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Opioid-mediated changes in nociceptive threshold during pregnancy and parturition in the sow.

This study aimed to investigate if pregnancy-induced hypoalgesia occurs in the sow, and to examine the role of endogenous opioids which are known to be released in response to nociception. Sixteen Large White x Landrace multiparous sows were tested in straw bedded pens (2.5 x 2.5 m) during weeks 4, 8 and 12 of pregnancy and over the farrowing period. Testing involved thermal stimulation of eight areas on the rear-quarters of the sows with a CO2 infra-red laser until a physical response was seen (tail flick, leg move or muscle twitch) or for a maximum of 16 s. Over the farrowing period testing was more frequent, and at 3.75 h after the birth of the first piglet, half the sows received an injection (i.m.) of an opioid antagonist naloxone (N) (1 mg kg(-1) body weight) with the remainder receiving a control dose of saline (S). Responses were recorded 15 and 30 min post-injection. There was no significant difference between response times over weeks 4, 8 and 12 of pregnancy (P = 0.152), however a significant rise was seen from week 12 to 5 days before parturition (P = 0.002). Response times continued to rise until the birth of the first piglet by which time the majority of sows had stopped responding within 16 s (P < 0.001). Response times fell over days 1, 2 and 7 post-partum. After administration of naloxone response times fell compared to control animals at 15 min (P < 0.001) and 30 min (P < 0.01) post-injection. These results suggest that nociceptive threshold increases during late pregnancy in the sow, perhaps as an endogenous defence against labour pain, and that during parturition this change in nociceptive threshold is, at least in part, opioid-mediated. Oxytocin is known to be inhibited by endogenous opioids at parturition, thus future research should consider the potential role of increased nociception at birth as a negative feedback to oxytocin release.

Animals↗

Restricting maternal space during parturition in the pig. Effects on oxytocin, vasopressin and cortisol secretion following vagino-cervical stimulation and administration of naloxone.

This experiment studied the effects on endocrine and birth parameters of parturient pigs produced by restricting maternal freedom of movement without otherwise altering environment. Six primiparous pigs (gilts) were each given a jugular catheter under anaesthesia 7 days before parturition and commenced birth in a strawed pen, 2.0 m x 1.5 m in size. Continuous automated blood sampling (3 ml min-1) from unrestrained gilts began following the birth of the first piglet (stage 1) and continued for 2 h. After at least 30 min of blood collection, maternal space was reduced to 2.0 m x 0.55 m by placing rails across the pen (stage 2). The scope for movement in stage 2 was similar to that offered by a farrowing crate. After at least 25 min each gilt was given the opioid antagonist naloxone (1 mg kg-1 i.v.: stage 3). At each stage, vagino-cervical stimulation (VCS) was applied to mimic foetal ejection. Non-cervically stimulated oxytocin (OT) secretion between stages 1 and 2 was unchanged (P > 0.05) but increased significantly relative to both stages 1 and 2 following naloxone treatment for 15-20 min (P < 0.05, paired t-tests on log10 data). Following VCS in all stages plasma OT rose (P < 0.05) for 1-2 min in a similar way to that seen previously following foetal ejection, the increases being proportionally similar irrespective of stage or baseline secretion. Cortisol secretion did not increase as a consequence of space restriction (mean +/- SEM concentrations were 28.6 +/- 8.51 pmol l-1 and 32.3 +/- 11.8 pmol l-1 in stages 1 and 2, respectively). In addition, VCS did not significantly affect cortisol output. Lysine vasopressin concentrations were not affected as a consequence of either stage or VCS. Parturition was not interrupted following space restriction of gilts. These data suggest that reducing maternal space allowance during parturition is not stressful when the process does not involve the movement of animals to novel surroundings.

Animals↗

Body weight, oestrous and ovarian activity in local Burundian ewes and goats after parturition in the dry season.

To compare body weight losses and post-partum anoestrus, twelve local Burundian ewes and twelve goats which had lambed or kidded at the middle of the dry season were followed from parturition until eight months. Each dam was weighed every month and bled three times a week to assess the ovarian activity resumption by plasma progesterone (P4) profiles. For the two species, the body weight decreased significantly (P < 0.05) compared to the body weight at parturition. The mean time during which the body weight decreased was longer (P < 0.05) for the ewes (3.2 +/- 1.2 months) than for the goats (2.3 +/- 1.4 months), however, the relative body weight losses did not significantly differ. The time to oestrous and ovarian activity resumption was highly correlated to the body weight losses for the ewes (r = 0.81; P < 0.01 and r = 0.58; P < 0.05) not for the goats. The first oestrus preceded the first ovarian activity by 4 days in the goats, but occurred 36 days later in the ewes. Nevertheless, after the first luteal function, the subsequent ovarian activity was regular and normal in the ewes but not in the goats and in some cases a return to anoestrus could be observed. These data indicate that in the ewe, not in the goat, the body weight losses are one of the major limiting factors of the oestrous and ovarian resumption after parturition during the dry season. Moreover, the occurrence of luteal function does not initiate a regular reproductive cyclicity in the goat in contrast to the ewes.

Analysis of Variance↗

Effects of porcine relaxin on induced parturition in beef heifers.

Two-year-old crossbred beef heifers were used to test the effects of porcine relaxin (pRelaxin) alone, or in combination with dexamethasone, on the induction of parturition, the incidence of dystocia, and retained placentas. Effects of treatment on pelvic area, postpartum interval, milk production, colostrum quality, calf birth weight, calf vigor, and calf performance were also evaluated. On Day 275 of gestation, heifers from two fetal-sire groups were randomly assigned to one of four groups in a 2 x 2 factorial design and received; no treatment (controls, n = 19), 20 mg of dexamethasone intramuscularly (im) (n = 22), 5 mg of pRelaxin (3,000 U/mg) im (n = 19), or 20 mg of dexamethasone plus 5 mg of pRelaxin (n = 17). Length of gestation (in days) was less (P < 0.05) in heifers treated with dexamethasone (279.8 +/- 1.0) than in controls (286.6 +/- 0.9), but was not influenced (P > 0.05) by treatment with pRelaxin. The incidence of retained placentas in heifers treated only with dexamethasone (27.3%) was not reduced by concomitant treatment with pRelaxin (35.3%). Retained placentas were not observed in any control heifers and in only one heifer (5.2%) treated solely with pRelaxin. Ease of calving (1 = unassisted, 5 = abnormal presentation) was not influenced by treatment (P > 0.05), even though birth weights (in kilograms) of calves from heifers treated with dexamethasone (36.4 +/- 0.8) were less (P < .01) than those of calves from nondexa-methasone-treated heifers (39.2 +/- 0.8). Dexamethasone tended to reduce (P < 0.07) calf vigor (1 = healthy and strong, 5 = dead on arrival; 1.48 +/- 0.11 vs. 1.18 +/- 0.11), but was not (P > 0.05) influenced by pRelaxin. The duration of the postpartum anestrous interval (73.1 +/- 1.8 d across groups) and pelvic areas following treatment and parturition were not influenced (P > 0.05) by dexamethasone or pRelaxin. Although determinants of colostrum quality (P < 0.01) and quantity (P < 0.08) of milk produced were influenced by dexamethasone, adjusted 205-d weights of calves did not differ (P > 0.05) among groups. In conclusion, treatment with pRelaxin alone failed to induce parturition or, when combined with dexamethasone, to reduce the incidence of retained placentas.

Animals↗

Neonatal adaptation to stress of parturition and dystocia.

The fetal animal undergoes a tremendous transition from intrauterine to extrauterine life at parturition. In this article, the maternal-fetal interactions of parturition are discussed with the aim of examining the normal stress reactions of parturition. Dystocia is discussed from the standpoint of additional distress of the newborn, with an aim toward the development of rational therapeutic support.

Animals↗

Ethanol and parturition: a role for prostaglandins.

A common pattern of birth defects was reported in children born to alcoholic women over 20 years ago. Shortly thereafter the constellation of defects became known as the Fetal Alcohol Syndrome, and reports from around the world served to acknowledge the pervasiveness of the disorder. Simultaneously with the clinical reports, animal models were developed to characterize the full spectrum of the teratogenic effects of ethanol. Not only did these animal models serve to define the actions of ethanol on fetal growth and development at the molecular pharmacological, neuroanatomical, and behavioral level, but unintentionally, they have resulted in renewed scientific interest in the effects of ethanol on pregnancy and parturition itself. The purpose of this review is twofold. First we will consolidate and summarize data from both clinical and basic research that pertains to ethanol and parturition. These data will demonstrate that ethanol consumption during pregnancy results in both delayed as well as premature delivery depending upon the pattern of consumption and timing of exposure. With these data as a background, the second objective will be to present a theoretical case for prostaglandins as possible mediators of ethanol-induced effects on the onset of parturition.

Alcohol Drinking↗

Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers.

Time profiles of the pregnanolone isomers epipregnanolone (3 beta-hydroxy-5 beta-pregnan-20-one), allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one), and isopregnanolone (3 beta-hydroxy-5 alpha-pregnan-20-one) were measured around parturition and in the postpartum period in the serum of 13 and three women with subarachnoidal and epidural analgesia, respectively. In addition, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. GC/MS analysis was used for the measurement of steroid levels. Changes in concentrations of free steroids exhibited a similar pattern, with a fall primarily within the first hour after delivery. The decrease in conjugated steroids was shifted to the interval within the first hour and first day after delivery, and the changes were more pronounced. The time profile of the conjugated/free steroid ratio exhibited a significant decrease within the first hour and the first day after delivery in all of the isomers investigated. A decrease was also observed in the ratio of 3 alpha/3 beta-isomers and 5 alpha/5 beta-isomers around parturition. The possible physiological consequences of the findings are indicated.

Adult↗

High levels of human chromogranin A in umbilical cord plasma and amniotic fluid at parturition.

OBJECTIVE: The human placenta is a neuroendocrine organ that produces several hypothalamic and pituitary hormones that are secreted during pregnancy and parturition into maternal and fetal circulation and amniotic fluid. Human chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla and released in response to several stressful events. During pregnancy, intrauterine tissues express and synthesize CgA mRNA and peptide and secret it into the biologic fluids of pregnancy, so we investigated whether maternal, umbilical, and amniotic human CgA levels are affected by the stress of parturition. METHODS: We measured pregnancy CgA levels in maternal and umbilical cord plasma and in amniotic fluid at term (39-40 weeks), by enzyme-linked immunosorbent assay at elective cesarean (n = 16), after spontaneous vaginal delivery (n = 12), and longitudinally throughout labor and 2 hours postpartum. RESULTS: CgA levels were highest in umbilical cord blood (P <.001). Umbilical cord plasma and amniotic fluid CgA levels were significantly higher at spontaneous vaginal delivery than at cesarean (P <.001), and the levels were not changed in maternal plasma according to cervical dilatation and postpartum. CONCLUSIONS: The present findings showed that the stress of parturition increased CgA levels in umbilical cord plasma and amniotic fluid and was probably of fetal origin. Whatever the mode of delivery, CgA levels in infants were much more elevated than in mothers, providing evidence for an unusual and sustained high level of sympathoadrenal stimulation in full-term neonates.

Adult↗

Effect of propylene glycol supplementation around parturition on milk yield, reproduction performance and some hormonal and metabolic characteristics in dairy cows.

Thirty-nine multiparous Holstein cows were used to measure the effect of propylene glycol treatment around parturition on milk yield, reproductive efficiency and some hormone and metabolite concentrations. Cows were assigned randomly to control (n = 19) or propylene glycol treated (n = 20) groups. Propylene glycol (300 g) was administered directly mixed with the diet from day 10 prior to the expected calving date until parturition (day 0) and orally after dilution in 1 l water on days 3, 6, 9 and 12. Blood samples were collected on days -20, -5, 0, 3, 10, 25 and 50 while milk samples were taken weekly until 13 weeks post partum. Body condition scores, recorded on days -20, 15 and 50, were not affected by propylene glycol administration. Propylene glycol did not significantly affect milk yield or composition but linear somatic cell score measured from the first 13 weeks post partum was reduced by propylene glycol administration (P < 0.01). Moreover, propylene glycol reduced milk urea (-25 mg/l, P < 0.05), especially during the first 9 weeks post partum. Plasma insulin concentrations were similar in both groups during the experiment while insulin-like growth factor I (P < 0.05) and insulin-like growth factor-binding protein 3 (P < 0.001) levels were higher on days 10, 25 and 50 post partum in the propylene glycol group. Propylene glycol administration decreased plasma non-esterified fatty acid concentrations (P < 0.05 to P < 0.01) but increased total cholesterol levels (P < 0.01) after parturition while 3-hydroxybutyrate levels were unaffected by the treatment. Changes in the hormone and metabolic concentrations after propylene glycol administration in the last few days of gestation and the first week of lactation seem to indicate that energy balance in the treated group was probably more positive than in the control group. There was also evidence that propylene glycol administration prevented fatty liver syndrome and hastened the resumption of oestrous cycles (P < 0.001).

Animals↗

Adrenal responsiveness and the timing of parturition in hypothalamo-pituitary disconnected ovine foetuses with and without constant adrenocorticotrophin infusion.

Ovine parturition results from an increase in foetal cortisol secretion in late gestation which is dependent on an intact hypothalamo-pituitary connection. The cortisol surge and parturition fails in hypothalamo-pituitary disconnected (HPD) foetuses but, paradoxically, immunoreactive (ir)-ACTH concentrations and secretory dynamics appear normal. This study compares the occurrence and timing of labour, basal ir-ACTH and cortisol concentrations and adrenal responsiveness in HPD foetuses (HPD/ACTH) receiving constant ACTH(1-24) infusion (43 ng/h/kg) from surgery (114+/-1 days gestational age (GA)) with those of saline-infused HPD or intact foetuses (HPD/SAL and INT/SAL). HPD/ACTH foetuses initiated labour at 147+/-2 days GA, which was not significantly different from INT/SAL foetuses (149+/-1 day GA). HPD/SAL foetuses were killed electively at 146+/-3 days GA with no signs of labour. Foetal ir-ACTH concentrations in all groups were indistinguishable, but only HPD/ACTH and INT/SAL foetuses had a significant cortisol surge. Adrenal responsiveness to ACTH(1-24)(1 microg/kg) was greater in HPD/ACTH foetuses than in HPD/SAL or INT/SAL foetuses at all GAs studied. Adrenal responsiveness in HPD/SAL foetuses exceeded that in INT/SAL foetuses at 120 and 130 days GA but did not change with GA. In summary, the basal cortisol and parturition defect in HPD foetuses was reversed by low-dose ACTH(1-24) infusion. Basal cortisol concentrations were unrelated to adrenal responsiveness. HPD/SAL foetuses had hyper-responsive adrenals compared to those of INT/SAL foetuses until 130 days GA, suggesting that the foetal hypothalamus exerts a negative influence on adrenal cortisol responses before 130 days GA, after which time stimulatory influences predominate.

Adrenal Glands↗

Changes in the concentrations of glucose, non-esterified fatty acids, urea, insulin, cortisol and some mineral elements in the plasma of the primiparous sow before, during and after induced parturition.

The concentrations of selected metabolites, minerals and hormones relative to parturition were studied in 12 primiparous sows. Blood sampling was performed on day -5, 0 and +5 relative to the farrowing day. On the day of parturition (d 0), samples were taken every hour from 07.00 to 24.00 hours. All sows had an indwelling catheter in the jugular vein, and the evolution of glucose, insulin, urea, non-esterified fatty acids (UEFA), calcium (Ca), phosphorus (P), magnesium (Mg) and cortisol were studied. The concentrations of NEFA, cortisol and P were significantly higher at d 0 than at d -5 or d +5, whereas the Mg level was lower. During the expulsion of foetuses, NEFA and cortisol levels increased (+18 and +30%, respectively), and they decreased immediately after the birth of the last piglet, to reach the initial levels observed before farrowing (around 700 microEq.L-1 and 110 ng.mL-1, respectively). Glucose and insulin levels remained unchanged during the expulsion of the piglets (105 ng.dL-1 and 5 microIU.mL-1, respectively), but they both increased immediately after the birth of the last animal. During the expulsion of the foetuses, the Ca concentration remained unchanged (93 mg.L-1), whereas the P level increased (+9%) and the Mg concentration decreased (-7.4%). These data suggested that parturition induces large variations in the concentrations of plasma metabolites that may affect its normal process.

Animals↗

Plasma levels of oxytocin and vasopressin before, during and after parturition in cows.

In cows, plasma oxytocin and vasopressin were determined by specific and sensitive radioimmunoassays before, during and after parturition. In no case, oxytocin is elevated until the forelimbs of the foetus were distending the vagina and presenting at the vulva, supporting the view that endogenous maternal oxytocin does not primarily induce parturition. This finding is confirmed by simultaneous recording of myometrial electrical activity in 3 animals. Maximal oxytocin levels of 60.4 to 116 pg/ml plasma were measured at delivery of the foetus. The elevation in plasma vasopressin (peak values at delivery: 4.74 to 41.5 pg/ml) might be due, at least partially, to the increase in plasma osmolality during parturition.

Animals↗

Investigations on hormonal changes around parturition in the dog and the occurrence of pregnancy-specific non conjugated oestrogens.

Concentrations of progesterone and estradiol-17 beta were determined throughout pregnancy in 6 to 10 bitches (exp. 1); in experiment 2 peripartal changes of estradiol-17 beta, estrone, progesterone, cortisol, prolactin and growth hormone were determined in 5 bitches; in experiment 3 total unconjugated oestrogens were determined by radioimmunoassay and radioreceptorassay in placental tissue from 25, 53, 60 and 64 days pregnant bitches. No pregnancy specific increase of estradiol-17 beta could be observed; estradiol-17 beta levels decreased prior to parturition concomitant with the decrease of progesterone, suggesting a likewise luteal origin of estradiol-17 beta in the pregnant and non pregnant dog. Cortisol and growth hormone concentrations were elevated at the time of parturition, prolactin concentrations remained unchanged but were higher in pregnant than in non pregnant dogs. No hints in respect to a specific placental oestrogen production were obtained when examining placental tissue. The hypothesis is put forward that the high sensitivity of the haematopoietic system of the dog to oestrogen was an important factor in respect to evolution of endocrine control of pregnancy and parturition in this species which-in respect to placental oestrogen production-seems to be different from most other domestic animal species.

Animals↗

[On the reliability of case history data on parturition (author's transl)].

Case history data on the course of parturition (recorded during the sixth week of life and the twelfth month of life) are compared with each other, as well as with the actual course of parturition, within the framework of a prospective study covering the first year of life. The information regarding auxiliary obstetrical measures, position anomalies, as well as deviations from the normal weight at birth, were associated with a probability of error of less than five per cent. All other data regarding umbilical cord complications, asphyxia, etc. were associated with various error probabilities up to 20 per cent. It is concluded from these results that data on the history of parturition merely have the character of good estimates on account of their poor validity and reliability. This must be taken into account both in the statistical processing of medical data and in the employment of case history data for the pathogenetic interpretation of an actual disease picture, especially minimal cerebral dysfunction in children (MCD).

Asphyxia Neonatorum↗

A study of the relationship between placenta growth factor and gestational age, parturition, rupture of membranes, and intrauterine infection.

OBJECTIVE: Placenta growth factor is a potent angiogenic factor produced by the human placenta that has been implicated in the pathogenesis of preeclampsia and intrauterine growth restriction. Placenta growth factor belongs to the vascular endothelial growth factor family and is capable of inducing proliferation, migration, and activation of endothelial cells. The objective of this study was to determine the relationship between amniotic fluid concentration of placenta growth factor and gestational age, parturition (term and preterm), spontaneous rupture of the membranes, and intra-amniotic infection. STUDY DESIGN: Amniotic fluid samples obtained from 273 pregnant patients were assayed in the following clinical groups: midtrimester pregnancy, preterm labor who delivered at term, preterm labor without microbial invasion of the amniotic cavity who delivered preterm, preterm labor with microbial invasion of the amniotic cavity, term not in labor, term in labor, term with microbial invasion of the amniotic cavity, preterm premature rupture of membranes with and without microbial invasion of the amniotic cavity, and term with premature rupture of membranes without microbial invasion of the amniotic cavity. The placenta growth factor concentrations were determined by an immunoassay that is both sensitive and specific. RESULTS: Placenta growth factor was detectable in 96.3% (263/273) of samples. Amniotic fluid placenta growth factor concentration decreased with advancing gestational age (r = -0.42; P <.001). Amniotic fluid placenta growth factor concentrations were significantly higher in women in midtrimester pregnancy than in those at term not in labor (midtrimester pregnancy: median, 43.1 pg/mL; range, 22.9-69.8 pg/mL; vs term not in labor: median, 28.7 pg/mL; range, 16.1-82.7 pg/mL; P <.01). Neither term nor preterm parturition was associated with a change in amniotic fluid placenta growth factor concentrations. Term premature rupture of membranes was associated with a significant decrease in amniotic fluid placenta growth factor concentration (term premature rupture of membranes: median, 16.5 pg/mL; range <5.2-195.1 pg/mL; vs term intact membranes: median, 28.7 pg/mL; range, 16.1-822.7 pg/mL; P <.005). Preterm premature rupture of membranes was not associated with changes in amniotic fluid placenta growth factor concentrations. Intra-amniotic infection in preterm labor, term labor with intact membranes, and preterm premature rupture of membranes were not associated with changes in amniotic fluid placenta growth factor concentrations. CONCLUSION: Placenta growth factor is a physiologic constituent of amniotic fluid. Amniotic fluid concentrations of placenta growth factor decrease with advancing gestational age. Neither parturition nor infection affects amniotic fluid placenta growth factor concentrations.

Amnion↗

Matrilysin (matrix metalloproteinase 7) in parturition, premature rupture of membranes, and intrauterine infection.

OBJECTIVE: Matrix metalloproteinases are enzymes capable of degrading extracellular matrix components. Matrilysin (matrix metalloproteinase 7), a novel member of this family, degrades fibronectin and proteoglycans. The objective of this study was to determine whether parturition (either term or preterm), premature rupture of the membranes, and microbial invasion of the amniotic cavity are associated with changes in the amniotic fluid concentration of matrilysin. STUDY DESIGN: A cross-sectional study was conducted with 275 women in the following categories: (1) second trimester, (2) term not in labor, (3) term in labor, (4) term with microbial invasion of the amniotic cavity, (5) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term, (6) preterm labor without microbial invasion of the amniotic cavity who delivered preterm, (7) preterm labor with microbial invasion of the amniotic cavity, (8) preterm premature rupture of membranes with and without microbial invasion of the amniotic cavity, and (9) term premature rupture of membranes not in labor and without microbial invasion of the amniotic cavity. Matrilysin concentrations were measured with a sensitive specific immunoassay that was validated for amniotic fluid. RESULTS: Matrilysin was detectable in 97.4% (268/275) of the samples. The concentration of matrilysin increased with advancing gestational age (r = 0.8; P <.001). Parturition at term was not associated with a significant increase in amniotic fluid concentration of matrilysin. Preterm parturition in the absence of microbial invasion of the amniotic cavity was associated with a significant increase in amniotic fluid concentration of matrilysin (preterm labor with preterm delivery: median, 1.7 ng/mL; range, 0.45-21.6 mg/mL; vs preterm labor with term delivery: median, 1.2 ng/mL; range, 0.17-42. 1 ng/mL; P <.05). Premature rupture of membranes without microbial invasion of the amniotic cavity (either term or preterm) was not associated with a significant change in the amniotic fluid matrilysin concentration. Intra-amniotic infection was associated with a significant increase in amniotic fluid matrilysin among both patients with preterm labor and patients with preterm premature rupture of membranes (preterm labor with microbial invasion of the amniotic cavity: median, 3.2 ng/mL; range, 0.16-21.9 ng/mL; vs preterm labor and delivery without microbial invasion of the amniotic cavity: median, 1.7 ng/mL; range, 0.45-21.6 ng/mL; vs preterm labor with term delivery: median, 1.2 ng/mL; range, 0.17-42. 1 ng/mL; P <.01 for each comparison; and preterm premature rupture of membranes without microbial invasion of the amniotic cavity: median, 1.7 ng/mL; range, 0.29-13.9 ng/mL; vs preterm premature rupture of membranes with microbial invasion of the amniotic cavity: median, 3.6 ng/mL; range, 0.59-20.3 ng/mL; P <.01). CONCLUSION: Matrilysin is a physiologic constituent of amniotic fluid, and its concentration increases with advancing gestational age. Microbial invasion of the amniotic cavity in preterm gestations was associated with a significant increase in amniotic fluid concentration of matrilysin. Matrilysin therefore may play a role in the host defense mechanism.

Amnion↗

Effects of bromocriptine at parturition in the tammar wallaby, Macropus eugenii.

Female tammar wallabies were treated with the dopamine agonist bromocriptine at the end of pregnancy to suppress the peripartum pulse of plasma prolactin. The animals were subsequently observed, and a series of blood samples taken to define the hormonal profiles before and immediately after parturition. Birth was observed in 4/5 control animals and occurred in 8/9 bromocriptine-treated animals. The peripartum peak in plasma PGFM concentrations was not affected by bromocriptine although the pulse of prolactin normally seen at parturition was completely abolished. The timing of luteolysis was apparently unaffected, as plasma progesterone concentrations fell similarly in both treated and control animals immediately after parturition. However, all of the neonates of the bromocriptine-treated animals died within 24 h, possibly because of a failure to establish lactation. Subsequent onset of post-partum oestrus was delayed or absent both in control and in bromocriptine-treated animals, suggesting that the frequent blood sampling and disturbances in the peripartum period interfered with these endocrine processes. It is concluded that both prolactin and prostaglandin can induce luteolysis in the pregnant wallaby, but that the normal sequence of events results from a signal of fetal origin inducing a prostaglandin release from the uterus, which in turn releases a pulse of prolactin that induces a progesterone decline.

Animals↗

Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition.

Parturition is timed to begin only after the developing embryo is sufficiently mature to survive outside the womb. It has been postulated that the signal for the initiation of parturition arises from the fetus although the nature and source of this signal remain obscure. Herein, we provide evidence that this signal originates from the maturing fetal lung. In the mouse, secretion of the major lung surfactant protein, surfactant protein A (SP-A), was first detected in amniotic fluid (AF) at 17 days postcoitum, rising progressively to term (19 days postcoitum). Expression of IL-1beta in AF macrophages and activation of NF-kappaB in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1beta and NF-kappaB expression in cultured AF macrophages. Studies using Rosa 26 Lac-Z (B6;129S-Gt(rosa)26Sor) (Lac-Z) mice revealed that fetal AF macrophages migrate to the uterus with the gestational increase in AF SP-A. Intraamniotic (i.a.) injection of SP-A caused preterm delivery of fetuses within 6-24 h. By contrast, injection of an SP-A antibody or NF-kappaB inhibitor into AF delayed labor by >24 h. We propose that augmented production of SP-A by the fetal lung near term causes activation and migration of fetal AF macrophages to the maternal uterus, where increased production of IL-1beta activates NF-kappaB, leading to labor. We have revealed a response pathway that ties augmented surfactant production by the maturing fetal lung to the initiation of labor. We suggest that SP-A secreted by the fetal lung serves as a hormone of parturition.

Animals↗