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M Seppala

Publications and source records attributed to M Seppala.

At least 19 recordsLinked to original sources

The synthesis and fate of glycodelin in human ovary during folliculogenesis.

The ontogeny of glycodelin in human ovarian follicles during folliculogenesis was studied. Glycodelin immunoreactivity began to be detected in the granulosa cells and thecal cells of late secondary follicles. Immunoreactivity was also found in both the luteinized granulosa cells and cumulus cells obtained from women undergoing the assisted reproduction treatment. However, only the luteinized granulosa cells, and not the cumulus cells, expressed glycodelin mRNA. Results also showed that the cumulus cells took up radiolabelled glycodelin and partially deglycosylated some of it. Glycodelin (and a partially deglycolsylated form of glycoldelin) appeared to complex with two cytoplasmic or membrane components of the cumulus cells. The data also demonstrated that ZIF-1, a glycoprotein isolated from human follicular fluid, was immunologically similar to glycodelin. In conclusion, we suggest that glycodelin is synthesized in the granulosa cells of ovarian follicles at late secondary follicle stage. It then may be released into the follicular fluid from where it is taken up and partially modified by the cumulus cells.

Binding, Competitive↗

Ligand activated hPR modulates the glycodelin promoter activity through the Sp1 sites in human endometrial adenocarcinoma cells.

Human endometrium produces glycodelin-A (GdA). The GdA mRNA is highly expressed in progestin-sensitized human endometrial glandular epithelial cells. The mechanism of GdA gene expression, however, is not clear. To understand the cell specific GdA gene transcription, our first approach was to identify the cis-element in the GdA promoter using transfection assay in a human endometrial adenocarcinoma cell line (HEC-1B, a cell line originally derived from the glandular component of the endometrium). The GdA promoter (-1900 to +20 bp) was linked to the luciferase reporter gene to construct p1900Luc, along with two shorter promoter constructs, p1100Luc and p304Luc. Deletion analysis showed that the basal promoter activity was derived from the region between -304 to +20 bp. This region contains three putative Sp1 binding sites (Sp1-1, -243 to -238 bp; Sp1-2, -207 to -202 bp; and Sp1-3, -56 to -49 bp). Mutation analysis at the Sp1 sites showed that p304Spm2Luc and p304Spm3Luc reduced the activity by 80%, while p304Spm1-2-3Luc reduced the activity by 95%. Sp1-1 mutation, however, had no effect. These results showed that two of the three Sp1 cis-elements mediate the basal promoter activity of the GdA gene. Electrophoretic gel mobility shift showed that at least two specific binding proteins in the nuclear extracts of HEC-1B cells bound to the oligo containing Sp1-2 or Sp1-3 cis-element. Sp1 antibody reduced the specific binding complex by 70% suggesting that Sp1 transcription factor regulates GdA gene expression. In addition, over expression of Sp1 increased the promoter activity. To determine whether progestin would modulate the promoter activity, HEC-1B cells were transfected with p304Luc and with progesterone receptor (either hPR-A or hPR-B) expression vector. Medroxyprogesterone acetate increased the promoter activity (3-fold) derived from p304Luc but not from the mutant, p304Spm1-2-3Luc. In contrast, the promoter activity was slightly reduced in cells treated with estradiol and co-transfected with estrogen receptor expression vector. These data indicate that ligand-activated PR stimulates GdA gene expression mediated through the functional Sp1 sites.

Adenocarcinoma↗

Cloning.

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Cloning, Organism↗

Endometrial glycodelin-A expression in the luteal phase of stimulated ovarian cycles.

OBJECTIVE: To determine if controlled ovarian hyperstimulation (COH) affects the endometrial expression of glycodelin-A (GdA). DESIGN: Prospective, controlled study. SETTING: Tertiary infertility clinic. PATIENT(S): Fifteen oocyte donors undergoing COH cycles and 19 natural-cycle control patients. INTERVENTION(S): COH, endometrial biopsies. MAIN OUTCOME MEASURE(S): Immunohistochemical scoring of endometrial GdA expression, morphologic endometrial dating, and serum E2, LH, and P4 concentrations. RESULT(S): GdA was detected in all subjects throughout the implantation window period. Immunolocalization was demonstrated in the endometrial glands and not in the stroma or on the surface. A significantly increased proportion of GdA-staining endometrial cells were noted in COH cycle patients as compared with natural-cycling control patients throughout the window of embryo implantation. Both cycle types demonstrated increasing GdA expression throughout the late luteal phase. A significant positive correlation was noted between GdA expression and serum E2 levels (r = 0.5, P<.001) in natural cycles and advanced histology in COH cycles (r = 0.63, P=.01). Neither LH nor P4 were correlated with endometrial GdA expression. CONCLUSION(S): COH cycles have a significantly increased endometrial GdA expression throughout the implantation phase of the luteal cycle when compared with normal menstrual cycles. The increased expression may affect implantation during COH cycles.

Adult↗

Histochemical localization of endometrial insulin-like growth factor binding protein-1 and -3 during the luteal phase in controlled ovarian hyperstimulation cycles: a controlled study.

OBJECTIVE: To determine if controlled ovarian hyperstimulation (COH) affects the endometrial expression of IGFBP-1 and IGFBP-3. DESIGN: Prospective, controlled study. SETTING: Tertiary infertility clinic. PATIENT(S): Eighteen oocyte donors undergoing COH cycles and 17 natural cycle controls. INTERVENTION(S): Controlled ovarian hyperstimulation, endometrial biopsies. MAIN OUTCOME MEASURE(S): Immunohistochemical scoring of endometrial IGFBP-1 and -3 expression, morphological endometrial dating, and serum estradiol (E(2)), LH, and progesterone (P(4)) concentrations. RESULT(S): No statistically significant difference was observed between natural and stimulated cycles in change in IGFBP-1 or -3 over standardized cycle days throughout the window of embryo implantation (days 17-24). The IGFBP-1 and -3 expression was zero or near zero for both the natural and COH cycles until day 12-13. Both IGFBPs showed increased production throughout the secretory phase. Advanced endometrial histology (>/=1 day) in glands and stroma was noted in COH cycles. Significant positive correlations of E(2) and P(4) were noted with IGFBP-1 and -3 but not with advanced endometrial morphology in the COH cycles. CONCLUSION(S): The COH cycles have no significantly increased endometrial IGFBP-1 or -3 expression throughout the implantation phase of the luteal cycle compared with normal menstrual cycles. Both IGFBPs were absent in the proliferative phase and increased throughout the secretory portion of the embryo implantation window.

Adult↗

Epithelial expression of glycodelin in biphasic synovial sarcomas.

Glycodelin is a 28 kDa glycoprotein of the lipocalin family that was previously considered to be specific for the reproductive tract. Glycodelin is found in the secretory glandular epithelium of endometrium and in seminal vesicles. Given the cyclic differentiation of normal endometrial epithelium, we studied by immunohistochemistry a possible expression of glycodelin in other tissues displaying stroma-to-epithelium maturation. We report here that 11/11 biphasic synovial sarcomas expressed glycodelin in the cells exhibiting epithelial or glandular differentiation while the sarcomatous spindle cells remained negative. Glycodelin was also found in secreted material in the lumina of the gland-like structures. In only 1 of the 7 monophasic synovial sarcomas studied, focal glycodelin reactivity was seen in some flattened spindle cells. The expression of glycodelin in biphasic synovial sarcoma tissue was further verified by the demonstration of glycodelin mRNA by reverse transcriptase-polymerase chain reaction. Considering the monoclonal origin of synovial sarcomas, our findings raise the intriguing possibility that activation of expression of the glycodelin gene is involved in the molecular regulation of mesenchyme-to-epithelium differentiation.

Epithelium↗

Somatotropic axis and body weight in pre-menopausal and post-menopausal women: evidence for a neuroendocrine derangement, in absence of changes of insulin-like growth factor binding protein concentrations.

The altered function of the somatotropic axis observed in perimenopause may underlie the changes in body weight and fat distribution. The aim of the present study was to evaluate, in pre-menopausal and post-menopausal women with body mass index (BMI) > or = or <25, the basal plasma levels of growth hormone (GH), insulin-like growth factor (IGF)-I and -II, IGF binding protein (IGFBP)-1 and -3, and the response of GH and IGFBP-1 and -3 to GH releasing hormone (GHRH) and GHRH plus arginine tests. GH and IGF-I basal concentrations were significantly higher in pre-menopausal than in post-menopausal women, while IGF-II, IGFBP-1 and IGFBP-3 concentrations did not vary significantly. IGFBP-1, but not IGFBP-3, concentrations were higher in lean than in obese patients. Insulin concentrations were significantly higher in obese patients, while no differences were observed between pre-menopausal and post-menopausal women. In all subjects, GH concentrations increased significantly during GHRH test; pre-menopausal and lean women showed a higher response compared to post-menopausal and obese women. The GHRH plus arginine test stimulated GH response in all women, irrespective of age and BMI. IGFBP-1 and -3 concentrations did not vary in response to GHRH or GHRH plus arginine tests. The somatotropic axis undergoes modifications in post-menopausal women, apparently not involving IGFBP-1 and -3. Arginine infusion restores the response of GH to GHRH, in both post-menopausal and obese subjects. A somatostatinergic hyperactivity at the climateric period may underlie the changes both in body weight and somatotropic axis.

Arginine↗

Expression of glycans linked to natural killer cell inhibition on the human zona pellucida.

Protection of the gametes from potential immune responses is a primary function in human reproduction. The primary cell type responsible for the innate immune response in the uterus is the natural killer (NK) cell. NK cells normally recognize Class I major histocompatibility (MHC) molecules on potential target cells. Since both human spermatozoa and human oocytes do not express Class I MHC molecules on their surfaces, the appropriate cell surface signal that abrogates potential NK cell-mediated responses directed against these gametes is unknown. Recent evidence indicates that surface expression of bisecting-type N-linked glycans protects cells sensitive to NK cell-mediated lysis. We report that the zona pellucida of the human egg and plasma membranes of human spermatozoa potentially bind a lectin probe specific for bisecting type glycans in a carbohydrate-dependent manner. Since the innate immune response in the uterus is primarily mediated by NK cells, our results indicate that human gametes may be protected from this response by expressing bisecting type N-linked glycans on their surfaces.

Carbohydrate Conformation↗

The role of relaxin in glycodelin secretion.

Glycodelin is a glycoprotein named for its unique carbohydrate structure. Glycodelin is produced by the secretory endometrium during the late luteal phase and returns to baseline during menses of the ensuing cycle, whereas in conceptive cycles it rapidly increases. Although progesterone and possibly estradiol are required for glycodelin production, they are not directly involved in the synthesis and release of this protein. Their role may be development of the endometrial secretory glandular elements, whereas other factors are required to initiate and maintain glycodelin secretion. The pattern of relaxin secretion during the luteal phase and early pregnancy is similar to that of glycodelin, but their profiles have not been determined simultaneously. To investigate the relationship of relaxin and glycodelin, two studies were conducted. In the first study, relaxin, glycodelin, and ovarian steroids were measured in daily serum samples from nonconceptive and conceptive natural cycles. Profiles of relaxin and glycodelin were closely associated, with the onset of relaxin preceding glycodelin secretion by 1-2 days in nonconceptive cycles, and the pregnancy-associated increases in each hormone differing by about 2 days. The second study tested the hypothesis that relaxin stimulates glycodelin secretion. Samples were obtained from patients injected with human relaxin for 28 days. In subjects demonstrating ovarian cyclicity, glycodelin secretion was elevated, but it was not detected in subjects without ovarian cyclicity or in placebo-treated control subjects. This study reveals a close temporal and quantitative relationship between relaxin and glycodelin profiles in the late luteal phase and early pregnancy. It also demonstrates that relaxin administration can stimulate glycodelin production from a developed endometrium. This is the first report of a nonsteroidal ovarian factor that controls glycodelin secretion, and these results suggest a function for relaxin during early pregnancy. Glycodelin is a potent inhibitor of sperm zona pellucida binding by virtue of its extensive carbohydrate structure, but it is normally at a nadir in the periovulatory period. The data demonstrate that relaxin can stimulate glycodelin secretion throughout the menstrual cycle, including the periovulatory period, when relaxin-induced glycodelin secretion could have a contraceptive effect.

Adolescent↗

Gender-specific glycosylation of human glycodelin affects its contraceptive activity.

We have recently demonstrated that a human amniotic fluid-derived glycoprotein, glycodelin-A (GdA; previously known as PP14 or PAEP), potently inhibits gamete binding in an established sperm-egg binding system and expresses immunosuppressive activities directed against a variety of different immune cell types. GdA has high mannose-, hybrid-, and complex-type biantennary oligosaccharides including structures with fucosylated or sialylated N, N'-diacetyllactosediamine (GalNAcbeta1-4GlcNAc) sequences, which are rare in other human glycoproteins. We now report the characterization of glycodelin-S (GdS). This is a human seminal plasma glycoprotein that is immunologically indistinguishable from GdA, but unlike the latter, does not inhibit human sperm-zona pellucida binding under hemizona assay conditions. Analysis of the N-glycans of GdS by mass spectrometry revealed that all glycoforms of GdS are different from those of GdA. GdS glycans are unusually fucose-rich, and the major complex-type structures are biantennary glycans with Lewisx (Galbeta1-4(Fucalpha1-3)GlcNAc) and Lewisy (Fucalpha1-2Galbeta1-4(Fucalpha1-3)GlcNAc) antennae. It is probable that these highly fucosylated epitopes contribute to the immunosuppressive activity of human seminal plasma and to the low immunogenicity of sperm. This study provides the first evidence for gender-specific glycosylation that may serve to regulate key processes involved in human reproduction.

Contraceptive Agents↗

Structural analysis of the oligosaccharides derived from glycodelin, a human glycoprotein with potent immunosuppressive and contraceptive activities.

Glycodelin, also known as placental protein 14 (PP14) or progesterone-associated endometrial protein (PAEP), is a human glycoprotein with potent immunosuppressive and contraceptive activities. In this paper we report the first characterization of glycodelin-derived oligosaccharides. Using strategies based upon fast atom bombardment and electrospray mass spectrometry we have established that glycodelin is glycosylated at Asn-28 and Asn-63. The Asn-28 site carries high mannose, hybrid and complex-type structures, whereas the second site is exclusively occupied by complex-type glycans. The major non-reducing epitopes in the complex-type glycans are: Gal beta 1-4GlcNAc (lacNAc), GalNAc beta 1-4GlcNAc (lacdiNAc), NeuAc alpha 2-6Gal beta 1-4GlcNAc (sialylated lacNAc), NeuAc alpha 2-6Gal beta 1-4GlcNAc (sialylated lacdiNAc), Gal beta 1-4(Fuc alpha 1-3)GlcNAc (Lewisx), and GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc (lacdiNAc analogue of Lewisx). It is possible that the oligosaccharides bearing sialylated lacNAc or lacdiNAc antennae may manifest immunosuppressive effects by specifically blocking adhesive and activation-related events mediated by CD22, the human B cell associated receptor. Oligosaccharides with fucosylated lacdiNAc antennae have previously been shown to potently block selectin-mediated adhesions and may perform the same function in glycodelin. The potent inhibitory effect of glycodelin on initial human sperm-zona pellucida binding is consistent with our previous suggestion that this cell adhesion event requires a selectin-like adhesion process. This result also raises the possibility that a convergence between immune and gamete recognition processes may have occurred in the types of carbohydrate ligands recognized in the human.

Amino Acid Sequence↗

Factors affecting fertilization: endometrial placental protein 14 reduces the capacity of human spermatozoa to bind to the human zona pellucida.

OBJECTIVE: To examine whether placental protein 14 (PP14) may affect directly those sperm functions crucial to fertilization and early embryo development. DESIGN: In these prospective studies, we evaluated semen samples of fertile men incubated under capacitating conditions with and without PP14. SETTING: Academic tertiary institution. INTERVENTIONS: Biologically active PP14 was purified from human midtrimester amniotic fluid by anion exchange and immunoaffinity chromatography. After separation of the motile fraction, spermatozoa were incubated for 30 minutes with or without PP14 (concentration range of 0.01 to 100 micrograms/mL), washed, and then aliquots were prepared for use in the different assays. Human sperm-zona pellucida (ZP) binding was assessed using the hemizona assay (HZA) in a 4-hour gametes coincubation period. Sperm motility parameters were evaluated using a computerized semen analyzer. The acrosome reaction (AR) was determined by fluorescein isothiocyanate-conjugated Pisum sativum agglutinin and indirect immunofluorescence. MAIN OUTCOME MEASURES: Sperm-ZP binding, sperm motility patterns, and AR. RESULTS: Preincubation of sperm (and not the hemizonae) with PP14 produced a significant and dose-dependent inhibition of binding in the HZA. Monoclonal antibodies generated against PP14 showed no direct effect in the HZA and partially neutralized the inhibitory activity of PP14 in the HZA. Insulin-like growth factor binding protein-1 (IGFBP-1), an endometrial stromal cell product, showed no effect in the HZA. Neither PP14 nor IGFBP-1 interfered with sperm motility parameters or the AR. CONCLUSIONS: Placental protein 14 produced a potent, fast, and dose-dependent inhibition of binding of human spermatozoa to the human ZP without affecting other prefertilization events (i.e., hyperactivated motility or AR). The detrimental effect on sperm-zona interaction seems to be specific for this endometrial epithelial protein (not observed with an endometrial stromal product) and may have fundamental bearance to the fertilization process thus providing a mechanism for endometriosis-related infertility.

Acrosome↗

Overnight secretion pattern of growth hormone, sex hormone binding globulin, insulin-like growth factor-1 and its binding protein in obese and non-obese women with polycystic ovarian disease.

The pathophysiological mechanism underlying polycystic ovarian disease (PCOD) is different in obese and lean women. In obese patients the basic disorder is insulin resistance and hyperinsulinemia. In non-obese women the dominant derangement is a relative excess of luteinizing hormone (LH) and growth hormone (GH) production. The levels of GH, LH, sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein-1 (IGFBP-1) were significantly lower and insulin levels considerably higher in obese PCOD women as compared to their non-obese counterparts. There was, however, no difference in the mean IGF-1 levels found in these two groups. The present study was designed to investigate whether, in addition to the mean levels, the overnight pattern of GH, IGF-1, IGFBP-1 and SHBG differed in obese women with polycystic ovaries as compared to that observed in the non-obese PCOD patients. Eight women with PCOD diagnosed by clinical, sonographic and hormonal means were studied. Four had basal body mass index exceeding 27. Blood samples were collected every 20 min over a period of 8 h, starting at 23:00 h. Twenty-four samples were collected from each patient and examined in one batch for GH, IGF-1, IGFBP-1, SHBG and insulin. The secretion patterns of the above substances during the late night (23:00-03:00 h) and early morning (03:00-07:00 h) hours were examined and compared in obese and non-obese PCOD women. Neither GH nor IGF-1 showed a distinct overnight secretion pattern. The overnight secretion patterns of IGFBP-1 and SHBG were similar in obese and non-obese women--the former showing a constant rising during the night and the latter exhibiting a converse trend. The integrated insulin levels were much higher during the late night as compared to early morning hours in all patients. It is proposed that the specific secretion pattern of IGFBP-1 is not directly dependent on body fat mass but is regulated by insulin in both obese and non-obese patients.

Adult↗

Hematopoietic placental protein 14. An immunosuppressive factor in cells of the megakaryocytic lineage.

Placental protein 14 (PP14), an immunosuppressive molecule previously known to be expressed in the female and male reproductive tracts only, was shown to be expressed by hematopoietic cells of the megakaryocytic lineage. Northern blot analysis confirmed the induction specificity of PP14 mRNA in phorbol ester-treated K562 cells. Potent immunosuppressive activity in conditioned medium from phorbol ester-treated K562 cells was attributed to hematopoietic PP14 by anti-PP14 antibody blocking. Immunoprecipitation with anti-PP14 antibodies from conditioned medium revealed two distinct PP14 protein isoforms, designated PP14.1 and PP14.2. Polymerase chain reaction cloning and analysis demonstrated the presence of distinct mRNA counterparts to PP14.1 and PP14.2 that had not been resolved by Northern blot analyses. Hematopoietic PP14.1 mRNA corresponds in size to endometrial PP14 mRNA, whereas the smaller hematopoietic PP14.2 mRNA displays an internal in-frame 66-nucleotide deletion that can be explained by alternative splicing and predicts a 22-amino-acid deletion in the encoded gene product. Both PP14 mRNA isoforms were additionally detected by reverse transcriptase polymerase chain reaction analyses in two human megakaryocytic cell lines and in normal human megakaryocytes and platelets. PP14 mRNA was not detected by reverse transcriptase polymerase chain reaction in a panel of nonhematopoietic, nonendometrial tissues examined. The finding of hematopoietic PP14 within the megakaryocytic lineage provides an additional regulatory link between the coagulation and immune systems in normal and pathological settings.

Base Sequence↗

Insulin-like growth factor-I (IGF-I) inhibits production of IGF-binding protein-1 while stimulating estradiol secretion in granulosa cells from normal and polycystic human ovaries.

We have investigated the actions of FSH and insulin-like growth factor-I (IGF-I) on the production of IGF-binding protein-1 (IGFBP-1) by granulosa cells from unstimulated normal and polycystic (PCO) human ovaries and related these effects to those on estradiol (E2). IGFBP-1 concentrations were measured in granulosa cell-conditioned medium (48-h culture with 10(-7) M testosterone) and follicular fluid. IGF-I (50 ng/mL), in the absence of FSH, stimulated E2 production by granulosa cells from both normal and polycystic ovaries, and there was a synergistic action between IGF-I and FSH. Granulosa cells secreted IGFBP-1 in concentrations ranging from 20-500 pg/1000 cells.48 h, with cells from two of four normal and three of four polycystic ovaries showing a dose-related increase in IGFBP-1 production in response to FSH. In contrast, the addition of as little as 100 pg/mL IGF-I to cells incubated with testosterone or testosterone plus FSH, caused complete inhibition of IGFBP-1 production. FSH treatment produced the expected dose-related increase in E2 accumulation. IGFBP-1 was detectable in fluid from all sizes of follicle tested, but there was no correlation of IGFBP-1 concentrations with follicle size and no difference between normal and polycystic ovaries. These data indicate that IGFBP-1 and E2 are differentially regulated by IGF-1 in the human ovary.

Carrier Proteins↗

Inhibitory effects of insulin-like growth factor-binding proteins on steroidogenesis by human granulosa cells in culture.

The effects of insulin-like growth factor-binding proteins (IGFBPs) 1 and 3 on steroidogenesis by human granulosa cells has been examined. Both IGFBP-1 and IGFBP-3 produced a dose-related inhibition of IGF-I-stimulated oestradiol accumulation in granulosa cell-conditioned medium with complete reversal of the effects of IGF-I in the presence of a molar excess of binding protein. IGFBPs 1 and 3 also exerted a small (25-40%) but significant and consistent inhibition of oestradiol secretion in response to follicle-stimulating hormone (FSH) alone. The progesterone response to IGF-I was inhibited by IGFBPs 1 and 3 but there was no effect on FSH-stimulated progesterone production. These data support the concept of a physiologically important intraovarian IGF system in the human ovary and demonstrate an unequivocally inhibitory effect of IGFBPs 1 and 3 on IGF-I-stimulated granulosa cell steroidogenesis.

Carrier Proteins↗

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.

Analysis of Variance↗