Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.

OBJECTIVE: To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.

Increased circulating lipid peroxides in severe preeclampsia activate NF-kappaB and upregulate ICAM-1 in vascular endothelial cells.

Preeclampsia is a systemic disease of pregnancy characterized by maternal hypertension, proteinuria, and edema. These clinical pathological findings may be attributed to abnormalities in vascular endothelial activation secondary to increased oxidative stress. To test the hypothesis that increased circulating lipid peroxides in preeclamptic women activate vascular endothelial cells, we determined NF-kappaB transcriptional activity and ICAM-1 expression in human umbilical vein endothelial cells (HUVEC) cultured with plasma from women with severe preeclampsia (preeclamptic plasma, N = 12) or plasma from normal pregnancies (normal plasma, N = 12). Preeclamptic women had increased circulating lipid peroxides compared with normal pregnant women, as demonstrated by a 4.5-fold higher concentration of plasma malondialdehyde (PkB luciferase reporter construct transfected into HUVEC, preeclamptic plasma was found to up-regulate HUVEC NF-kappaB activity by 2.5-fold when compared with normal plasma (PkB activation in response to preeclamptic-plasma by 77% (PkB activation and ICAM-1 expression on HUVEC, which can be inhibited by vitamin E and N-acetyl-cysteine.

Cytokines in implantation.

Implantation is a process that involves development, attachment and invasion of the blastocyst into the endometrium. Successful implantation requires appropriate communication between the embryo and maternal endometrium. There is evidence to suggest that cytokines produced by the maternal endometrium and the developing embryo play a crucial role in this signalling process. Although numerous cytokine-receptor pairs are expressed by the maternal endometrium and the embryo during implantation, functional knowledge of these cytokines is limited. Compelling data demonstrating a functional role for cytokines in implantation comes from studies using specific cytokine and cytokine receptor knockout mice. There are limited similar data for human implantation, but clinical correlative data and studies using in vitro models indicate that cytokines may have an important functional role in this process. Cytokines that appear to have a functional role in mammalian implantation include leukaemia inhibitory factor, interleukin 1, hepatocyte growth factor, stem cell factor, macrophage colony-stimulating factor and insulin-like growth factors. As implantation failure is a significant cause of natural and in vitro fertilization pregnancy failure, a better understanding of the functional role of these cytokine-receptor pairs is important for improving the diagnosis and treatment of infertility.

Hepatocyte growth factor stimulates trophoblast invasion: a potential mechanism for abnormal placentation in preeclampsia.

Hepatocyte growth factor (HGF) is a cytokine that is produced in the placental villous core and acts in a paracrine manner on trophoblasts that express the HGF receptor Met. Because HGF stimulates the invasion of many epithelial cell types, villous core HGF could regulate placental trophoblast invasion. As preeclampsia is characterized by inadequate trophoblast invasion, we investigated the hypothesis that decreased placental HGF production is a mechanism for inadequate trophoblast invasion in this disease. Placental villous explant HGF production over 24 h was 25% lower in patients with preeclampsia (n = 5; 7.29 +/- 0.8 ng/mL) than in normal patients (n = 5; 9.76 +/- 0.5 ng/mL; P < 0.05). The human first trimester trophoblast cell line (ED27) used in subsequent invasion studies was found to express c-met messenger ribonucleic acid by RT-PCR and Met protein by Western analysis, and underwent phosphorylation of tyrosine residues on Met with HGF exposure. A Boyden chamber invasion assay using collagen type I showed that HGF caused a specific dose-response increase in trophoblast invasion first seen at 10 ng/mL (2.2-fold increase; P < 0.05). The stimulation of trophoblast invasion by HGF may in part be due to the 2-fold induction of 92-kDa collagenase as determined by zymogram analysis of the trophoblast-conditioned medium. These studies suggest that HGF has an important role in placental trophoblast invasion through the activation of Met and the subsequent induction of 92-kDa collagenase in these cells. In addition, decreased placental production of HGF in preeclampsia provides a potential mechanism for the lack of trophoblast invasion that is seen in this pregnancy disorder.

Placental Fas ligand expression is a mechanism for maternal immune tolerance to the fetus.

Fas ligand (FasL) is a peptide that plays an important immunoregulatory role in limiting the host immune response. Several studies have shown that the expression of FasL in the anterior chamber of the eye and the testis allows these tissues to be immunoprivileged sites. Immunotolerance is achieved by binding of FasL to its receptor (Fas) on activated immune cells, which results in cell apoptosis. To determine whether FasL has a role in maternal immune tolerance to the fetus, we looked for the expression of FasL in the human placenta. Immunoperoxidase staining localized FasL to both syncytiotrophoblast and cytotrophoblast in placental villi and chorionic extravillous trophoblast. Western analysis demonstrated FasL in placental villi and a human first-trimester trophoblast cell line (ED27). In contrast, Fas was colocalized to CD45 (leukocyte common antigen) positive cells found in maternal decidua. When isolated peripheral blood lymphocytes were induced to express Fas with phytohemagglutinin (PHA) and interleukin-2 (IL-2) and then cocultured with trophoblast, 30% of the lymphocytes underwent apoptosis, as determined by the in situ death (TUNEL) assay. Neutralizing antibodies to FasL inhibited apoptosis by 40% in these studies. In contrast, activated lymphocytes cocultured with non-FasL-expressing fibroblasts or unactivated non-Fas-expressing lymphocytes cocultured with ED27 trophoblast showed little evidence of apoptosis. These findings suggest that FasL expressed by fetal trophoblast cells can induce apoptosis in activated lymphocytes there by providing a mechanism for maternal immune tolerance to the fetus.

Characteristics of luteinizing hormone secretion in younger versus older premenopausal women.

OBJECTIVES: The objectives of this study were to document specific attributes of pulsatile luteinizing hormone secretion in middle-aged women before discernible alterations in their menstrual cycles and to compare the results to corresponding data obtained in younger women. STUDY DESIGN: After documenting normal cycle length, biphasic basal body temperatures, and normal midluteal progesterone in younger and middle-aged women during an initial cycle, daily blood samples and samples withdrawn at 10-minute intervals for 8 hours during the midfollicular phase were obtained during a subsequent cycle. RESULTS: Assessment of luteinizing hormone pulses with the pulse detection algorithm Cluster demonstrated a prolonged interpulse interval and increased pulse width in the older women. Assessment of luteinizing hormone secretory bursts and half-life with the deconvolution analysis procedure demonstrated a prolonged interburst interval and half-life in the older women. Appraisal of approximate entropy revealed greater orderliness of luteinizing hormone release in the older women. CONCLUSIONS: Middle-aged women exhibit alterations in hypothalamic-pituitary function that may account in part for age-related changes in reproductive potential.

Reproductive immunology update: the 52nd annual meeting of the American Society of Reproductive Medicine.

The American Society of Reproductive Medicine meeting (formerly the American Fertility Society) was held in Boston, Massachusetts, USA, on November 2-6, 1996. Numerous abstracts concerning original research in reproductive immunology were presented at the meeting. In addition, seminars and round table discussions were held on the topics of hormonal immunocontraception, immunologic testing in reproduction, antiphospholipid syndrome, endometriosis, and immunologic infertility.

Interleukin-1 beta and tumor necrosis factor-alpha stimulate granulocyte colony-stimulating factor production by placental villous core mesenchymal cells.

OBJECTIVE: To test the hypothesis that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) regulate granulocyte colony-stimulating factor (G-CSF) production by human placental villous core mesenchymal cells. METHODS: Villous core mesenchymal cells were isolated from placentas at 14-20 weeks' gestation and cultured in vitro. Cells were treated with IL-1 beta or TNF-alpha in dose-response and time-course studies. We measured G-CSF mRNA expression by Northern blot analysis and G-CSF protein production by enzyme-linked immunosorbent assay of the conditioned media. RESULTS: Unstimulated mesenchymal cells expressed negligible G-CSF. Steady-state G-CSF mRNA expression was maximal 3-6 hours after IL-1 beta treatment and 6-18 hours after TNF-alpha treatment. Each cytokine induced G-CSF protein production in dose-and time-dependent manners, with IL-1 beta more potent than TNF-alpha. The G-CSF mRNA expression and G-CSF protein production induced by the combination of both cytokines exceeded that induced by either cytokine alone. CONCLUSIONS: Interleukin-1 beta and TNF-alpha stimulate G-CSF production by placental villous core mesenchymal cells in vitro. These results identify a potential mechanism by which villous core mesenchymal cells mediate, in part, the placental response to these two cytokines.

Preeclampsia is associated with decreased placental interleukin-6 production.

OBJECTIVE: The etiology of preeclampsia is poorly understood, but may involve abnormal fetal-maternal immunologic interactions. Interleukin-6 (IL-6) is a multifunctional immunologic cytokine that is normally produced by the placenta during pregnancy. Recent studies have shown that amniotic fluid IL-6 is decreased in pregnancies complicated by preeclampsia. Consequently, this study was designed to test the hypothesis that placental IL-6 production is decreased in preeclampsia. METHODS: Placental explants from normal (N = 6) and preeclamptic (N = 6) pregnancies were cultured in vitro, and the media were sampled at 0, 2, 6, 16, 28, and 48 hours. Production rates of IL-6 were measured by enzyme-linked immunosorbent assay, and relative IL-6 mRNA expression was measured by Northern and dot blot analyses. RESULTS: Production rates of IL-6 were 2.3-fold lower in preeclamptic placentas than in normal placentas, at 146 pg/microgram/hour versus 341 pg/microgram/hour (P < .05). However, relative steady-state IL-6 mRNA expression was identical in preeclamptic and normal placentas. CONCLUSIONS: Placental IL-6 production is decreased in preeclampsia. The decrease in placental IL-6 production and secretion in preeclampsia is regulated by a post-transcriptional mechanism.

Coculture cells that express leukemia inhibitory factor (LIF) enhance mouse blastocyst development in vitro.

PURPOSE: Leukemia inhibitory factor is a cytokine that plays an important role in implantation and enhances mouse preimplantation embryo development in vitro. Since leukemia inhibitory factor enhances early embryo development, we tested the hypothesis that coculture cells that express leukemia inhibitory factor would enhance mouse blastocyst development in vitro. In this study, Northern analysis for leukemia inhibitory factor was performed on total RNA extracted from Vero cells, human embryonic fibroblasts, and human placental fibroblasts. METHODS: Two-cell mouse embryos were cultured to blastocyst in Ham's F-10 with 15% human cord serum (control) or with the coculture cells. Northern analysis demonstrated expression of LIF mRNA in Vero cells and embryonic fibroblasts but not in placental fibroblasts. Development to blastocyst was significantly enhanced in two-cell embryos cultured with Vero cells (86%, 140/163) and embryonic fibroblasts (83%, 118/142) when compared to controls (71%, 67/94, P < 0.05) or placental fibroblasts (71%, 95/134), P < 0.05). CONCLUSION: These data suggest that coculture cells that express leukemia inhibitory factor may be superior to nonleukemia inhibitory factor expressing cells for early preimplantation embryo development.

Interleukin-1 beta stimulates interleukin-6 production in placental villous core mesenchymal cells.

Interleukin-6 (IL-6) is a pleiotropic mediator of immune function and a growth factor for a variety of hematopoietic cell types. Because IL-1 beta is known to induce IL-6 production in nonplacental mesenchymal cells and is locally produced by maternal decidua, this study was designed to determine whether IL-1 beta could regulate IL-6 production by second trimester placental villous core mesenchymal cells (VCMC) in vitro. VCMC were prepared for culture by enzymatic digestion of placentas (14-20 weeks gestation; n = 7). Immunohistochemistry performed on the confluent cells demonstrated that more than 95% of the cells had a fibroblast-like morphology and were vimentin positive, less than 5% were leukocyte common antigen (CA-45) positive, and no trophoblast contamination was demonstrated by the lack of cytokeratin staining. In dose-response experiments, a specific dose-response induction of IL-6 mRNA expression and IL-6-immunoreactive protein production by IL-1 beta was demonstrated; this was first seen at 100 pg/ml IL-1 beta [455 +/- 191 ng/ml (+/- SEM); controls, 42 +/- 16 ng/ml; P < 0.05]. In time-course studies, the addition of 10 ng/ml IL-1 beta significantly increased IL-6 production rates; this was first seen at 8 h of culture and increased in a linear fashion up to 48 h. At 48 h of culture, IL-6 levels were 17 times higher in treated VCMC (861 +/- 179 ng/ml) compared to those in nontreated VCMC (51 +/- 14 ng/ml). In summary, IL-1 beta stimulates VCMC IL-6 production in a specific dose- and time-dependent manner. From these results, we conclude that VCMC are an important source of IL-6 in second trimester placenta and that production of placental IL-6 be may regulated by decidual IL-1 beta.

Differential mRNA expression and production of interleukin-6 in placental trophoblast and villous core compartments.

PROBLEM: Interleukin-6 (IL-6) is a pleiotropic protein that functions as an immunoregulatory peptide, growth factor, and endocrine hormone. IL-6 has been shown to be produced in whole placental tissue and isolated trophoblast (TC). In addition, the villous core (VC) compartment of the placenta contains cell types (fibroblasts, macrophages) capable of IL-6 production. Consequently, the present study was designed to determine the relative contribution of the TC and VC compartments to placental IL-6 production. METHOD: The VC and TC compartments from term pregnancies were separated using CR-Dispase digestion and Percoll density gradient centrifugation. The VC, TC, and whole placental tissues were cultured in Dulbecco's modified Eagle's medium over a 28-h period. Relative IL-6 mRNA expression was determined by dot blot analysis and secreted IL-6 protein was determined by enzyme-linked immunosorbent assays. RESULTS: All three tissues demonstrated linear production of IL-6 protein over the culture period. At 28 h, whole placental tissue produced the most IL-6 (5.1 ng +/- 0.8 ng/microgram/protein) followed by TC (4.0 ng +/- 1.3 ng/micrograms) and VC (0.55 ng +/- 0.24 ng/microgram). Although production rates of IL-6 were 8.4-fold higher in TC compared to VC (P < .05), steady-state IL-6 mRNA expression was 3.5-fold higher in freshly isolated VC compared to TC (P < .0001) and 13-fold higher in VC compared to TC (P < .01) after 24 h in culture. CONCLUSIONS: These results demonstrate that: (1) the placenta can produce large quantities of immunoreactive IL-6 in vitro, (2) TC produce significantly more IL-6 than VC although both compartments contribute to placental IL-6 production, (3) placental IL-6 production and secretion are probably posttranscriptionally regulated since steady-state IL-6 mRNA expression in VC and TC compartments did not correlate with IL-6 production.

Interleukin-1 beta stimulates colony-stimulating factor-1 production in human term placenta.

The human placenta produces hematopoietic growth factors including colony stimulating factor-1 (CSF-1). We have previously demonstrated Interleukin-1 beta (IL-1 beta) production by decidualized endometrium during pregnancy. Since IL-1 beta stimulates CSF-1 production in a variety of mesenchymal cell types including second trimester villous core mesenchymal cells, the present study was designed to determine if IL-1 beta could also regulate CSF-1 production in term placental explants in vitro. Placental villous explants from normal term placentas (n = 5) were cultured with or without recombinant human IL-1 beta. A dose response relationship between increased added IL-1 beta and increased CSF-1 production as measured by enzyme-linked immunosorbent assay was observed with 1 ng/mL IL-1 beta being the lowest dose to significantly increase CSF-1 production (P < 0.01). In time course experiments, 10 ng/mL maximally induced CSF-1 messenger RNA expression 2.7 fold (P < 0.005) compared to controls at 8 h of culture as determined by dot blot analysis. Production rates of CSF-1 were linear up to 24 h at which time IL-1 beta (10 ng/mL)-treated samples had 1.7-fold higher levels of CSF-1 in the media than nontreated controls (8.38 ng/gm tissue vs. 4.94 ng/gm tissue, P < 0.01). These results demonstrate that IL-1 beta can regulate placental CSF-1 production in vitro and suggest that maternal decidual IL-1 beta may regulate placental CSF-1 production in vivo.

Alterations in the postovariectomy increases in gonadotropin secretion in middle-aged persistent-estrous rats: correlation with pituitary gonadotropin subunit gene expression.

This study compared the changes in pituitary and serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at various times following ovariectomy (OVX) between young cyclic and middle-aged persistent-estrous (PE) rats and related these to the relative gene expression of the pituitary gonadotropin subunits. In intact animals, both pituitary and serum levels of LH were similar between these two age groups, while the LH beta mRNA expression was significantly (p < 0.05) greater in young rats. Following OVX in young rats, the serum LH levels markedly increased (p < 0.05) beginning on day 7 and reaching a maximum fourfold increase by day 9. In contrast, the post-OVX increases in serum LH in middle-aged females were significantly delayed. OVX significantly (p < 0.05) increased pituitary LH contents of young rats by day 5, but had no effect on LH contents in middle-aged females until day 30 post-OVX. These changes were associated with increases in LH beta mRNA expression in both young and middle-aged females, but the levels were significantly (p < 0.05) lower in middle-aged females. Both pituitary and serum levels of FSH were significantly (p < 0.05) higher in middle-aged PE than in young rats prior to OVX, while the FSH beta mRNA expression was similar in both age groups. Following OVX in young rats, serum FSH levels rapidly increased (p < 0.05) on day 3 and attained tenfold higher values by day 30.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-1 is induced in the human placenta by endotoxin and isolation procedures for trophoblasts.

Although freshly obtained placenta contains little or no interleukin-1 (IL-1) mRNA, placenta and isolated trophoblast have been reported to produce significant quantities of bioactive IL-1 in vitro. The present study was designed to determine if endotoxin, a common contaminant of culture medium, and trophoblast isolation procedures could induce IL-1 expression in the placenta. Tissue-extractable IL-1 alpha and IL-1 beta immunoreactive proteins were readily detected in fresh placental membranes, but not placental villi. As little as 10 ng/mL endotoxin were found to induce the expression of IL-1 alpha and IL-1 beta mRNA in intact placental villi cultured in vitro. Intact placenta cultured in the presence of 1.0 microgram/mL endotoxin demonstrated expression of IL-1 alpha and IL-1 beta mRNA and cumulative production and release of immunoreactive IL-1 alpha and IL-1 beta into the medium during 24 h of culture. Placenta incubated in endotoxin-free medium, however, exhibited no detectable IL-1 alpha or IL-1 beta mRNA expression and little or no release of IL-1 alpha or IL-1 beta immunoreactive protein into the medium. When trophoblast cells were freshly isolated by enzymatic digestion, followed by Percoll separation at reduced temperatures to inhibit cell activation, no IL-1 alpha or IL-1 beta mRNA expression was initially detectable. However, IL-1 alpha and IL-1 beta mRNA in isolated trophoblast cells were induced after 30 min of culture in endotoxin-free medium, with maximal induction at 4 h. These results suggest that normally the placenta produces very little, if any, IL-1, and that endotoxin and trophoblast isolation procedures induce IL-1 expression in placental tissues cultured in vitro.

Interleukin-1 beta stimulates colony-stimulating factor-1 production in placental villous core mesenchymal cells.

The human placenta is known to produce hematopoietic growth factors, including colony-stimulating factor-1 (CSF-1). We have previously demonstrated interleukin-1 beta (IL-1 beta) production by decidualized endometrium during pregnancy. Since IL-1 stimulates CSF-1 production in fibroblasts, endothelial cells, and bone marrow stromal cells, our present study was designed to determine whether IL-1 could also regulate CSF-1 production by placental villous core mesenchymal cells. Initial studies using enzymatic digestion separation of the trophoblast and villous core demonstrated that CSF-1 mRNA is mainly expressed in the placental villous core. Subsequently, long term monolayer cultures of villous core mesenchymal cells isolated from 9- to 16-week gestation placentas were established after enzymatic dissociation of intact placental villi to study the regulation of villous core cell CSF-1 production. The morphology of the cells and immunohistochemical staining for vimentin, cytokeratin, and CD45 antigen confirmed that cultured cells were more than 95% mesenchymal fibroblasts. Time-course experiments demonstrated a maximal increase in CSF-1 mRNA expression of approximately 6.0-fold over baseline levels 3 h after IL-1 beta treatment (10 ng/mL), whereas increased CSF-1 protein production was first detected in the culture medium 3 h after IL-1 beta treatment and rose progressively over 42 hours. Villous core mesenchymal cells incubated with 0-10 ng/mL IL-1 beta demonstrated a specific dose-response relationship for CSF-1 mRNA expression and protein production, first seen at 0.10 ng/mL and maximal with 10 ng/mL IL-1 beta. These results demonstrate that production of CSF-1 by placental villous core mesenchymal cells can be stimulated by IL-1 beta in vitro and suggest that decidual IL-1 may regulate placental CSF-1 production in vivo.

Colony-stimulating factor-1 and c-fms expression in human endometrial tissues and placenta during the menstrual cycle and early pregnancy.

Colony-stimulating factor-1 (CSF-1), a growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells, has been implicated in the functional regulation and growth of the murine placenta through the presence of the CSF-1 receptor, c-fms, found in this tissue. In this study we examined the tissue levels of CSF-1 by RIA and the relative expression of CSF-1 and c-fms mRNA by Northern blot analysis in human endometrial, decidual, and placental tissues during the normal menstrual cycle and early pregnancy. All endometrial, decidual, and placental tissues demonstrated extractable immunoreactive CSF-1 and expressed the 4.0-kilobase CSF-1 mRNA species. First trimester decidual tissue expressed higher levels of CSF-1 mRNA than proliferative (3.2-fold higher; P less than 0.01) or secretory (2.4-fold higher; P less than 0.01) endometrial tissues, whereas proliferative and secretory endometrial tissues expressed similar levels of CSF-1 mRNA. Tissue extractable levels of immunoreactive CSF-1 were 3.2-fold (P less than 0.05) higher in first trimester decidual tissue and 2.9-fold (P less than 0.05) higher in secretory endometrial tissue compared to levels in proliferative endometrial tissue, whereas first trimester decidua and secretory endometrial tissues had similar levels of immunoreactive CSF-1. There was expression of c-fms mRNA in all endometrial and first trimester decidual tissue samples, with little change during the menstrual cycle and early pregnancy. In placenta, there was a positive correlation of increasing CSF-1 and c-fms mRNA expression with increasing gestational age. These results suggest that there is increased local production of CSF-1 in tissues found at the maternal-fetal interface during the time of implantation and early pregnancy. This increased production of CSF-1 may play a role in decidual function and placental growth through the presence of c-fms in these tissues.

Localization of prostaglandin endoperoxide synthase in the human corpus luteum.

Prostaglandins have been implicated in both maintenance and luteolysis of the primate corpus luteum. Central to the production of prostaglandins is the enzyme prostaglandin endoperoxide synthase (PGHS). In the present study, we identified the cell types which contain PGHS in 44 human corpora lutea, using immunoperoxidase staining techniques. Intense granular staining was present in the cytoplasm of granulosa lutein cells of tissues obtained from the mid-luteal phase. Theca lutein cells demonstrated a diffuse cytoplasmic staining which was less intense than that observed in granulosa lutein cells. Staining appeared less intense in tissues from the early or late phase. Ovarian stromal cells demonstrated little or no PGHS immunoreactivity. PGHS staining in the corpus luteum of pregnancy was similar in intensity and cell distribution to that of mid-luteal corpus luteum. In summary, human corpus luteum contains immunoreactive PGHS which localized mainly to well-differentiated granulosa lutein cells.

Immunohistochemical localization of prostaglandin endoperoxide synthase in human fetal membranes and decidua.

Prostaglandins play an important role during the maintenance of pregnancy and the initiation of parturition. Prostaglandin endoperoxide synthase activity has been demonstrated in human fetal membranes and decidua. Using immunohistochemical techniques, we identified in these tissues the cell types that contain prostaglandin endoperoxide synthase. A total of 33 specimens, ranging from 8 wk to 42 wk gestation, were studied. Decidualized stromal cells stained the most intensely and consistently of all cell types. Cytotrophoblast of the chorion and early placental villi and syncytotrophoblast of all gestational ages demonstrated a lighter, more variable staining pattern. Regardless of gestational age, amnion stained in a heterogeneous fashion, with some cells demonstrating an intense staining and other cells having no staining. There were no observable differences in laboring compared to nonlaboring term specimens. In summary, the specific cell types that contain immunoreactive prostaglandin endoperoxide synthase have been identified in fetal membranes and decidua.