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Biomedical subjects

J A McCoshen

Publications and source records attributed to J A McCoshen.

At least 19 recordsLinked to original sources

Prostaglandin F2 alpha output by amnion-chorion-decidua: relationship with labor and prostaglandin E2 concentration at the amniotic surface.

OBJECTIVE: Our purpose was to evaluate prostaglandin F2 alpha output at fetal membrane surfaces relative to labor and to assess amniotic prostaglandin E2 concentration changes on prostaglandin F2 alpha output. STUDY DESIGN: Intact and separated fetal membranes from 10 elective cesarean sections and nine vaginal deliveries were incubated in double-sided perfusion chambers. Prostaglandin F2 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output was measured by radioimmunoassay. Alterations of prostaglandin F2 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output were assessed after exogenous prostaglandin E2 addition at amniotic surfaces of intact membranes. RESULTS: Prostaglandin F2 alpha concentration was higher at maternal surfaces of intact but not separated membranes after labor (p = 0.0001). Amniotic 13,14-dihydro-15-keto-prostaglandin F2 alpha was increased in association with preceding labor (p = 0.038). Addition of prostaglandin E2 at the amniotic surface did not alter prostaglandin F2 alpha or 13,14-dihydro-15-keto-prostaglandin F2 alpha production. CONCLUSION: Prostaglandin F2 alpha concentration at the maternal surface of fetal membranes likely plays a critical role in induction or maintenance of myometrial contractions associated with term labor independent of amniotic fluid prostaglandin E2 concentrations.

Amniotic Fluid↗

The role of fetal membranes in regulating production, transport, and metabolism of prostaglandin E2 during labor.

The level of prostaglandin E2, a potent stimulator of myometrial contractions, increases in amniotic fluid during labor. We tested whether amniotic prostaglandin E2 crosses the reflected fetal membranes to the myometrium during labor. Disks of amnion, chorion-decidua, and amnion chorion-decidua from 10 term pregnancies before labor and nine vaginal deliveries after normal spontaneous labor were incubated in two-sided perfusion chambers in the absence or presence of 1 mumol/L indomethacin, or in the presence of a bolus of prostaglandin E2 and radiolabeled prostaglandin E2 added to the fetal chamber. Net amniotic prostaglandin E2 increased significantly (p = 0.003) after labor. However, there was no significant difference in prostaglandin E2 concentrations on the maternal side of amnion chorion-decidua between labor conditions. High-pressure liquid chromatography identified the transport of intact tritiated prostaglandin E2 across amnion but not across chorion-decidua or amnion chorion-decidua in which prostaglandin E2 was completely metabolized. Because of 15-hydroxyprostaglandin dehydrogenase activity in chorion, we suggest that amniotic prostaglandin E2 transport to the myometrium is impaired. Thus the increase in prostaglandin E2 production that occurs in amnion tissue after labor commences does not result in an increase in prostaglandin E2 concentration on the myometrial side of the fetal membranes in the in vitro preparation.

Adult↗

Quantitative analysis of the effect of freezing on donor sperm motion kinetics.

One hundred ninety-two semen specimens from 14 donors were analyzed on a CellSoft Semen Analyzer (CRYO Resources, New York, NY) before and after freezing. Mean post-thaw motility decreased by 52%. Correlation of the percent decrease in post-thaw versus prefreeze motility was significant but of poor predictive value. Comparisons of the percent change in post-thaw motility and sperm motion kinetics between four discrete ranges of prefreeze motility (32% to 66%, 67% to 76%, 77% to 84%, 85% to 94%) revealed that the effect of freezing on sperm cell survival was equivalent between all ranges. However, significant differences occurred between these ranges for curvilinear velocity, straight line velocity, and mean amplitude of lateral head displacement but not for linearity nor beat cross frequency. All correlations between prefreeze and post-thaw motion variables were significant but closest for curvilinear velocity and straight line velocity. Furthermore, correlations of prefreeze versus post-thaw velocity measurements were strongest for those cells within the 65% to 85% range of prefreeze motility. We suggest that sperm survival is independent of prefreeze motility. However, velocity kinetics appear stable after freezing for those specimens that had an initial motility of 65% to 85%.

Analysis of Variance↗

Umbilical cord is the major source of prostaglandin E2 in the gestational sac during term labor.

The umbilical cord is an amniotic structure histologically resembling amnion lining the basal plate and reflected chorion. Prostaglandin E2 is secreted by amnion and is present in amniotic fluid. This study measured prostaglandin E2 production by amnion from all three locations to determine the relative contributions of prostaglandin E2 to amniotic fluid at term. Total surface areas and weights of umbilical cord, basal placental plate, and reflected chorionic amnion were measured in afterbirths from 20 normal patients delivered at term by elective repeat cesarean section before the onset of labor or vaginally after spontaneous onset of labor. Subsequently, 2 cm lengths of umbilical cord and 8 cm2 disks of basal placental plate and reflected chorionic amnion were incubated in perfusion chambers, and prostaglandin E2 production was measured by radioimmunoassay. Umbilical cord accounted for the least surface area (16% to 17%) but greatest tissue mass (75% to 76%). Both basal placental plate and reflected chorionic amnion increased prostaglandin E2 production 2.3-fold and 4.1-fold, respectively, after labor versus before labor, whereas umbilical cord prostaglandin E2 output was unchanged. However, umbilical cord accounted for 66% and 44% of the total prostaglandin E2 output before labor (697 +/- 169 ng/hr) versus (1201 +/- 380 ng/hr) after labor. Thus, of the three amniotic locations, umbilical cord represents the principal site of prostaglandin E2 production within the gestational sac.

Amnion↗

Fetal control of maternal prolactin production and bioactivity in utero.

Amniotic fluid prolactin is a product of maternal decidualized endometrium that is derived by translocation of the hormone across the reflected fetal membranes. Amniotic fluids from 26 second-trimester (14 to 23 weeks) and 75 third-trimester (29 to 40 weeks) normal singleton pregnancies were evaluated for prolactin content by radioimmunoassay and bioassay with the Nb2 rat lymphoma cell line. The relative bioactivity was calculated as the ratio of bioassay to radioimmunoassay for each fluid. Data segregated by gestational age and fetal genetic sex identified a highly significant difference (p = 0.0004) in amniotic fluid prolactin radioimmunoassay concentrations (mean +/- SEM) that surround male (682 +/- 49, n = 42) versus female (440 +/- 39, n = 33) fetuses of third-trimester age. Paired bioassay values were significantly lower (p = 0.002) than radioimmunoassay values among males (626 +/- 52) but equivalent (p = 0.1066) among females (464 +/- 44). The bioassay/radioimmunoassay ratios of third-trimester fetal female-associated amniotic fluid prolactin were significantly higher (p = 0.0004) than those of third-trimester males and second-trimester males and females. The results suggest a fetal gender-related factor is associated with both the production and the biologic activity of the maternally derived hormone. Thus the fetus appears to have some control over the dynamics of uterine prolactin production.

Amniotic Fluid↗

Prostaglandin E2 release on the fetal and maternal sides of the amnion and chorion-decidua before and after term labor.

Release of prostaglandin E2 on each of the fetal and maternal sides of the fetal membranes (8 cm2) from term cesarean (no labor) and spontaneous vaginal (labor) deliveries was studied with the use of dual-compartment perfusion chambers. Postlabor amnion released significantly (p less than 0.05) more total prostaglandin E2 (5.66 +/- 1.02 ng, mean +/- SEM) than prelabor tissue (3.34 +/- 1.76 ng) with equivalent prostaglandin E2 levels being released on both sides. A net decrease (p less than 0.001) in prostaglandin E2 release by chorion-decidua was identified after labor (fetal = 0.12 +/- 0.05 ng; maternal = 0.17 +/- 0.09 ng) when compared with that before labor (fetal = 1.28 +/- 0.69 ng; maternal = 2.31 +/- 0.56 ng). Amnion-chorion-decidua released more prostaglandin E2 on the fetal side after labor (2.37 +/- 1.43 ng) than prior to labor (1.49 +/- 0.60 ng); however, prostaglandin E2 on the maternal side was significantly less (p less than 0.05) after labor (0.24 +/- 0.12 ng) when compared with that of the prelabor membrane (2.03 +/- 1.08 ng). Elution of prostaglandin E2 from preincubated membranes and endogenous membrane prostaglandin E2 content showed similar results. Thus concentrations of prostaglandin E2 on the maternal side of the fetal membranes appear diminished after spontaneous labor despite an increased release from the fetal surface.

Amnion↗

Epithelial regulation of prolactin effect on amnionic permeability.

The permeability of human amnion to tritiated water is reduced in the presence of both human and ovine prolactin. The cellular composition of amnion is such that the action of prolactin on this membrane probably occurs by way of the epithelium lining the fetal surface. The present study sought to confirm an epithelial site of action of prolactin on the permeability of amnionic membrane to tritiated water. In addition, radioautography and competition experiments were conducted to determine a possible receptor-mediated mechanism for prolactin action. Membrane permeability to tritiated water was found to be equivalent for both intact membranes and membranes enzymatically stripped of the lining epithelial cells. However, when ovine prolactin was presented to the fetal surface of amnion, only intact membrane displayed decreased permeability to tritiated water. Although localization of iodine 125-labeled prolactin to the light cell population of amniotic epithelium was observed, positive evidence of a receptor-mediated mechanism could not be established. The results indicate that the permeability of human amnion to water is influenced principally by cells of the epithelium in response to prolactin.

Autoradiography↗

Intrauterine insemination for infertility due to cystic fibrosis.

Mild CF is not associated with increased obstetric risk to patients or offspring. These patients can be identified on the basis of Shwachman-Kulczycki scores, nutritional status, normal chest x-ray and pulmonary function tests, normal lung volumes, and mild to moderate airway obstruction. Spontaneous pregnancy has been achieved in women with CF, but they appear to have a decreased fertility. One possible cause in mild disease is a cervical factor due to abnormal viscous mucus. This mucus has been shown to fail to hydrate, and at midcycle contains less than 80% water, whereas 93% to 96% hydration appears to be necessary for sperm migration. Cyclic electrolyte changes in cervical mucus are not noted in CF patients, and sodium concentration in dry residue at midcycle is 10% of normal. Intrauterine insemination with a washed sperm fraction offers a theoretically safe method of bypassing this barrier. Preliminary data have revealed that this may be a useful therapy in other cases of infertility in which the abnormality is an unexplained, negative postcoital test. CF patients should be carefully evaluated and advised of risks before becoming pregnant. In cases of mild CF in which no factor for infertility exists other than consistently abnormal cervical mucus, intrauterine insemination with washed motile sperm may be beneficial. We believe this to be the first case of a CF patient successfully treated in this manner.

Adult↗

Prolactin bioactivity following decidual synthesis and transport by amniochorion.

Current evidence suggests that high concentrations of prolactin in human amniotic fluid result from the transport of human decidual prolactin across reflected amniochorion. In this study, tritiated leucine placed on the isolated maternal side of amniochorion with adherent decidua was incorporated into newly synthesized tritiated human decidual prolactin. Identification of tritiated decidual prolactin on the fetal side of suspended membranes was confirmed within 4 hours of incubation. A heterologous species of human decidual prolactin identified on the maternal side of membranes was also detectable on the fetal side, and its bioactivity was found to be equivalent in both fetal and maternal chambers separated by amniochorion. These results confirm the de novo synthesis of human decidual prolactin and transport by amniochorion to the fetal side. Subsequent to transport, the biologic activity of human decidual prolactin is retained. Thus concentrations and biologic activity of amniotic-fluid prolactin can be accounted for by the transport of newly synthesized human decidual prolactin by the reflected amniochorion.

Amnion↗

Inhibition of fetal membrane prostaglandin production by prolactin: relative importance in the initiation of labor.

Production of a biologically active prolactin by human decidual tissue and its influence on the permeability of amniochorion to water suggests a functional relationship between the polypeptide and fetal membrane metabolism. Under in vitro circumstances, we used ovine prolactin and the Ussing chamber technique to determine the role of prolactin in prostaglandin E2 production by human fetal membrane. Fresh reflected membranes obtained from elective cesarean sections were exposed to ovine prolactin (10 micrograms/ml). Aliquots of incubation media were sampled at 0, 30, 60, 120, and 240 minutes, quick-frozen, and later assayed for prostaglandin E2. Multifactorial analysis of variance revealed that ovine prolactin significantly reduced prostaglandin E2 production (f = 13.42, p less than 0.005). Prostaglandin E2 output was greatest by amnion (3581 +/- 596 pg/ml/gm declining to 1819 +/- 452 pg/ml/gm during 4 hours). Other combinations of fetal membranes including amnion-chorion-decidua produced only 12% to 15% prostaglandin E2 per gram compared with that produced by amnion alone. Those membranes similarly responded to prolactin with a reduction in prostaglandin E2 output of 34% to 59%. Correlation analysis identified a significant relationship between prostaglandin E2 production and time (r = 0.298; p less than 0.001), which was abolished by ovine prolactin (r = 0.115, p greater than 0.10). This model illustrates that ovine prolactin modifies the production of prostaglandin by fetal membranes in vitro. By analogy, endogenous prolactin by human decidual tissue might also inhibit the elaboration of prostaglandin E2 from its precursors residing within the fetal membranes.

Amnion↗

Variances in mucus architecture as a cause of cervical factor infertility.

A cervical factor accounts for 5% to 10% of infertility among women. In the absence of an immunologic or endocrine-related basis for incompetent sperm/mucus interaction, an idiopathic cause is usually ascribed. This study describes quantitative analyses of the microstructure of mucin strands, observed under scanning electron microscopy, from infertile women displaying incompetent sperm/mucus interaction unrelated to any apparent immunologic or endocrine-associated cause. The results revealed a highly significant reduction in the spacing of mucin fibers incompatible to sperm penetrability and migration. Additional quantitative measurements of mucin strand diameter and number and geometry of strand crosslinks suggest inadequate hydration of the mucin gel as a causative basis for the structural inadequacies observed in some cases of cervical-factor infertility.

Cervix Mucus↗

Altered prolactin bioactivity in amniotic fluid of hypertensive pregnancy.

The high concentrations of prolactin (hPRL) in human amniotic fluid appear to be derived principally from maternal decidua. The present study evaluated both the biologic and immunologic activity of amniotic fluid hPRL obtained from normal and selected complicated pregnancies. Biologic and immunologic activities of amniotic fluid hPRL were also compared with lecithin:sphingomyelin ratios and phosphatidylglycerol content. No significant correlation existed between amniotic fluid hPRL activities and fetal lung maturation. However, a significant increase in amniotic fluid hPRL concentration as well as specific biologic activity of the hormone was found in pregnancies complicated by hypertension. These findings suggest alterations in the synthesis of decidual hPRL and/or its transport to the amniotic fluid that may influence pregnancy-induced hypertension.

Amniotic Fluid↗

Simulation of a probable biologic action of decidual prolactin on fetal membranes.

As evidence continues to accumulate supporting a specific effect of prolactin on the permeability of reflected fetal membranes to tritiated water, no information on the role of decidual prolactin in this process is available. Simulation of in vivo events was conducted with the use of isolated membrane preparations of human amnion or chorioamnion with adherent decidua. In the presence of ovine prolactin in equal concentrations on both sides of human amnion, membrane permeability (cm X 10(-4) X sec-1) was reduced from 1.52 +/- 0.16 to 1.18 +/- 0.07 (mean +/- SEM) from the fetal to the maternal surface. Permeability in the opposite direction was significantly increased from 1.15 +/- 0.10 to 1.39 +/- 0.08. No osmotic effect of ovine prolactin was noted. With the use of chorioamnion with adherent decidua, permeability was significantly reduced from the maternal to the fetal surfaces only when ovine prolactin bathed the maternal surface. These in vitro results may suggest that the accumulation of decidual prolactin at the choriodecidual interface in vivo supports bulk water flow across fetal membrane from the amniotic to the maternal compartments.

Biological Transport↗

Ovarian factors inhibit and fetal factors stimulate the secretion of rat placental lactogen.

Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same time, a great increase in serum rPL-II levels is seen. This occurs despite a significant decrease in placental weight. When Ftx14 was performed on day 14 and Ovx was delayed 1, 2, or 3 days, the expected large increase in serum rPL-II was progressively attenuated compared to that seen when Ftx and Ovx were carried out simultaneously. Daily administration of 17 beta-estradiol (4 micrograms/rat X day) to Ftx14 Ovx14 pregnant rats resulted in a significant suppression of rPL-II and elevation of rPRL levels, a reversal of what is seen for these hormones in untreated Ftx14 Ovx14 animals. To test whether 17 beta-estradiol was acting through rat PRL (rPRL), serum levels of rPRL were elevated in Ftx13 Ovx13 animals with pimozide (0.6 mg/kg), a dopamine receptor blocker. There was no effect of this treatment on rPL-II levels. In late pregnancy (day 17) serum rPL-II levels remained high after removal of half the fetuses (1/2 Ftx), compared to the rapid fall in pregnant rats in which all fetuses were removed (Ftx17). Serum levels were also elevated in 1/2 Ftx animals compared to those in which half of the fetuses and placentas were removed by hemi-hysterectomy, suggesting that the increase in rPL-II levels in 1/2 Ftx animals was due to a stimulatory effect of the remaining fetuses on all of the placentas. These results indicate that the presence of the fetus is necessary for the normally observed increase in rPL-II levels in late pregnancy. In conclusion, fetal stimulators and ovarian inhibitors influence rPL-II secretion.

Animals↗

Quantitation of sex chromosomal influence(s) on the somatic growth of fetal gonads in vivo.

Matings between mice carrying the heterozygous autosomal gene Steel produce 25% homozygous Sl/Sld mutants having agametic gonads composed of somatic tissue alone. Mutants show a normal 1:1 male:female sex ratio and gonadal sex corresponds to genotypic sex. Gonads from both normal and mutant male and female fetuses were obtained on a daily basis from the twelfth day of gestation to birth and morphometrically evaluated for determination of the quantitative expression of XY and XX chromosomal combinations on growth of gonadal somatic tissue. Growth of testicular soma was found to be independent of a germ cell influence throughout the entire course of gestation whereas a germ cell influence on growth of ovarian gonadal soma was apparent from day 18 and thereafter. By birth, testicular somatic growth displayed a ten-fold increase over that of the ovary. These results suggest that early gonadal somatic growth is independent of a germ cell influence. The significant impact of a Y-chromosomal influence on gonadal somatic growth may suggest that male-specific gene product(s) regulate growth as well as differentiation of the somatic elements of the fetal testis.

Animals↗

Immunologic and biologic characteristics of human decidual prolactin.

An increasing and consistent production of prolactin by decidual tissue (dhPRL) has been shown during a 24-hour incubation in a chemically defined buffer medium. No difference in dhPRL release was observed in tissue obtained from first- and third-trimester pregnancy. Estradiol had neither a stimulatory nor an inhibitory influence on dhPRL release, although release of this polypeptide by decidual tissue incubated with cycloheximide was blocked. The precise mechanism controlling the production and release of dhPRL is not known. Addition of theophylline, dibutyryl cyclic adenosine monophosphate, or guanosine triphosphate had no effect on dhPRL release during a 4-hour incubation. In contrast, these substances provoked a statistically significant increase in PRL release from rat hemipituitaries coincubated in vitro. Displacement curves for dhPRL against a human PRL standard suggest molecular homogeneity between both hormones. The biologic activity of dhPRL was next confirmed by means of a new bioassay system with a lower level of sensitivity of 20 pg/ml. In addition, dissociation of the biologic and immunologic activity of dhPRL has been completed and suggests that at least three isohormones are produced by human decidual tissue. The dhPRL production rate per gram of decidual tissue wet weight is far below that reported for the pituitary homologue. These studies not only provide confirmatory evidence of the immunologic and biologic activity of dhPRL but also intensify speculation as to its role in human gestation, including that related to osmoregulation across human amnion.

Bucladesine↗

In vivo sex differentiation of congeneic germinal cell aplastic gonads.

Gonads of mice carrying a genetic mutation (Sl/Sld), which results in failure of germinal ridges to become populated by the primordial germ cell line, continue to differentiate according to the genetic sex of the animal. The gonads from fetuses of 11, 12, 13, and 14 days' gestation were examined histochemically and histologically for the presence of germ cells and sex cord formation. In both normal and mutant fetuses, sex differentiation was found to progress according to the genetic sex. Testes from mutant adult male mice display well-developed seminiferous tubules populated by Sertoli cells only. Germinal cell aplastic ovaries have the appearance of streak gonads in that stromal tissue alone is present. These results affirm the concept that gonadal sex differentiation is an inherent function of the somatic gonadal elements, is not dependent upon the presence of the germ cell line, and may further help in explaining the etiology of some cases of germinal cell aplastic gonads.

Animals↗