Anti-endometrial antibodies in women measured by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure anti-endometrial antibody concentrations in the serum of women with endometriosis. Pooled cytosolic protein extracts from the endometrial gland cells of 10 women were used as an antigen source. Serum samples were obtained from women with endometriosis before (n = 51) and after 6 months treatment with danazol or nafarelin (n = 30). Control sera came from women with a normal pelvis at laparoscopy, performed for sterilization (n = 23) or the investigation of pain and/or infertility (n = 22), 13 women with Rokitansky syndrome, and 10 umbilical cord bloods and adult males. There were no significant differences in serum anti-endometrial antibody concentrations before and after treatment, or between women with endometriosis and without endometriosis. Concentrations were lower in male and cord blood serum than in female's serum (P < 0.0001). We conclude that the ELISA is not a useful diagnostic tool for endometriosis unless more specific antigens can be isolated.

Anti-endometrial and anti-endothelial auto-antibodies in women with endometriosis.

The present study investigates the specificity of anti-endometrial antibodies present in serum of women with endometriosis. A two colour indirect immuno-histochemical method was used, so that the antigenic reactivity of endogenous immunoglobulins was blocked and specific anti-endometrial antibodies were readily distinguishable. Serum was collected from women with endometriosis, before and after 6 months of treatment, and from women without the disease. The reactivity of serum with uterine and ectopic endometrium from women with and without the disease was studied. The frequency of anti-endometrial antibodies in the serum of women with endometriosis was higher (P < 0.001) than in control sera. Most antibodies specifically reacted with glands in ectopic and uterine endometrium. Antibody reactivity was strongest with endometrium from control women, compared with uterine and ectopic endometrium from women with endometriosis (P < 0.01). A proportion of sera containing anti-endometrial antibodies also reacted with vascular endothelium. Binding was strongest to vessels in uterine and ectopic endometrium from women with endometriosis compared to endometrium from women without the disease (P < 0.01). The presence of anti-endometrial antibodies was associated with infertility.

Localization of anti-endometrial antibody binding in women with endometriosis using a double-labelling immunohistochemical method.

Anti-endometrial antibody binding was localized using a double-labelling immunohistochemical method on frozen sections of endometrium taken from a woman without pelvic disease. Serum from 40 women with endometriosis was tested and, as controls, serum samples from 20 adult males and 20 umbilical cords. The method allowed compensation for endogenous immunoglobulins in endometrium and accurate localization of anti-endometrial antibody binding in the cytoplasm of the glandular epithelium. Significantly more women with endometriosis (14/40) were found to have anti-endometrial antibodies than controls (1/40) (P less than 0.001; chi 2). There was no correlation between disease severity and the presence of anti-endometrial antibodies or the intensity of staining.

Antiendometrial antibodies in endometriosis measured by an enzyme-linked immunosorbent assay before and after treatment with danazol and nafarelin.

No previous study has investigated prospectively the quantitative effect of treatment on antiendometrial antibody levels in endometriosis. We measured antiendometrial antibody levels by an enzyme-linked immunosorbent assay in 35 women with laparoscopically proved endometriosis who were treated for 6 months with danazol (N = 11) or nafarelin (N = 24) in a randomized double-blind study. Levels before treatment were significantly higher than in a control group (P less than .001). Levels were lowered by treatment, but to a significant extent only in the nafarelin group (P less than .001) (danazol group: P = .091). Our data suggest that in relation to antiendometrial antibodies, nafarelin has a suppressive effect which has previously been ascribed only to danazol.

Effect of relaxin on prostaglandin E production by human amnion: changes in relation to the onset of labour.

The effect of relaxin on prostaglandin E (PGE) production by human amnion in vitro was investigated. When amniotic discs were incubated in the presence of increasing concentrations of relaxin, two distinct effects were observed. Discs prepared from women delivered by caesarean section before the onset of labour showed a significant decrease in PGE output at relaxin concentrations of 0.5-2 micrograms/ml; the effect was abolished at higher relaxin concentrations. Discs obtained from women delivered after labour of spontaneous onset responded to the addition of relaxin (4-8 micrograms/ml) with a significant increase in PGE output, although this increase was only evident in patients in whom labour had started with intact membranes. These results suggest that relaxin, which is present in decidua and chorion laeve at term, may have a paracrine effect on the amnion, inhibiting PGE production during continuing pregnancy but favouring its production during spontaneous labour.

Fetal and maternal metabolism of prostaglandin F2 alpha in the guinea pig.

Metabolism of prostaglandin F2 alpha (PGF2 alpha) was studied with both qualitative and quantitative techniques in liver, kidney and lung of fetal and maternal guinea pigs at term. In the pregnant guinea pigs 15-hydroxyprostaglandin dehydrogenase (PGDH) activities were highest in the kidney, followed by the lung and then by the liver. In fetuses PGDH activity was highest in the liver, followed in decreasing order by kidney and lung. The kidneys and lungs of the mothers showed a 6- to 10-fold higher PGDH activity than those of the litter (P less than 0.005), but the mean PGDH activity of liver was lower in the mothers than in the fetuses. It is suggested that the liver may play a major role in prostaglandin metabolism during fetal life, and may fulfil part of the function reserved to the lung during adult life. Maternal and fetal lungs differed greatly in their handling of PGF2 alpha. This was not due to a difference in aeration, for the differences in the metabolism of PGF2 alpha between mother and litter increased when well-aerated neonatal lungs were considered instead of non-aerated fetal lungs. The observed differences in enzyme activity between fetal and neonatal lungs add yet another dimension to the role of prostaglandins in the establishment of neonatal respiration.

Intra-uterine tissues from late-pregnant rhesus monkeys (Macaca mulatta) produce 6-oxo-prostaglandin F1 alpha in vitro.

The rates of production of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) in vitro by intra-uterine tissues taken from late-pregnant monkeys at Caesarean section have been determined. For tissues obtained between days 140 and 149 of pregnancy (late pregnancy) the general quantitative order of rates of production (per unit weight) was decidua basalis greater than placenta greater than decidua parietalis greater than amnion greater than chorion = myometrium. When tissues were taken between days 160 and 168 of pregnancy (near term) this order was placenta greater than decidua parietalis = amnion greater than myometrium = decidua basalis greater than chorion. There was a significant reduction near term in the rate of production of 6-oxo-PGF1 alpha by decidua basalis; all other tissues exhibited similar rates of production at the two gestational periods investigated.

Thromboxane B-2 in the plasma and amniotic fluid of late pregnant and periparturient sheep.

The concentration of thromboxane (TX) B-2 was similar in plasma from all sources but was significantly greater (P less than 0.01) in amniotic fluid. Fetal hypophysectomy was without effect on maternal or fetal levels of TXB-2 (P greater than 0.1). Neither normal parturition at term nor prematurely induced delivery was associated with any significant trend in TXB-2 levels. During late pregnancy (105--145 days of gestation) the concentrations of TXB-2 and 13, 14-dihydro-15-keto-prostaglandin F (PGFM) in maternal and fetal plasma were significantly correlated (P less than 0.001). There was, however, no correlation between TXB-2 and PGFM levels in samples taken during the 36 h before delivery. These data suggest that thromboxanes play little part in the mechanism of parturition in sheep.

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.

Production of thromboxane B2 by the intra-uterine tissues from late pregnant Rhesus monkeys (Macaca mulatta) in vitro.

The rates of production of thromboxane B2 in vitro by intra-uterine tissues obtained from late pregnant monkeys by Caesarean section have been determined. The general quantitative order of rates of production was decidua basalis = decidua parietalis greater than placenta greater than chorion greater than amnion = myometrium. Myometrial production of thromboxane B2 was greater at term than during late pregnancy; no other tissue showed a significant trend with advancing gestation. These data demonstrate that the production of thromboxane B2 by intra-uterine tissues from late pregnant monkeys is both qualitatively and quantitatively different from the production of prostaglandins described previously. It is suggested that prostaglandins rather than thromboxanes are more intimately involved in the onset of labour in the rhesus monkey.

Thromboxane B2 and human parturition: concentrations in the plasma and production in vitro.

The concentration of thromboxane B2 has been measured in the plasma of women during late pregnancy, during term and pre-term labour, in women with pre-eclampsia and in umbilical cord arterial and venous plasma. In addition, the rates of production of thromboxane B2 in vitro were determined for placental tissues obtained after spontaneous vaginal delivery or elective Caesarean section. The results obtained indicate significant differences during parturition between the sources and controlling mechanisms of thromboxane and prostaglandin production.

Comparison of intrauterine prostaglandin metabolism during pregnancy in man, sheep and guinea pig.

Metabolism of prostaglandin F2 alpha (PGF2 alpha) was studied in uterine tissues from pregnant women (n = 10), sheep (n = 6) and guinea pigs (n = 6). Two maternal tissues, myometrium and decidua or maternal placenta, and two fetal tissues, fetal placenta and membranes, were studied in each species. PGF2 alpha was metabolized via the well-known pathway into 15-keto-PGF2 alpha and 13,14-dihydro-15-keto-PGF2 alpha, while 13,14-dihydro-PGF2 alpha was tentatively identified in some tissues. The presence of 15-hydroxyprostaglandin dehydrogenase (PGDH) and 13,14-prostaglandin reductase was demonstrated in all tissues from each of the three species studied, but the quantitative intrauterine distribution of these enzymes differed from one species to another. In man, PGDH activities were highest in fetal membranes followed by fetal placenta and then by decidua and myometrium. In sheep, PGDH activities were highest in the maternal placenta followed in decreasing order by myometrium, fetal placenta and membranes. In the guinea pig, PGDH activity was highest in the fetal membranes followed in decreasing order by maternal placenta, fetal placenta and myometrium. Quantitative assay of PGDH showed that PGDH activity in the pregnant uterus is higher in women than in sheep and guinea pig. The results are discussed in relation to the involvement of prostaglandins in parturition.

Specific production of prostaglandin E by human amnion in vitro.

Prostaglandin production by intra-uterine human tissues has been investigated using a method of tissue superfusion. Tissues were obtained at elective Caesarean section and after spontaneous vaginal delivery. It was found that all the tissues studied (amnion, chorion, decidua and placenta) produced more prostaglandin E (PGE) and 13,14-dihydro-15-keto-prostaglandin F (PGFM - the major circulating metabolite of prostaglandin F) than prostaglandin F (PGF). Amnion produced significantly more PGE (but not PGF or PGFM) than any other tissue. Prostaglandin production by each tissue was similar whether it was taken at elective Caesarean section or after spontaneous vaginal delivery.

Increase of the prostaglandin precursor, arachidonic acid, in amniotic fluid during spontaneous labour.

Concentrations of free arachidonic acid have been measured by gas liquid chromatography in amniotic fluid obtained during spontaneous labour at term. Levels of arachidonic acid ranged from 0.14 to 2.9 microgram/ml and increased significantly (P less than 0.01) with advancing cervical dilatation. Concentrations of arachidonic acid showed no significant relation to concentrations of either prostaglandin F or 13,14-dihydro-15-keto-prostaglandin F. These findings are discussed with respect to the role of arachidonic acid in the control of prostaglandin biosynthesis during human parturition.

Prostaglandin dehydrogenase in the placenta before and after the onset of labour.

Inactivation of prostaglandins in the placenta was studied using an assay for 15-hydroxy-prostaglandin dehydrogenase (PGDH). Forty-four patients with normal single pregnancies between 38 and 42 weeks gestation were studied. Placentae were obtained before the onset of labour in 9, after spontaneous labour in 18, and after oxytocin-induced labour in 17 cases, PGDH-activity ranged from 54 to 495 nanomoles PGF2alpha/g placenta/minute, with a mean +/- SEM of 207 +/- 18 nanomoles/g/minute. The results indicate that the PGDH content of the human placenta does not change markedly with the onset or during the process of labour. The length of either spontaneous or oxytocin-induced labour was not influenced by the PGDH content of the placenta.