Activity In Placenta Research Articles

Prostaglandin dehydrogenase activity in placenta and in maternal lung, kidney, and gastric mucosa during rat pregnancy

The purpose of this study was to investigate the changes in prostaglandin dehydrogenase (PGDH) activity in various organs of the rat during pregnancy. PGDH activity was evaluated in lung, kidney, and gastric mucosa of male and nonpregnant female rats, and in these tissues as well as in placenta of pregnant rats at various stages of gestation. The specific activity of PGDH in placenta decreased until day 15 of pregnancy; thereafter, the specific activity of PGDH increased, reaching maximal levels at term. The specific activity of PGDH in lung and kidney tissue of pregnant rats was greater than that in the same tissues of nonpregnant rats; in these tissues the specific activity increased from early pregnancy through day 21 of pregnancy but was decreased significantly on day 22. The specific activity of PGDH in kidney of male rats was significantly greater (10 times) than that in kidney of female rats. This sex-related difference in renal PGDH activity was not found in lung and gastric mucosa. In gastric mucosa, the specific activity of PGDH on day 10 of pregnancy was significantly lower than that in gastric mucosa of nonpregnant rats. A rapid decrease in the specific activity at term was a phenomenon common to lung, kidney, and gastric mucosa, and was distinctly different from the marked increase in the activity in placenta at term. Thus, in this study, we present evidence that the activity of PGDH is modulated in a tissue-specific manner during pregnancy. We speculate that PGDH in maternal, fetal, and placental tissues serves a role in the maintenance of pregnancy and in growth and development of the fetus by regulating the tissue levels of bioactive prostaglandins.

Identification of ATP diphosphohydrolase activity in human term placenta using a novel assay for AMP

Human term placenta contains an ATP diphosphohydrolase activity which hydrolyses ATP to ADP and inorganic phosphate and ADP to AMP and a second mole of inorganic phosphate. The activity has a pH optimum between 8.0 and 8.5. Magnesium or calcium ions are required for maximum activity. Other nucleoside phosphates, p-nitrophenyl phosphate or sodium pyrophosphate, are not hydrolysed. The activity is not due to ATPases, or to myokinase, as determined by the use of inhibitors. NaF and NaN3 were found to inhibit strongly the activity thus identifying it as an ATP diphosphohydrolase. A sensitive enzymatic assay for measurement of AMP, one of the products of the reaction, was established, based on the strong inhibition of muscle fructose 1,6-biphosphatase by AMP. The range of the assay was 0.05-0.8 microM AMP. ATP diphosphohydrolase was found to have a rate of AMP production from ADP twice the rate from ATP. Under the same conditions, the assay for Pi release, on the other hand, gave velocities similar to each other for the two substrates. The activity appears to be identical to the ADP-hydrolysing activity in placenta reported by others.

Differential expression and regulation of members of the cytochrome P450IA gene subfamily in human tissues

Cigarette smoking increases phenacetin O-deethylase (POD) activity in both the liver and placenta in man, but aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity is increased only in the placenta. Whilst there was no correlation between hepatic POD and AHH activities (rs = 0.42, P greater than 0.1), there was a highly significant correlation between these two activities in placenta (rs = 0.76, P less than 0.02). On Western blotting of human liver samples with an antibody specific to cytochrome P450IA2 in the rat, only the orthologue of P450IA2 could be detected. This antibody inhibited greater than 70% of hepatic high-affinity POD activity but had no effect on the placental activity. Furafylline, a methylxanthine that acts as a highly specific inhibitor of P450IA2-dependent activities in man, inhibited all of the high-affinity component of POD activity in human liver, but was at least three orders of magnitude less potent an inhibitor of placental POD and of both hepatic and placental AHH activities. As previously shown in the rat, exposure of man to polycyclic aromatic hydrocarbons, present in cigarette smoke, differentially induces P450IA2 in the liver and P450IA1 in extrahepatic tissues, at least in the placenta. Again, as in the rat, POD activity in the liver is catalysed by P450IA2, but in the placenta of women exposed to polycyclic aromatic hydrocarbons in cigarette smoke POD activity is catalysed by another isoenzyme, most likely P450IA1. Thus, tissue-dependent induction and substrate specificity of members of the P450IA family in man, at least in the placenta, appear to be the same as previously shown in the rat.

Aryl hydrocarbon hydroxylase activity in human placenta of passive smokers

The levels of smoke components and metabolites in maternal blood and urine are useful in assessing direct exposure but they do not appear to be sufficiently sensitive as a long-term indicator of passive smoke exposure. Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta as a result of maternal smoking has been well documented. This enzyme oxidizes various polycyclic aromatic hydrocarbons abundantly present in cigarette smoke. We hypothesized that passively inhaled tobacco smoke may induce placental AHH activity. Placental AHH levels were determined in 207 pregnancies at birth. As has been found in previous studies, we demonstrated that smoking during pregnancy is associated with a marked increase in placental AHH activity. A relationship was found between the recorded number of cigarettes smoked per day and the placental AHH activity. Moreover, AHH activity was significantly higher in pregnant women passively exposed to tobacco smoke relative to controls. The usefulness of analysis of placental AHH activity as a biological marker of in utero smoke exposure in epidemiological studies is considered.

Biochemical, ultrastructural and histochemical studies of cat placentae deficient in activity of lysosomal α-mannosidase

Lysosomal alpha-mannosidase activity, oligosaccharide profiles, light and electron microscopy and lectin histochemistry studies were performed on full-term placentae obtained from five litters of cats. They resulted from breeding related cats who are obligate heterozygotes for lysosomal alpha-mannosidase deficiency. alpha-Mannosidase activity in placentae from affected kittens was less than 10 per cent of control, while in placentae from presumptive heterozygotes the activity was less than 50 per cent of control. High-pressure liquid chromatographic analysis of oligosaccharides revealed massive accumulation of undegraded oligosaccharides in placentae of affected kittens. A small elevation was found in placentae from presumptive heterozygous kittens, and none was detected in placentae of normal kittens. Light and electron microscopic examinations revealed vacuolization of fetal endothelial and mesenchymal cells only in placentae of affected kittens. Succinylated wheat germ agglutinin and concanavalin A stained the fetal fibroblasts only in placentae of affected kittens.

Monoamine oxidase activity in the term human placenta.

Using a radioenzymatic assay, placental monoamine oxidase (MAO) activity was measured at term after delivery in normal and high-risk pregnancies where decreases in placental blood flow previously were shown. MAO activity in placentas of healthy controls after spontaneous labor was similar to that after elective cesarean section not in labor (mean +/- SE, 133 +/- 18 versus 100 +/- 15 nmol/min/mg protein, respectively). Compared to controls, there was a significant reduction in placental MAO activity in high-risk pregnancies (chronic hypertension, toxemia, and diabetes mellitus), 71 +/- 14, 69 +/- 22, and 69 +/- 7, respectively (P less than 0.05). These differences also were maintained when data were expressed per total placental weight. Effects of antihypertensive drugs on MAO activity in healthy placental tissue were assessed. In homogenates, both hydralazine and magnesium sulfate reduced enzyme activity, while in explants this was not observed. The effects of certain metabolites (which are elevated in plasma of diabetic patients) on healthy homogenates also were studied. Only butyrate reduced enzyme activity. In conclusion, placental MAO activity in vitro is low in term high-risk pregnancies. This may reduce local metabolic inactivation of catecholamines and serotonin and consequently lead to a decrease in blood flow. Such a direct relationship must be confirmed in further studies.

ALCOHOL AND DRUG METABOLISM IN HUMAN PLACENTA

Alcohol and drug metabolizing activity in placenta is one of the important factors influencing fetal health status, especially when the gravida is exposed to alcohol or drugs. In the present investigation, we measured the activities of alcohol and drug metabolizing enzymes of microsomes obtained from twenty-six human placentas and compared these activities with those of rat liver. Aminopyrine N-demethylase activity of human placental microsomes was 37.3 ± 6.2 (n mol formaldehyde/mg protein/15 min), while that of rat liver microsomes was 90.6 ± 18.4. Rat liver microsomes showed distinct activity for aniline hydroxylase and benzpyrene hydroxylase. In contrast, human placental microsomes had no activity for either of these enzymes. Activities of alcohol dehydrogenase and the microsomal ethanol-oxidizing system (MEOS) in human placental microsomes were approximately one-tenth of those in rat liver microsomes. No relationship was found between the activities of microsomal enzymes in placenta and the properties of gravida, placenta and pregnancy including term of pregnancy, frequency of delivery and weight of placenta. However, between the activities of microsmal enzymes in placenta and the age of gravida, a negative interrelation was found.

3β-Hydroxysteroid [formula omitted] activity in the rhesus monkey placenta and fetal adrenal, testis and ovary during late gestation

3β-Hydroxysteroid dehydrogenase Δ 5−4isomerase (3β-HSDH) was measured in the rhesus monkey ( Macaca mulatta ) placenta, fetal adrenal (whole organ minus medulla), testis and ovary during late gestation (Days 145–162). Activities were evaluated from the conversion of [ 3H]-pregnenolone to [ 3H]progesterone. The maximum enzyme velocity (V m) in adrenal microsomes (100,000 g pellet) was significantly higher (146 nmoles progesterone/h x mg −1protein) than in microsomes from the other tissues. Testicular V m was greater than either ovarian or placental V m which were not different from one another (11.5 versus 1.9, 1.2 nmoles progesterone/h x mg −1protein, respectively). Apparent Michaelis-Menten constants in the adrenal, placenta, testis and ovary averaged 1.8,2.5,0.27 and 0.16 μM, respectively. In some cases, substrate inhibition was noted. Estimated dissociation constants for pregnenolone were 2.3 μM (adrenal), 2.1 μM (placenta), 0.74 μM (testis) and 0.13 μM (ovary). 3β-HSDH was less active in a crude mitochondrial preparation from the fetal adrenal (10,000 g pellet) than in microsomes, whereas activity in the placenta and testis appeared to be equally distributed between mitochrondria and microsomes. Rate measurements were consistent with the apparent potentials of these organs to synthesize their characteristic hormones. Thus, 3β-HSDH activity may be an important rate determining step in hormone synthesis. The importance of substrate inhibition in progesterone formation remains to be assessed.

3β-hydroxysteroid dehydrogenase-isomerase activity in placentae from pregnancies complicated by steroid sulphatase deficiency

The 3β-hydroxysteroid dehydrogenase-isomerase activity of preparations of human placentae was determined in vitro by measuring the conversion of [ 3H]-pregnenolone to [ 3H]-progesterone. The mean activity (330 ± 40 c.p.m./mg protein/30 min, mean ± SD, n = 8) of placentae deficient in steroid sulphatase, previously stored at −20°C, was significantly less ( P < 0.001, t-test) than that of control placentae which had been treated in an identical manner (600 ± 60 c.p.m./mg protein/30 min, n = 15). However, when tested without freezing, the mean activity of the same control placentae was 2240 ± 675 c.p.m./mg protein/30 min ( n = 15) and the activity of a fresh sulphatase deficient placenta (2170 c.p.m./mg protein/30 min) was indistinguishable from that of the controls. 3β-Hydroxysteroid dehydrogenase-isomerase activity therefore appears to be sensitive to freezing and thawing and the effect is more marked in sulphatase deficient placentae. This finding confirms the earlier reports of lower activities of steroid metabolising enzymes (other than sulphatase) in steroid sulphatase deficient placentae. The results from the deficient placenta studied fresh and after freezing imply that the lower 3β-hydroxysteroid dehydrogenase-isomerase activity in steroid sulphatase deficient placentae is due to the study of tissue which had been stored at −20°C rather than of fresh tissue. Mean 3β-hydroxysteroid dehydrogenase-isomerase activity of fresh placenta from male infants was significantly less ( P < 0.05) than that of placentae where the fetus was female.

Sialyltransferase in fetal tissues: Incorporation of sialic acid into endogenous and exogenous glycoprotein acceptors

The properties of exogenous sialyltransferase activity in fetal mouse liver were compared with the endogenous enzyme activity. Nonionic detergents such as Tergitol inhibited endogenous activity but released the enzyme from the 30,000 g particulate fraction and allowed it to react with the exogenous glycoprotein acceptors, partially desialylated α-fetoprotein and calf fetuin. Zinc ions partially transferred the enzyme activity from the particulate fraction to the supernatant, while incubation at 45 °C preferentially inhibited endogenous enzyme activity. α-Fetoprotein, sialylated by the endogenous enzyme preparation, was determined to be 7% of the total incorporation of radioactivity by immunoprecipitation with mouse anti-α-fetoprotein and subsequent sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. Sialyltransferase activity in fetal liver, yolk sac, placenta and embryo (minus liver) was measured during development. Exogenous enzyme activity of liver in early development (day 13.5) was twice as high as that in yolk-sac tissues that synthesize α-fetoprotein. Furthermore, enzyme activity increased 12-fold in fetal liver and 4-fold in yolk sac by day 18.5 of development. Activity in placenta increased 2.9-fold and then decreased, while embryo (minus liver) showed no increase. Endogenous enzyme activity increased temporally in these tissues, but the increase was less than that measured by using exogenous acceptors.

α- l-Fucosidase and other glycosidases in human placenta, foetus liver and amniotic fluid at various stages of gestation

It has been shown that α- l-fucosidase, α- d-mannosidase, β- d-galactosidase and α- d-galactosidase in placenta and liver of human embryos were active even at 5–7 weeks of gestation. α- l-Fucosidase and α- d-mannosidase were also found in the amniotic fluid at various stages of pregnancy. The glycosidase activity in placenta increased during embryogenesis. The highest activity of these enzymes was observed at gestational phase 11–12 weeks and decreased then considerably toward the end of pregnancy. α- l-Fucosidase in placenta possessed the highest specific activity—81.8. The activity of β- d-galactosidase and α- d-mannosidase were lower—44.1 and 19.9 respectively. The specific activity of α- d-galactosidase was the lowest—0.3. The role of these glycosidases in the development of various mucopolysaccharidoses and glycolipidoses is discussed. It is supposed that the detection of these glycosidase activities in amniotic fluid and placenta can be useful in diagnosis of mucopolysac-charidoses at the earliest stages of these diseases.

Hydroxysteroid dehydrogenase activity in the placenta of the domestic pig.

A histochemical method was used for the detection and localization of Δ5-3β- and 17β-hydroxysteroid dehydrogenase activity in the epitheliochorial placenta of the domestic pig, Sus scrofa. Placentas were obtained from the fourth week of gestation until term (114 days) and showed much the same substrate specificity throughout pregnancy. Both dehydroepiandrosterone and 3β,17β-dihydroxyandrost-5-ene (androstenediol) were better substrates than pregnenolone, particularly in the earlier stages. 17α- Hydroxypregnenolone was not utilized. With testosterone and estradiol-17β as substrates, the presence of both neutral and phenolic 17β-hydroxysteroid dehydrogenase enzymes could be demonstrated. No activity was seen with estradiol- 17α. The significance of these findings is discussed in relation to the possible role of the placenta in estrogen production in the sow. (Endocrinology 84: 426, 1969)

Sulfatase activity in placenta, liver and small intestine of human fetuses.

Sulfatase activity in placenta, liver and small intestine of human fetuses.

Glucose-6-phosphatase-like activity in the human placenta, fetal liver, and decidual tissue

An enzymatic activity breaking down glucose-6-phosphate to glucose and phosphate is found in first, second, and third trimester placentas and in early decidual tissues. The total activity in the placenta, when related to fetal growth, decreases considerably as the gestation increases. These activities in the decidual plate area may be of importance in governing and regulating the placental growth and implantation.Histochemical and biochemical analyses of two fetal livers (at 11 and 18 weeks) for glucose-6-phosphatase, alkaline phosphatase, and acid phosphatase are reported.

Cholinesterase activity in the myometrium, placenta and serum of the rats

It is a well known fact that Cholinesterase (ChE) is important in acetylcholine cycle. Moreover, it has been assumed that uterine contraction might be related to ChE activity in myometrium. ChE activities of rat myometrium were observed in sexual cycle, various stages of pregnancy and puerperium by Hesterin-Miyazaki method. The effects of castration, administration of sexual hormones and contraction induced by various substances were investigated on ChE activities of non-pregnant, dregnant and puerperal myometrium. The administrated sexual hormones were various estrogens and progestins. Oxytocin, Methylergometrine tartrate and Acetylcholine chloride were used for inducing the contraction of rat uterus. ChE activities of serum and placenta were simultaneously measured. The obtained results were as follows : 1) ChE activities in myometrium decreased in estrus and after castration, and increased in diestrus. However, ChE activities in serum were high in estrus and low in diestrus. 2) ChE activity in myometrium showed a rapid decrease up to the 14th day of pregnancy, and very slowly decreased from the 14 day through labor. Then, ChE activity was recovered to the value in non-gravid period 3 to 6 days after delivery. ChE activity in antiplacental site of myometrium was higher than in placental site. ChE activity in placenta was higher in late pregnancy than in mid pregnancy. ChE activity in serum increased during pregnancy but its deviation range was rather large. Then, this activity in serum gradually decreased during puerperium and became lower on the 6th day post partum than in non-gravid period. 3) Effects of estrogens and progestins on ChE activities in pregnant myometrium were nct remarkable. ChE activities in placenta and serum were also unchanged by estrogens and progestins. 4) ChE activities in puerperal myometrium were diminished by the administration of estradiol benzoate (1 mg or 100μg), estrone (1 mg or 100μg) or estriol (1 mg) for 6 days, but not changed by the administration of 10μg of these estrogens or 100μg of estriol. On the other hand, ChE activities of puerperal myometrium were slightly diminished by the administration of progestins (1 mg). ChE activities of serum in puerperium became high, as in pregnancy, after the administration of 1 mg of estrogens for 6 days. 5) ChE activity was slightly low after the administration of oxytocin, but no effect of it was found in vitro. Methylergometrine tartrate and acetylcholine chloride had no remarkable effects on ChE activities in myometrium. ChE activities in serum and placenta were almost unchanged after administration of oxytocin, methylergometrine tartrate and acetylcholine chloride. 6) ChE activities were low in myometrium and placenta of uterine horn with dead fetus.

LIPOPROTEIN LIPASE ACTIVITY OF RAT AND HUMAN PLACENTA.

SummaryLipoprotein lipase activity was found to be present in homogenates of placentas of rats pregnant 18–21 days and of human placentas obtained post partum. In the rat, the LPL activity in placenta was equal to that in heart, but much less than that found in adipose tissue. LPL activity in human placenta was smaller than that in rat placenta. Placental lipase activity was inhibited by DFP, protamine and 1 M NaCl, and considerably reduced in the absence of serum in the incubating medium. LPL activity in placenta may be related to the vascularity of this organ and may act to supply the fetus with fatty acids by hydrolyzing lipoproteins obtained from the maternal circulation.

Phosphoprotein Phosphatase in Rat Young, Embryos, and Placentas

Summary1. A study has been made of the level of phosphoprotein phosphatase activity in placentas, whole embryos, and whole young growing rats of various ages.2. The total phosphoprotein phosphatase activity of the placenta and of the embryo and young rats continually rises. The activity was followed in placenta and embryo from thirteen days post-conception to parturition, and in young rats to 28 days of age.3. The activity per gram of body weight rises slowly in early embryos, rapidly in the period immediately preceding and following parturition, and remains essentially constant during the age period of 12 to 28 days.4. The activity per gram of placenta decreases from the 14th to the 20th day after conception, then rises again just before parturition. The preliminary decrease is due to the rate of weight gain of the placenta being greater than the rate of gain of total placenta phosphoprotein phosphatase; the reversal of direction of the curve is due to continued enzyme increase while the placenta gains e...