Perspectives of Immigrant Women on the Gender of Provider During Childbirth.

OBJECTIVE: This study sought to gain an understanding of the importance and effect of provider gender for immigrant women accessing obstetrical care. METHODS: A focused ethnography was conducted using purposive sampling of 38 immigrant women from one hospital in Edmonton, Alberta. Data collection consisted of semistructured interviews conducted antenatally (n = 38); an attempt was made to conduct interviews postpartum (n = 21), and intrapartum observations were made (n = 17). Interviews were audio-recorded and transcribed verbatim. Data were managed using qualitative data analysis software and analyzed through thematic analysis. RESULTS: Study participants came from varied educational and ethnic backgrounds (predominately North/East African, Middle Eastern, and South Asian), but most were Muslim (n = 30) and married (n = 36), with a mean age of 27.7. All of the women stated that they preferred a female provider, which they explained in terms of the high value they placed on modesty, often as part of the Muslim faith. The women deemed provider competency and having safe childbirth more important, however, and said that they would accept intrapartum care from a male provider. A small minority of the women reported experiencing psychological stress as a consequence of having received care from a male provider. CONCLUSION: As a whole, our study population accepted care from male providers, yet for some women this compromise came at a price, and a small minority of women perceived it as profoundly detrimental. There is a need to identify those women for whom gender of provider is a substantial barrier, so that optimal support can be provided.

Gender of Provider-Barrier to Immigrant Women's Obstetrical Care: A Narrative Review.

OBJECTIVE: To explore the preference for female obstetrician/gynaecologists among immigrant women, and providers' understandings of these preferences, to identify challenges and potential solutions. METHODS: Five databases (Medline, Embase, CINAHL, Global Health, and Scopus) were searched using combinations of search terms related to immigrant, refugee, or Muslim women and obstetrics or gynaecological provider gender preference. STUDY SELECTION: Peer reviewed, English-language articles were included if they discussed either patient or provider perspectives of women's preference for female obstetrics or gynaecological care provider among immigrant women in Western and non-western settings. After screening, 54 met inclusion criteria and were reviewed. DATA EXTRACTION: Studies were divided first into those specifically focusing on gender of provider, and those in which it was one variable addressed. Each category was then divided into those describing immigrant women, and those conducted in a non-Western settings. The research question, study population, methods, results, and reasons given for preferences in each article were then examined and recorded. CONCLUSION: Preference for female obstetricians/gynaecologists was demonstrated. Although many will accept a male provider, psychological stress, delays, or avoidance in seeking care may result. Providers' views were captured in only eight articles, with conflicting perspectives on responding to preferences and the health system impact.

The sup-pf-2 mutations of Chlamydomonas alter the activity of the outer dynein arms by modification of the gamma-dynein heavy chain.

The sup-pf-2 mutation is a member of a group of dynein regulatory mutations that are capable of restoring motility to paralyzed central pair or radial spoke defective strains. Previous work has shown that the flagellar beat frequency is reduced in sup-pf-2, but little else was known about the sup-pf-2 phenotype (Huang, B., Z. Ramanis, and D.J.L. Luck. 1982. Cell. 28:115-125; Brokaw, C.J., and D.J.L. Luck. 1985. Cell Motil. 5:195-208). We have reexamined sup-pf-2 using improved biochemical and structural techniques and by the analysis of additional sup-pf-2 alleles. We have found that the sup-pf-2 mutations are associated with defects in the outer dynein arms. Biochemical analysis of sup-pf-2-1 axonemes indicates that both axonemal ATPase activity and outer arm polypeptides are reduced by 40-50% when compared with wild type. By thin-section EM, these defects correlate with an approximately 45% loss of outer dynein arm structures. Interestingly, this loss is biased toward a subset of outer doublets, resulting in a radial asymmetry that may reflect some aspect of outer arm assembly. The defects in outer arm assembly do not appear to result from defects in either the outer doublet microtubules or the outer arm docking structures, but rather appear to result from defects in outer dynein arm components. Analysis of new sup-pf-2 mutations indicates that the severity of the outer arm assembly defects varies with different alleles. Complementation tests and linkage analysis reveal that the sup-pf-2 mutations are alleles of the PF28/ODA2 locus, which is thought to encode the gamma-dynein heavy chain subunit of the outer arm. The sup-pf-2 mutations therefore appear to alter the activity of the outer dynein arms by modification of the gamma-dynein heavy chain.

Synthesis of oxytocin in amnion, chorion, and decidua may influence the timing of human parturition.

Despite the widespread clinical use of oxytocin (OT) as a potent and specific stimulant of labor, previous research data have not supported a role for OT in the physiology of normal human parturition. We have demonstrated synthesis of OT mRNA in amnion, chorion, and decidua using Northern blot analysis, ribonuclease protection assays, and in situ hybridization. Probes directed towards both the 3' and 5' ends of the gene have been used. Levels were highest in decidua with considerably less in chorion and amnion and very low levels in placenta. The transcript size in decidua appears to be 60-80 nucleotides smaller than the transcripts in amnion and chorion. OT gene expression in chorio-decidual tissues increased three- to fourfold around the time of labor onset. Estradiol stimulated synthesis of OT mRNA during in vitro incubation. These results support the hypothesis of a paracrine system involving OT and sex steroids within intrauterine tissues wherein significant changes could occur without being reflected in the maternal circulation. Such a paracrine system could rationalize a long-sought role for oxytocin in the physiology of human labor. These data may lead to novel approaches towards prevention or treatment or preterm labor.

Decidual activation: abundance and localization of prostaglandin F2alpha receptor (FP) mRNA and protein and uterine activation proteins in human decidua at preterm birth and term birth.

OBJECTIVE: To study how the decidua contributes to parturition, we examined prostaglandin F(2alpha) concentrations as well as prostaglandin 15-hydroxy dehydrogenase, prostaglandin F(2alpha) receptor, matrix metalloproteinases 2 and 9, oxytocin receptor, prostaglandin-H synthase-2, and the prostaglandin E(2) receptor expression in human decidua. MATERIALS AND METHODS: Decidual samples were isolated from placentas collected from patients at preterm not in labor (PTNIL), preterm labor (PTL), term not in labor (TNIL), and term labor (TL). For immunohistochemistry, fresh membranes which included chorion, amnion and decidua from term patients were collected. RESULTS: Prostaglandin F(2alpha) receptor mRNA was low in all preterm patients and then significantly increased towards term (p=0.049). Prostaglandin F(2alpha) receptor protein was identified in the amnion epithelium and mesoderm, chorion trophoblasts and decidua by immunohistochemistry, and levels were highest at TNIL (p=0.007) as measured by western blot. Prostaglandin F(2alpha) levels were higher at PTNIL than TNIL. Matrix metalloproteinases 2 and 9 protein and pro-enzyme activities were higher at TL than TNIL. There were no significant changes among the groups for any of the other factors measured. CONCLUSIONS: These results suggest that the induction of Prostaglandin F(2alpha) receptor at term may facilitate the decidua contribution to parturition, and its regulation and role should be examined further.

Accommodating Immigrant Women's Preferences for Female Health Care Providers.

OBJECTIVE: To investigate obstetricians' perspectives of the importance, effect, and challenges of providing intrapartum care to immigrant women who request a female obstetrician. METHODS: A focused ethnography was conducted at a large teaching hospital, which serves a high proportion of immigrant clientele (predominantly North or East African, Middle Eastern, and South Asian) in Edmonton, Alberta, Canada. Data collection comprised single, semistructured interviews with a purposive sample of 20 obstetric health care providers (10 resident and 10 staff obstetricians). Interviews were audio-recorded and transcribed verbatim. Data were managed with Quirkos and analyzed using thematic analysis. RESULTS: A total of 13 female and seven male physicians were interviewed. Physicians recognized the validity of immigrant women's preference and requests for female health care providers and expressed sympathy for them. However, they were also resistant and expressed several concerns about accommodating these requests, including fear of perpetuating and exacerbating gender inequalities in medicine, the extent to which patient decision-making was coercion-free, the ability of the health system to meet the demands, and implications for training and quality of care. CONCLUSION: Although physicians were sympathetic to immigrant women's requests for female obstetricians, they placed greater value on maintaining gender equity both within the medical profession and in wider society and resisted accommodating gender-of-health-care-provider requests. Our qualitative study suggests a need for greater research to inform policy that meets the professional and personal values of both physicians and patients.

Perspectives on the management of the short cervix identified by transvaginal ultrasound during pregnancy: an update for Canadian obstetrical caregivers.

A shortened cervix is often considered to be equivalent to cervical insufficiency, and a cerclage may be offered as an intervention to prolong pregnancy; however, we may not be differentiating between true cervical insufficiency and intrauterine causes of cervical shortening. A recent meta-analysis found no significant reduction in preterm birth < 35 weeks' gestation in women with cerclage compared with no cerclage in the total population of women studied. However, there was a potentially significant reduction in preterm birth < 35 weeks among women with a singleton pregnancy (relative risk [RR] 0.74; 95% confidence intervals [CI] 0.57-0.96), with a singleton pregnancy and a previous preterm birth (RR 0.61; 95% CI 0.40-0.92), and with a singleton pregnancy with a previous mid-trimester loss (RR 0.57; 95% CI 0.33-0.99). An increase was found in preterm birth among twin gestations with cerclage placed for a shortened cervix on transvaginal ultrasound (RR 2.15; 95% CI 1.15-4.01). This unexpected finding underscores the possibility of harm with this intervention. This intervention deserves further study. A national registry or database would allow us to identify women who may benefit more significantly from cerclage by collecting data on possible confounding effects such as concomitant intrauterine infection or placental disease.

Regulation of neural oxytocin gene expression by gonadal steroids in pubertal rats.

We have previously demonstrated that neuronal oxytocin mRNA increases during the pubertal development of female rats. In this paper we have examined the factors that regulate this developmental increase in both male and female rats. Northern blot analysis demonstrated that neural oxytocin mRNA increased 5- to 10-fold from postnatal day 20 (P20) to P60 in animals of both sexes, coincident with puberty. Mature male rats and females at all stages of the estrous cycle expressed similar levels of neural oxytocin mRNA. Pubertal up-regulation of oxytocin mRNA was largely, but not completely, inhibited by prepubescent gonadectomy, indicating a requirement for intact gonads as well as some other as yet undefined factor(s). Pubertal treatment of gonadectomized animals with estradiol or testosterone abolished the effects of gonadectomy; treated animals expressed levels of neural oxytocin mRNA similar to those in controls. However, treatment of prepubertal animals with estradiol or testosterone from P10 to P20 had no effect on oxytocin mRNA levels, suggesting that neural maturation or other factors are necessary requisites for steroid sensitivity. To determine whether neural activin played any role in regulating oxytocin mRNA during puberty, we examined levels of inhibin/activin beta A-chain mRNA. This mRNA was expressed at similar levels in all brain regions and did not vary as a function of gonadectomy or steroid treatment, making it unlikely that activin mediates the observed changes. Together, these data indicate that neural oxytocin mRNA is induced by gonadal steroids during puberty, and suggest a mechanism for coordinating development of reproductive functions with other pubertal changes.

Transcriptional regulation of oxytocin receptor by interleukin-1beta and interleukin-6.

The up-regulation of oxytocin (OT) receptors in late pregnancy results principally from increased synthesis of messenger RNA. The 5'-flanking region of the human OT receptor gene contains several putative binding sites for nuclear factor-interleukin-6 (NF-IL6), also known as CAAT/enhancer binding protein-beta. This trans-acting factor modulates the expression of genes involved in acute inflammatory responses. Proinflammatory cytokines, such as IL-1beta or IL-6, have been implicated as mediators in both preterm and term labor, particularly in association with intrauterine infection. We hypothesized that IL-1beta and IL-6 induce OT receptor gene expression in human myometrial cells, and this is mediated by NF-IL6 and cognate response elements in the 5'-flanking region of the OT receptor gene. Contrary to the hypothesis, both IL-1beta and IL-6 treatment resulted in a significant decrease in OT receptor messenger RNA measured by ribonuclease protection analysis. Using electrophoretic mobility shift assay, we have shown that NF-IL6 is present at low levels that appear to be increased after treatment with either IL-1beta or IL-6. Using deletion analysis and functional transfection studies in HeLa cells, we demonstrated that the OT receptor gene promoter displays constitutive basal activity and is negatively regulated by both IL-1beta and IL-6. This suppressive ability of IL-1beta and IL-6 depends on the -1203/-722 region of the OT receptor promoter, which contains binding sites for NF-IL6, acute phase response element, and NF-kappaB. Our findings suggest a role for IL-1beta and IL-6 in the transcriptional regulation of the human OT receptor gene.

Effects of RU486 on estrogen, progesterone, oxytocin, and their receptors in the rat uterus during late gestation.

Oxytocin (OT) and its receptor (OTR) are synthesized in the endometrium and myometrium of the pregnant rat during late gestation. Both are regulated by estrogen and progesterone (P4), and tissue concentrations of both increase markedly before parturition. The P4 antagonist RU486 will induce parturition in the rat. The purpose of the present studies was to investigate changes in OT and OTR messenger RNA (mRNA) and peptide synthesis within the pregnant rat uterus during RU486-induced parturition. Pregnant rats were given a single injection of RU486 (2.5 mg/rat in oil) on day 15 of pregnancy (normal delivery occurs on day 22). Control animals received injections of oil only. Groups of animals (n = 5 in each group) were euthanized at 0, 6, 12, 24, and 48 h after injection and during labor (immediately after delivery of the first pup). Maternal serum estradiol (E2), P4 and uterine OT, and PGE2 concentrations were measured by RIA. Prostaglandin F2alpha and estrogen receptor levels were measured by enzyme immunoassay (EIA). OTR and P4 receptor (PR) were measured using radioligand-binding assays. OT, OTR, and estrogen receptor mRNAs were measured with ribonuclease protection assays. The average time to delivery, after RU486 injection, was 27.0 +/- 1.2 h. Serum E2 and P4 levels were increased slightly, but significantly, at 24 h after RU486. In controls, OT mRNA increased significantly, and this increase was blocked in the RU486 treatment group. OTR mRNA levels increased within 6 h of RU486 and remained elevated until delivery. OTR peptide was increased by 12 h. PGE2 and PGF2alpha were increased 3-fold and 16-fold, respectively, but not until after the increase in OTR had occurred. We conclude that the mechanism of action of RU486 is to inhibit the P4 suppression of OTR synthesis, allowing increased expression of OTR, which may directly stimulate myometrial contractions or act indirectly through increased synthesis of PGs.

Relationships among sex steroids, oxytocin, and their receptors in the rat uterus during late gestation and at parturition.

Sex steroids and oxytocin (OT) produced within intrauterine tissues have been implicated in the regulation of parturition. The purpose of these studies was 1) to determine the relationships among estradiol (E2), progesterone (P4), OT, and their receptors in uterine tissues during late gestation and parturition in the rat; 2) to observe the effects of the estrogen antagonist tamoxifen (TAM) on these factors; and 3) to evaluate the rat as a potential model for events at human parturition. Concentrations of E2, P4, PGE2, and OT were measured by RIA. E2 receptor (ER) was measured by enzyme immunoassay, and P4 receptor (PR) and OT receptor (OTR) were measured by binding assays. OT messenger RNA (mRNA) was measured by ribonuclease protection assay. Groups (n = 5) of pregnant rats (normal gestation = 22 days) were treated with TAM (200 mg/day) or vehicle and killed on gestation day 19, 21, 21.5, or 22 or after delivery of the first pup. Serum E2 increased throughout late gestation accompanied by an increase in uterine OT mRNA and ER. Serum P4 declined after day 19, and uterine PR did not change significantly. Uterine PGE2 increased progressively, reaching peak levels the evening before delivery. Uterine OTR did not increase until the morning of delivery, and uterine OT peptide concentrations increased only during parturition. Parturition was significantly delayed by 24 h in the TAM-treated group. TAM inhibited the increase in serum E2, uterine ER, and OT mRNA and peptide, but had no effect on serum P4 or uterine PR levels. With TAM, the responses of uterine OTR and PGE2 were significantly delayed, but still underwent a significant increase before the delayed parturition. These results support the hypothesis that E2 stimulates the synthesis of ER, OT, and OTR within the rat uterus and is essential for normal parturition. P4 withdrawal may be more important to the increases in OTR and PGE2, but these are delayed in the absence of estrogen. These data also suggest that the rat may be a relevant model for human parturition.

Androstenedione metabolism in the late gestation sheep fetus.

We have determined metabolic parameters for androstenedione (A) in chronically catheterized late gestation (day 130) sheep fetuses. The MCR (MCRA) was 3210 +/- 229 (SEM, n = 12) ml/min, the fetal arterial whole blood concentration of A [A] was 65 +/- 5 pg/ml, and the blood production rate (PRA) was 204 +/- 20 ng/min. Pulsatile administration of ACTH in amounts that raised fetal arterial plasma cortisol concentrations by 5- to 7-fold increased [A] to 154 +/- 20 pg/ml and PRA to 471 +/- 31 ng/min with no change in MCRA. In the presence of metopirone to block fetal adrenal cortisol output, ACTH treatment still provoked elevations in [A] (to 198 +/- 23 pg/ml) and PRA (539 +/- 158 ng/min), without altering MCRA. The major radiolabeled product in blood of infused [3H]A was [3H]testosterone; smaller amounts of phenolic steroids were formed. Extensive metabolism of [3H]A occurred in whole blood in vitro. The major product was [3H]testosterone; the 17-oxidoreductase activity was associated with the red blood cells. Umbilical vein [A] was greater than umbilical artery [A]; ACTH treatment increased [A] in both vessels. Concomitant metopirone abolished the arteriovenous difference by eliminating the ACTH-induced increase in venous [A], although arterial [A] rose significantly. The venous [A] and the arteriovenous gradient were restored with exogenous glucocorticoid treatment to the fetus. Collagenase-dispersed fetal adrenal cells secreted A. Adrenal cells from fetuses pretreated with ACTH in vivo had higher basal and ACTH-induced output of A in vitro than cells from fetuses pretreated with saline in vivo. We conclude that the MCRA in fetal sheep is extremely high, in part due to conversion of A to testosterone in fetal blood. The elevated PRA after ACTH plus metopirone and the lack of an umbilical arteriovenous gradient of [A] in this, but not other groups of fetuses, suggests a source of A production independent of the cortisol-induced changes in the placenta. Direct evidence is provided for fetal adrenal secretion of A which is enhanced by ACTH pretreatment of the fetus in vivo and for the utilization of circulating A in the fetus as a precursor for estrogen in both fetal and maternal compartments.

Cortisol-cortisone interrelationship in the late gestation rhesus monkey fetus in utero.

The metabolic interrelationship between cortisol (F) and cortisone (E) was studied in four long term catheterized rhesus monkey fetuses in utero during the last third of gestation. The MCR of E (50.8 +/- 5.4 liters/day) was greater than that of F (22.4 +/- 2.1, P less than 0.005) as was the plasma concentration (187.9 +/- 5.0 vs 86.1 +/- 2.5 ng/ml, P less than 0.001). The production rate of E (9.6 +/- 1.4 mg/day) was several-fold greater than for F (1.9 +/- 0.2, P less than 0.005). Of all fetal F, 79.5 +/- 7.0% was metabolized to E, and 43.4 +/- 3.9% originated from E within the fetal circulation. A significant mass of F was infused in these experiments because of the low specific activity of [14C]F. Nevertheless, the fetus was able to maintain F concentrations in the normal range. The MCR of F was similar to that which we previously found using trace amounts of [3H]F. This indicates that the fetus regulates the amount of F in the fetal compartment, probably by decreasing fetal; adrenal secretion rate. We conclude that F in the primate fetus is extensively oxidized to E. We conclude also that E is produced and metabolized much more extensively than is F. Reduction of E back to F could be an important source of fetal F, and increasing activity of this pathway, if present, could contribute to the increase in fetal F levels observed in late gestation in the primate.

Modulation by cortisol of adrenocorticotropin-induced activation of adrenal function in fetal sheep.

We examined the hypothesis that cortisol (F) modulates the activation of adrenal function induced by treating fetal sheep in vivo with pulsatile ACTH (P-ACTH). Chronically catheterized sheep fetuses were infused in utero for 100 h between day 127 and day 131 of pregnancy with P-ACTH; P-ACTH plus metopirone; P-ACTH plus metopirone plus F; P-ACTH plus metopirone plus dexamethasone, or saline (controls). After 100 h, basal and ACTH-stimulated output of 11-desoxycortisol (S), F, and progesterone from collagenase-dispersed fetal adrenal cells was measured. Adrenal cells from fetuses treated with P-ACTH in vivo had significantly greater basal and stimulated (delta) outputs of F and S in vitro than controls. These effects were attenuated in fetuses pretreated with P-ACTH plus metopirone. Concurrent in vivo treatment with ACTH plus metopirone plus F restored basal and delta outputs of F and S to values that were not significantly different from those after P-ACTH alone. In vivo treatment with dexamethasone in addition to P-ACTH plus metopirone significantly raised basal outputs of F and S, but the cells were unresponsive to ACTH in vitro. Basal output of progesterone was significantly greater after in vivo P-ACTH plus metopirone plus dexamethasone, but no treatment raised delta progesterone output over controls. These results support a role for glucocorticoids in modulating ACTH-induced activation of adrenal function in late gestation fetal sheep.

Activation of ovine fetal adrenal function by pulsatile or continuous administration of adrenocorticotropin-(1-24). I. Effects on fetal plasma corticosteroids.

ACTH given as a continuous infusion to fetal sheep causes an increase in plasma cortisol concentrations and premature labor. However, the effects on fetal adrenal responsiveness in vivo and the mode of ACTH administration on plasma corticosteroids are unknown. We examined the effects on plasma corticosteroids of giving the same total amount of ACTH to fetal sheep in utero either as pulses (P-ACTH; 66.7 ng/min for 15 min every 2 h) or continuously (C-ACTH; 0.5 micrograms/h) for 72 h. We determined the changes in vivo in fetal adrenal responsiveness during P-ACTH treatment, and we examined the ability of continued P-ACTH administration to induce premature labor. Both modes of ACTH administration led to a significant (P less than 0.05) increase in the fetal plasma cortisol (F) concentration compared with that in saline-treated controls, but C-ACTH resulted in significantly higher (P less than 0.05) F values than P-ACTH treatment. There was a small increase in the F-binding capacity of fetal plasma during both P-ACTH and C-ACTH, but there was no difference in the cortisol-binding capacity between the two treatments. Twenty minutes from the start of P-ACTH, there was an acute elevation in plasma F to values similar to those found with C-ACTH administration. The magnitude of this response rose significantly (P less than 0.05) between days 1-4 of P-ACTH treatment. There was no significant change in fetal plasma corticosterone during either P-ACTH or C-ACTH, resulting in a 4- to 6-fold increase in the plasma F to corticosterone ratio of both groups. In animals in which P-ACTH treatment was continued beyond 72 h, fetal plasma F continued to rise, and premature labor occurred after 99.0 +/- 4.1 (+/- SE) h. Fetal adrenal weights were not significantly different between P-ACTH for 72 or 100 h or C-ACTH for 72 h, although in each of these groups, the glands were heavier than those in control fetuses. We conclude that activation of fetal adrenal function is demonstrable in vivo during P-ACTH administration. This is reflected by selective F hypersecretion and may lead to premature delivery.

Steroid sulfohydrolase activity in human chorion. I. Interactions of other steroids with estrone sulfate as substrate.

Human chorion contains steroid sulfohydrolase activity and synthesizes free estrogens from estrone sulfate (E1S). We hypothesized that the free estrogen thus formed may influence the contractility of the adjacent myometrium in late pregnancy. In this study we measured the abilities of various steroids and steroid conjugates to influence the hydrolysis of E1S by the 105,000 x g pellet of chorion tissue obtained from women after spontaneous onset of labor and vaginal delivery and from women delivered by cesarean section before labor onset. No differences were found in tissues obtained before or after the onset of labor. None of the steroids increased the rate of hydrolysis. Several unconjugated steroids caused significant inhibition, but only at concentrations well beyond physiological ranges in maternal or fetal blood. However, conjugated steroids had marked inhibitory effects at circulating concentrations. At equimolar concentrations with the E1S substrate, the sulfoconjugates of dehydroepiandrosterone, pregnenolone, and cholesterol caused 27 +/- 1% (+/- SE), 64 +/- 1%, and 40 +/- 1% inhibition, respectively. These results were confirmed using a tissue explant system. Using enzyme inhibition kinetic analysis, we determined that the inhibition by dehydroepiandrosterone sulfate was non-competitive, with Ki = 8.7 +/- 1.7 mumol/L. The inhibition by pregnenolone sulfate was competitive, with Ki = 1.6 +/- 0.4 mumol/L, and that by cholesterol sulfate was primarily noncompetitive, with Ki = 7.4 +/- 1.2 mumol/L. We conclude that there is significant interaction among sulfurylated steroids that may influence local free estrogen synthesis within human chorion. This interaction may affect the contractility of the late pregnancy myometrium.

Metabolism of oxytocin in human decidua, chorion, and placenta.

Oxytocin (OT) synthesized within human decidua may influence the timing of human parturition. Metabolism of OT within intrauterine tissues may regulate local concentrations. We hypothesized that a decrease in OT metabolism may contribute to an increase in local tissue concentrations around the time of parturition. Thus, we compared OT degradation in human decidua with that in chorion and placenta obtained before or after labor onset at term. We measured kinetic parameters for OT metabolism and determined pathways of degradation. Both cytosol and microsomal fractions contained aminopeptidase and postproline endopeptidase activities. Metabolism in the microsomal fractions was predominantly by an aminopeptidase enzyme that cleaves the ring structure of OT and removes amino acid residues from the N-terminal end. Metabolism in the cytosol fractions was predominantly via postproline endopeptidase activity, which cleaves the C-terminal Leu8-Gly9NH2. The resultant OT-(1-7) also is a substrate for aminopeptidase activity. The apparent maximum velocities of OT metabolism in the cytosol subcellular fractions of decidua (0.87 +/- 0.30 nmol/mg protein.min) and chorion (1.04 +/- 0.47) were significantly (P < or = 0.05) higher than those in corresponding microsomal fractions (0.17 +/- 0.05 and 0.29 +/- 0.10, respectively). Placental cytosols (1.08 +/- 0.34) were similar to decidua and chorion, but the microsomal fractions had significantly greater activity (0.82 +/- 0.22). The Km values for all tissues were in the range of 8-20 mumol/L. There were no significant changes in the kinetic parameters for OT metabolism around the time of labor onset. We conclude that human decidua and chorion as well as placenta actively metabolize OT, but changes in metabolism do not occur around parturition. If increasing decidual concentrations of OT play a role in the timing of human labor onset, mechanisms that increase production or secretion are of primary importance.

Steroid sulfohydrolase in human chorion and decidua: studies using pregnenolone sulfate and dehydroepiandrosterone sulfate as substrate.

Human chorion and decidua use pregnenolone sulfate (P5S) and dehydroepiandrosterone sulfate (DHAS) as substrates for local estrogen and progesterone synthesis. We hypothesized that the local estrogen/progesterone ratio may influence contractility of the adjacent myometrium and hence effect the timing of parturition. Thus, we studied steroid sulfohydrolase activity for P5S in these tissues and investigated the potential interaction of other steroids on the rates of hydrolysis of P5S and DHAS. The enzyme was present in both tissues, predominantly in the microsomal fraction. With P5S as substrate, the Michaelis-Menten constant (Km) was similar in chorion (1.3 +/- 0.2 mumol/L, mean +/- SEM) and decidua (0.9 +/- 0.1 mumol/L) but the maximum velocity (Vmax) was significantly greater in chorion (2.6 +/- 0.4 vs. 1.1 +/- 0.3 nmol/mg protein/15 min, P less than 0.05). In both tissues there was a tendency towards greater activity in tissues obtained before labor compared to tissues obtained after spontaneous labor onset. Using either DHAS or P5S as substrate, there was significant inhibition of sulfohydrolase activity by other steroids at concentrations similar to those in late pregnancy fetal and maternal plasma. In microsomal preparations using DHAS as substrate, activity was inhibited by equimolar concentrations of estrone sulfate (E1S, by 38 +/- 2%), P5S (by 74 +/- 2%), and cholesterol sulfate (C27S, by 38 +/- 3%). With P5S as substrate, equimolar concentrations of E1S, DHAS, and C27S caused inhibition of sulfohydrolase activity by 19 +/- 5%, 16 +/- 4%, and 18 +/- 2%, respectively. These inhibitory effects also were observed using a tissue explant system with intact cells. In kinetic inhibition studies using DHAS as substrate, E1S and P5S were competitive inhibitors with inhibition constants (Ki) of 4.8 +/- 1.3 and 0.7 +/- 0.1 mumol/L, respectively. Using P5S as substrate, E1S and DHAS also were competitive inhibitors with Ki values of 8.2 +/- 2.1 and 9.6 +/- 1.2 mumol/L, respectively. For both substrates, the pattern of inhibition by C27S was complex. Preliminary experiments to distinguish, on the basis of differing physical-chemical properties, separate enzymes for different substrates were inconclusive. We conclude that human chorion and decidua can hydrolyze several steroid sulfoconjugates and this activity may regulate local estrogen and progesterone synthesis. There are significant interactions among steroid sulfoconjugates in regulating this activity. These activities may be important components of a paracrine system that determines myometrial contractility and the timing of parturition.

Sulfohydrolase activity for estrone sulfate and dehydroepiandrosterone sulfate in human fetal membranes and decidua around the time of parturition.

We examined the distribution and kinetic parameters of sulfohydrolase activity in human amnion, chorion, and decidua using estrone sulfate (E1S) and dehydroepiandrosterone sulfate as substrates. Amnion contained low levels of sulfatase activity. Chorion had active sulfohydrolase activity for both substrates, but a significantly greater maximum velocity (Vmax) for E1S. The Km was not different between the two substrates. However, there was a slight but statistically significant decrease in Km and increase in Vmax for sulfohydrolase activity using E1S in chorion from patients delivering vaginally after the spontaneous onset of labor compared to those delivering by elective cesarean section before the onset of labor but at a similar gestational age. Decidua possessed sulfohydrolase for E1S with similar Km and Vmax as chorion. There were no changes occurring around the onset of labor. Using dehydroepiandrosterone sulfate as substrate, the decidua had a similar Km as the chorion, but its Vmax was significantly less. In both tissues for both substrates, the enzyme had highest specific activity in the 105,000 X g pellet, with almost no activity in the soluble fraction. The greatest total sulfohydrolase activity was contained in the 800 X g pellet despite several methods of homogenization and washing of the 800 X g pellet. We conclude that the sulfohydrolase activity of human chorion and decidua may be an important factor in regulating free steroid levels within the pregnant uterus. The significant change in the kinetic parameters of E1S sulfatase may partially explain the increased ability of chorion to hydrolyze E1S which occurs in association with the spontaneous onset of labor.

The dynamics of prostaglandin metabolism in human fetal membranes and decidua around the time of parturition.

To address whether prostaglandins (PGs) produced in the amnion can gain access to the myometrium, we used three in vitro systems to determine the characteristics of PG secretion, metabolism, and transfer in amnion, chorion, and decidua around the time of parturition. PG metabolism, measured in explant cultures or cytosol preparations, occurs predominantly by the enzyme PG dehydrogenase, which was highest in chorion and was 2- to 3-fold more active for PGE2 than PGF2 alpha. The activity increased significantly around the time of labor onset. The activity of PG-9-ketoreductase, which interconverts the E and F series of PGs, was 2-3 orders of magnitude less than that of PG dehydrogenase. Using a dual chamber perfusion apparatus, we demonstrated that similar amounts of PGE2 were secreted from the fetal (amnion) and maternal (chorio-decidua) surfaces, and this ratio did not change with labor. Using radiolabeled PGE2, radioactivity traversed full thickness membranes at the rate of 4%/h. Only approximately 12% of the transferred radioactivity remained as intact PGE2, and very little conversion to PGF2 alpha was detected. No changes in transfer were detected around the onset of labor. We conclude that it is unlikely that PGE2 produced in the amnion acts directly on the myometrium.