Serum levels of placental protein 14 reflect ovulation in nonconceptional menstrual cycles

Placental protein 14 (PP14), originally isolated from the human placenta and its adjacent membranes, was detected in the serum of nonpregnant women. The levels were measured by radioimmunoassay in 218 serum samples from 19 women throughout the menstrual cycle. In 13 women with a normal ovulatory cycle, the levels showed consistent variation. They were highest (up to 172 ng/ml) in the late secretory phase and remained high for the first days of the next cycle. Low concentrations were found from the midproliferative to the early luteal phase of the cycle. No similar variation was seen in anovulatory cycles of six other women. Compared with ovulatory cycles, anovulatory cycles exhibited lower PP14 levels in the latter part of the cycle (P less than 0.001) and in the beginning of the next cycle (P less than 0.01). In ovulatory cycles, the sustained elevation of serum PP14 concentration over the following period may be explained by the fairly long half-life (42 hours) of PP14 in serum: once the level has increased, it declines slowly. These results suggest that PP14 measurement may become a novel means to distinguish between ovulatory and anovulatory cycles even after the onset of the next period.     

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.     

The secretory endometrial protein, placental protein 14, in women with ectopic gestation.

OBJECTIVE: To determine the serum level of the secretory endometrial protein, placental protein 14 (PP14) and progesterone (P) in women with ectopic gestation. DESIGN: Blood samples were collected prospectively and preoperatively. Reference range was determined from a prospective population of 98 women with uncomplicated pregnancies and normal outcome. SETTING: The women were admitted to a university hospital. PATIENTS: Fifty-nine women with laparoscopically verified ectopic pregnancy entered the study. INTERVENTION: At the time of diagnosis PP14 and P were measured. MAIN OUTCOME MEASURE: After observing the low serum levels of PP14 and P, a correlation analysis was made and compared with the findings in normally pregnant women. RESULTS: A significant positive correlation was found between the level of PP14 and P (P less than 0.00002), not found in normal intrauterine pregnancies. CONCLUSIONS: These findings suggest that the regulation of the PP14 production involves either a control mechanism from the ovary or is mediated by paracrine secretion.     

Catecholamine physiology in the ovine fetus. I. Gestational age variation in basal plasma concentrations

Fifty-five ewes with chronically catheterized singleton gestations were studied to assess changes in basal concentrations of fetal catecholamines with increasing gestational age. All pregnancies were time dated, and measurements of catecholamines were conducted at least 5 days after placement of fetal catheters when fetal metabolic parameters had normalized. Plasma concentrations of catecholamines were measured by radioenzymatic assay. Additionally, fetal heart rate (FHR) and corrected mean blood pressure were analyzed in 32 of the fetuses for correlation with plasma levels of catecholamines. Multiple regression analysis revealed significant inverse correlations of fetal plasma concentrations of catecholamines with gestational age, as follows: norepinephrine (p less than 0.001), epinephrine (p less than 0.05), and dopamine (p less than 0.01). FHR correlated inversely with gestational age (p less than 0.001) and positively with circulating levels of norepinephrine (p less than 0.001).     

Clinical applications of serum placental protein 14 (PP14) measurement in the IVF-ET cycle

OBJECTIVE: Placental protein 14 (PP14) is known to be one of the endometrial proteins that reflect endometrial functioning throughout the menstrual cycle. In this study, we examined PP14 as a marker for human endometrial receptivity in order to predict the outcome of in vitro fertilization and the embryo-transfer (IVF-ET) cycle. PATIENTS AND METHODS: The subjects were 72 women who had 96 IVF-ET cycles and who were examined at Tokyo Medical University Hospital during the period of January 1998 to June 1998 because of mechanical or unexplained infertility for a duration of at least 2 years. Serum samples were collected from all patients during treatment cycles, and serum PP14 concentrations were measured by a newly established enzyme-linked immunosorbent assay (ELISA). RESULTS: In the pregnant group, serum PP14 concentrations were markedly increased after ET, and a significant difference between the pregnant group and the nonpregnant group was observed 8 days following ET (p < 0.01). PP14 concentrations were higher in patients with endometria that exhibited homogenous patterns and that were more than 7 mm thicker than in other patients, as determined by ultrasound on the day of oocyte collection (p < 0.005). The pregnancy rates of patients with homogeneous patterns were lower than those of patients showing a trilaminar pattern. No pregnancies were observed when serum PP14 concentrations were greater than 6.85 U/l on the day of oocyte collection. CONCLUSION: PP14 might be a useful marker for human endometrial receptivity to predict the outcome of IVF-ET cycles.     

Serum placental protein 14 (PP14) levels in patients with threatened abortion

 Serum placenta protein 14 (PP 14) were significantly lower serum levels in patients with threatened abortion at 10 to 20 weeks controls than in normal (normal group, n = 133, median: 52,0 μg/l [16 – 83, SD: 17,9], risk group: n = 20, median: 34,0 μg/l [13 – 63, SD: 13,7]). Received: 3 February 1995 / Accepted: 18 December 1995     

The variation of endometrial protein PP14 in different parts of the human endometrium.

The levels of the endometrial protein PP14 were shown to vary greatly in different sites in the endometrium (coefficient of variation ranged from 55% to 92%, mean = 73%). The variation was found to have no consistent pattern in the seven subjects studied and was unlikely to be the result of problems related to tissue sampling, processing or assay (intra-assay coefficient of variation of the PP14 assay used was less than 10%). Such a large variation in results suggests that the measurement of PP14 concentration in endometrial tissue may be of limited diagnostic value.     

Distribution of placental protein 14 in tissues and body fluids during pregnancy

Placental protein 14 (PP14) levels were measured in serum samples from non-pregnant and pregnant women, amniotic fluid, cord blood, and extracts of placenta, decidua and fetal membranes. The levels were low (15-40 micrograms/l) in serum of non-pregnant women. In four pregnancies following in-vitro fertilization, the serum PP14 levels started to rise 2-12 days after embryo replacement. In normal pregnancy, the highest serum PP14 concentrations (up to 2200 micrograms/l) were detected between 6 and 12 weeks. After 16 weeks the level decreased and plateaued at 24 weeks to around 200 micrograms/l. In amniotic fluid, the highest PP14 levels (232 mg/l) were found between 12 and 20 weeks, being considerably higher than those in maternal serum throughout pregnancy. In cord blood, the levels were low (15-22 micrograms/l) or undetectable. In early pregnancy decidua, the PP14 content was higher (41-160 mg/g total protein) than in late pregnancy decidua (60-2700 micrograms/g total protein). In amnion and chorion laeve, the PP14 concentration varied from 50 to 750 and 50 to 1000 micrograms/g protein, respectively. Early pregnancy placenta contained 0.25-15 mg/g and late pregnancy placenta 3-430 micrograms/g protein of PP14. These results show that the levels of PP14 in pregnancy serum have a similar profile to hCG, but in contrast to other placental proteins, the amniotic fluid PP14 levels are remarkably high. This may be explained by suggesting that decidua is a source of PP14.     

Distribution of placental protein 14 in tissues and body fluids during pregnancy

Summary. Placental protein 14 (PP14) levels were measured in serum samples from non-pregnant and pregnant women. amniotic fluid, cord blood, and extracts of placenta, decidua and fetal membranes. The levels were low (15–40 μg/ l ) in serum of non-pregnant women. In four pregnancies following in-vitro fertilization, the serum PP14 levels started to rise 2–12 days after embryo replacement. In normal pregnancy, the highest serum PP14 concentrations (up to 2200 μg/l) were detected between 6 and 12 weeks. After 16 weeks the level decreased and plateaued at 24 weeks to around 200 μg/l. In amniotic fluid, the highest PP14 levels (232 mg/l) were found between 12 and 20 weeks, being considerably higher than those in maternal serum throughout pregnancy. In cord blood, the levels were low (15–22 μg/l) or undetectable. In early pregnancy decidua. the PP14 content was higher (41–160 mg/g total protein) than in late pregnancy decidua (60–2700 μg/g total protein). In amnion and chorion laeve, the PP14 concentration varied from 50 to 750 and 50 to 1000 μg/g protein, respectively. Early pregnancy placenta contained 0-25-15 mg/g and late pregnancy placenta 3–430 μg/g protein of PP14. These results show that the levels of PP14 in pregnancy serum have a similar profile to hCG, but in contrast to other placental proteins, the amniotic fluid PP14 levels are remarkably high. This may be explained by suggesting that decidua is a source of PP14.     

Suppression of in vitro lymphocyte reactivity to phytohemagglutinin by placental protein 14

Crude human decidual extracts containing up to 26.6 mg/l of placental protein 14 (PP14) and purified PP14 were assessed for their effects on the in vitro lymphocyte reactivity to phytohemagglutinin (PHA). Both decidual extract and purified PP14 suppressed the mitogenic response to PHA with the suppression being dose-dependent over the range of PP14 concentrations investigated (0-26.6 mg/l). On the specific reduction of the PP14 content by a monoclonal anti-PP14 immunoadsorbant the suppression was reduced. The suppressive activity of PP14 was related to the degree of proliferation of the stimulated lymphocytes. These results suggest that PP14, which is present at peak levels in the first trimester of pregnancy and constitutes up to 10% of the soluble protein content of decidual tissue, may be an immunomodulator important for the survival of the implanting embryo and maintenance of early pregnancy.     

HLA-G protein concentrations in maternal serum and placental tissue are decreased in preeclampsia

OBJECTIVE: The aim of this study were to determine whether soluble human leukocyte antigen-G protein levels in serum and/or human leukocyte antigen protein in placental tissues differ between women with preeclampsia versus uncomplicated pregnancies.Study design human leukocyte antigen-G levels were determined with the use of a specific enzyme-linked immunosorbent assay in 20 subjects with preeclampsia and 14 normal control subjects. RESULTS: Both serum and placental human leukocyte antigen-G levels were decreased significantly in the preeclampsia group (median, 0.026 microg/mL in serum; median, 0.026 microg/mg protein in placenta), in comparison with normal pregnant women (median, 0.093 microg/mL in serum; median, 0.088 microg/mg protein in placenta; P=.0112 and P=.0406, respectively). There was a significant correlation between serum and placental human leukocyte antigen-G levels (r=0.603; P=0.0002). CONCLUSION: The reduced expression of placental human leukocyte antigen-G and reduced release of this protein into the maternal circulation in preeclampsia may alter the maternal-fetal immune relationship and thus be involved in the cause of this disorder.     

The relationship of placental protein 14 (PP14) in the mother and fetus to specific products of the human placenta

Levels of placental protein 14 (PP14), human placental lactogen (hPL) and unconjugated oestriol (E3) were measured in maternal peripheral and umbilical arterial and venous blood obtained from 65 normal pregnancies at term delivery. PP14 levels were one order of magnitude higher in the mother than in the fetus. Neither maternal nor fetal levels of PP14 were related to the birthweight of the fetus. There was a relationship between maternal and umbilical venous levels of PP14, which suggests that fetal PP14 is derived by transfer from the mother, or that there is an independent fetal source with a control mechanism similar to that of the mother. The findings are compatible with earlier observations to the effect that PP14, in contrast to products such as hPL and E3, is not specific to the trophoblast.     

13, 14-dihydro-15-keto-prostaglandin F2alpha concentrations in human plasma and amniotic fluid.

An antiserum to 13,14-dihydro-15-keto-prostaglandin F2alpha (PGF2alphaM) was prepared and a radioimmunoassay evaluated in various reproductive states. PGF2alphaM plasma concentration was 63.6 +/- 10.3 pg/ml (mean +/- SEM) in cycling women. The concentration fluctuated throughout the menstrual cycle and pregnancy, but no discernible patterns were noted. PGF2alphaM concentrations were elevated at the time of urea + oxytocin induced abortion (238 +/- 54 pg/ml) and during late stages of normal labor (352 +/- 107 pg/ml) but were not elevated during labor prior to 7 cm dilatation. Following intra-amniotic instillation of 5 mg of PGF2alpha tromethamine into the amniotic sac, PGF2alphaM concentration increased in the amniotic fluid. In the plasma of these patients there was an eighteenfold rise in plasma PGF2alphaM concentration compared to a 3.5-fold rise in PGF2alpha at 1 hour, suggesting changes in PGF2alphaM may be more easily detected than the parent compound. While PGF2alphaM may be a useful index of PGF2alpha production, it appears that PGF2alphaM is of little value in predicting the occurrence of uterine contraction.