONCLUSION: Reproductive history of lactation and parity does not seem to be a major determinant of BMD later in life.

Absorptiometry, Photon↗

Increase in prostaglandin bioavailability precedes the onset of human parturition.

The traditional paradigm that prostaglandins (PGS) are of central importance in the initiation of labor has been challenged. A group of investigators has recently reported that the amniotic fluid concentrations of PGE(2) and PGF(2 alpha) increase only late in the course of labor implying that "the accumulation of prostaglandins in amniotic fluid is an after-effect of labor and not indicative of a role of these compounds in the initiation of human parturition." The present study was conducted to determine whether amniotic fluid prostaglandin concentrations increase prior to the onset of human labor, the central question in this controversy. Three amniocenteses were performed in 17 women with intrahepatic cholestasis of pregnancy -- the first two prior to the onset of labor and the third during early spontaneous labor. PGE(2) and PGF(2 alpha) were measured with sensitive and specific radioimmunoassays. Amniotic fluid concentrations of PGE(2) and PGF(2 alpha) increased prior to the onset of spontaneous labor. An additional increase in the concentrations of PGE(2) and PGF(2 alpha) was found in samples obtained in early labor. We conclude that an increase in prostaglandin bioavailability precedes the onset of spontaneous human parturition.

Amniocentesis↗

The effects of photoperiod on the switching of myometrial contractility patterns of pregnant baboons: relationship to surgery and parturition.

OBJECTIVES: Pregnant baboons were studied to determine the precise time of the switch from myometrial contractures to contractions in relation to photoperiod after laparotomy and at parturition. We compared the patterns recorded in baboons to those we have previously reported in pregnant rhesus monkeys to determine fundamental primate characteristics. METHODS: Seven pregnant baboons (126-160 days' gestation) were instrumented with femoral arterial and venous catheters and electrodes for myometrial electromyogram. All animals were subjected to a 14-hour light:10-hour dark photoperiod. Myometrial activity was monitored using a computer-based data acquisition system. Onset time for all switches was noted and standardized against time of lights off. Animals were studied at three stages of pregnancy (stage 1, first 10 days after laparotomy; stage 2, more than 10 days after laparotomy and more than 10 days before cesarean; and stage 3, 10 days before cesarean section or vaginal delivery). RESULTS: All baboons demonstrated myometrial switches for a variable number of days preceding parturition. Onset of darkness was 0 hours. Average time of stage 1 switch onset was 2.17 +/- 0.60 hours and was not different from stage 3 switch onset, which was -1.00 +/- 0.27 hours. CONCLUSIONS: Myometrial contractile patterns showed clear photoperiodicity in the switch from contractures to contractions in late pregnancy in the baboon. The relationship of the switch from contractures to contractions was not altered by surgical laparotomy. There was a significant difference in the time of switch in relation to photoperiod between pregnant rhesus monkeys and baboons. However, the fact that a significant photoperiod exists in both species indicates a fundamental similarity in the switch from contractures to contractions in primate pregnancy.

Animals↗

Role and regulation of nitric oxide in the uterus during pregnancy and parturition.

OBJECTIVE: To review the English-language literature as it relates to the role and regulation of uterine nitric oxide (NO) during pregnancy and parturition, special emphasis being placed on the interactions of NO with other uterotonic agents. METHODS: A thorough literature review of the English-language literature using a Medline search was performed. RESULTS: Current data support the view that NO is generated in the uterus and inhibits uterine contractility. Gestation, parturition, steroid hormones, and prostaglandins modulate both the generation and the effects of NO on the uterus. The changes in NO and its effects are consistent with the theory that NO plays a role in uterine quiescence during pregnancy. A change in this system at term or preterm could play a role in inhibition of labor and delivery. CONCLUSION: Uterine NO may play a role in maintaining uterine quiescence during pregnancy.

Animals↗

Down-regulation of the mitogen-activated protein kinase cascade immediately before parturition in the rat myometrium.

OBJECTIVE: This study tested the hypothesis that mitogen-activated protein kinase (MAPK) pathway is up-regulated during the course of pregnancy concomitant with uterine hypertrophy. METHODS: The expression and intracellular distribution of components of the MAPK cascade and the activation of MAPKs erk1 and erk2 were examined in the pregnant rat myometrium (day 10-22 of gestation). Protein expression was detected by Western analysis of myometrial subcellular fractions. Mitogen-activated protein kinase activation was studied by detection of tyrosine phosphorylation of erk1 and erk2 kinases and enzymatic activity. RESULTS: Mitogen-activated protein kinase activity increased from day 15 to day 20 of pregnancy. Immediately before parturition, MAPK activity, but not expression, declined sharply. During the same interval, membrane expression of the mitogenic-switching protein ras and the ras activator sos declined. CONCLUSION: The shift in intracellular distribution ras and ras chaperone proteins may precede the down-regulation of membrane-dependent mitogenic signaling and uterine hypertrophy as pregnancy approaches parturition.

Animals↗

Effects of parturition and maternal experience on noradrenaline and acetylcholine release in the olfactory bulb of sheep.

Acetylcholine (ACh) and noradrenaline (NA) release in the olfactory bulb (OB) of ewes was monitored using microdialysis. Both ACh and NA release increased at parturition in multiparous but not in primiparous ewes. However, vaginocervical stimulation performed 6 hr postpartum induced an increase of ACh and NA release in both primiparous and multiparous ewes, indicating that a maturation process had occurred. Finally, pharmacological challenges to the ACh and NA inputs revealed differential responsiveness between nulliparous and multiparous nongestant ewes. These results suggest that the first parturition induces changes in neural circuitry involving ACh and NA inputs to the OB.

Acetylcholine↗

Local paracrine effects of estradiol are central to parturition in the rhesus monkey.

The central biochemical mechanisms involved in primate parturition are still unclear. Studies in both humans and nonhuman primates such as the baboon and rhesus monkey indicate that many factors play a part in the cascade of interactive positive feedforward loops that progressively promote parturition: changes in maternal endocrinology, a nocturnal switch in myometrial activity from low amplitude, infrequent contractures to high amplitude, high frequency contractions (see Fig. 1), dilation of the cervix and biochemical changes in the fetal membranes that lead to rupture. Here we demonstrate that infusion of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA) inhibits conversion of androgen to estrogen and prevents premature delivery caused by administration of androgen to pregnant rhesus monkeys at 0.8 of pregnancy term. 4OHA also inhibited the androstenedione induced maternal endocrine and fetal membrane biochemical changes, and alteration of myometrial activity patterns. Secondly, peripheral estrogen infusions increased myometrial activity but did not produce preterm delivery or fetal membrane changes. We conclude that paracrine functions of estrogen at its site of production play critical and central roles in delivery in the non-human primate.

Androstenedione↗

Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition.

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk injection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk injection, but not for mating, parturition and milk production, in mice.

Animals↗

Post-parturition and late lactation urine: long-term effects of exposure on mouse activity and sniffing behaviour.

From the time of separation from their mothers infant mice were exposed for 10 consecutive days to urine from post-parturitional and late-lactational donor mice. They were then tested when adult on activity and sniffing behaviour. The sample of mice exposed to urine from late-lactational donors was associated with reduced activity when compared with mice exposed to post-parturitional urine and a water control sample. The long term effects of the urine on behaviour were also apparent in positional preferences in an open arena as judged by frequency of entry, and to a lesser extent, the time spent in the left and right hand segments. Mice exposed to late-lactational urine sniffed less than the other treatment samples though preferences for sniffing the urine that they had been exposed to in infancy were less marked. The urine did not accelerate puberty, but mice in the control sample had more vaginal dioestrous smears and fewer smears with a predominance of epithelial cells.

Animals↗

Evaluation of L-selectin expression and assessment of protein tyrosine phosphorylation in bovine polymorphonuclear neutrophil leukocytes around parturition.

Impaired polymorphonuclear neutrophil leukocyte (PMN) function around parturition has been associated with increased clinical mastitis in dairy cows. Rolling and attachment of PMN to the endothelium is the first step in the recruitment process and is accomplished by interaction between L-selectin on PMN and its ligand on endothelial cells. Furthermore, tyrosine phosphorylation is involved in the initiation of many PMN functions. The objective of this work was to determine changes in expression of L-selectin and tyrosine phosphorylation in the perinatal period. Eight clinically healthy Holstein cows were used as PMN donors at d-21, -14, -7,0 (calving), +1, +2, +7, +14, +28. Evaluation of L-selectin expression was carried out on activated and resting PMN. Anti-bovine L-selectin monoclonal antibody (MAB) and flow cytometric analysis were used to measure the percentage of PMN fluorescing and receptor expression (log mean fluorescent channel, LMFC). Activated and resting PMN showed similar trends in % PMN fluorescence and LM FC. The percentage of PMN fluorescing tended to decrease at parturition, followed by a significant increase at d +14 and +28 (P < 0.02). For LMFC a decrease was observed on d +1 followed by an increase through d +28 (P < 0.01). Protein tyrosine phosphorylation of lysates prepared from PMN isolated throughout the study was detected by electrophoresis and western blotting using anti-phosphotyrosine MAB. Several protein bands were tyrosine phosphorylated. Two of these bands (42-44 kDa and 90 kDa) varied in intensity over time. The intensity of the 42-44 kDa band gradually increased from d -7, peaked at d +7 (P < 0.03), and steadily decreased to d +28 (P < 0.02). Antibody to activated mitogen protein kinase reacted with the 42-44 kDa band. Reduced PMN function during the periparturient period could be related to reduced L-selectin adhesion molecules on the cell surface, and to modulation in the phosphorylation of functionally important molecules.

Animals↗

Production of monoclonal antibodies and enzyme immunoassay to bovine retinol-binding protein and determination of retinol-binding protein serum levels and retinol concentrations in serum and liver in dairy cows before and after parturition.

To study vitamin A transport in dairy cows and heifers around parturition, an enzyme immunoassay for bovine retinol binding protein (RBP) was developed and serum levels determined. Serum and liver concentrations of retinol were assayed by HPLC. Four weeks before expected calving the cows and heifers were divided into two groups each, and half of the animals received a protein supplementation during the dry period. The mean serum RBP concentration 4 weeks before calving was 42 mg l-1 for the cows and 44 mg l-1 for the heifers. The serum retinol concentrations were 0.53 mg l-1 for the cows and 0.42 mg l-1 for the heifers, and the liver retinol concentrations 0.30 mg l-1 and 0.13 mg g-1, respectively. In the groups without protein supplementation there was a significant decrease in serum RBP at sampling 1 week before parturition compared to initial values. The measurement of serum RBP may prove useful in assessment of amino acid availability in dairy cows.

Animals↗