Immunohistochemical localization of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4 isomerase in human placenta and fetal membranes throughout gestation.

The regulation of steroid production by the placenta and fetal membranes is important for both the maintenance of pregnancy and the timing of parturition. 3 beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4-isomerase (3 beta HSD) catalyzes an obligatory step in the biosynthesis of steroid hormones. We have determined the localization of 3 beta HSD in the human placenta, fetal membranes, and umbilical cord throughout gestation by immunohistochemical analysis, using a polyclonal antibody raised in rabbits against a purified preparation of human placental 3 beta HSD. In placenta, immunoreactive (IR-) 3 beta HSD was localized in the syncytiotrophoblast and intermediate trophoblast cells at both villous and extravillous sites, but not in cytotrophoblast cells from 6 weeks gestation to term. At 6-7 weeks gestation, IR-3 beta HSD was distributed in the cytoplasm of syncytiotrophoblast in about half of placental villi. By 12-14 weeks, the syncytiotrophoblast of all placental villi stained positively for 3 beta HSD. In the fetal membranes, strong IR-3 beta HSD staining was found in the trophoblast and reticular layers of chorion and in invasive trophoblast cells in decidua, and weakly in decidual stromal cells and amniotic epithelium. No IR-3 beta HSD was found in amnion on the placental plate, but in the umbilical cord, IR-3 beta HSD was present in the amniotic epithelium and also in fibroblast cells in Warton's jelly. These observations demonstrate that the localization of 3 beta HSD immunoreactivity and, therefore, the presumed sites of delta 5- to delta 4-steroid interconversion throughout gestation are principally the syncytiotrophoblast and intermediate trophoblast cells in placenta and the trophoblast cells in chorion and decidua in fetal membranes.     

Corticotropin-releasing hormone and urocortin induce secretion of matrix metalloproteinase-9 (MMP-9) without change in tissue inhibitors of MMP-1 by cultured cells from human placenta and fetal membranes

CONTExt: Matrix metalloproteinases (MMPs) are essential for human parturition due to their degrading of the extracellular matrix. CRH and urocortin (Ucn) are thought to play a central role in the mechanisms controlling human pregnancy and parturition. OBJECTIVE, DESIGN, AND SETTING: The aim of this study was to assess the effects of CRH and Ucn on MMP-9 and tissue inhibitors of MMP-1 (TIMP-1) protein and/or mRNA levels in vitro. Zymography, Western blotting, real-time RT-PCR, and culture/treatments of purified sycytiotrophoblast, chorion trophoblast, and amniotic epithelial cells from human placenta and fetal membranes were performed. RESULTS: CRH and Ucn significantly increased MMP-9 protein secretion from cultured chorionic trophoblast, amnion epithelial, and syncytiotrophoblast cells (P < 0.01, compared with control, respectively), but there was no effect on TIMP-1 secretion and MMP-9 mRNA expression. Antalarmin (a CRH receptor type 1 antagonist) significantly blocked CRH- and Ucn-induced pro-MMP-9 secretion from three cell types (P < 0.01, compared with treatment with CRH and Ucn alone, respectively). Antisauvagine 30 (a CRH receptor type 2 antagonist) resulted in a significant reduction in CRH- and Ucn-induced secretion from chorionic trophoblast cells (P < 0.05) and syncytiotrophoblast cells (P < 0.01) compared with treatment with CRH and Ucn alone, respectively, but had no significant effect on amniotic epithelial cells. CONCLUSION: Our results suggest that CRH and Ucn may play a role in the mechanisms controlling human parturition and preterm delivery not only by affecting myometrial contractility, but also by increasing local MMP activity in placenta and fetal membranes, thereby contributing to membrane rupture with the onset and progression of human labor.     

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.     

Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor

Extensive extracellular matrix (ECM) remodeling is found in many processes during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases (MMPs) are the main mediators of ECM degradation. The present study was designed to investigate the expression of MMP-2 and MMP-9 in human fetal membranes (FMs) and placental (PL) tissues with or without labor at preterm and term parturition. Both zymography and Western blot analysis showed that MMP-9 was significantly (P < 0.01) increased in preterm and term labor FM, compared with nonlabor. Term labor PL also had a much higher (P < 0.05) level of MMP-9 than that of term nonlabor. No significant difference in MMP-2 expression was found between labor and nonlabor tissues. Immunolocalization studies revealed a specific distribution pattern for MMP-2 and MMP-9. MMP-2 was localized to the amnion mesenchyme, chorion laeve trophoblast, decidua parietalis, and blood vessels in PL villi. MMP-9 was localized mainly to amnion epithelia, chorion laeve trophoblast, decidua parietalis, and PL syncytiotrophoblasts. Separate cell culture from different layers of FM and culture of purified PL trophoblast cells showed that PL syncytiotrophoblast and amnion epithelial cells exclusively produced MMP-9; chorion trophoblast cells secreted both MMP-2 and MMP-9, but amnion mesenchymal cells produced only MMP-2. We concluded that MMP-2 and MMP-9 exhibited cell-specific expression in the human PL. An increase in MMP-9 expression may contribute to degradation of the ECM in the FM and PL, thereby facilitating FM rupture and PL detachment from the maternal uterus at labor, both preterm and term.     

Exposure of human amnion to amniotic fluid obtained before labor causes a decrease in chorion/decidual prostaglandin release.

Prostaglandin (PG) production by fetal membranes has been implicated in the initiation of human parturition, but its regulation is not well understood. We used an in vitro system to study paracrine control of term, fetal membrane PG production. Using a modified Ussing chamber, full thickness fetal membranes with attached decidua were sealed into a chamber so that each hemichamber was a compartment for either the fetal (amnion) or maternal (chorion/decidua) side. Released PGs from maternal and fetal sides were then measured after exposure of the amnion to either buffer or amniotic fluid. We found that basal release of PGs from both the fetal and maternal sides was 2- to 3-fold higher in membranes obtained after labor compared to those obtained before labor. When amnion obtained after labor was exposed to amniotic fluid, we found a 3- to 5-fold increase in the net release of PGE2 from the amnion; however, the maternal side showed an unexpected relative decrease in PGE2 and PGF2 alpha release. This was a paracrine effect, since direct exposure of chorion/decidua to amniotic fluid caused increased release of the PG precursor, arachidonic acid. Direct transfer of radiolabeled PG from fetal to maternal side was minimal.     

Late gestation increase in 11beta-hydroxysteroid dehydrogenase 1 expression in human fetal membranes: a novel intrauterine source of cortisol

Late human gestation is associated with an increase in the concentration of cortisol (F) in the fetal circulation and amniotic fluid. It had been assumed that most of the F measured in the amniotic fluid came from the fetal adrenal gland. However, local production of F can also occur in human intrauterine tissues from inactive cortisone under the influence of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1. Recent studies have shown that 11beta-HSD 1 activity is up-regulated by prostaglandins (PG) E2 and F2alpha, hormones that are produced in the fetal membranes (FM) at term. In the present study, we hypothesized that 11beta-HSD 1 expression would increase in FM during pregnancy and at labor, creating the potential for local increase in F production at term. We examined 11beta-HSD 1 expression in placenta and FM obtained during normal pregnancy from nonlaboring women [26-28 wk (n = 3); 29-30 wk (n = 3); 32-33 wk (n = 3); 35-36 wk (n = 3)] and from uncomplicated term pregnancies after elective cesarean section (n = 6). 11beta-HSD 1 expression was also examined in amnion and chorionic tissues in relation to term labor (n = 12). Immunohistochemistry and Western blot analysis were used to examine 11beta-HSD 1 localization and expression. 11beta-HSD 1 activity was also measured in microsomal fractions prepared from whole fetal membranes. At term, immunoreactive 11beta-HSD 1 expression was localized predominantly to the chorion trophoblast cells, attached decidua, and amnion epithelial cells. 11beta-HSD 1 expression in FM increased with gestational age and reflected increased enzyme reductase activity. No change in 11beta-HSD 1 expression was found in placental tissue from the same patients. There was a significant increase in 11beta-HSD 1 expression in amnion but not in chorion with the onset of labor. We suggest that increases in 11beta-HSD 1 expression/activity by intrauterine membranes during late gestation may result in increased potential for a local increase in F production and that FM should be considered as an extraadrenal source of F during late gestation. This local F production may be involved in different pathways contributing to the regulation of parturition.     

Indirect immunofluorescent localization of prolactin to the cytoplasm of decidua and trophoblast cells in human placental membranes at term.

An indirect immunofluorescent technique was used to determine the localization of cytoplasmic human PRL (hPRL) in fresh and incubated human placental membranes at term. In both fresh and 8-h incubated samples of amnion, amniochorion decidua, or chorion decidua obtained from three placentas, we found specific reproducible localization of hPRL to the cytoplasm of decidua and trophoblast cells. The decidua cells appeared to be the most intensely fluorescent. No specific hPRL immunofluorescence was noted in the amniotic epithelium of fresh or incubated samples of amnion and amniochorion decidua. These data suggest that the trophoblast decidua cell layer is the site of PRL localization and possibly synthesis in placental membranes at term and may be the origin of amniotic fluid PRL in humans.     

Parathyroid hormone-related protein(1-34) in gestational fluids and release from human gestational tissues

Parathyroid hormone-related protein (PTHrP) is present in fetal and gestational tissues, in which its proposed roles include stimulation of epithelial growth and differentiation, vasodilatation of the uteroplacental vasculature, relaxation of uterine muscle and stimulation of placental calcium transport. The aim of this study was to determine whether the release of PTHrP from gestational tissue explants was tissue specific. In addition, PTHrP concentrations were measured in maternal plasma, umbilical artery and vein plasma, and amniotic fluid from term, uncomplicated pregnancies before the onset of labour. PTHrP was detected in low concentrations in the mother, fetus and placental tissue. Amniotic fluid had ten times the PTHrP concentration compared with that in the maternal or fetal circulations. Using late pregnant human gestational tissues in an in vitro explant system, we found that amnion over placenta, choriodecidua, reflected amnion, and placenta released PTHrP into culture medium in progressively greater amounts over 24 h (P<0.05). This release was not associated with a loss of cell membrane integrity, as indicated by measurement of the intracellular enzyme, lactate dehydrogenase, in the incubation media. After 24 h incubation, the fetal membranes released significantly (P<0.05) greater amounts of PTHrP than did the placenta (placenta 3. 7+/-0.5 pmol PTHrP/g protein). Amnion over placenta released significantly more PTHrP (139.3+/- 43.1 pmol PTHrP/g protein) than did reflected amnion (29.0+/-8.3 pmol PTHrP/g protein) (P<0.05). This study unequivocally demonstrated that human gestational tissues release PTHrP and it was concluded that the main contributors to PTHrP in amniotic fluid were the human fetal membranes, particularly amnion over placenta. Fetal membrane-derived and amniotic fluid PTHrP are proposed to have stimulatory effects on epithelial growth and differentiation in fetal lung, gut, skin and hair follicles and paracrine effects on placental vascular tone and calcium transport.     

Expression of betaglycan in pregnant tIssues throughout gestation

BACKGROUND: Betaglycan is a membrane-anchored proteoglycan involved in mediating the passage of transforming growth factor-beta (TGF-beta), inhibin and activin activities into cells. TGF-beta and inhibin-related proteins are growth factors that are expressed by several tIssues and in pregnancy. They have a function in modulating the growth, differentiation and invasion of the placental trophoblast. OBJECTIVE: To evaluate whether betaglycan is expressed by intrauterine tissues throughout gestation. DESIGN AND METHODS: Expression of betaglycan mRNA and protein was evaluated (by RT-PCR and immunohistochemistry, respectively) in trophoblast, decidua and fetal membranes collected during the first (n=6 elective terminations of pregnancy, between 8 and 12 gestational weeks) and third (n=6 elective caesarean sections, between 39 and 40 weeks) trimesters of pregnancy. RESULTS: Betaglycan mRNA was expressed by all gestational tIssues, independently of gestational age. Immunoreactive protein was found in decidual cells and in some chorionic, but not epithelial, amniotic cells. With respect to the placental localization, syncytiotrophoblast, but not cytotrophoblast, cells were intensively stained both in the placental bed and in the villous trophoblast, and in some cells within the stroma of terminal villi, of the first and third trimesters of pregnancy. Immunoreactive betaglycan was demonstrated in the endothelial cells of decidual vessels in both the first and third trimesters of pregnancy, whereas endothelial cells of fetal blood vessels in the villous were clearly represented only in first trimester samples, not in those of term placenta. CONCLUSIONS: Betaglycan mRNA and peptide are expressed by the trophoblast, the decidua and the fetal membranes, but the localization of the peptide in vessel walls is dependent on gestational age.     

Expression of membrane prostaglandin E synthase in human placenta and fetal membranes and effect of labor

Initiation and maintenance of labor in humans is associated with an increase in prostaglandin synthesis by intrauterine tissues. The objective of the present study was to characterize the distribution of membrane-bound PGES (mPGES) protein and mPGES mRNA in human placenta, fetal membranes, and decidua at term and to determine whether any changes occurred with labor. Immunoreactive mPGES was found to be highly concentrated in amnion epithelial cells and the chorion laeve trophoblasts, with lower levels in the mesenchymal layers. The enzyme was at very low levels or undetectable in the decidual tissue. Much lower levels of mPGES protein and mRNA were found in placenta than in fetal membranes. mPGES was associated with the syncytiotrophoblast and in cells surrounding blood vessels. The expression of mPGES mRNA did not change with labor in full membranes or placenta, but Western analysis showed an increase in mPGES protein in chorion laeve and a decrease in mPGES protein in placenta during labor, with no change in the amnion. The differences in expression found among placenta, chorion, and amnion before and after labor would indicate that this enzyme is differentially regulated in these tissues at this time.     

Immunocytochemical localization of the human growth hormone variant in the human placenta

Two monoclonal antibodies (Mab 5B4 and K24) were used for the immunocytochemical localization of human GH (hGH) and human placental GH in the human pituitary and placenta. On the basis of prior selection by RIA, Mab 5B4 was known to be directed to the N-terminal of hGH and was able to detect both pituitary and placental hGH, since their primary amino acid sequences are identical in this domain. Mab K24 was directed to an epitope present in hGH, but not in placental hGH, and was able to detect pituitary hGH only; neither the 5B4 or K24 Mab detected human placental lactogen. Five placentas were studied from women at term after elective cesarean section without labor. The cells of the anterior pituitary gland and the syncytiotrophoblast of the placental villi were stained with Mab 5B4, whereas K24 only stained the pituitary cells; results consistent with the RIA screen. Mab 5B4 specifically stained two different cell types in the placental basal plate. Neither antiserum stained any cell in the amniotic or chorionic membranes or the adherent decidua. The results demonstrate that pituitary hGH and placental hGH are expressed uniquely in the pituitary and fetal placenta, respectively. In addition, the placental hGH gene is also expressed in the placental basal plate, a region of mixed fetal and maternal cells.     

Steroid, corticotrophin-releasing hormone, ACTH and prostaglandin interactions in the amnion and placenta of early pregnancy in man

Corticotrophin-releasing hormone (CRH) is produced by both the placenta and fetal membranes at term in man, and CRH mRNA has been detected in human placental tissue. The synthesis of CRH and its control during early pregnancy, however, have not been established, and the role of CRH produced in the placenta and fetal membranes is not known. We examined whether amnion and placental tissue obtained between 12 and 15 weeks of gestation produced CRH in vitro, whether steroid modulation of output occurred and whether CRH affected prostaglandin (PG) output by the placenta and amnion. Immunoreactive (ir) CRH output by amnion (2.8 +/- 0.31 (S.E.M.) nmol/10(5) cells) was significantly (P less than 0.01) greater than that from placenta (1.76 +/- 0.21 nmol/10(5) cells). Output of ir-CRH decreased in the presence of progesterone, but increased in the presence of cortisol and dexamethasone. There was no significant effect of progesterone or ir-CRH output by placental cells; however, ir-CRH output was increased in the presence of dexamethasone and cortisol. There was no significant effect of corticosterone on ir-CRH output by either amnion or placental cells. Both ACTH and CRH stimulated the output of PGE2 and PGF2 alpha by amnion cells. In contrast, there was no significant effect of PGE2 output by placental cells maintained in the presence of either human CRH or ACTH. Output of PGF2 alpha by placental cells was increased in the presence of both CRH and ACTH. We conclude that both amnion and placental tissue produce CRH in early gestation, and that this output is modulated by steroids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human placenta and fetal membranes express follistatin-related gene mRNA and protein

Activin A is a placental glycoprotein and possible biological actions during pregnancy, suggested by experimental data, are the modulation of cytotrophoblast differentiation, placental hormonogenesis and uterotonins secretion. Follistatin-related gene (FLRG) is a 70 amino acids protein which binds activin A with high affinity, and which modulates its biological effects on target tissues by preventing the activin A interaction with its receptors. The present study investigated whether trophoblast, decidua and fetal membranes express FLRG mRNA (by RT-PCR) and peptide (by immunohistochemistry). Tissue specimens were collected at first and third trimester of pregnancy, from patients undergoing voluntary pregnancy interruption (no.=6; from 8 to 12 gestational weeks) and elective caesarean section at term (no.=6; 39-40 weeks of pregnancy). FLRG mRNA was expressed by the various gestational tissues both at early gestation and at term pregnancy. Immunoreactive protein was found in the trophoblast cells, epithelial amniotic and chorionic cells and maternal decidua; nevertheless, the most intense FLRG stain was detected in the walls of decidual and placental blood vessels. In conclusion, FLRG mRNA and peptide are expressed by placenta and fetal membranes. Its different immunolocalization with respect to follistatin and activin A supports a different role for FLRG in modulating activin A actions into gestational tissues.     

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.     

The progesterone receptor in human term amniochorion and placenta is isoform C

The mechanism that initiates human parturition has been proposed to be functional progesterone withdrawal whereby the 116-kDa B isoform of the progesterone receptor (PR-B) switches in favor of the 94-kDa A isoform (PR-A) in reproductive tissues. Recently other PR isoforms, PR-S, PR-C, and PR-M generated from the same gene have been identified and partially characterized. Using immunohistochemical, Western blotting, and RT-PCR techniques, evidence is provided that the major PR isoform present in human term fetal membranes (amnion and chorion) and syncytiotrophoblast of the placenta is neither of the classical nuclear PR-B or PR-A isoforms but is the N terminally truncated 60-kDa PR-C isoform. Evidence is also provided that the PR-C isoform resides in the cytoplasm of the expressing cell types. Data are also presented to show that PR-B, PR-A, and PR-S isoforms are essentially absent from the amnion and chorion, whereas PR isoforms A, B, C, and S are all present in the decidua, with PR-A being the major isoform. The syncytiotrophoblast of the placenta contains the cytoplasmic PR-C isoform but not PR-A, PR-B, or PR-S. The major PR isoform in the amnion, chorion, and placenta is PR-C, suggesting that the cytoplasmic PR-C isoform has a specific role in extraembryonic tissues and may be involved in the regulation of human parturition.     

Expression and localization of prostaglandin E synthase isoforms in human fetal membranes in term and preterm labor

Increased prostaglandin (PG) synthesis by fetal membranes occurs at parturition. PGE(2) synthesis from arachidonic acid involves multiple enzymes and two isoforms of the terminal enzyme of this biosynthetic pathway, PGE synthase (PGES), were recently identified. Cytosolic PGES (cPGES) is identical to the heat shock protein 90 chaperone, p23, and is reportedly functionally coupled to constitutive PG endoperoxide H synthase-1. Microsomal PGES (mPGES) is inducible by proinflammatory cytokines such as IL-1 beta. We have studied expression and localization of both enzyme isoforms in human fetal membranes either at term or preterm, with or without labor. The cPGES was immunolocalized in the amnion epithelium, and associated with fibroblasts and macrophages in the choriodecidual layer, whereas mPGES was localized in the amnion epithelium as well as the chorion trophoblast. Both enzymes were found to be associated with lipid particles present in the amnion epithelium, which are more prevalent in term tissues. Western blot analysis of the amnion and choriodecidua showed no differences in amounts of either cPGES or mPGES at term or preterm, with or without labor, in either tissue with advancing gestation. It does not appear that expression of PGES is the rate-limiting step in PGE2 synthesis in fetal membranes at labor.     

Tissue levels of active and total renin, angiotensinogen, human chorionic gonadotropin, estradiol, and progesterone in human placentas from different methods of delivery

The components of the renin system are present in placental tissue, but their function in this tissue is not known. We investigated the relative distribution of the various components throughout the placenta to determine whether the distribution is consistent with a role for them in parturition or in stimulation or inhibition of placental hormone biosynthesis. Thus, active and total renin were measured in fetal membranes (chorion laeve and amnion) and in discoid placenta (chorion frondosum and chorion plate) of women who were delivered vaginally (n = 12) or by cesarean section with (n = 6) or without labor (n = 9). The interrelationships between active and total renin and angiotensinogen, progesterone, hCG, and estradiol concentrations were investigated. Labor had no significant effect on the concentration of active or total renin, angiotensinogen, hCG, or estradiol in any part of the placenta. Tissue progesterone concentrations were higher in placentas from women who underwent vaginal deliveries than in those who had cesarean sections with or without labor (P less than 0.02). The chorion laeve had 20 times more total renin per g than the discoid placenta and 3 times more than the amnion. In contrast the discoid placenta had 5 times more hCG per g and 3 times more progesterone per g than the fetal membranes. The concentration of estradiol was lower in amnion, while that of angiotensinogen was lower in the chorion frondosum than in all other regions. The tissue concentrations of active renin, prorenin, or total renin were not related to those of any of the other hormones. Altogether these data do not provide evidence of a role for the placental renin system in parturition or placental hormone biosynthesis.     

Suppressors of cytokine signaling proteins in human preterm placental tissues

Decreased suppressors of cytokine signaling (SOCS) activity in human gestational tissues may play a part in the onset/progression of term labor. Since SOCS proteins negatively regulate cytokine-mediated inflammatory processes, we hypothesized that SOCS proteins are elevated in gestational tissues from spontaneous preterm deliveries with intrauterine infection. SOCS1, -2 and -3 mRNAs and proteins were detectable by RT-PCR and immunoblotting respectively, in preterm amnion, choriodecidua and placenta, irrespective of infection status. Immunoperoxidase staining localized SOCS1, -2 and -3 to all cell types of the gestational membranes, with infiltrating leukocytes reacting strongly in infected tissues. In villous placenta, SOCS was immunolocalized to the syncytiotrophoblast with marked staining of round mesenchymal cells, possibly Hofbauer cells. Nuclear SOCS staining was seen in amnion, chorion and placental syncytiotrophoblasts. SOCS proteins were, in general, significantly more abundant in placenta compared with amnion or choriodecidua. Placental SOCS1 and interleukin-1beta concentrations were positively correlated (r(2)=0.47; P<0.05). However, no changes in SOCS levels in any tissues were observed with intrauterine infection. The relatively large amounts of SOCS proteins in the placenta may reflect a placenta-specific immunoprotective response to minimize the elaboration and effects of cytokines with potential to harm the placenta and fetus. Lack of labor-associated changes in SOCS levels suggests that the regulation of SOCS expression in preterm gestational tissues differs from those at term, perhaps reflecting roles in regulating placental somatotropic responses.