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Markku Seppälä

Publications and source records attributed to Markku Seppälä.

16 recordsLinked to original sources

Extracellular matrix-induced changes in expression of cell cycle-related proteins and proteasome components in endometrial adenocarcinoma cells.

OBJECTIVE: Extracellular matrix (ECM) components regulate growth and differentiation of epithelial cells, and impaired cell-ECM interaction may lead to increased cell proliferation and tumorigenesis. Whereas ECM has been shown to alter cellular morphology and reduce proliferation of HEC-1B endometrial adenocarcinoma cells, little is known about the underlying changes in gene expression. The purpose of this study was to investigate these changes. METHODS: We studied by cDNA array the effects of ECM components, as present in Matrigel basement membrane cell culture matrix, on gene expression in HEC-1B endometrial adenocarcinoma cells in respect of the same cells cultured on conventional plastic surface. Some of the changes were confirmed by protein analyses. RESULTS: As expected, several growth-promoting genes were downregulated, while many genes associated with growth restriction were upregulated in Matrigel-grown carcinoma cells. Also, the expression of many 20S proteasome components was downregulated. The observed changes point to a less malignant phenotype of Matrigel-grown tumor cells, supported by reduced growth characteristics and morphology. CONCLUSION: The study provides further insight into the mechanisms whereby ECM components may participate in the regulation of cell growth--by reducing expression of growth-promoting genes and increasing expression of the genes associated with growth restriction.

Adenocarcinoma↗

Glycodelin is present in pinopodes of receptive-phase human endometrium and is associated with down-regulation of progesterone receptor B.

OBJECTIVE: To test the hypothesis that glycodelin is localized on pinopodes and correlates with temporal immunostaining of leukemia inhibitory factor (LIF), LIF receptor (LIFR), and progesterone receptor B (PRB). DESIGN: Prospective clinical study. SETTING: Hospital-based reproductive health unit and research laboratories. PATIENT(S): Twenty-five healthy fertile women with normal menstrual cycles. INTERVENTION(S): Endometrial biopsy specimens were obtained from healthy fertile women in the luteal phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Immunohistochemical staining of glycodelin, ultrastructural immunostaining of glycodelin, and double staining of glycodelin and PRB. RESULT(S): Glycodelin is present in the glands when pinopodes appear. Glycodelin is localized on pinopodes but is also secreted from luminal epithelial cells regardless of pinopode formation. There was a negative correlation between glycodelin secretion from the glands and PRB staining. A weak correlation between the presence of LIFR (but not LIF) and glycodelin was found. CONCLUSION(S): Pinopode appearance, intense staining of LIFR in pinopodes and glycodelin staining in the glands are synchronized events. Down-regulation of PRB in the endometrium is concomitant with the presence of glycodelin in the endometrium, suggesting interaction.

Adult↗

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Journal Article↗

Glycodelin reduces carcinoma-associated gene expression in endometrial adenocarcinoma cells.

OBJECTIVE: Glycodelin is a major secretory glycoprotein of differentiated endometrial epithelium, rarely expressed in proliferative endometrium or endometrial cancer. We aimed to elucidate its role in growth and gene expression of endometrial adenocarcinoma cells, and hypothesized that glycodelin affects cell growth and tumor-associated gene expression. STUDY DESIGN: Endometrial adenocarcinoma HEC-1B cells were transfected with glycodelin cDNA in both antisense and sense orientations. Cellular morphology, cell proliferation, and gene expression were compared between native and transfected cells. RESULTS: Compared with native and antisense-transfected carcinoma cells, sense-transfected, glycodelin-producing carcinoma cells showed reduced proliferation, morphologic changes, and altered expression of cancer-related genes. Notably, anti-apoptotic Bcl-XL and MUC1 genes were down-regulated. CONCLUSION: Reduction by glycodelin transfection of carcinoma cell proliferation and expression of MUC1 and Bcl-XL is significant because these genes are often overexpressed in human cancers--MUC1 is linked to invasive growth and metastases, and both confer resistance to chemotherapy. These results suggest a novel mechanism whereby malignant growth of endometrial adenocarcinoma cells is regulated.

Adenocarcinoma↗

Glycodelin responses to hyperinsulinaemic clamp vary according to basal serum glycodelin concentration.

OBJECTIVE: Treatment with metformin, an insulin-lowering agent, increases serum glycodelin, a progesterone-regulated lipocalin protein of the reproductive axis that may play a role in foeto-maternal defence mechanisms. This finding led to the hypothesis that insulin might decrease serum glycodelin concentration. DESIGN, PATIENTS AND MEASUREMENTS: Euglycaemic hyperinsulinaemic clamp experiments (n = 50) were carried out on 28 women of reproductive age (range 25-47 years; mean +/- SEM 39 +/- 1.0 years), and the results were analysed with respect to their baseline serum progesterone (< 10 or > or = 10 nmol/l) and glycodelin (< 10 or > or = 10 microg/l, equivalent to < 357 or > or = 357 pmol/l) concentrations at the onset of the clamp. Ten clamp experiments were performed on five women wearing a levonorgestrel-releasing intrauterine device (IUD), and these were analysed as a separate group. RESULTS: Contrary to the hypothesis, no acute glycodelin-lowering effect of insulin was found in any of the groups studied. All the small rises in glycodelin levels detected during acute hyperinsulinaemia occurred in the comparisons of medians and not means, and all such changes took place within the limits seen in the women with no progesterone exposure. In the group with low progesterone/low glycodelin (n = 21), glycodelin showed a small but significant increase at 30 and 90 min of the clamp (P < 0.01). In the group with elevated progesterone/low glycodelin (n = 11), there was a slight glycodelin increase at 30 min (P < 0.05), whereas no increase was found in the group with elevated glycodelin levels (n = 8). In the clamp experiments on women with levonorgestrel-releasing IUD, the basal glycodelin level was low in all cases and, as in the other women with low glycodelin levels, glycodelin was slightly increased at 30, 60 and 90 min of hyperinsulinaemia (P < 0.01). CONCLUSIONS: The results rule out any acute glycodelin-reducing effects of insulin, although indirect long-term effects mediated by insulin on glycodelin secretion cannot be excluded.

Adult↗

Sex hormone-binding globulin and insulin-like growth factor-binding protein-1 as indicators of metabolic syndrome, cardiovascular risk, and mortality in elderly men.

Two binding proteins, SHBG and IGF-binding protein-1 (IGFBP-1), are both down-regulated by insulin and therefore could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk. We compared serum SHBG and IGFBP-1 as potential markers of abnormal glucose tolerance, the metabolic syndrome, diabetes mellitus, cardiovascular risk factors, and total, cardiovascular, and coronary heart disease mortality in elderly men. Of the original cohort of 1711 men, 524 were alive on January 1, 1989, and 413 participated in the 30-yr examination, of whom 335 men, aged 70-89 yr, formed the study group for the present analysis. Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus. SHBG was less influenced by body mass index than IGFBP-1. Low SHBG indicated increased cardiovascular and coronary disease mortality; the association remained after adjustment for abnormal glucose tolerance, but not after adjustment for prevalent cardiovascular disease. IGFBP-1 had no association with mortality. It is concluded that low SHBG is a better indicator of increased cardiovascular mortality than low or high IGFBP-1.

Aged↗

Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy.

The polycystic ovary syndrome (PCOS) is associated with an increased rate of early pregnancy loss (EPL). Hyperinsulinemia is an independent risk factor for EPL and has been found to decrease levels of glycodelin and IGF binding protein-1 (IGFBP-1), two major endometrial proteins. We hypothesized that serum glycodelin IGFBP-1 concentrations would be reduced in women with PCOS during the first trimester of pregnancy. Fasting serum insulin, glycodelin, and IGFBP-1 were measured, and oral glucose tolerance tests were performed in 72 women with PCOS and 62 normal women. Each woman was seen once and assigned to one of three gestational groups: wk 3-5, 6-8, and 9-11. The insulin sensitivity index during oral glucose tolerance test was lower in women with PCOS compared with normal women throughout the first trimester (P < 0.0001). Both serum glycodelin and IGFBP-1 were markedly lower in women with PCOS (for glycodelin: wk 3-5, P < 0.0001; wk 6-8, P = 0.03; wk 9-11, P = 0.19; and for IGFBP-1: wk 3-5 and 6-8, P < 0.0001; wk 9-11, P = 0.0003). Comparing women with PCOS who experienced EPL with those who did not, serum glycodelin was significantly lower during wk 3-8 (P < 0.02) and serum IGFBP-1 during wk 9-11 (P = 0.003). During the first trimester, serum glycodelin and IGFBP-1 concentrations are markedly decreased in PCOS, implicating endometrial epithelial and stromal dysfunction during periimplantation and early pregnancy as a possible mechanism for EPL in PCOS. These decreases are likely to be secondary to hyperinsulinemia and reduced insulin sensitivity.

Abortion, Spontaneous↗

Glycodelin in ovarian serous carcinoma: association with differentiation and survival.

Ovarian cancer consists of many subtypes, serous carcinoma being the most common of them. In addition to the histopathological subtype, grading, clinical staging, and the amount of residual tumor, a great number of putative prognostic markers have been introduced. This study addresses in ovarian serous carcinoma the role of glycodelin, the major progesterone-regulated lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation. Glycodelin expression was determined by immunohistochemistry of tissue microarrays in ovarian serous carcinomas from 460 patients, and the results were analyzed with respect to progesterone receptor subtype A (PRA) and progesterone receptor subtype B (PRB), clinical parameters, and survival. Glycodelin was localized to the cytoplasm of tumor cells, whereas vascular endothelium in tumor tissue was glycodelin-negative. Glycodelin expression was more frequent in well-differentiated (grade I, 79%) than in poorly differentiated carcinomas (grade III, 51%; P < 0.0001), and it was also more frequent in early-stage compared with advanced-stage carcinomas (P = 0.002). Nuclear PRA and PRB were often coexpressed with cytoplasmic glycodelin. Although this was not consistent in all tumors, there was a positive correlation between the presence of glycodelin and PRs in the tumor (P < 0.02), but not between the presence of, or the absence of, glycodelin in tumor and the CA-125 serum concentration. Although in multivariate analysis glycodelin was not an independent variable, the patients with glycodelin-expressing tumors showed a higher 5-year overall survival compared with those with glycodelin-negative tumors (55 versus 39%; P < 0.0001; hazard ratio in univariate analysis, 0.57; confidence interval, 0.44-0.74). This difference was notable in patients with grade I tumors and stage III disease. In the latter group, the 10-year survival probability of patients with glycodelin-positive tumors was more than twice as high as that in women with glycodelin-negative tumors. This was also found within well-defined clinical categories, e.g., stage III/grade II and stage III/grade III carcinomas, in which patients with glycodelin-positive tumors carried significantly better 10-year overall survival compared with those with glycodelin-negative tumors. It is concluded that, in ovarian serous carcinoma, glycodelin expression portends better prognosis, probably because of its differentiation-related disposition.

Adolescent↗

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-1 in elderly people: relationships with cardiovascular risk factors, body composition, size at birth, and childhood growth.

The IGF system is important in regulation of fetal and childhood growth. In later life, IGF-I and IGF-binding protein-1 (IGFBP-1) have been implicated in the pathogenesis of arteriosclerosis. They are, thus, potential candidates in explaining the link between early growth and adult cardiovascular disease. We measured fasting serum IGF-I and IGFBP-1 concentrations in 394 men and women from a cohort of 7086 individuals, born between 1924 and 1933 in Helsinki, Finland, whose weight and height were recorded at birth and from 7 to 15 yr of age. They also underwent clinical examination, including measurement of body fat using bioimpedance, blood pressure, glucose tolerance, and plasma insulin and fibrinogen concentrations. Serum IGF-I was positively correlated with fasting glucose (r = 0.10, P = 0.06) and fibrinogen (r = 0.19, P = 0.0001) concentrations and blood pressure (systolic and diastolic r = 0.10, P </= 0.05) and inversely with percentage body fat (r = -0.13, P = 0.01) and waist circumference (r = -0.11, P = 0.03). IGFBP-1 was inversely correlated with adult body mass index (BMI) (r = -0.46, P < 0.0001), fasting glucose and insulin concentrations, and blood pressure. There were correlations between the adult level of IGFBP-1 and birth weight (r = 0.11, P = 0.03) and ponderal index (weight/length(3)) at birth (r = 0.13, P = 0.01), but IGF-I was not related to birth measurements. There were interactive effects between childhood height or BMI and adult BMI on IGF-I and IGFBP-1 in adulthood. Tall height and high BMI at 7 yr were associated with low IGF-I (P = 0.03 for height and P = 0.003 for BMI) and high IGFBP-1 (P = 0.02 and P = 0.06) in adulthood but only in those subjects whose current BMI was below median. On further analysis these interactive effects were particularly strong for height in childhood and adult lean BMI (lean body mass/height(2)). Among men and women of below-average lean BMI, tall height at 7 yr was associated with low adult IGF-I (P = 0.007) and high IGFBP-1 (P = 0.0004) concentrations [interaction (7-yr height x adult lean BMI); P = 0.008 for IGF-I and 0.001 for IGFBP-1]. There is no evidence that reduced fetal growth programs IGF-I concentrations in old age. An association between small size at birth and low IGFBP-1 concentrations may in part reflect fetal programming effects on insulin resistance. Given the anabolic effects of the GH-IGF-I axis, subjects with tall height in childhood but low adult lean body mass may be at risk of late-life GH-IGF-I axis dysfunction. Prospective studies should address whether this group is susceptible to type 2 diabetes, coronary heart disease, and osteoporosis.

Adolescent↗

Prostate-specific antigen and other prostate-derived proteases cleave IGFBP-3, but prostate cancer is not associated with proteolytically cleaved circulating IGFBP-3.

BACKGROUND: Proteolysis of insulin-like growth factor-binding proteins (IGFBPs) may increase IGF-mediated growth stimulation and development of cancer in the organs producing large amounts of proteases, such as the prostate. METHODS: We studied proteolysis of IGFBP-3 by three prostate-derived proteases, namely prostate specific antigen (PSA), human kallikrein 2 (hK2), and trypsin, and also by native seminal plasma. Cleavage of 125I-IGFBP-3 was studied by SDS-PAGE and autoradiography. We also used two different sandwich-type IGFBP-3 immunoassays, called "intact" and "total" IGFBP-3 assays. These assays differ in their capacity to recognize proteolytically degraded IGFBP-3. RESULTS: HK2, PSA, and trypsin all cleaved IGFBP-3 at the concentrations normally present in seminal plasma. The IGFBP-3 cleavage by seminal plasma was inhibited by ZnCl2, which strongly inhibits hK2 and PSA, but not by a specific trypsin inhibitor. The IGFBP-3 fragments resulting from proteolytic cleavage by PSA, hK2, or trypsin were undetectable in the "intact IGFBP-3 assay," whereas the "total IGFBP-3 assay" also detected the proteolytic fragments. No increased fragmentation of IGFBP-3 was found in serum of 659 men with elevated PSA concentrations, of whom 178 had a proven prostate cancer. Furthermore, the IGFBP-3 levels were not associated with the PSA concentrations. CONCLUSIONS: These results show that, while seminal plasma and prostate-derived proteases can cleave IGFBP-3, in patients with prostate cancer the circulating IGFBP-3 is not significantly proteolyzed by either PSA, hK2, or trypsin.

Cell Division↗

Effect of normal endometrial stroma on growth and differentiation in Ishikawa endometrial adenocarcinoma cells.

Endometrial cancer is characterized by alterations in the stromal cells and the supporting extracellular matrix in addition to the intrinsic alterations of the malignant epithelial cells. We have developed a cell culture model that demonstrates the role of stromal cells in the regulation of proliferation, hormone responsiveness, and differentiation of an endometrial adenocarcinoma cell line (Ishikawa). Conditioned medium (CM) was collected from normal primary human endometrial stromal cells grown on plastic or within the basement membrane extract, Matrigel. The CM produced by stromal cells cultured in contact with Matrigel markedly inhibited Ishikawa cell proliferation compared with CM from stromal cells cultured on plastic. Ishikawa cell proliferation varied with steroid hormone treatment in the presence of CM from stromal cells embedded in Matrigel. When the Ishikawa cells were placed in coculture in contact with stromal cells in Matrigel, production of a differentiated epithelial secretory product, glycodelin, was induced. Gene expression of stromal cell hormone receptors, growth factors, and integrins was analyzed by reverse transcription-PCR in the presence of Matrigel to determine the potential factors involved in stromal regulatory function. These combined studies imply that the phenotype of the Ishikawa cells can be induced to differentiate to more closely resemble normal endometrial epithelium by reintroduction of stromal factors and appropriate extracellular matrix. Additionally, the study shows that basement membrane proteins influence the regulatory function of stromal cells as they mediate epithelial cell growth.

Adenocarcinoma↗

Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 in premature rupture of membranes.

BACKGROUND: The aim of the study was to evaluate whether the circulating levels of insulin-like growth factor-I (IGF-I) and its major circulating binding protein, IGFBP-3, are affected in premature rupture of membranes (PROM) and preterm delivery. METHODS: The levels of IGF-I and IGFBP-3 were measured in 32 pregnant women with PROM and in 27 healthy gestational age-matched pregnant women. Statistical analyzes were performed by analysis of variance. RESULTS: All the patients with PROM had preterm delivery, at a gestational age of 31.9 +/- 0.4 weeks (mean +/- SEM). In the control subjects, pregnancy proceeded to term. In the PROM patients, the serum IGF-I and IGFBP-3 levels (289 +/- 21 ng/ml and 8248 +/- 407 ng/ml, respectively) were not statistically different from those in the control subjects (275 +/- 22 ng/ml and 7579 +/- 488 ng/ml). Seventeen patients with PROM showed a rise in serum C-reactive protein, indicating subclinical intrauterine infection. Also in this subgroup of patients the levels of serum IGF-I (281 +/- 27 ng/ml) and IGFBP-3 (9010 +/- 633 ng/ml) were not different from those in the control subjects. Before delivery, serial serum samples were available from 22 patients with PROM. No consistent changes in IGF-I or IGFBP-3 concentrations were seen during the mean follow-up period of 9 days. CONCLUSIONS: IGF-I and IGFBP-3 do not appear to play any significant role in the maintenance of pregnancy in PROM patients with preterm delivery, whether or not associated with emerging intrauterine infection.

Adult↗

Monoclonal antibodies, immunofluorometric assay, and detection of human semenogelin in male reproductive tract: no association with in vitro fertilizing capacity of sperm.

Semenogelin plays an important role in sperm clotting and is degraded into smaller fragments by prostate-specific antigen (PSA) during clot liquefaction. Semenogelin and its fragments inhibit sperm motility in vitro. We studied the expression of semenogelin I mRNA and its localization in various tissues of the male genital tract. We also studied semenogelin concentrations with respect to sperm parameters and the outcome of in vitro fertilization. Semenogelin protein was detected by immunohistochemical staining and semenogelin I mRNA was detected by Northern blot analysis in the seminal vesicles and ampullary part of the vas deferens, whereas specimens from the prostate, epididymis, testis, and the female genital tract were negative. Using monoclonal antibodies against semenogelin, an immunofluorometric assay was developed to measure semenogelin levels in seminal plasma and to evaluate possible correlations with sperm parameters and fertilization in vitro. No correlation was found between the semenogelin concentration and the volume of the ejaculate, sperm concentration, sperm motility, or in vitro fertilization rate. Semenogelin levels were positively correlated with the total protein concentration in seminal plasma, and there was an inverse correlation between the concentration of semenogelin and that of PSA. The levels of semenogelin appear to bear no relationship to the in vitro fertilization capacity of the spermatozoa.

Adult↗

Glycodelin: a major lipocalin protein of the reproductive axis with diverse actions in cell recognition and differentiation.

Glycodelin is a glycoprotein that belongs to the lipocalin superfamily. Depending on glycosylation, glycodelin appears in various isoforms. In the uterus, glycodelin-A is the major progesterone-regulated glycoprotein secreted into uterine luminal cavity by secretory/decidualized endometrial glands. The other tissues expressing glycodelin include fallopian tubes, ovary, breast, seminal vesicle, bone marrow, and eccrine glands. Glycodelin-A potently and dose-dependently inhibits human sperm-egg binding, whereas differently glycosylated glycodelin-S from seminal plasma has no such effect. Absence of contraceptive glycodelin-A in the uterus during periovulatory midcycle is consistent with an open "fertile window." Glycodelin induced by local or systemic administration of progestogens may potentially reduce the fertilizing capacity of sperm in any phase of the menstrual cycle. Glycodelin also has immunosuppressive activity. Its high concentration at the fetomaternal interface may contribute to protection of the embryonic semiallograft. Besides being an epithelial differentiation marker, glycodelin appears to play a role in glandular morphogenesis, as transfection of glycodelin cDNA into a glycodelin-negative breast cancer cells resulted in formation of gland-like structures, restricted proliferation, and induction of other epithelial markers. These various properties, as well as the chemistry, biology, and clinical aspects of glycodelin, continue to be areas of active investigation reviewed in this communication.

Cell Differentiation↗

IGF-I, IGF binding protein (IGFBP)-3, phosphoisoforms of IGFBP-1, and postnatal growth in very low birth weight infants.

Impaired postnatal growth in very low birth weight (VLBW, <1500 g) infants is per se a major clinical challenge and may also serve as a model in studying the mechanisms of growth retardation in general. This study was undertaken to characterize the role of IGFs and their binding proteins (IGFBPs), key regulators of fetal and infant growth, during the postnatal period in VLBW infants. Forty-eight VLBW infants (gestational age 27.6 +/- 2.2 wk, birth weight 923 +/- 257 g) were studied. Blood samples were drawn at 1, 2, 4, and 8 wk of age for measurements of IGF-I, IGFBP-1 (lesser phosphorylated, lpIGFBP-1, and highly phosphorylated, hpIGFBP-1), IGFBP-3, and insulin, simultaneous growth velocities being assessed by a rigorous protocol of repeated, frequent lower leg length and body weight measurements. All regression analyses were adjusted for postnatal age and repeated measurements. Lower leg growth velocity showed a positive correlation with IGF-I (P = 0.01) and IGFBP-3 (P = 0.03), and weight growth velocity with IGFBP-3 (P = 0.057) and with lpIGFBP-1/hpIGFBP-1 ratio (P = 0.01). Moreover, concurrent glucocorticoid dose showed a negative correlation with both IGFBP-1 isoforms, observable, however, only in samples with high (>10 U/liter) insulin (lpIGFBP-1, P = 0.02; hpIGFBP-1, P = 0.007). In backward multiple regression analysis, the factor remaining significantly associated with lower leg growth velocity (R(2) = 0.63) was IGF-I, and factors associated with weight growth velocity (R(2) = 0.81) were IGFBP-3 and the lpIGFBP-1/hpIGFBP-1 ratio. In conclusion, circulating IGF-I and IGFBP-3, and the lpIGFBP-1/hpIGFBP-1 ratio, reflect short-term growth velocity in VLBW infants. lpIGFBP-1 isoforms, abundant in the circulation of these infants, may thus also have properties that are at least less inhibitory, if not promoting, on the growth-stimulating action of IGF-I. Finally, the regulation of IGFBP-1 by glucocorticoids may be divergent in situations with a high or low insulin concentration.

Aging↗

Maternal serum glycodelin in premature rupture of membranes.

AIM: Few studies address decidual function in abnormal pregnancies, due obviously to shortage of appropriate markers. Glycodelin is produced by epithelial cells of pregnancy decidua. We investigated whether serum glycodelin concentrations are altered in premature rupture of membranes (PROM). METHODS: Serum glycodelin concentrations were measured in 32 women with PROM and in 27 gestational age-matched healthy women. Serum C-reactive protein (CRP) concentrations were measured to indicate infection. RESULTS: Glycodelin concentrations were similar in PROM patients and control subjects. No difference was found in glycodelin concentrations between the 17 PROM patients with CRP > 12 mg/l and controls, or between the 15 PROM patients with CRP < or = 12 mg/l and controls. There was no correlation between the highest antepartum glycodelin level and the interval from PROM to delivery. A negative correlation between the last glycodelin concentration and the birth weight of the newborns was found in the PROM patients (rs = -0.369, p = 0.038). CONCLUSIONS: Decidual epithelial cell function does not seem to be compromised in PROM. The inverse correlation between serum glycodelin and the birth weight of the newborns in PROM may be explained by the normally occurring decline of serum glycodelin with advancing pregnancy in the third trimester.

Adult↗