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PubMed1999

Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process.

Inflammatory mediators in the cervix, placenta and fetal membranes play a crucial role in human parturition. The aim of this study was to determine whether the upper and lower segments of the myometrium are infiltrated by inflammatory cells during pregnancy and parturition. Myometrial biopsies were obtained from non-pregnant women, and pregnant women at term before and after the onset of spontaneous labour. Subpopulations of inflammatory cells were identified using immunocytochemistry. The intercellular adhesion molecules, 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin were immunolocalized to investigate their involvement in leukocyte accumulation. Histological analysis demonstrated that inflammatory cells, predominantly neutrophils and macrophages, infiltrate human myometrium during spontaneous labour at term. The infiltrate is predominant in the lower uterine segment but is also present in the upper segment. Increased expression of E-selectin was found on the vascular endothelium of biopsies obtained during labour, suggesting a role for this molecule in the accumulation of leukocytes. These results suggest that inflammatory cell infiltration is part of the physiological mechanisms that occur in the myometrium during parturition. Further understanding of this process may suggest new strategies aimed at preventing preterm delivery.

Cell Adhesion Molecules↗
PubMed1975

Induction of parturition in mares.

Thirty-seven induced parturitions involving thirty-one mares were studied over a 2-year period using various doses of oestrogen and oxytocin. The time of appearance and degree of expression of the major clinical signs of parturition, and the time for completion of delivery and the passage of the placenta were significantly influenced by increasing doses of oxytocin. Oestrogen was useful in softening and relaxing the cervix when it was tight, but was not essential to induction when the cervix was already soft and dilating. Fertility was not adversely affected by induced parturition.

Animals↗
PubMed2000

Immunohistochemical assessment of progesterone, oestrogen and glucocorticoid receptors in bovine placentomes during pregnancy, induced parturition, and after birth with or without retention of fetal membranes.

Steroid hormones play an important role in placental development. However, the exact cellular site of hormone action has not been evaluated in bovine placentomes. Thus, the present immunohistochemical study was designed to assess the distribution of progesterone receptors, oestrogen receptors and glucocorticoid receptors in bovine placentomes. Tissue specimens were obtained from cows at slaughter and from cattle during pre-term Caesarean section 27 h after prostaglandin administration, immediately after spontaneous parturition and from cattle that had retained the fetal membranes. Specific antibodies were used for receptor demonstration in tissue sections. Progesterone receptors were only detected in maternal connective tissue cells, whereas oestrogen receptors were also present in maternal crypt epithelium. At specific sites, both receptor immunoreactivities remained constant or changed significantly during pregnancy, were generally higher during Caesarean section and decreased post partum, but were less pronounced in cattle that released the fetal membranes than in those that retained the fetal membranes. Glucocorticoid receptors were evident in fetal connective tissue cells as well as in fetal and maternal blood vessels. Maternal crypt epithelial cells showed increasing immunoreactivities for glucocorticoid receptors during pregnancy. Receptor immunoreactivities tended to be lower after spontaneous parturition than during Caesarean section; these results were significant for progesterone and oestrogen receptors in animals that released the fetal membranes but not for those that retained the fetal membranes. The results indicate that in bovine placentome steroid hormone receptors are distributed in patterns that are specific to the type of cell, the stage of pregnancy and the tissue location, implying highly specific modulation of placental metabolism. Retention of the fetal membranes is reflected by altered placental receptor states at parturition.

Analysis of Variance↗
PubMed2000

Profile of organ weights and plasma concentrations of melatonin, estradiol and progesterone during gestation and post-parturition periods in female Indian palm squirrel Funambulus pennanti.

Todate, report about the role of pineal gland in maintaining the normal physiology of gestation is scanty. Present study is the first of its kind giving a detail profile of organ weights and plasma concentration of melatonin, estradiol and progesterone to suggest a possible role of pineal gland in maintaining normal physiology during gestation and post-parturition periods of female Indian palm squirrel F. pennanti. Inspite of, inverse pineal-gonadal/melatonin-steroids interrelationship in adult (non-pregnant) females, the present results study suggest a direct relationship of pineal gland activity with ovarian steroids especially during the gestation period. The inverse relationship of melatonin and ovarian steroids is again established after parturition and maintained throughout the life. Thus the pineal gland (activity as judged by its weight, biochemical contents i.e. protein and cholesterol and plasma melatonin level) maintained ovarian/uterine physiology and regulated plasma concentrations of estradiol and progesterone during gestation and post-parturition periods. It is suggested that the pineal gland and its hormone melatonin play an important role to maintain the normal physiology of gestation and the post-partum recovery in Indian palm squirrel F. pennanti.

Animals↗
PubMedDate not supplied

Oxytocin and its receptor in the process of parturition.

OBJECTIVE: To review the potential roles of oxytocin (OT) and its receptor (OTR) in the regulation of parturition. METHODS: We reviewed the literature to describe the molecular aspects of the mechanisms of action and the regulation of OT and its receptor, particularly in relation to changes that occur at parturition. RESULTS: The literature provides strong support for a role for the OT/OTR system in the regulation of human parturition. Paracrine rather than endocrine mechanisms might be more important, and the regulation of the receptor might be more important than the ligand. The system is regulated by a wide variety of chemical and physical factors, including sex steroids, orphan receptors, uterine stretch, and many others. There also might be important interactions with the immune system. CONCLUSION: The OT/OTR system provides a potentially important therapeutic target for regulating the timing of human birth.

Animals↗
PubMed2001

Effect of amniotic sac puncture on parturition in rat.

Pregnant Charles Foster rats were subjected to amniotic sac puncture on day 15 of gestation and the effect was observed on parturition. All the control rats as expected delivered on day 22 of gestation. In the group where all the sacs were punctured, only 12.5% rats delivered on day 22 while rest either failed to deliver (62.5%) or died (25%). In the group with unpunctured sacs at vaginal ends, 75% rats delivered on day 21 while 25% on day 22. In the group with unpunctured sacs at ovarian ends, 75% rats delivered on day 23 and rest 25% failed to deliver. The resorption rates ranged between 61 to 94% in different groups. Malformations were observed only in one pup. The results suggest that amniotic sac puncture interferes with parturition in the form of either failure or delayed parturition. Nonpatency of the birth canal due to puncture induced fetal deaths and tissue adhesions were presumed to be the contributing factors.

Amniocentesis↗
PubMed2002

Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle.

First postpartum dominant follicles are preferentially selected in the ovary contralateral to the previously gravid uterine horn. The aim of the present study was to test the hypothesis that uterine bacterial contamination alters the location of ovarian follicle emergence and selection, and inhibits follicle growth and function. Swabs were collected from the uterine body lumen of cattle on days 7, 14, 21 and 28 after parturition. Bacteria were identified by aerobic and anaerobic culture; bacterial growth was scored semiquantitatively and animals were categorized into standard or high bacterial contamination categories on the basis of the number of colonies detected. Follicular growth and function were monitored by daily transrectal ultrasonography, and estimation of plasma FSH, oestradiol and progesterone concentrations. There was no effect of bacterial contamination on plasma FSH concentration profiles or emergence of the ovarian follicle wave. When uterine bacterial growth scores were high on day 7 or day 21 after parturition, fewer first (1/20 versus 15/50; P < 0.05) or second (1/11 versus 13/32; P < 0.05) dominant follicles were selected in the ipsilateral compared with the contralateral ovary, respectively. The diameter of the first dominant follicle was smaller in animals with a high day 7 bacterial score (P < 0.001), dominant follicle growth was slower (P < 0.05) and oestradiol secretion was decreased (P < 0.05). The present study provides evidence for an effect of the uterus on the ovary after parturition, whereby uterine bacteria have a contemporaneous localized effect on ovarian follicle selection and subsequent growth and function, but not on initial emergence.

Animals↗
PubMed2003

Oxytocin regulates neurosteroid modulation of GABA(A) receptors in supraoptic nucleus around parturition.

In this study, we investigate how neurosteroid sensitivity of GABA(A) receptors (GABA(A)Rs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA(A)Rs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABA(A)Rs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABA(A)Rs from a neurosteroid-sensitive mode toward a condition in which the receptors are not sensitive. This indicates that there may be an inverse causal relationship between the extent to which the GABA(A)R or one of its interacting proteins is phosphorylated and the neurosteroid sensitivity of the GABA(A)R. Neurosteroid sensitivity was not affected by changes in subunit composition of GABA(A)Rs known to occur concurrently in these cells.

Animals↗
PubMed2003

Pregnanolone isomers, pregnenolone and their polar conjugates around parturition.

The levels of four pregnanolone isomers and their polar conjugates and pregnenolone sulfate were measured in the plasma of 13 and 7 women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma using a simple quadrupole GC/MS system with electron impact ionization (pregnenolone isomers), RIA following HPLC separation (pregnenolone) and specific RIA (pregnanolone sulfate). The concentration of epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one) in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3beta-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal, while the differences in 3alpha-hydroxy-isomers were insignificant. The differences in conjugates were insignificant with the exception of allopregnanolone, the levels of which were lower in umbilical plasma. In all the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. In addition, time profiles of the steroids were measured around parturition and in the postpartum period in the maternal serum. Similarly, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. 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 profiles 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 3alpha/3beta-isomers and 5alpha/5beta-isomers around parturition. The possible physiological consequences of the findings are indicated.

Female↗
PubMed1992

Oxytocin and prostaglandin interactions in pregnancy and at parturition.

The demise of the corpus luteum is brought about by an interaction between ovarian oxytocin and uterine prostaglandin F2 alpha (PGF2 alpha) release in sheep. Indirect evidence suggests that a similar, but intra-ovarian, mechanism may also be involved in luteal regression in primates. During early pregnancy, a specific class of interferon (omega interferon) is released from the developing embryo in sheep and this interferon inhibits pulsatile release of uterine PGF2 alpha. Studies in ovariectomized, steroid-treated ewes indicate that conceptus secretory proteins inhibit pulsatile secretion of PGF2 alpha directly via an effect on prostaglandin synthesis and indirectly by maintaining plasma progesterone concentrations that inhibit the development of endometrial oxytocin receptors which normally occurs at the time of luteolysis. As pregnancy progresses, there is an increase in basal secretion of PGF2 alpha and PGE2 from the uterus into the fetal and maternal circulation. The release of maternal PGF2 alpha, but not PGE2, in response to oxytocin is also increased in late pregnancy. Endometrial oxytocin receptor concentrations follow a similar pattern, except at parturition where there appears to be downregulation of receptors. However, the release of PGF2 alpha in response to oxytocin remains high at this time and is further increased if the progesterone receptors are blocked with the anti-progestin RU486. The dissociation between oxytocin receptor numbers and release of prostaglandins in response to oxytocin is also observed under other physiological situations, such as during seasonal anoestrus and after long-term ovariectomy, and requires further investigation. The role of oxytocin in the initiation of labour remains controversial. Although oxytocin concentrations in maternal and fetal plasma are not increased until parturition, uterine oxytocin receptor concentrations, uterine activity and maternal PGF2 alpha release in response to oxytocin are high in late pregnancy. Uterine activity and PG release is not altered by oxytocin in the fetal circulation at any stage of late gestation. We have used the oxytocin analogue CAP to investigate further the possible role of oxytocin in the initiation of labour. CAP can inhibit oxytocin-induced PGF2 alpha release in cyclic sheep, at luteolysis, and in late pregnant sheep by binding to, and blocking, uterine oxytocin receptors. CAP does not inhibit basal fetal or maternal PGF2 alpha or PGE2 concentrations in late pregnancy or at parturition. CAP inhibits oxytocin-induced uterine activity and delays, but does not prevent, the increase in uterine activity associated with labour in this species.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1976

Initiation of human parturition. IV. Demonstration of phospholipase A2 in the lysosomes of human fetal membranes.

In this study we sought to define the subcellular localization of phospholipase A2 in human fetal membranes. Others have postulated a role for decidual lysosomes in the initiation of human parturition. We hypothesized that if phospholipase A2 were localized within lysosomes of fetal membranes the accelerated expression of the activity of this enzyme could be prevented until such time as the metabolic events of parturition begin. At parturition a perturbation of the lysosomal membrane within the chorio-amnion could result in an increased release of free arachidonic acid through an accelerated activity of phospholipase A2. The results of this study suggest that at least a portion of phospholipase A2 in the chorion laeve and amnion is localized in the lysosomal fraction.

Acid Phosphatase↗
PubMed1991

The trigger for parturition in sheep: fetal hypothalamus or placenta?

The fetal pituitary-adrenal axis plays a pivotal role in the mechanisms leading to parturition in sheep. Fetal cortisol concentrations gradually increase in the last 15 days before term, with a marked increase occurring in the last 3-4 days. Some mechanism causes a marked increase in the stimulatory drive to the fetal pituitary resulting in increased secretion of ACTH from the pituitary, and subsequent cortisol secretion from the adrenal gland. In this paper we discuss the roles of the hypothalamus and placenta in triggering the onset of labour in sheep. We have shown that prostaglandin E2 can stimulate the release of ACTH and cortisol in the intact fetus and we believe that this could be mediated by the release of CRH and AVP. Although CRH and AVP are present in the fetal hypothalamus and are capable of being released, these factors may not be released until approximately 135 days of gestation. One fundamental question in relation to parturition remains unanswered: how are the high concentrations of cortisol in fetal plasma sustained given that cortisol has an inhibitory feedback effect on the release of CRH and ACTH secretion? We discuss the possibility that the placenta provides an additional trophic drive to both the pituitary and adrenal glands which contributes towards the sustained elevated cortisol concentrations needed to initiate parturition. The placenta may initiate the hypothalamus and PGE2 and/or CRH, secreted by the placenta, may stimulate pituitary ACTH release.

Animals↗
PubMed1991

[Enzymatic activity in the placenta in cows in relation to the course of parturition].

The activity of aminopeptidases and cathepsins was determined in placentoma homogenates; placentomas of cows were extirpated immediately after parturition and in four and eight hours. In cows with afterbirth retention (a. r.) following induced parturition, the activity of these enzymes was always higher than in cows without a. r., no matter if after induced and spontaneous parturitions; it was at a similar or slightly higher level than in the eighth month of pregnancy. The content of total proteins in placentomas of cows with a. r. was also higher. These findings point to the insufficient ripening, or aging of placental tissue, which is related to a release of lysosomal enzymes. The enzymes are active through hydrolysis in the separation of foetal placenta from the maternal one and in the modification of proteins participating in intercellular linkages.

Aminopeptidases↗
PubMedDate not supplied

Timing of parturition in the rat: an analysis of successive births.

To determine whether consecutive parturitions within individual rats are likely to occur around the same time of the 24h day, female rats mated prior to ovulation and maintained on a LD 12:12 photoperiod, were observed over either two or three parturitions. A subgroup of females was placed on constant light during the second gestation in order to determine the role of photoperiod in the temporal synchronization of consecutive births. The major findings were 1. individual females tended to give birth around the same time of the day on consecutive births so long as the photoperiod remained constant; 2. the small percentage of births occurring during darkness, the less-prevalent time of the photoperiod for birthing, were anomalous births for individual females; and 3. litter weight was a significant factor in predicting time of birth for females, but this effect interacted with photoperiod. These data elucidate the importance of knowing previous birth time, litter weight, and photoperiod on predicting the time of parturition in the rat.

Animals↗
PubMed1990

Sequential changes in plasma progesterone, total oestrogens and corticosteroids in cow throughout pregnancy and around parturition.

Blood samples were taken thrice a week for 2 weeks from 33 pregnant cows in 9 groups, 1 month apart. In addition, blood samples were collected twice daily 1 week from 8 cows before parturition. Plasma progesterone and total oestrogens were quantified by validated radioimmunoassays and total corticosteroids by a competitive protein binding technique. During the 1st 3 month of pregnancy, no remarkable changes were observed from the 3 hormones studied. From the 4th month on, concentrations of progesterone and total corticosteroids decreased significantly (P less than 0.05) and remained fairly constant until the 9th month. Values of total oestrogens increased significantly (P less than 0.05) from the 4th to 6th months and stayed unchanged afterwards. Progesterone levels in periparturient cows decreased linearly (P less than 0.01) during 3 days preceding delivery. Concentrations of total oestrogens rose sharply from day -5 and peaked at calving. Values of total corticosteroids increased dramatically on the 6th day and 24 hours before parturition. The results obtained suggest that in contrast to studies cited earlier plasma corticosteroids could play a key role for triggering parturition in cows.

Adrenal Cortex Hormones↗
PubMed1989

[Catecholamine and cortisol concentrations in plasma from cattle at parturition].

Cows with spontaneous parturition (n = 8) and cows with flumethasone (n = 3) or prostaglandin (n = 3) induced parturition were used in this study. Catecholamine concentrations from cows in the periparturient period were measured in order to evaluate the stress of birth on the dam and the calf. The plasma content of both norepinephrine and epinephrine in late pregnancy was not different from control values in the 3rd to 6th month of pregnancy (norepinephrine 3.27 +/- 0.99 nmol/l plasma and epinephrine 0.98 +/- 0.45 nmol/l plasma), though both parameters appear elevated in the pregnant group. Norepinephrine concentrations rose to a value of 4.50 nmol/l immediately after birth, whereas epinephrine levels did not show an increase post partum. In two neonates norepinephrine and epinephrine values were 2-3 times higher than in the dams and decreased to the values of the dams within 48 hours. Synthetic glucocorticoids can mimic the increase of cortisol, which leads to birth. Cortisol concentrations in the cows remained unaffected by induction of parturition by prostaglandins. Newborn calves showed values of about 330 nmol/l, which also declined within 48 hours to values similar to those measured in the dam (9-28 nmol/l). As stress and exogenous glucocorticoids may affect antibody production, the IgG-content of the colostrum was examined. Prostaglandin induction of birth did not alter the IgG-content of colostrum, but flumethasone produced a decrease of about 14.5%. It is therefore concluded that pre-term birth induction does not produce negative effects on the supply of IgG.

Animals↗
PubMed1989

Biology and endocrinology of ovulation, pregnancy and parturition in the dog.

There is considerable variation among bitches in commonly encountered intervals between cycles (5-12 months), durations of anoestrus (1-8 months), durations of follicular phase pro-oestrus (3-21 days) and periovulatory oestrous behavior (3-21 days), intervals from preovulatory LH surge to oestrus onset (-2 to 5 days), and intervals from fertile mating to parturition (57-68 days). The extent of variation within bitches ranges from slight to great. However, there appears to be very little variation in the intervals from LH surge to ovulation (2 days), to post-ovulatory oocyte maturation (approximately 4 days), to implantation (approximately 18 days), to selected developmental stages of pregnancy, or to parturition (64-66 days). There are no tests diagnostic of early pregnancy. The onset times of persistent pregnancy-specific changes have been estimated, including radio-opaque fetal details (Day 46), elevated blood prolactin values (Day 35), elevated blood relaxin values (Day 25), echogenic heart beats (Day 24) and embryonic vesicles (Day 19), and potentially palpable uterine enlargements (Day 21). As in humans, there is an anaemia of pregnancy involving a 30% reduction in haematocrit and an increased incidence of insulin resistance during the second half of gestation. Ovarian progesterone is required throughout pregnancy. LH and prolactin are luteotrophic in the pregnant bitch as well as during the 2-month luteal phase of the non-pregnant bitch. Parturition follows a luteolysis which occurs during an increase in prostaglandin F-2 alpha that begins 36 h pre partum. Factors regulating the duration of anoestrus are not known but termination of anoestrus is associated with increased pulsatile secretion of LH.

Animals↗
PubMed1987

[Hormones and parturition in primates].

In primates, the endocrine signals which correlate with the end of gestation, i.e. account for fetal maturity, and initiate the parturition, i.e. trigger the myometrium contractility, remain unknown. Direct and indirect evidence supports the view that, as with domestic mammals, progesterone (or the estrogen/-progesterone ratio) plays a prominent role in inhibiting the contractility of the pregnant uterus. In the past few years an increasing number of endocrine factors have been identified in the placenta. They may contribute to the control of local or systemic steroid production but their effects are extraordinarily intermingled and it is impossible today to state whether any of them are relevant to the mechanism of parturition. The trophoblast and the myometrium establish close contact in the primate pregnancy. This is evidenced by histological studies and also by the influence of the proximity of the placenta on tissue steroid concentrations and the mechanisms of hormone coupling in the myometrium. Specific types or subtypes of myometrium hormone receptors are now well identified (e.g. to oxytocin, to catecholamines) and this now permits a better understanding of the role of their endogenous agonists in the course of parturition. However, such data are still lacking for other factors (e.g. prostanoids, VIP, relaxin...) involved to varying degrees in this process.

Animals↗