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Induction of parturition in the mare with prostaglandin F2 alpha.

Thirty-one mares of Quarter Horse and Thoroughbred breeding were utilized in two experiments to evaluate the efficacy of prostaglandin F2 alpha (PGF2 alpha) for induction of equine parturition and to monitor the effects of this treatment on viability of the resulting foals. Three of five mares given 5 mg PGF2 alpha (im) on day 338 of gestation foaled 19.6+/-8.2 hr postinjection. In the second experiment immediately following 3 daily injections of 10 mg estradiol cypionate (ECP) given on days 326, 327 and 328 of gestation, seven mares were infused (iv) with PGF2 alpha at the rate of 1.3 mg/hr for 24 hr or until parturition occurred. Four of the seven mares foaled in 8.8+/-1.8 hr after the start of infusion. Side effects including sweating, hypothermia, increased respiration rate and diarrhea were evident in both injected and infused mares, but effects were transient. Neither the injection, nor infusion route of administration of PGF2 alpha adversely affected the viability of foals. However, some mares induced to foal 12 days prior to expected parturition had foals with slightly weaker pasterns than those of control mares.

Animals↗

Clinical evaluations of a new prostaglandin analog in pigs: 1. Control of parturition and of the MMA-syndrome.

In two field trials, the parturition inducing and MMA preventing effects of the prostaglandin F(2alpha) analog (PGFA), K 11941, were explored. In trial 1, 100 sows were treated with 2 mg and 30 with 3 mg of K 11941 i.m. on day 112 of gestation; 125 sows treated on day 112 with 175 mcg cloprostenol (Planate, ICI) served as positive controls, and 248 sows treated with saline on day 112 of gestation were used as negative controls. Both PGF analogs were equally effective in inducing early parturiton: 84.6% and 83.2% of the sows had farrowed between 20 and 30 hours after treatment. Both treatments reduced stillbirth rate and piglet losses during the first 10 days of life, and lowered the incidence of MMA significantly (6.2 and 5.6% vs 27.3 and 24.2%; p<.001). In a second trial, parturitions were induced in four groups of 60 sows each with 2 mg K 11941, housed in farms with either a chronic high incidence of MMA (A: 45 to 65% or only a seasonal rise in MMA during summer (B: 10 to 50%). Groups were treated either in April/May or August/September; 240 salinetreated, control sows were used. K 11941-induced parturition reduced MMA incidence in farm A during both seasons and prevented the summer rise in farm B (p<.01). Fertility after weaning was impaired in herds with an increased incidence of MMA.

Journal Article↗

Early induction of parturition and initiation of lactation in sheep.

Dexamethasone and estradiol benzoate were used to induce parturition in ewes at about day 120 of gestation as part of a program to reduce the time taken to progeny-test carpet-wool rams by evaluating the birthcoats of their offspring. Ten ewes received 5 injections of 12 mg dexamethasone over 2.5 days commencing on day 117. Eight lambed 3.1 +/- 0.53 days after the final injection. Of 14 ewes which received 20 mg estradiol benzoate on day 118, three delivered lambs, 2.0 +/- 0.41 days after injection. All lambs were born dead or died within 2 hours of birth. Following parturition all ewes came into lactation. The dexamethasone group produced more colostrum, with higher total solids content than the estradiol group. However, the volume was less than in a control group which lambed at full term. It was concluded that dexamethasone could be used successfully to induce parturition at 120 days and that onset of lactation was similar to that which occurs at full term.

Journal Article↗

Induction of parturition in the pig using a new prostaglandin analogue (K11941).

Eighty seven sows, taken from a herd whose mean gestation length was 116 days, were allotted at random on day 114 of gestation to one of five treatment groups as follows: (1) 175 mug prostaglandin analogue (closprostenol I.C.I. Ltd) (2) 1 mg K11941 (alfaprostol VETEM Ltd), (3) 2 mg K11941, (4) 3 mg K11941 (5) 2 ml saline (control). All prostaglandin analogues induced parturition significantly earlier than controls (P < 0.05), but there were no differences between any of the prostaglandin treatments in the interval to birth of the first piglet (P > 0.05). The mean intervals to parturition were 24.6, 22.3, 24.9, 30.7 and 53.0 hours for treatments 1, 2, 3, 4 and 5 respectively. Almost two-thirds of treated sows farrowed during the working period of the day following injection compared with a small proportion of control animals. Induction of parturition had no effect on birth weight, piglet survival to 3 weeks or on subsequent weaning to service interval in treated sows. Results show that this new analogue of prostaglandin (K11941) is effective in inducing farrowing in the sow.

Journal Article↗

Induction of parturition in swine with a prostaglandin analog and oxytoxin: A trial involving dose of oxytocin and parity.

The purpose of this experiment was to compare a range of oxytocin doses in order to find the most suitable dose to improve predictability and precision of timing of PGF-induced parturition in sows. Sows randomly allotted to 6 groups - group size varying between 28 and 39 - were either untreated controls (group 1) or received an IM injection of 2 mg of the PGF-analog Alfaprostol (Vetem) on day 111 of pregnancy (day 0 = last day of standing heat), followed 20 h later by 0, 5, 10, 20 or 30 IU oxytocin, respectively (groups 2 - 6). Both length and variability of the time from injection of oxytocin to the onset of parturition decreased with increasing dose. The response was faster and more predictable with older sows than with first litter gilts. A disadvantage of higher doses of oxytocin was the necessity of manual aid (11 % in controls, 52 % with the maximum level of 30 IU oxytocin). Litter size, weight and percentage of piglets weaned and time from weaning to subsequent estrus were not affected by any of the treatments. An oxytocin dose of 20 IU applied 20 h after PGF appeared to give the most effective response, although this will occasionally necessitate manual assistance with parturition.

Journal Article↗

Lambing and placental expulsion time after dexamethasone-induced parturition in Corriedale and Polwarth ewes.

To study breed differences in ewes induced to parturition with dexamethasone (DXM), 15 Corriedale and 16 Polwarth ewes were injected with 15 mg of DXM four days before the expected lambing date (Days 144 and 145, respectively) in Experiment 1. Interval from treatment to parturition was twice as long for the Polwarth than for the Corriedale breed (57.9 vs 28.8 hours, P </= 0.001). In Experiment 2, the effect of DXM on the interval from parturition to expulsion of the placenta and on biological parameters of the lambs (birth weight, ability to stand after birth and daily weight gain during the first week of life) was studied in 30 Corriedale ewes. On Day 144 of gestation, ewes were given 15 mg of DXM (n= 22) or 15 ml of saline (controls, n= 8). The DXM group lambed 33.8 +/- 2.7 hours after injection. Treatment caused an increase in the time of placental expulsion (4.3 vs 3.4 hours, P>/= 0.05) and on the percentage of ewes retaining the placenta beyond 6 hours (18% vs 0%, P>/= 0.05). Birth weight of lambs was lower in the induced group (3.9 vs 4.5 kg, P</= 0.03), but this did not affect the other parameters of the lambs studied.

Journal Article↗

Fos expression in the hypothalamic magnocellular neurons of rats during pregnancy, parturition and lactation.

Changes in Fos expression of magnocellular neurons in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of the rat hypothalamus were investigated using immunohistochemistry during pregnancy, parturition and lactation. Quantitative morphometrical analysis revealed that Fos-positive cells in the hypothalamic magnocellular neurons were rarely seen in days 10 and 20 pregnant rats, however, significantly numerous Fos-positive cells were found in parturient rats. The number of Fos-positive cells was drastically decreased within a few days after parturition. Moreover, it was found using dual immunohistochemistry that the percentage of Fos-positive cells in vasopressin (AVP) magnocellular neurons of the SON was higher than that of the PVN in parturient rats, although oxytocin (OXT) magnocellular neurons showed the same percentage of Fos-positive cells between the SON and PVN. These results demonstrate that the hypothalamic magnocellular neurons express Fos during a limited period after parturition, and Fos expression in AVP magnocellular neurons is heterogeneous between the SON and PVN.

Animals↗

Parturition in the camel (Camelus dromedarius) and some behavioral aspects of their newborn.

Symptoms of approaching parturition and the stage of parturition were described for eight pluriparous camels. The average time for the complete process of parturition was 373.9 +/- 38.2 min. The body weights at birth of the newborn males and females were 31.3 +/- 1.69 and 24.5 +/- 2.5 kg, respectively. Standing and first suckling by the neonatal camels occurred at 68.6 +/- 6.2 and 98.6 +/- 11.3 min, respectively.

Allantoin↗

The effects of pregnancy and parturition on the levels of substance P-like immunoreactivity in different areas of the hypothalamus.

1. The concentrations of substance P-like immunoreactivity (SPLI) have been measured in the rostral and caudal areas of the hypothalamus of male rats and of virgin, pregnant and puerperal female rats. 2. The rostral:caudal ratio of SPLI is similar in males and virgin females, but diminishes in pregnancy and decreases further during the puerperium. In the pre-optic area, the SPLI concentration fell significantly during parturition, from 241.8 to 177.2 pmols/g wet weight (P < 0.05), and in the medio-basal hypothalamus, the concentration rose during pregnancy and parturition, from 87.4 to 145.5 pmols/g wet weight (P < 0.001). 3. The results are discussed in relation to the endocrine and nociceptive aspects of pregnancy and parturition.

Animals↗

Changes in 17 beta,20 alpha-hydroxysteroid dehydrogenase activity supporting an increase in the estrogen/progesterone ratio of human fetal membranes at parturition.

OBJECTIVE: Our purpose was to measure the activity of the reversible enzyme 17 beta,20 alpha-hydroxysteroid dehydrogenase around parturition with estrogen and progestogen substrates. STUDY DESIGN: Classic kinetic studies and explant cultures were used to determine kinetic parameters and net enzyme activities in both oxidative and reductive directions for both sets of substrates. RESULTS: Affinity constant values for estrone, estradiol, and 20 alpha-dihydroprogesterone were 1 to 8 mumol/L. Affinity constant for progesterone was 9 to 25 mumol/L. Maximal velocities for all substrates in the chorion were 20- to 70-fold higher than in amnion and severalfold higher for estrogen substrates compared with the progestins. Around parturition there was a significant change toward net formation of the stronger estrogen (estradiol) and the weaker progestin (20 alpha-dihydroprogesterone), suggesting an increase in the local estrogen/progesterone ratio. CONCLUSION: The enzyme 17 beta,20 alpha-hydroxysteroid dehydrogenase may be an important regulator of the local estrogen/progesterone ratio in fetal membranes around the time of parturition.

20-Hydroxysteroid Dehydrogenases↗

Evidence for a local change in the progesterone/estrogen ratio in human parturition at term.

The purpose of this study was to determine if a local change in the concentrations of estrogen and progesterone occurs in the amniotic fluid during human parturition at term. Amniotic fluid was retrieved from 20 women in active labor and from 20 women not in labor. Patients were matched for maternal age and gestational age. Estradiol, estriol, progesterone, and dehydroepiandrosterone sulfate were measured in amniotic fluid by radioimmunoassay. For women in active labor, the median concentrations (range) of these steroid hormones were 2.4 ng/ml (1 to 9.2 ng/ml), 1661.2 ng/ml (556.6 to 3928.1 ng/ml), 12.3 ng/ml (4.7 to 41.4 ng/ml), and 187.5 ng/ml (61.2 to 470 ng/ml), respectively. The median concentrations (range) for women not in labor were 1.6 ng/ml (0.3 to 5.7 ng/ml), 684.2 ng/ml (70.6 to 2103.1 ng/ml), 13.2 ng/ml (7.5 to 63 ng/ml), and 65.6 ng/ml (20 to 334 ng/ml), respectively. Thus spontaneous human parturition at term was associated with significantly increased amniotic fluid concentrations of estradiol, estriol, and dehydroepiandrosterone sulfate (p = 0.02, p = 0.002, p = 0.003, respectively). The progesterone/estrogen ratios (progesterone/estradiol and progesterone/estriol) were significantly lower for women in active labor compared with those not in labor (p = 0.002 and p = 0.0006, respectively). We conclude that a local change in the progesterone/estrogen ratio occurs during human parturition at term.

Amniotic Fluid↗

Stimulation of expression of the oxytocin gene in rat supraoptic neurons at parturition.

We measured expression of the oxytocin gene in the supraoptic nucleus (SON) during pregnancy, parturition and lactation to examine its relationship to states of accumulation or depletion of oxytocin stores and to conditions of strong excitation of oxytocin neurons. The primary transcript (heterogeneous nuclear RNA, hnRNA) of the oxytocin gene was measured using a 3H-cDNA probe against intron 1 for in situ hybridisation. Autoradiographs of the SON showed the hnRNA as discrete clumps of silver grains within the nucleus of each neuron. The number of cells expressing oxytocin hnRNA did not change during pregnancy but increased during parturition; 10-day lactating animals showed similar increases. Oxytocin mRNA was also measured by in situ hybridisation using a 3H- or 35S-labelled oligonucleotide probe against exon C: hybridisation was seen over the cytoplasm of supraoptic neurons, but no differences were measured between virgin, mid-pregnant, preparturient, parturient or 2-day lactating rats. The data suggest that enhanced oxytocin gene transcription is not necessary to increase oxytocin stores in pregnancy. However, acute stimulation of magnocellular oxytocin neurons at parturition, which strongly increases neuron activity and secretion, results in a rapid increase in the number of cells expressing oxytocin hnRNA, and increased expression is sustained in lactation.

Animals↗

Attraction and repulsion by amniotic fluids and their olfactory control in the ewe around parturition.

The reaction of ewes towards amniotic fluids was studied in intact multiparous ewes in various physiological states (oestrus, luteal phase, mid-pregnancy and around parturition), using a test of preference for food associated or not with the presence of amniotic fluids in the food. Fluids were collected on alien newborn lambs. Results indicate that ewes are strongly repelled by amniotic fluid at all of the times tested except for a short period around parturition. Immediately before expulsion of the foetus ewes become strongly attracted by amniotic fluids. This attraction persists just after parturition, but fades within 4 hours in most animals. This attraction-repulsion behavior appears to rely heavily on olfactory cues. Ewes made anosmic with zinc sulphate do not show repulsion or attraction towards amniotic fluids at any of the physiological states studied. These results are discussed in the light of our knowledge about the factors controlling the onset of maternal behavior in the ewe (hormones and genital stimulation).

Amniotic Fluid↗

Temporal and behavioral patterning of parturition in rabbits and rats.

Although the rabbit (Oryctolagus cuniculus) continues to play an important role in the study of parturitional processes, a detailed behavioral description of birth in this species, necessary for accurately assessing the effects of experimental manipulation, is lacking. It is the aim of this report to provide such a description and to compare it with corresponding behavior in the better-studied rat. Ten pregnant chinchilla-breed rabbits and 10 pregnant Wistar rats were placed in glass-bottomed observation cages 2 days before term, and their behavior recorded on closed-circuit video, viewing the animals from below. All aspects of parturition were accomplished much faster in rabbits than rats; latency to birth of first pup, rate of delivery, duration of vaginal retention, time spent by mothers eating placentas, and in licking and nursing pups. In contrast to rat pups, rabbits were usually born separated from the placenta and already free from membranes. They were much more active, and well able to cast off any remaining membranes, suckle, and survive, whether directly attended to by the mother or not. We conclude that the tight temporal organization of events in the rabbit provides an unusually sensitive assay for investigating mechanisms underlying mammalian parturition.

Animals↗

Effects of indomethacin and prostaglandin F2alpha on parturition in the hamster.

In the hamster administration of indomethacin twice a day on days 14 to 16 of pregnancy delayed the onset of parturition; a delay of 5 and 8 hours was observed following treatments of 300 or 600 mug/injection of indomethacin, respectively. Injection of PGF2alpha to the indomethacin treated hamsters on day 15 of pregnancy, on the other hand, advanced the onset of parturition. Treatments of indomethacin and/or PGF2alpha did not affect the duration of parturition.

Animals↗

Messenger ribonucleic acid levels of interleukin-1 beta, interleukin-6 and interleukin-8 in the lower uterine segment increased significantly at final cervical dilatation during term parturition, while those of tumor necrosis factor alpha remained unchanged.

OBJECTIVE: To investigate the content of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and interleukin-8 messenger ribonucleic acid (mRNA) in the lower uterine segment during term parturition. STUDY DESIGN: mRNA extracts from the lower uterine segment obtained from 53 women undergoing non-elective caesarean section at term were analyzed by semi-quantitative reverse transcriptase polymerase chain reaction. The patients were grouped according to cervical dilatation (less than 2 cm, n=18; 2 to less than 4 cm, n=13; 4-6 cm, n=7; more than 6 cm, n=15) at the time of caesarean section. RESULTS: Interleukin-1 beta and interleukin-8 mRNA-contents at more than 6 cm cervical dilation were significantly higher than at less than 2 cm. The levels of interleukin-6 were already significantly increased in the 4-6 cm group, while the tumor necrosis factor alpha ribonucleic acid content did not change during parturition. CONCLUSION: The process of cervical dilatation during parturition at term is associated with an increased expression of interleukin-1 beta, interleukin-6 and interleukin-8 mRNA in the lower uterine segment. These findings support the theory that the activation of the inflammatory network plays an important role in the progress of cervical dilatation.

Cervix Uteri↗

Quantitative reverse transcription and polymerase chain reaction analysis of oxytocin and vasopressin receptor mRNAs in the rat uterus near parturition.

Oxytocin receptors (OT-R) are known to be involved in the course of labor since a massive increase in OT-binding sites is observed in the uterus just before parturition. Vasopressin (AVP)-binding sites have also been observed and have been shown to mediate uterotonic responses. To determine exactly which subtypes of OT/AVP receptors are expressed in the rat uterus near parturition, we carried out absolute quantitations of the neurohypophysial hormone receptor (OT-R and the vasopressin receptors V1a-R, V1b-R and V2-R) mRNAs with an assay based on reverse transcription-polymerase chain reaction (RT-PCR) using in vitro transcribed mutated cRNAs as internal standards. The number of mRNA molecules/ng of total RNA was 35 +/- 6, 220 +/- 33 and 39 +/- 9 for OT-R (P < 0.01) and 16 +/- 1, 25 +/- 8 and 31 +/- 5 for V1a-R (P > 0.05) on day (D) 21, 22 and 23 of gestation (post-parturient), respectively. We did not detect V1b-R and V2-R mRNAs in the pregnant uterus. Therefore, the heterogeneity of OT and AVP receptors in the rat uterus can only be assigned to the presence of OT-R and V1a-R neurohypophysial hormone receptor subtypes, whereas V1b-R and V2-R can not be invoked. Only OT-R mRNA levels change in the uterus near parturition.

Animals↗

Pregnancy induced mammary tumor specific effector cells are present long after parturition in a breast cancer model in rats.

Pregnancy is known to provide protection against 7,12 dimethylbenz[a]anthracene-(DMBA) induced mammary carcinogenesis in rats. We observed in earlier studies that splenocytes of parous rats have significant cytotoxicity against mammary tumor cells both in vitro and in vivo. However, it remains to be established how long these cytolytic cells persist after parturition in parous host. The present study was designed using parous rats, 36 or more days after parturition. We observed that fresh splenocytes from these rats had low cytolytic activity against mammary tumor cells. However, when these cells were re-stimulated with irradiated mammary tumor cells in vitro, they had significantly higher cytotoxicity against mammary tumor cells. These studies show for the first time that pregnancy induced cytotoxic splenocytes are present long after parturition and they can be restimulated in vitro to enhance the cytotoxic effect.

9,10-Dimethyl-1,2-benzanthracene↗