Biomedical subjects

S C Riley

Publications and source records attributed to S C Riley.

At least 37 records · Page 2Linked to original sources

PubMed1999

Matrix metalloproteinases-2 and -9 and their inhibitors are produced by the human uterine cervix but their secretion is not regulated by nitric oxide donors.

We have investigated the presence of matrix metalloproteinases (MMP)-2 and -9 and their tissue inhibitors (TIMP) in the human uterine cervix. We postulate that during the process of cervical ripening, there is an increase in the activity of MMP in order to facilitate cervical connective tissue change. We have previously demonstrated that nitric oxide (NO) donors induce cervical ripening in vivo. A secondary hypothesis is that NO donors regulate MMP activity within the human uterine cervix. Cervical tissue biopsies were obtained from both pregnant and non-pregnant subjects. Cervical fibroblasts were cultured from the non-pregnant tissue. MMP-2 was present in conditioned media from pregnant and non-pregnant cervical explants and non-pregnant cervical fibroblasts. MMP-9 secretion was only detected in explants from non-pregnant women. TIMP-1, -2 and -4 were released by all cervical explants and fibroblast preparations. Pregnant women, in the first trimester, were treated with an NO donor (isosorbide mononitrate) in vivo. Cervical explants and fibroblasts from non-pregnant women were treated with the NO donor spermine nonoate in vitro. Treatment with an NO donor either in vivo or in vitro had no effect on the secretion of the MMP or TIMP studied. Further studies evaluating the mechanisms involved in cervical ripening are required.

Cells, Cultured↗

PubMed1999

Secretion of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases into the intrauterine compartments during early pregnancy.

Matrix metalloproteinases (MMPs) are important enzymes in tissue remodelling, a key event for the development of the fetal membranes and placenta and establishing the feto-maternal interface during early pregnancy. This study has examined the secretion of the gelatinases, MMP-2 (72 kDa) and MMP-9 (92 kDa), and the endogenous tissue inhibitors of metalloproteinases (TIMPs) into extra-embryonic coelomic and amniotic fluids, the two principal intra-uterine compartments of the first trimester, and compared them to amniotic fluid collected later in gestation. In extra-embryonic coelomic fluid, gelatin zymography demonstrated that MMP-2 (72 kDa) was the predominant gelatinase, with some MMP-9 present. A broad range of TIMPs corresponding to TIMP-1 and TIMP-2, glycosylated and unglycosylated TIMP-3 and TIMP-4 was detected in this compartment by reverse zymography and immunoblot analyses. There was little gelatinase or TIMP activity in amniotic fluid in the first trimester. In amniotic fluid from the second trimester after fusion of the membranes obliterating the extra-embryonic coelom, and at term elective caesarean section, MMP-2 is the predominant gelatinase present, with a broad spectrum of TIMPs. These findings demonstrate that predominantly MMP-2 and also MMP-9, regulated by a range of TIMPs, are involved in intra-uterine tissue remodelling during the establishment of pregnancy.

Adult↗

PubMed1999

A feasibility study of adolescent sex education: medical students as peer educators in Edinburgh schools.

OBJECTIVES: To determine the feasibility of medical students being involved in sex education in secondary schools, as lesson leaders in peer group discussions. DESIGN: 1. Questionnaires and interviews to determine pupil and professional opinions about the present sex education provision and the possible involvement of medical students. 2. A pilot scheme in one school involving medical students as peer educators. SETTING: Six central Edinburgh secondary schools; local sex education services; Edinburgh University. SAMPLE: 1. Thirty schoolteachers and 205 pupils returned questionnaires. From this, 18 teachers and 12 pupil groups (six to eight pupils each) were interviewed. 2. Pilot scheme involved three sessions with three groups of six to eight pupils per session. Twenty-nine returns for the evaluative (pupil) questionnaire were received. MAIN OUTCOME MEASURES: Questionnaire analysis; anecdotal evidence from interviews; evaluative questionnaire given to pupils participating in pilot study. RESULTS: Ninety-four percent of teachers and 93% of pupils were in favour of medical student involvement in schools. Teachers identified large class size and lack of resources for small group work as factors limiting the effectiveness of present sex education. Pupils identified teacher embarrassment in certain issues as a barrier to communication, and 89% found communication to be easier with medical students. CONCLUSIONS: Response to the idea of medical student involvement was very favourable from all parties involved, and a continuation of the study has been integrated as an options course into the Edinburgh University undergraduate medical curriculum.

Adolescent↗

PubMed1999

Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus.

Secretory leukocyte protease inhibitor is a potent inhibitor of neutrophil function, a mediator of mucosal immunity and an inhibitor of NF|gkB regulated inflammatory responses. However, its source, function and regulation within the uterus during pregnancy and at parturition are not well defined. In amniotic fluid, the concentration of secretory leukocyte protease inhibitor increased significantly from 2nd trimester (24+/-3 ng/ml; mean+/-s.e.m.; n=20) to term (751+/-53 ng/ml; P<0.05; n=15) with a further profound increase (P<0.005) with the onset of labour (3929+/-1076 ng/ml; n=15). To establish the intra-uterine sites of secretion, explants (n=6 different patients per tissue) were collected at term after elective caesarean section. High levels of secretory leukocyte protease inhibitor were released by decidua (135.2+/-12.4 pg/mg; mean+/-s.e.m.) and chorio-decidua (325.1+/-26.4 pg/mg) with less by amnion (55.6+/-6.0 pg/mg) and placenta (9.2+/-1.9 pg/mg). Intense immunoreactivity for secretory leukocyte protease inhibitor was detected predominantly in decidua parietalis cells adherent to the chorion laeve and myometrium, and also in decidua basalis. We propose that, within the pregnant uterus, secretory leukocyte protease inhibitor is released by decidua, fetal membranes and potentially the fetal lung. The increase in secretory leukocyte protease inhibitor may act to modulate pro-inflammatory paracrine interactions for the maintenance of pregnancy and limit those occurring at parturition within the uterus.

Amnion↗

PubMed1999

Secretion of tissue inhibitors of matrix metalloproteinases by human fetal membranes, decidua and placenta at parturition.

At parturition, breakdown of extracellular matrix in the fetal membranes may play a part in the rupture of the membranes and in the aetiology of premature rupture, in addition to having a regulatory role in the cell-cell interactions and signalling at the feto-maternal interface to stimulate myometrial contractility. The matrix metalloproteinases (MMPs) are important enzymes for the breakdown of extracellular matrix and their activity is regulated by a family of endogenous inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs). At parturition, alteration in the balance between MMPs and TIMPs may mediate this extracellular matrix breakdown during rupture of fetal membranes. The aims of this study were to determine if the intrauterine secretion of TIMPs changes at labour, and to characterise their cellular sources. A broad range of TIMP activities (27-30 kDa, 24 kDa and 21 kDa) were detected by reverse zymography in term amniotic fluid. There was a significant (P<0.05) decrease in the amount of TIMPs in amniotic fluid and their release with the onset of labour. The TIMPs were characterised by immunoblot as TIMPs-1, -2, -3 and -4. High levels of TIMPs were secreted by explants of chorio-decidua, decidua parietalis and placenta, with less being released by amnion. Immunolocalisation studies revealed a specific distribution pattern for each of the TIMP isoforms. Trophoblast cells of chorion laeve, decidua parietalis and placental syncytiotrophoblast demonstrated specific immunoreactivity for all four isoforms. TIMPs were also found bound to selective regions of extracellular matrix. The decrease in TIMPs during labour may permit increased breakdown of extracellular matrix in the fetal membranes and decidua at parturition, thus altering cell signalling at the feto-maternal interface and facilitating membrane rupture.

Amniotic Fluid↗

PubMed1999

Cytokines and the regulation of apoptosis in reproductive tissues: a review.

PROBLEM: To determine the role of apoptosis-regulating genes bax and bcl-2 in reproduction. METHOD OF STUDY: Review of literature and current data. RESULTS: The bcl-2 family of apoptotic regulatory gene products interact and form dimers of anti- and pro-apoptotic proteins (e.g., bcl-2 and bax respectively), the ratio of which determines cell death or survival. Menses is associated with increased apoptosis in the glands, a change in bcl-2:bax ratio and increased levels of the pro-apoptotic cytokine TNFalpha. Apoptosis occurs in all placental cell types and increases from first to third trimester. Placental apoptosis is induced by TNFalpha in vitro and increased levels in utero characterize most failing pregnancies, intra-uterine growth restriction (IUGR) and labour. An increased bcl-2:bax ratio and apoptosis in the syncytiotrophoblast characterizes failing first trimester pregnancies. Apoptosis in the syncytiotrophoblast is also associated with IUGR. In a rat model, maternal vitamin A deficiency perturbs fetal development. This is associated with a placental infiltrate of TNFalpha positive neutrophils (day 20) and increased placental apoptosis in areas of infiltration. A similar infiltrate occurs in a mouse model of early pregnancy loss. In the fetal membranes, clusters of bcl-2 negative chorion trophoblast cells undergo apoptosis. This may allow passage of myometrial stimulatory factors that induce labour. CONCLUSION: The ratio of bcl-2:bax is crucial in the regulation of apoptosis, particularly in the human placenta. Changes in trophoblast apoptosis characterize (1) early pregnancy failure, (2) IUGR and (3) pre-term and term labour. Regardless of gestational age, TNFalpha plays a major role in the induction of placental apoptosis.

Animals↗

PubMed1998

Regulation of interleukin 8 production in the term human placenta during labor and by antigestagens.

OBJECTIVE: Our purpose was to assess the effects of labor and antigestagens on production of interleukin 8 by the term human placenta and to localize interleukin 8 in first- and third- trimester placentas. STUDY DESIGN: The study was conducted by the Department of Obstetrics and Gynaecology of the University of Edinburgh. Five placentas were collected after spontaneous and cesarean deliveries. Explants were cultured in the presence of mifepristone, lilopristone, or onapristone. The production of interleukin 8 was determined by specific radioimmunoassay, and the immunolocalization of interleukin 8 was determined in sections of first- and third-trimester placentas. RESULTS: All explants produced interleukin 8. Production was significantly increased (P < .05) after spontaneous delivery. In placentas delivered spontaneously, onapristone significantly increased production of interleukin 8 (P < .05), whereas in those from cesarean deliveries lilopristone caused a significant increase in production (P < .05). In the third-trimester placenta interleukin 8 was localized in the perivascular area of fetal vessels. In first-trimester villi it was peripherally located in syncytiotrophoblast. CONCLUSION: The human placenta at term is capable of producing interleukin 8, which is localized around the perivascular area of the villi. Production is increased after spontaneous labor and to varying degrees by the antigestagens studied. Interleukin 8 may have a role in the onset of parturition by recruiting and activating neutrophils at the placental site.

Culture Techniques↗

PubMed1998

Follistatin and activin A production by the male reproductive tract.

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.

Activins↗

PubMed1998

Cytokine secretion by human fetal membranes, decidua and placenta at term.

Cytokines such as monocyte chemotactic peptide-1 (MCP-1), interleukin-8 (IL-8), RANTES (Regulated on Activation and Normally T-cells Expressed and presumably Secreted) and interleukin-10 (IL-10) are thought to play pivotal roles in immune recognition, acceptance of the fetal allograft, maintenance of pregnancy and parturition. Their secretion and regulation within the third trimester uterus is, however, less well defined. We therefore investigated the release of these cytokines by third trimester amnion, chorion, placenta and decidua, and studied the influence of prostaglandin E2 (PGE2) infusion on their release in a dynamic placental cotyledon perfusion system. MCP-1 was released predominately by the chorion (78.2 +/- 7.3 pg/mg wet tissue weight; mean +/- SEM), decidua (112.4 +/- 5.2 pg/mg) and placenta (101.8 +/- 5.0 pg/mg) with low amounts from the amnion (1.3 +/- 0.4 pg/mg). High concentrations of IL-8 were released by the amnion (39.9 +/- 5.3 pg/mg), chorion (52.8 +/- 1.9 pg/mg), decidua (42.2 +/- 1.5 pg/mg) and placenta (45 +/- 1.3 pg/mg). Release of RANTES was not detectable from the amnion but was detected in moderate amounts from the chorion (6.0 +/- 1.2 pg/mg), decidua (15.2 +/- 1.4 pg/mg) and placenta (26.9 +/- 1.6 pg/mg). Low concentrations of IL-10 were secreted by the chorion (6.8 +/- 0.8 pg/mg), decidua (9.0 +/- 0.9 pg/mg) and placenta (3.3 +/- 0.3 pg/mg) with none detectable from the amnion. MCP-1, IL-8, RANTES and IL-10 were all released by perfused placental cotyledons. PGE2 stimulated release of MCP-1, IL-8 and IL-10 into the maternal and of MCP-1 and IL-8 into the fetal circulation of the placenta but had no effect on RANTES release. It is suggested that MCP-1 and IL-8 may be involved in the inflammatory process of parturition and IL-10 in the protection of the fetal allograft. In addition, PGE2 may have an important immunomodulatory role within the uterus at term.

Culture Techniques↗

PubMed1998

Inhibin B in seminal plasma: testicular origin and relationship to spermatogenesis.

In men, inhibin B is the circulating isoform involved in the regulation of follicle stimulating hormone (FSH) secretion. Within the testis, inhibin B may have a role in Sertoli and germ cell interactions, thus secretion into seminal plasma may reflect seminiferous tubule function. Using specific immunoassays, inhibin B was present in seminal plasma in fertile men (n = 105) and in unselected men attending an infertility clinic (n = 174) with a wide range in concentration from undetectable (<15 pg/ml) up to 54,100 pg/ml (geometric mean 280 pg/ml). There was a highly significant correlation between seminal plasma inhibin B concentration and sperm concentration (r = 0.46, P < 0.001), but no correlation with percentages of spermatozoa with progressive motility or normal morphology. Inhibin A and isoforms containing pro and alphaC immunoreactivity were not detectable. In post-vasectomy seminal plasma samples (18 of 20) inhibin B was undetectable, indicating that the testis is the predominant source. In unselected men attending an infertility clinic, inhibin B was undetectable in 17% (present in remainder; maximum concentration 26,200 pg/ml; mean 263 pg/ml), with a highly significant correlation between seminal plasma inhibin B and sperm concentration (r = 0.55, P < 0.0001). In men with oligo/ azoospermia (sperm concentration <20 x 10(6)/ml), seminal plasma inhibin B concentrations were lower in those with elevated plasma FSH concentrations (mean values 42 and 205 pg/ml, P < 0.05). Inhibin alpha and betaB subunits were localized predominantly in Sertoli and Leydig cells, using immunohistochemistry. We conclude that inhibin B of testicular origin is present in normal human seminal plasma, but with a very wide range in concentration, and may reflect the functional state of the seminiferous epithelium.

Adult↗

PubMed1998

Differential concentrations of monocyte chemotactic protein-1 and interleukin-8 within the fluid compartments present during the first trimester of pregnancy.

Monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) are important chemokines which effect the chemotaxis of monocytes and neutrophils, respectively. There is increasing evidence that such chemokines play an integral role in the control and maintenance of a normal pregnancy from implantation to parturition. However, little is known about the sites of secretion and function of MCP-1 and IL-8 in particular with respect to establishment of the placenta and membranes during first trimester. The aim of this study was therefore to investigate the concentrations and localization of MCP-1 and IL-8 in amniotic fluid and extra-embryonic coelomic fluid (EECF) collected by ultrasound-guided needle aspiration and maternal serum during the first trimester of pregnancy. Using specific enzyme-linked immunosorbent assays, MCP-1 was present at high concentrations in the EECF, significantly higher than those in amniotic fluid and maternal serum. IL-8 was also present predominantly in the EECF with concentrations being significantly higher than the low values detected in maternal serum and the very low amounts found in amniotic fluid. This strict compartmentalization of these cytokines in the fluid compartments of early pregnancy may be important for establishment and development of a viable pregnancy.

Amniotic Fluid↗

PubMed1998

Follistatin and activin A in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy.

Follistatin is a specific binding protein which controls bioavailability of activins and inhibins which have an important role in fetal development. In the first trimester of pregnancy bioactive dimeric inhibins are found at high concentrations in the extra-embryonic coelomic fluid, but the distribution of follistatin and activins is not known. We have used recently developed immunoassays for follistatin, activin A and activin AB to determine their presence in the intrauterine compartments during early pregnancy. Follistatin was present in highest concentrations in the extra-embryonic coelomic fluid (11.72 +/- 1.70 ng/ml; median +/- SEM), with less in maternal serum (6.35 +/- 4.58) and lowest amounts in amniotic fluid (0.97 +/- 0.52). Follistatin concentrations in extra-embryonic coelomic fluid were highly correlated with both dimeric inhibin isoforms. Activin A was present in only barely detectable amounts in some samples of extra-embryonic coelomic fluid (41% of samples) and maternal serum (26%) and was undetectable in all amniotic fluid samples. Activin AB was undetectable in all compartments. The presence of follistatin in the amniotic and extra-embryonic coelomic fluids may regulate the availability of bioactive activins and inhibins which are released into the intrauterine compartments during the development of the fetus and placenta in early pregnancy.

Activins↗

PubMed1998

Inhibin-B and pro-alphaC-containing inhibins in amniotic fluid from chromosomally normal and Down syndrome pregnancies.

In second-trimester Down syndrome pregnancies, levels of inhibin-A (the alpha-betaA dimer) in maternal serum and amniotic fluid (AF) are significantly higher and lower than in normal pregnancy, respectively. Since AF also contains inhibin-B (the alpha-betaB dimer) and precursor inhibins, we have examined whether the secretion of these inhibin isoforms may also be altered in association with Down syndrome. AF from 45 Down syndrome and 150 chromosomally normal pregnancies between 16 and 19 weeks' gestation were analysed, blinded to whether the sample was from a Down syndrome or a normal pregnancy. The median (10th-90th percentiles) inhibin-B level in the control pregnancies increased from 310.0 (80.8-1112.5) pg/ml at 16 weeks to 459.5 (193.7-1386.8) pg/ml at 19 weeks' gestation. The corresponding figures for precursor inhibins (pro-alphaC inhibins) were 541.8 (206.9-1322.8) pg/ml at 16 weeks and 1391.8 (433.3-2652.6) pg/ml at 19 weeks. Expressed as multiples of the median (MOM), the levels of inhibin-B and pro-alphaC inhibins in the Down syndrome samples were 0.85 and 0.79, respectively. Neither was significantly different from the controls. These data suggest that, of the three inhibin subunits, abnormal production or secretion of the inhibin betaA-subunit may underlie the decreased inhibin-A levels previously observed in Down syndrome. Confirmation of this by quantitative assessment of the inhibin subunit messenger ribonucleic acids would now be useful.

Amniocentesis↗

PubMed1997

The inhibition of synthesis of a beta-chemokine, monocyte chemotactic protein-1 (MCP-1) by progesterone.

The control of chemokines in reproductive tissues has not been well characterised. Progesterone plays a major part in many reproductive processes and an interaction between progesterone and the immune system has been postulated. MCP-1 is a beta chemokine that attracts and activates macrophages, controls vascular smooth muscle cells, and can modulate T helper cell cytokine production. MCP-1 may also play a role in reproductive processes such as ovulation and parturition. MCP-1 synthesis is stimulated by the transcription factor NF-kappa B and is inhibited by glucocorticoid but the relevance of progesterone control in reproductive tissue is unknown. The effects of progesterone on the production in both choriodecidual cells and a breast cancer cell line T47D, which expresses an oestrogen insensitive progesterone receptor, were investigated. A synthetic progestin (medroxyprogesterone acetate) inhibits choriodecidual cell production of MCP-1; this inhibition was reversed by the antiprogestin RU486. MCP-1 release from T47D cells can be stimulated by IL-1 and this production is inhibited by progesterone with an ED50 of less than 10(-9) M. A glucocorticoid (dexamethasone) had no effect on MCP-1 release in this system, suggesting that glucocorticoid receptor-mediated responses were impaired under these conditions. These results demonstrate that an indirect effect of progesterone on the immune system is possible in reproductive tissues, whereby the initial effect of progesterone on epithelial or fibroblast cells would be transmitted to leukocytes.

Breast Neoplasms↗

PubMed1997

Dimeric inhibins in amniotic fluid, maternal serum, and fetal serum in human pregnancy.

Using new specific and sensitive enzyme-linked immunosorbent assays for inhibin A and inhibin B, we measured these proteins in amniotic fluid (AF), maternal serum (MS), and umbilical cord serum in normal pregnancies. Inhibin A levels in AF rose from a median (10-90th percentile) level of 615 (158.2-1124.6) pg/mL at 14 weeks to 1336.0 (489.4-2084.1) pg/mL at 20 weeks, and inhibin B rose from 216.6 (67.4-554.6) to 1078.2 (439.3-2482.2) pg/mL over the same period. In MS, inhibin A levels fell from a median (10-90th percentile) level of 177.5 (101.4-290.7) pg/mL at 10 weeks to a nadir of 111.9 (59.5-200.3) pg/mL at 17 weeks, rising again to 180.3 (74.1-327.2) pg/mL at 20 weeks. No inhibin B was detectable in MS. In 47 pairs of matched samples (14-16 weeks gestation) there was no correlation of inhibin A levels in AF with those in MS (r = 0.19; P > 0.05). In 45 term umbilical cord serum samples, no dimeric inhibin was detectable in serum from female babies, but inhibin B was detectable in male sera; the median (10-90th percentile) concentration was 167.4 (111.2-224.8) pg/mL. These data suggest that for the gestation periods studied, although the placenta secretes inhibin A, another source, probably the fetal membranes, secretes both inhibin A and inhibin B. Further, the presence of inhibin B in male fetuses is consistent with a testicular origin, suggesting that inhibin B may be important in the development of the fetal hypothalamo-pituitary-testicular axis.

Amniocentesis↗

PubMed1997

Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study.

To investigate the role of inhibin in the control of follicle-stimulating hormone (FSH) secretion, we have measured levels of immunoreactive inhibin (ir-inhibin), inhibin B, Pro-alpha C containing inhibins, FSH, luteinizing hormone (LH), and testosterone in twelve men with hematological malignancies before, during, and after chemotherapy. Inhibin B levels fell significantly by 1 month from a mean +/- SE baseline level of 273.2 +/- 32.8 pg/mL, reaching a nadir of 52.6 +/- 15.3 pg/mL at 4 months (P < 0.0001). FSH levels increased within the first month from a baseline level of 3.9 +/- 0.6 IU/L, reaching a peak level of 22.4 +/- 3.3 IU/L at 4 months (P < 0.0001). FSH and inhibin B were significantly and inversely correlated (r = 0.69, P < 0.0001). Pro-alpha C containing inhibin levels increased significantly (P < 0.05) at 3 months and were significantly and positively correlated with FSH (r = 0.38, P = 0.002). LH levels increased significantly but to a much lesser extent than FSH, the increase becoming evident only 4 months after treatment commenced (P < 0.03). Levels of ir-inhibin and testosterone remained unchanged throughout the study. These data provide strong support to the hypothesis that inhibin B is the physiologically important form of inhibin in men, negatively regulating FSH secretion at the pituitary. Furthermore, they suggest that FSH stimulates inhibin alpha-subunit secretion by the testis.

Adult↗

PubMed1997

Endothelins-1, 2 and 3 are released in vitro from the human bilaterally perfused placenta.

Immunoreactive-endothelin (ir-ET) has previously been detected in human fetal effluents from in vitro perfused placentae. To date however, because of a lack of radio-immunoassay specificity, the ET isoforms in fetal effluents had not been determined, nor had placental maternal effluents been examined for ETs. The aim of this study was to identify the isoforms of ET released into the maternal and fetal circulations of the human in vitro bilaterally perfused placenta. Both circulations of placentae, obtained after normal vaginal delivery, were perfused with a modified Krebs solution and maternal and fetal effluents from the start of the second hour of perfusion were collected, extracted on Scp-pak C18 cartridges, concentrated by vacuum evaporation and separated by reverse-phase HPLC separation. HPLC fractions were measured by ET-RIA and compared to known synthetic standards. Maternal and fetal effluents contained ET-1 (natural and oxidised ET-1), ET-2 and ET-3 (n = 5). Maternal and fetal release of ET-1 was 2.2 +/- 0.7 and 1.4 +/- 0.1 fmol/min/g wet weight of tissue respectively, ET-2 was 0.4 +/- 0.2 and 0.5 +/- 0.2 and fmol/min/g respectively, and ET-3 was 0.5 +/- 0.2 and 0.7 +/- 0.4 fmol/min/g respectively. There were no significant differences between the release of either ET-1, ET-2 or ET-3 in the maternal or fetal circulations. In conclusion, this study indicated that ET-1, ET-2 and ET-3 were all released into both the maternal and fetal effluents from the in vitro perfused human placenta.

Chromatography, High Pressure Liquid↗

PubMed1996

Inhibin in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy.

Inhibins are present in maternal serum during pregnancy. However, the presence of inhibins in the compartments surrounding the fetus in early pregnancy is not well defined. Using novel specific enzyme-linked immunosorbent assays we have demonstrated that the bioactive dimeric inhibin forms, inhibin-A and inhibin-B, and the immunoreactive inhibin forms containing pro- and alpha C sequences are present in different amounts in the extra-embryonic coelomic and amniotic fluids and maternal serum between 8-11 weeks gestation. Of the bioactive dimeric inhibins, both inhibin. A (mean +/- SEM 236.0 +/- 24.8 pg/ml) and inhibin-B (62.0 +/- 8.6 pg/ml) are present in extra-embryonic coelom whereas no dimeric inhibin is present in the amniotic fluid and only inhibin-A (360.2 +/- 32.9 pg/ml) is present in maternal serum. Furthermore, pro-alpha C-related immunoreactivity is present at high concentrations in the extra-embryonic coelom (591.7 +/- 60.5 pg/ml), amniotic fluid (452.4 +/- 76.8 pg/ml) and maternal serum (539.4 +/- 39.5 pg/ml). These findings would indicate that at this stage of gestation inhibin-A, inhibin-B and immunoreactive pro- alpha C-containing inhibin production are likely to arise from different sources including the fetus, placenta and fetal membranes and maternal sources including the ovary. Inhibins may be important regulators of fetal and placental development and involved in the establishment of pregnancy.

Amniotic Fluid↗