Adrenal and plasma corticosterone levels in the pregnant, foetal and neonatal rat, in the perinatal period.

A group of pregnant control rats was sacrificed before parturition, in the morning, afternoon and evening of day 20 and 21 and in the morning of day 22. Another group was sacrificed during parturition, when 2 to 8 foetuses had been expelled. The onset of parturition occurred for the first rat in the afternoon of day 21 and for the last rat in the afternoon of day 22. Corticosterone was extracted from maternal, foetal and neonatal adrenals and plasma, and was assayed by a fluorometric procedure. The maternal adrenal and plasma corticosterone levels, before parturition, were lower in the morning than in the afternoon excepting day 22 when morning values were as high as those in the afternoon of day 21. Adrenal and plasma corticosterone concentrations were elevated during parturition in the mother but not the foetus. Plasma corticosterone values were raised in the newborn compared to their littermates in utero.     

Foetal loss in dairy goats: function of the adrenal glands, corpus luteum and the foetal-placental unit.

To investigate the causes and mechanisms of foetal loss in Norwegian dairy goats, blood parameters in 40 goats that lost foetuses were compared with those in 40 goats that experienced a normal pregnancy. High mean levels of 15-ketodihydro-PGF2alpha, and low mean levels of oestrone sulphate throughout pregnancy were associated with foetal loss. The mean oestrone sulphate level was low before abortion, and the distinct peak that occurred at parturition in the control goats was not observed in connection with abortion. Association of other blood parameters with foetal loss was not detected. Infectious agents and toxins did not appear to be major causes of foetal loss in this study. The normal level of progesterone and cortisol in goats with foetal loss indicated that the function of the corpus luteum and adrenal glands, respectively, were not disturbed. The rapid decline in progesterone level associated with foetal loss may therefore be a result, rather than the cause, of foetal death. The lowered level of oestrone sulphate and elevated level of 15-ketodihydro-PGF2alpha in goats with foetal loss clearly indicated that the endocrine foetal-placental function was disturbed.     

Changes in concentrations of follistatin in maternal plasma and foetal fluids during pregnancy and parturition in sheep

Studies have shown that follistatin may be involved in the regulation of ovarian development, pregnancy and parturition. The aim of the present study was to measure follistatin levels in maternal plasma and foetal fluids during pregnancy and parturition in sheep. Using a previously described follistatin radioimmunoassay, we found that follistatin in foetal plasma and allantoic fluid was higher in the female than in the male at days 50-75 of gestation. Follistatin concentrations in maternal plasma declined from -9 to -3h before the completion of lamb delivery, and increased from 21 to 39 h after parturition. These results suggest that follistatin may play a role in femaleness development, and that follistatin may be involved in the mechanism of normal parturition and in regulation of the tissue repair after parturition.     

Chemotactic activity of cotyledons for mononuclear leukocytes related to occurrence of retained placenta in dexamethasone induced parturition in cattle

Induction of parturition with glucocorticosteroids in cattle is used for research purposes, in diseased or injured pregnant cows, and as a management tool to time parturition. A negative side effect of induction of parturition with glucocorticosteroids is the high incidence of retained placenta that occurs after these calvings. Reaction of the maternal immune system against the ‘foreign’ foetal membranes contributes to the breakdown of the foetal-maternal attachment. Several studies indicate that failure of this immune assisted detachment increases the occurrence of retained placenta. We hypothesized that retained placenta occurring after induction of parturition with glucocorticosteroids is caused by failure of immune assisted detachment of the foetal membranes. The chemotactic activity of cotyledons for mononuclear leukocytes was used as a parameter to see whether immune assisted detachment of the foetal membranes had occurred. Cotyledons were collected from spontaneously calving non-retained placenta cows and from dexamethasone induced non-retained placenta and retained placenta cows. The study showed that the chemotactic activity of cotyledons for mononuclear leukocytes was lower (P < 0.001) in cotyledons obtained from retained placenta cows in which parturition was induced with dexamethasone compared to the chemotactic activity of cotyledons obtained from spontaneously calving non-retained placenta cows, whereas the chemotactic activity of cotyledons obtained from induced non-retained placenta cows was not lower (P = 0.10) than the chemotactic activity of cotyledons obtained from spontaneously calving non-retained placenta cows. We concluded that induction of parturition with dexamethasone causes a failure of immune assisted detachment of the foetal membranes and the accompanying release of chemotactic factors. As a result, the chemotactic activity of cotyledons for mononuclear leukocytes is lower in induced retained placenta cows than in cotyledons from non-retained placenta cows in which successful immune assisted detachment of the foetal membranes occurs.     

Ultrastructural changes in the placenta of the ewe following foetal infusion of cortisol.

The placental changes which followed continuous infusion of cortisol into the sheep foetus in the later stages of gestation were, like the hormonal changes, broadly similar to those of spontaneous parturition. There was, however, a premature separation of foetal and maternal tissues in certain areas of the placental cotyledons, and this separation appeared to protect the foetal epithelium from the degenerative changes which normally take place in the short space of time between the birth of the lamb and the delivery of the foetal membranes. The results suggest that an experimental model in which premature labour is induced by the administration of cortisol to the foetus is probably incomplete, and that additional factors almost certainly contribute to the cascade phenomenon of spontaneous parturition.     

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

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

Reproductive synchrony and annual variation in foetal growth rate in the long-fingered bat (Miniopterus schreibersii)

Mating in the long-fingered bat (Miniopterus schreibersii) from the East Cape region of South Africa occurred during a four-week period in April and May, and implantation was delayed until August. Analyses of foetal age and estimated dates of conception indicate that after implantation, the progression of pregnancy within the population was synchronous both within and between years. It is suggested that implantation, probably initiated by increasing day length, occurred at about the same time throughout the population and thus synchronized reproduction. In the final month of pregnancy foetal growth rate and, consequently, the timing of parturition in the three years of the study varied. These variations were correlated with variations in rainfall and it is suggested that the failure of the November rains in 1990 would have caused a reduction in insect abundance and that this was responsible for the decrease in foetal growth rate and the delay in parturition.     

圈养条件下狍繁殖行为的研究

本试验研究了狍(东北亚种)在人工饲养条件下的繁殖行为。研究结果表明:(1)在交配季节,雄狍具有卷唇嗅闻、扒土等行为;雄狍与雌狍的卧息、冲突行为差异显著,尾阴探究差异极显著。(2)妊娠雌狍选择隐蔽处分娩产仔。(3)在临产前,雌狍有临产表现,采取侧卧分娩姿势,仔狍娩出后,舔食仔狍的胎水和胎膜。     

Biotransformation of pregnenolone - 7alpha-3H, progesterone - 7alpha-3H and dehydroepiandrosterone - 7alpha-3H by porcine fetal and maternal adrenal homogenate preparations.

The biotransformation of pregnenolone-7alpha-3H and of progesterone-7alpha-3H by porcine fetal and maternal adrenal homogenates at 56 and 112 days of pregnancy and of dehydroepiandrosterone-7alpha-3H by fetal adrenal homogenates has been investigated in vitro. Both pregnenolone-7alpha-3H and progesterone-7alpha-3H were metabolized extensively by maternal adrenal preparations, the principal radioactive metabolites isolated being cortisol, corticosterone, 11-deoxycortisol, deoxycorticosterone, 11beta-hydroxyprogesterone and androstenedione. In addition, 17alpha-hydroxyprogesterone, 20alpha-dihydroprogesterone and cortisone were formed from both substrates and 17alpha-hydroxypregnenolone and progesterone were formed from pregnenolone. Although essentially the same radioactive metabolites were isolated after incubation of fetal adrenal glands with pregnenolone-7alpha-3H or progesterone-7alpha-3H, a greater proportion of the radioactivity was associated with corticosteroids at 112 days of pregnancy than at 56 days. 11beta-Hydroxyandrostenedione and androstenedione were isolated and identified together with an unknown polar metabolite, after incubation of fetal adrenal tissue with dehydroepiandrosterone-7alpha-3H. These results are discussed in relation to feto-placental steroid biosynthesis and metabolism and the role of the fetal adrenal in the initiation of parturition in the pig.     

Expression of the gene for the alpha-subunit of inhibin in human adrenocortical tumours

BACKGROUND: To determine whether the pathogenesis of human adrenocortical tumours is associated with variations of inhibin expression, we assayed the mRNA of the alpha-subunit of inhibin in 5 normal adrenals and 48 adrenocortical tumours, including 10 paediatric tumours. RESULTS: mRNA of alpha-subunit of inhibin was detected in all adrenocortical tissues. It was similarly abundant in the three pathological groups of adult tumours (benign, suspect and malignant) and in normal adrenal tissues, irrespective of the hormonal pattern. However, in paediatric tumours, the levels of the mRNA for the alpha-subunit of inhibin were significantly higher than those in adult tumours (p < 0.01). CONCLUSION: Inhibin is more abundant in the foetal than in the adult adrenal cortex and therefore these data suggest that the paediatric tumours may have a foetal pattern.     

15-Ketodihydro-PGF2α, Progesterone and Cortisol Profiles in Heifers after Induction of Parturition by Injection of Dexamethasone

In order to study rapid changes in 15-ketodihydro-PGF_2α, cortisol and progesterone in the period preceding parturition in cattle, pre-term parturition was induced in 4 late pregnant heifers. Parturitions were induced by 2 intramuscular injections of 20 mg dexamethasone with a 24-h interval. The first injection was made on days 254, 258, 264 and 265 in gestation, respectively. Twenty-four h before the first injection an intravenous polyurethane cannula was inserted. Blood samples were collected at least every hour until 12 h after parturition and during the second stage of labour at least 6 times per hour. Plasma was analysed for 15-ketodihydro-PGF_2α and progesterone by radioimmunoassays, and for cortisol by an ELISA. The average time from injection to parturition was 7.7 (6.6–8.9) days (mean (range)). Two of the heifers had retained foetal membranes (RFM). At the start of the experiment the levels of PGF_2α metabolite were low (< 300 pmol/L) and increased slowly to levels between 1000 and 2000 pmol/L at one day before parturition. During the last day, however, the levels increased rapidly and the highest levels (>10000 pmol/L) were reached at the time of delivery. No pulsatile release was seen. Immediately after foetal expulsion the PG-metabolite levels decreased rapidly in all animals. In the 2 animals with RFM, however, this decline ceased within a few h. The PG-metabolite levels in these animals then started to increase and reached levels as high as during parturition. Luteolysis occurred between 1.6 and 0.4 days before parturition in all animals. The cortisol profile showed a distinct peak at the time of parturition in the RFM heifers. This peak was absent in the non-RFM heifers. This study shows that the PGF_2α release at prepartal luteolysis and parturition is not pulsatile in cattle and that cortisol profiles in heifers with retained foetal membranes might differ from the profiles in non-RFM heifers at the time of parturition.     

Pain and discomfort caused by parturition in cows and sows

This review focuses on parturition as a painful process in cows and sows. Firstly, the different stages of parturition associated to the origin and transmission of pain stimuli are described. Hypoalgesia during the late pregnancy and parturition has been shown, perhaps as an endogenous defence against the pain of parturition. The principal factors affecting parturition pain are parity and dystocia, which are more likely in cases of long parturition, feto-pelvic disproportion and/or foetal malpresentation. The main consequences of pain caused by parturition are reviewed; parturition is an intrinsically risky process for both mother and young and can cause a stress response, health problems and maternal mortality, in addition to decreased food intake and production. The assessment of parturition pain has tended to use one of three approaches: measures of general indices, physiological and behavioural indicators. Finally, the impact of analgesia after parturition in cows and sows is reviewed. It is concluded that pain caused by parturition in animals deserves more research in order to optimize the parturition process and reduce its negative consequences on health, welfare and productivity.     

Possible role for prostacyclin in human parturition.

Human amnion, chorion, decidua and placenta produced 6-oxo-PGF1alpha when superfused in vitro. Furthermore amnion, an avascular tissue, produced more 6-oxo-PGF1alpha after labour than all other tissues investigated and its production of 6-oxo-PGF1alpha was significantly greater after labour than before the onset of labour. These findings suggest that prostacyclin production by foetal membranes may have a role in the mechanisms controlling human parturition. Moreover, this is the first evidence for the production of prostacyclin by an avascular tissue.     

Hormonal measurements in late pregnancy and parturition in dairy cows--possible tools to monitor foetal well being

Three dairy heifers (A, B and C) were induced to parturition with two prostaglandin (PG) F(2alpha) injections on day 268 and 269 of pregnancy. Signs of approaching parturition were carefully observed. The following parameters were registered: degrees of calving difficulty, date and time of parturition, calf's birth weight and calf's sex. Body temperature was measured and blood samples were taken every 3 h 3 days before the first PGF(2alpha) injection until 3 days after parturition. The plasma concentrations of the PGF(2alpha) metabolite, progesterone, cortisol, oestrone sulphate and pregnancy associated glycoproteins (PAGs) were analysed. Heifers A, B and C delivered 48, 51 and 57 h after the first PGF(2alpha) injection, respectively. Heifer A delivered without any signs of calving difficulty, whereas, the parturition was considered to be slight and moderate difficulty occurred in the delivery of heifers B and C, respectively. The calf of heifer C, without any abnormal gross-evidences, was stillborn. All animals had retained foetal membranes. A slight increase of the PGF(2alpha) metabolite at the time of parturition was found only in heifer C, whereas the levels dramatically increased in all animals 15-24 h after parturition. At the same time, progesterone levels decreased within 3 h after the first PGF(2alpha) injection (P < 0.05) and reached 0.8, 2.7 and 12.4 nmol/l at the time of parturition in heifers A, B and C, respectively. High release of cortisol at the time of parturition was seen in heifer C. Rising levels of oestrone sulphate around the time of parturition were recorded in all heifers, whereas, increasing levels of PAGs were recorded only in heifer A. In conclusion, the patterns of the PGF(2alpha) metabolite, cortisol, progesterone and PAGs were changed in the cases of calving difficulty and stillbirth after PGF(2alpha)-induction of parturition. However, the relationship between oestrone sulphate and PAGs and the status of foetal well being prior to parturition require further elucidation.     

Review: significance of the inhibition by prostaglandins and cyclic GMP of oxytocinase activity in human pregnancy and labour

The uterotonic action of oxytocin has been known for many decades. This neurohypophysial hormone is thought to play a functional role in human parturition. Since 1968, prostaglandins have also been implicated in parturition. These two groups of uterotonic agents have now a recognized therapeutic role, and are widely used in the induction of labour and in fertility control. However, the mechanism of action and the interrelationship between these endogenous compounds in pregnancy are poorly understood. In this article, the role and interaction of oxytocin, oxytocinase and prostaglandins in human pregnancy and labour have been reviewed. Inhibition of oxytocinase activity by prostaglandins has been suggested as a mechanism in parturition. Possible involvement of cyclic GMP in the initiation of labour has also been discussed.     

哺乳类动物妊娠晚期孕激素撤退的三种机制

内分泌激素是维持妊娠和启动分娩的重要因素。孕激素是静息子宫、维持妊娠的主要激素,而糖皮质激素、前列腺素和雌激素等激素则与分娩启动密切相关。孕激素水平的下降是很多哺乳类动物分娩启动的前提条件,然而有些哺乳类动物包括灵长类在整个妊娠过程包括分娩中均维持着高水平的孕激素,此现象令人费解。越来越多的证据表明,人类分娩启动时孕激素同样出现了撤退,但是发生在孕激素的受体水平,主要表现为孕激素受体亚型表达比值和孕激素受体转录辅助因子表达的改变。本文比较了人类和其它哺乳类动物分娩启动时孕激素撤退的三种模式,即黄体溶解、胎盘P450c17羟化酶上调和孕激素受体功能改变,旨在进一步阐明人类分娩启动机制,从而为防治早产提供新的思路。     

Progesterone concentrations and contents in the plasma, ovary, adrenal gland and placenta of the pregnant Natal clinging bat Miniopterus schreibersii natalensis

Reproduction in the Natal clinging bat in South Africa at 25°S is characterized by fertilization in April, implantation during July and parturition in November. In the present study plasma progesterone concentrations peaked two months before implantation, this coinciding with significant peaks in ovarian progesterone content and concentration. Plasma progesterone concentrations remained relatively low during and after implantation, but increased significantly during the limb bud stage to peak levels one month before parturition. Adrenal progesterone content and concentration did not follow a specific trend; post-implantation ovarian progesterone content and concentration remained at baseline values. Placental progesterone content increased significantly with foetal weight (age). The present study showed that pregnancy in these bats is characterized by two major sources of progesterone, with the ovary as the primary source before implantation and the placenta the primary source during embryonic and foetal development.     

Hormonal correlates for the initiation of breast-feeding in Bangladeshi women

Hormonal changes that occur before or during parturition are known to trigger early postpartum maternal behaviors in many mammals. In humans, little evidence has been found for hormonal mediation of early postpartum maternal behavior. In this paper, we investigate associations between fetoplacental hormone concentrations in late pregnancy on the time from parturition to initiation of breast-feeding. A sample of 91 pregnant rural Bangladeshi women, enrolled in a 9-month prospective study, provided twice-weekly urine specimens and structured interviews. The subjects provided self-reports of time from parturition to initiation of breast-feeding. Specimens were assayed for urinary concentrations of human chorionic gonadotropin (hCG), pregnanediol-3alpha-glucuronide (PdG, a metabolite of progesterone), and urinary estrone conjugates (E1C). Parametric hazards analysis was used to investigate the effects of hCG, PdG, and E1C concentrations and other covariates (mother's age, parity, and child's sex) on the duration from parturition to breast-feeding. Mother's age, parity, the child's sex, hCG, and PdG showed no association with the onset of breast-feeding. Urinary E1C was significantly associated with time to initiation of breast-feeding, explaining about 4% of the variation in the behavior. The relationship was positive so that higher prepartum concentrations of EIC were associated with later times to initiation of breast-feeding. The direction of this relationship is opposite that found for many other species of mammals but is consistent with some recent findings in primates.     

Organ Culture of Foetal Rat Pancreas

The differentiation and growth of the foetal rat pancreas (20 days postcoitum) was studied in parabiotic organ culture with foetal adrenal tissue. In such co-cultures, characteristic pancreatic morphology was preserved and further acinar cell differentiation was fostered. Acinar cells continued to represent about 65% of the total explant volume following short-term incubation. The selective islet cell proliferation, previously observed in control pancreatic explants cultured alone, did not occur when adrenals were co-cultured. In addition, the amylase content of the incubation media and of the explanted pancreatic tissue remained high with adrenal co-culture, while the insulin content of the media and of the explanted tissue was markedly suppressed when compared to control pancreatic explants cultured alone. The effects of the adrenal in maintaining the differentiated acinar component of the pancreas and suppressing media insulin concentration diminished over extended incubation. The addition of adrenals to culture of foetal pancreatic explants after 6 days of control culture (at a time when differentiated acinar cells were not identifiable in the explant) did not result in redifferentiation of the acinar component, but did markedly depress media insulin content. Removal of adrenals after 4 days of co-culture resulted in an immediate rise in media insulin concentration and a rapid decline in pancreatic acinar mass. An adrenal-exocrine pancreatic axis is proposed and it is suggested that foetal adrenal secretions may play an important role in the development of the exocrine pancreas in vivo as well as in vitro.