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Cell migration is a pivotal step in metastatic process, which requires cancer cells to navigate a complex spatially‐confined environment, including tracks within blood vessels and in the vasculature of target organs. Here it is shown that during spatially‐confined migration, the expression of insulin‐like growth factor‐binding protein 1 (IGFBP1) is upregulated in tumor cells. Secreted IGFBP1 inhibits AKT1‐mediated phosphorylation of mitochondrial superoxide dismutase (SOD2) serine (S) 27 and enhances SOD2 activity. Enhanced SOD2 attenuates mitochondrial reactive oxygen species (ROS) accumulation in confined cells, which supports tumor cell survival in blood vessels of lung tissues, thereby accelerating tumor metastasis in mice. The levels of blood IGFBP1 correlate with metastatic recurrence of lung cancer patients. This finding reveals a unique mechanism by which IGFBP1 sustains cell survival during confined migration by enhancing mitochondrial ROS detoxification, thereby promoting tumor metastasis. [ABSTRACT FROM AUTHOR]

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of Scd1 display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how Scd1 deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Abstract Purpose Subendometrial myometrium exerts wave‐like activity throughout the menstrual cycle, and uterine peristalsis is markedly reduced during the implantation phase. We hypothesized that abnormal uterine peristalsis has an adverse effect on the endometrial decidualization process. We conducted an in vitro culture experiment to investigate the effect of cyclic stretch on the morphological and biological endometrial decidual process. Methods Primary human endometrial stromal cells (HESCs) were isolated from hysterectomy specimens and incubated with or without 8‐bromo‐cyclic adenosine monophosphate (8‐br‐cAMP) and medroxyprogesterone acetate (MPA) for 3 days. After decidualization, cultures were continued for 24 hours with or without cyclic stretch using a computer‐operated cell tension system. Results Cyclic stretch significantly repressed expression of decidual markers including insulin‐like growth factor‐binding protein 1 (IGFBP1), prolactin (PRL), forkhead box O1 (FOXO1), and WNT4 on decidualized HESCs. In addition, cyclic stretch of decidualized HESCs affected the decidual morphological phenotype to an elongated shape. The alternation of F‐actin localization in decidualized HESCs was not observed in response to cyclic stretch. Conclusions These data suggest that cyclic stretch inhibits the morphological and biological decidual process of HESCs. Our findings imply that uterine abnormal contractions during the implantation period impair endometrial decidualization and contribute to infertility.

Abstract Background Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes. Methods This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined. Results In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p

Purpose: Subendometrial myometrium exerts wave‐like activity throughout the menstrual cycle, and uterine peristalsis is markedly reduced during the implantation phase. We hypothesized that abnormal uterine peristalsis has an adverse effect on the endometrial decidualization process. We conducted an in vitro culture experiment to investigate the effect of cyclic stretch on the morphological and biological endometrial decidual process. Methods: Primary human endometrial stromal cells (HESCs) were isolated from hysterectomy specimens and incubated with or without 8‐bromo‐cyclic adenosine monophosphate (8‐br‐cAMP) and medroxyprogesterone acetate (MPA) for 3 days. After decidualization, cultures were continued for 24 hours with or without cyclic stretch using a computer‐operated cell tension system. Results: Cyclic stretch significantly repressed expression of decidual markers including insulin‐like growth factor‐binding protein 1 (IGFBP1), prolactin (PRL), forkhead box O1 (FOXO1), and WNT4 on decidualized HESCs. In addition, cyclic stretch of decidualized HESCs affected the decidual morphological phenotype to an elongated shape. The alternation of F‐actin localization in decidualized HESCs was not observed in response to cyclic stretch. Conclusions: These data suggest that cyclic stretch inhibits the morphological and biological decidual process of HESCs. Our findings imply that uterine abnormal contractions during the implantation period impair endometrial decidualization and contribute to infertility. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.Methods: This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined.Results: In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p < 0.0001) and all IGFBP-1 phosphoisoforms (p < 0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain.Conclusions: Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.Trial Registration: The trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov ( NCT01240785 ) November 3, 2010. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objective: To investigate the long-term prognostic value of insulin-like growth factor-binding protein 1 in patients with acute myocardial infarction. Methods: Patients (n = 180) with admission glucose < 11 mmol/L without previously known diabetes admitted for an acute myocardial infarction in 1998-2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/ acute myocardial infarction/stroke/severe heart failure) until the end of 2011 (median 11.6 years). Fasting levels of insulinlike growth factor-binding protein 1 at day 2 were related to outcome in Cox proportional hazard regression analyses. Results: Median age was 64 years, 69% were male and median insulin-like growth factor-binding protein 1 was 20 |jg/L. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event during a median follow-up time of 11.6 years. After age adjustment, insulin-like growth factor-binding protein 1 was associated with all-cause (1.40; 1.02-1.93, p = 0.039) and cancer mortality (2.09; 1.15-3.79, p = 0.015) but not with cardiovascular death (p = 0.29) or cardiovascular events (p = 0.57). After adjustments also for previous myocardial infarction, previous heart failure and body mass index, insulin-like growth factor-binding protein 1 was still associated with all-cause mortality (1.38; 1.01 -- 1.89, p = 0.046). Conclusion: In patients with acute myocardial infarction without previously known diabetes, high insulin-like growth factor-binding protein 1 was associated with long-term all-cause and cancer mortality but not with cardiovascular events. [ABSTRACT FROM AUTHOR]

• Intracellular IGFBP1 attenuated hepatotoxicity induced by 24-epibrassinolide. • The accumulation of secreted IGFBP1 inhibited the phosphorylation of Akt. • IGFBP1 induced by 24-epbrassinolide was partially transcribed by ATF4. • The upregulation of IGFBP1 could be suppressed by ISRB and SCH772984. 24-epibrassinolide (EBR) is a ubiquitous steroidal phytohormone with anticancer activity. Yet the cytotoxic effects and mechanism of EBR on hepatocarcinoma (HCC) cells remain elusive. Cell counting kit-8 (CCK-8) assay was performed to evaluate cell viability. Real-time cell analysis (RTCA) technology and colony formation assays were used to evaluate cell proliferation. The apoptosis ratio was measured by flow cytometry. Seahorse XFe96 was applied to detect the effects of EBR on cellular bioenergetics. RNA-seq analysis was performed to investigate differences in gene expression profiles. Western blot and qRT-PCR were used to detect the changes in target molecules. EBR induced apoptosis and caused energy restriction in HCC, both of which were related to insulin-like growth factor-binding protein 1 (IGFBP1). EBR rapidly and massively induced IGBFP1, part of which was transcribed by activating transcription factor-4 (ATF4). The accumulation of secreted and cellular IGFBP1 had different important roles, in which secreted IGFBP1 affected cell energy metabolism by inhibiting the phosphorylation of Akt, while intracellular IGFBP1 acted as a pro-survival factor to resist apoptosis. Interestingly, the extracellular signal-regulated kinase (ERK) inhibitor SCH772984 and MAP/ERK kinase (MEK) inhibitor PD98059 not only attenuated the EBR-induced IGFBP1 expression but also the basal expression of IGFBP1. Thus, the treatment of cells with these inhibitors further enhances the cytotoxicity of EBR. Taken together, these findings suggested that EBR can be considered as a potential therapeutic compound for HCC due to its pro-apoptosis, restriction of energy metabolism, and other anti-cancer properties. Meanwhile, the high expression of IGFBP1 induced by EBR in HCC contributes to our understanding of the role of IGFBP1 in drug resistance. As a natural plant hormone, 24-epibrassinolide (EBR) resulted in HCC cells apoptosis and blocked energy metabolism. Meanwhile, HCC cells responded to the cytotoxicity of EBR by inducing apoptosis-related proteins (red font) and pro-survival proteins (green font) through transcription factors such as ATF4 and FOXO1, among which IGFBP1 acted as a pro-survival factor to inhibit mitochondrial-mediated apoptosis, but its extracellular aggregation suppressed the PI3K/Akt signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

O-GlcNAcylation on serine/threonine is a post-translational modification that controls the activity of nucleocytoplasmic proteins according to glucose availability. We previously showed that O-GlcNAcylation of FoxO1 in liver cells increases its transcriptional activity. In the present study, we evaluated the potential involvement of FoxO1 O-GlcNAcylation in the context of pancreatic β-cell glucotoxicity. FoxO1 was O-GlcNAcylated in INS-1 832/13 P cells and isolated rat pancreatic islets. O-GlcNAcylation of FoxO1 resulted in a 2-fold increase in its transcriptional activity toward a FoxO1 reporter gene and a 3-fold increase in the expression of the insulin-like growth factor-binding protein 1 (Igfbp1) gene at the mRNA level, resulting in IGFBP1 protein oversecretion by the cells. Of note, increased IGFBP1 in the culture medium inhibited the activity of the insulin-like growth factor 1 receptor (IGF1R)/phosphatidyl inositol 3 kinase (PI3K)/Akt pathway. We reveal in this report a novel mechanism by which O-GlcNAcy-lation inhibits Akt activity through an autocrine mechanism. However, although inhibition of IGFBP1 expression using siRNA restored the PI3 kinase/Akt pathway, it did not rescue INS-1 832/13 cells from high-glucose- or O-GlcNAcylation-induced cell death. In contrast, FoxO1 down-regulation by siRNA led to 30 to 60% protection of INS-1 832/13 cells from death mediated by glucotoxic conditions. Therefore, whereas FoxO1 O-GlcNAcylation inhibits Akt through an IGFBPl-mediated autocrine pathway, the deleterious effects of FoxO1 O-GlcNAcylation on cell survival appeared to be independent of this pathway [ABSTRACT FROM AUTHOR]

SIRT1 regulates survival, DNA repair, and metabolism in human cells and has pleiotropic effects on age-related diseases through either deacetylating target proteins or inhibiting gene transcription. Forkhead box O1 (FOXO1) is one of the most important transcription factors during decidualization. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) are well-known FOXO1-dependent genes in decidualizing cells. To determine whether SIRT1 plays a role in decidualization, we investigated morphological changes in cells following artificially stimulated decidualization and expression levels of PRL, IGFBP1, and FOXO1 in the immortalized non-neoplastic human endometrial stromal cell line T HESCs. SIRT1 expression decreased in the decidualization condition and SIRT1 inhibited morphological changes caused by decidualization of T HESCs. SIRT1 suppressed PRL, IGFBP1, and FOXO1 expression; inhibited FOXO1, PRL, and IGFBP1 promoter activity; and decreased histone protein acetylation of the FOXO1 promoter. We found that FOXO1 expression increased in the secretory phase compared with the proliferative phase, whereas SIRT1 expression decreased in the secretory phase in the human endometrium. We also revealed that SIRT1 may inhibit embryo implantation according to the blastocyst-like spheroid implantation assay. Collectively, these results indicate that SIRT1 suppresses decidualization of human endometrial stromal cells by inhibiting FOXO1 expression., (Copyright © 2022 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

BACKGROUND ‘Pregnancies of unknown location’ (PULs) include viable and failing intrauterine and extrauterine pregnancies. The aim of this study was to evaluate the role of novel biochemical markers in the prediction of spontaneous resolution of PULs. METHODS Serum samples were taken at the first visit to the pregnancy unit for measuring the traditional markers β-hCG and progesterone, and for inhibin A, inhibin pro-αC-related immunoreactivity (inhibin pro-αC-RI) and insulin-like growth factor-binding protein 1 (IGFBP-1). Follow-up was continued until the pregnancy had resolved, the location of the pregnancy and viability was determined or treatment was required. Outcomes were dichotomized into ‘spontaneous resolution’ and ‘other outcome’ categories. RESULTS One-hundred and nine cases of PUL were included in the data analysis. Spontaneous resolution occurred in 70% and a further scan was required in 30% to reach a diagnosis. Levels of progesterone and inhibin A were significantly lower (both P < 0.001) and levels of IGFBP-1 significantly higher (P = 0.02) in the pregnancies that spontaneously resolved than in those pregnancies that required further intervention. In decision tree analysis, the novel markers were less useful than progesterone and β-hCG in predicting spontaneously resolving PULs. Inhibin pro-αC-RI and IGFBP-1 were not useful in the prediction of spontaneously resolving PULs. Inhibin A is more predictive than β-hCG alone, but serum progesterone is the best single marker and progesterone and hCG together continues to be the best way of predicting spontaneously resolving PULs. CONCLUSIONS These novel biochemical markers are not clinically useful in predicting spontaneously resolving PULs. [ABSTRACT FROM AUTHOR]

Subcutaneous microdialysis has been used for continuous glucose monitoring in patients with diabetes mellitus (DM) to facilitate tight regulation of blood glucose levels. The aims of this study were therefore to investigate (i) the relationship between capillary and interstitial glucose in patients with type 1 or 2 DM and healthy subjects and (ii) the feasibility of using microdialysis to assess local insulin sensitivity in adipose tissue. Using subcutaneous microdialysis, interstitial glucose, lactate, pyruvate and glycerol were determined as measures of glucose and lipid metabolism in adipose tissue, before and after an oral glucose tolerance test (OGTT) in 14 patients and seven controls. The results were correlated to whole-body insulin sensitivity and insulin sensitivity in liver estimated from the levels of insulin-like growth factor-binding protein 1 (IGFBP-1). Capillary and interstitial glucose correlated before and after OGTT in healthy subjects and in type 1 DM but not in type 2 DM. In fasting state, the glycerol levels were higher in both type 1 and type 2 DM compared with controls. After the OGTT, the insulin levels were sufficient to suppress lipolysis in type 1 but not in type 2 DM. The glucose/lactate ratio was higher at fasting in type 1 DM and after OGTT in type 1 and 2 DM. In type 1 DM, basal interstitial glycerol levels correlated to whole-body glucose utilization. In type 2 DM, correlations were found between the basal glycerol levels and whole-body insulin sensitivity and between glucose/lactate and per cent decrease in IGFBP-1 levels 120 min after OGTT. Capillary and interstitial glucose correlated before and after OGTT in healthy subjects and patients with type 1 DM. Correlations were also found between insulin sensitivity in whole body and in adipose tissue in both type 1 and type 2 DM and between insulin sensitivity in subcutaneous adipose tissue and liver in type 2 DM. This study shows that microdialysis technique can be used to study in vivo insulin sensitivity in adipose tissue over time and may be useful in the evaluation of, for example, the effects of new drugs on insulin sensitivity. [ABSTRACT FROM AUTHOR]

BACKGROUND Clinical criteria and the presence of auto-antibodies might not be sufficient to discriminate type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in children with new onset of disease. OBJECTIVE To determine whether biochemical markers can be used to distinguish T1DM from T2DM. DESIGN AND INTERVENTION This was a single-center, US-based, prospective study of children with newly diagnosed primary diabetes. Children with secondary diabetes as a result of medication, cystic fibrosis, or other medical conditions were excluded. Eligible participants were enrolled between July 1999 and July 2000. T1DM was presumptively diagnosed in nonobese children who were dependent on insulin to maintain glycemic control. T2DM was presumptively diagnosed in children with a BMI >85% for age and sex and a family history of T2DM, who were insulin-independent and glutamic acid decarboxylase autoantibody-negative. Glucose, CO2, urinary ketones, and HbA1c levels were measured at diagnosis. A fasting blood sample was collected on the morning of diagnosis or on the morning after diagnosis to determine the levels of C-peptide and insulin-like-growth-factor-binding protein 1 (IGFBP-1). C-peptide was assessed by immuno-chemiluminescent assay and IGFBP-1 was assessed by radioimmunoassay. OUTCOME MEASURES The main outcome measures were the receiver operator characteristic (ROC), area under the curve (AUC), sensitivity, specificity, and cut-off value of each biochemical marker. RESULTS The study enrolled a total of 175 children, 149 of whom were presumptively diagnosed with T1DM. The mean age of children with T1DM was 8.7 years, compared with a mean age of 14.2 years for children with T2DM (P<0.001). Children with T1DM were most likely be non- Hispanic whites (78%, P<0.001). By contrast, children with T2DM were most likely to be non- Hispanic blacks (58%, P<0.001). Markers of insulin resistance demonstrated a significant difference between T1DM and T2DM. The mean fasting C-peptide level was 0.13 nmol/l in T1DM and 0.88nmol/l in T2DM (P<0.001). The ROC curve for fasting C-peptide determined a cut-off value of 0.28nmol/l, with a sensitivity of 83%, a specificity of 89%, and an AUC of 0.94. The mean fasting IGFBP-1 level was 38.1 ng/ml in T1DM and 3.6ng/ml in T2DM (P<0.001). The ROC curve for fasting IGFBP-1 determined a cut-off value of 3.6ng/ml, with a sensitivity of 93%, a specificity of 79%, and an AUC of 0.92. The CO2 level for children with TIDM was 17.9mmol/l, versus 22.7mmol/l for children with T2DM (P= 0.016). The ROC curve for CO2 determined a cut-off value of 21.5 mmol/l, with a sensitivity of 83%, a specificity of 64%, and an AUC of 0.76. Urinary ketones were present in 79% and 56% of children with T1DM and T2DM, respectively. A cut-off value of 10 mg/dl was associated with a sensitivity of 74%, a specificity of 52%, and an AUC of 0.73. CONCLUSION Children with new-onset T1DM and T2DM can be distinguished by a combination of biochemical markers. [ABSTRACT FROM AUTHOR]

Study Question: Do branched-chain amino acids (BCAAs) influence the migration of human extravillous trophoblast (EVT) cells through changes in insulin-like growth factor-binding protein 1 (IGFBP1) production in decidual cells?, Study Finding: Decidua-derived IGFBP1 had a stimulating effect on migration of EVT., What Is Known Already: IGFBP1 is abundantly secreted from human decidual cells and influences trophoblast migration in human placenta of early pregnancy. In hepatic cells, the expression of IGFBP1 is influenced by nutritional status and BCAAs regulate IGFBP1 production., Study Design, Samples/materials, Methods: This is a laboratory-based study using human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy (n = 50) and grown as primary cultures. Production of IGFBP1 from decidual cells was examined by enzyme-linked immunosorbent assay and immunoblotting after incubation with or without BCAAs. EVT migration was evaluated using the media conditioned by decidual cells. The effect of conditioned media on phosphorylation of focal adhesion kinase (FAK) in EVT was also analyzed by immunoblotting. The same experiments were repeated in the presence of RGD peptide, which inhibits IGFBP1 binding to α5β1 integrin. An EVT migration assay and the immunoblotting of phosphorylated FAK were also conducted with exogenous IGFBP1. The effect of the conditioned media on cytotrophoblast cell number was also assessed using WST-1 in a cell proliferation assay., Main Results and the Role of Chance: Deprivation of BCAAs on decidual cells significantly suppressed IGFBP1 secretion (P < 0.05, versus BCAA+). Exogenous IGFBP1-stimulated EVT migration (P < 0.05) and phosphorylation of FAK (P < 0.05), and the RGD peptide inhibited these effects. EVT migration and phosphorylation of FAK were stimulated by the conditioned media, presumably by IGFBP1 in the media. RGD treatment abrogated the stimulating effects of conditioned media. The conditioned media deprived of BCAAs had suppressive effects on EVT migration (P < 0.05, versus BCAA+) and phosphorylation of FAK (P < 0.05, versus BCAA+). The conditioned media did not affect number of cytotrophoblast cells., Limitations, Reasons for Caution: The conclusions are based on in vitro experiments with human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy, and we were unable to ascertain whether these mechanisms actually operate in vivo. We investigated the effect of decidua-derived IGFBP1 on EVT migration, however, we cannot completely rule out the possibility that endogenous IGF could also influence cell migration., Wider Implications of Findings: Interruption of the BCAA supply to uterine decidual cells in early pregnancy may suppress EVT migration through reduced IGFBP1 secretion, which may be one of the pathophysiological conditions responsible for pre-eclampsia., Large Scale Data: None., Study Funding/ and Competing Interests: All funds were obtained through Kyorin University School of Medicine. The authors have no conflict of interest to declare., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Marine medaka (Oryzias melastigma) were exposed to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) to investigate the gender-specific transcriptional profiles of liver tissue in response to this flame retardant. A cDNA library of O. melastigma was constructed, and 2304 clones were amplified from the library to fabricate a cDNA microarray. Sequences of these genes were assembled into 1800 sequences using Geneious, a bioinformatics software. Corresponding expressed sequence tags were blasted against the National Centre for Biotechnology Information non-redundant database and further classified into various biological categories according to the Gene Ontology project. Male and female three-month-old were fed a diet of BDE-47 contaminated Artemia at low dosage (290.3±172.3ng BDE-47/day) and high dosage (580.5±344.6ng BDE-47/day) for 5 and 21 days, respectively. The transcriptional profiles of O. melastigma liver were then generated by the species-specific cDNA microrarray. The results from microarray analysis suggested very different gene expression patterns between males and females for both BDE-47 exposure-dose and exposure-time, with male livers having stronger gene regulatory responses than female livers. Importantly, our results revealed that in male O. melastigma only, BDE-47 exposure may activate phosphoinositide-3-kinase and mitogen-activated protein kinase, proteins that play importance roles in cell growth, proliferation and survival., (© 2013.)