Workshop report: biological consequences of early placental loss: report of the meeting, and issues for further investigation San Juan, Puerto Rico 21-23 November 1991.
Explore the source record for details and available documents.
Brain↗
Biomedical subjects
J R Challis
Publications and source records attributed to J R Challis.
Immunoreactive 15-hydroxyprostaglandin dehydrogenase (PGDH) is reduced in fetal membranes from patients at preterm delivery in the presence of infection.
Previously we reported that the proportion of trophoblast cells that were immunopositive for 15-OH prostaglandin dehydrogenase (PGDH) in the chorionic membranes was reduced in women in preterm labour without infection, compared with women at term, but was not altered in preterm labour patients with an underlying infective process. Subsequently, we found that PGDH activity and PGDH mRNA were significantly lower in membranes of this latter group of patients than in women at preterm labour without infection or at term. To resolve this issue we used immunohistochemistry to examine the distribution and frequency of immunoreactive (ir)-PGDH positive cells in full-thickness fetal membranes in patients at preterm labour in the presence or absence of infection. Trophoblast and decidual stromal cells were identified using antibodies against cytokeratin and vimentin, respectively. There was considerable variation in the number of chorionic trophoblast cells that were positive for ir-PGDH, but in some patients there was little or no ir-PGDH staining, and this was associated with loss of trophoblast cells from the tissue. The mean intensity and number of ir-PGDH positive cells was significantly lower in membranes from patients in preterm labour with infection than in idiopathic preterm labour at which the diagnosis of infection was not made. We conclude that in the setting of preterm labour with infection there may be loss of trophoblast cells from membranes, with corresponding reduction in the number of ir-PGDH positive cells. Loss of PGDH activity removes the initial step in activating primary prostaglandins, which are then able to pass unmetabolized to the decidua and myometrium, and contribute to the stimulus to preterm birth.
Chorion↗
Chorionic prostaglandin catabolism is decreased in the lower uterine segment with term labour.
We have examined the hypothesis that regional differences in 15-hydroxyprostaglandin dehydrogenase (PGDH) activities occur within the human fetal membranes. Further, we reasoned that a specific reduction in PGDH in the fetal membranes at the lower uterine segment might occur with labour, providing a potential mechanism for local generation of primary prostaglandins (PG) that could contribute to cervical ripening. Full-thickness membranes were obtained from patients at caesarean section in the presence or absence of labour. Membranes were sampled from three regions: close to the site of placental attachment, in the region of the internal cervical os, and from a 'middle' area between these two. PGDH activities (sum of PGF2 alpha to 15-keto PGF2 alpha and 13, 14-dihydro 15-keto PGF2 alpha conversion) and immunoreactivity varied appreciably between the three regions. PGDH activity was highest in chorion in the cervical region of patients not in labour, but was significantly lower in the chorion from membranes taken closest to the internal os of patients in labour. Loss of PGDH activity was not attributable to a diminution in the number of trophoblast cells in this area. We conclude that regional loss of PGDH in the fetal membranes (chorion) at the lower uterine segment occurs with labour. Reduced PG catabolism could facilitate local generation of bioactive PG at this site for cervical effacement.
Cesarean Section↗
Glucocorticoid actions and metabolism in pregnancy: implications for placental function and fetal cardiovascular activity.
The isoforms of the enzyme 11beta hydroxysteroid dehydrogenase (11betaHSD) are expressed in placental tissue and fetal membranes. The two major isoforms, 11betaHSD-1 and 11betaHSD-2, are compartmentalized discretely, and regulated differentially by steroids (oestrogen, progesterone), activators of cAMP pathway, and nitric oxide. 11BetaHSD-2 appears important in human pregnancy in regulating the amount of maternal cortisol that crosses the placenta to reach the fetal compartment. On the other hand, 11betaHSD-1 may allow the local conversion of biologically inactive cortisone to biologically active cortisol, particularly within chorion trophoblasts. The localization, regulation, and importance of these isozymes are examined.
11-beta-Hydroxysteroid Dehydrogenases↗
Rapid increase of foetal corticosteroids after prostaglandin E2.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
Temporal expression of prostaglandin H synthase type 2 (PGHS-2) and P450(C17)in ovine placentomes with the natural onset of labour.
Labour in the sheep is preceded by increased tissue and plasma prostaglandin (PG) concentrations, and PGs could potentially contribute to the regulation of P450(C17)in placental tissue. Therefore, we determined the cellular localization and temporal pattern of expression of P450(C17)and prostaglandin H synthase type 2 (PGHS-2), the primary PG synthetic enzyme, in intrauterine tissues from three groups of pregnant ewes at term; animals not in labour (NIL;n=5; 140-145 days of gestation), animals in early labour (EL;n=6; 143-149 days) and animals in active labour (L;n=6; 145-149 days). Allocation of animals into the three groups was based on continuous monitoring and assessment of myometrial contractile activity (EMG) and changes in the intrauterine pressure (IUP). Levels of mRNA encoding PGHS-2 and P450C17 were determined by in situ hybridization. Localization and levels of immunoreactive (ir-) P450(C17)and ir-PGHS-2 protein were determined by immunohistochemistry and Western blotting. PGHS-2 mRNA and ir-PGHS-2 were already elevated in placentomes of NIL animals and did not increase further with the progression of labour, whereas P450C17 mRNA increased progressively with labour, and ir-P450C17 rose significantly only in animals in active labour. The rise in P450C17 expression corresponded temporally to a progressive increase in maternal plasma concentration of oestradiol. We suggest that the temporal relationship and subsequent co-localization of PGHS-2 and P450(C17)proteins in the uninucleate trophoblast cells of the placentomes are consistent with the possibility that placental PGs could act to enhance placental output of oestrogen leading to labour and delivery.
Animals↗
Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus.
OBJECTIVE: To determine whether repeated hypoxic insults with umbilical cord occlusion over 4 days will lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus. METHODS: Umbilical cord occlusions of 90 seconds duration were performed every 30 minutes for 3 to 5 hours each day (experimental group n = 7, control group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization. RESULTS: During umbilical cord occlusions fetal arterial oxygen pressure (approximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dioxide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions for any of the 4 study days. Plasma ACTH increased, as measured after cord occlusion and over the course of successive cord occlusions on days 1 and 4, and returned to control values by the next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15 +/- 3 compared with 101 +/- 25 pg/mL, P <.05). Plasma cortisol increased, as measured after cord occlusion and over the course of successive cord occlusions on day 4 only (2.7 +/- 0.4 to 4. 7 +/- 0.3 ng/mL, P <.05). POMC mRNA increased 2.5-fold in the pars distalis of the pituitaries from cord occlusion compared to control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was detected in the pars distalis only, was unaltered. CONCLUSION: Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical responsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but with no change in GR.
Adrenal Glands↗