scholarly journals Expression of Tissue Factor and Tissue Factor Pathway Inhibitors during Ovulation in Rats: A Potential Biomarker for Ovarian Hyperstimulation Syndrome

2021 ◽  
Author(s):  
You Jee Jang ◽  
Hee Kyung Kim ◽  
Bum Chae Choi ◽  
Sang Jin Song ◽  
Jae Il Park ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Ovarian Hyperstimulation Syndrome ◽  
Ovarian Hyperstimulation ◽  
Mrna Levels ◽  
Expression Levels ◽  
Potential Biomarker ◽  
Preovulatory Follicles ◽  
Tissue Factor Pathway ◽  
Factor System ◽  
Follicular Fluids

Abstract Background: Blood coagulation has been associated with ovulation and female infertility. In this study, the expression of the tissue factor system was examined during ovulation in immature rats; the correlation between tissue factor and ovarian hyperstimulation syndrome (OHSS) was evaluated both in rats and human follicular fluids. Methods: Ovaries were obtained at various times after human chorionic gonadotropin (hCG) injection to investigate the expression of tissue factor system. Expression levels of ovarian tissue factor, tissue factor pathway inhibitor (Tfpi)-1 and Tfpi-2 genes and proteins were determined by real-time quantitative polymerase chain reaction (qPCR), and Western blot and immunofluorescence analyses, respectively. Expression levels of tissue factor system were also investigated in ovaries of OHSS-induced rats and in follicular fluid of infertile women.Results: The expression of tissue factor in the preovulatory follicles was stimulated by hCG, reaching a maximum at 6 h. Tissue factor was expressed in the oocytes and the preovulatory follicles. Tfpi-2 mRNA levels were mainly increased by hCG in the granulosa cells whereas the mRNA levels of Tfpi-1 were decreased by hCG. Human CG-stimulated tissue factor expression was inhibited by the progesterone receptor antagonist. The increase in Tfpi-2 expression by hCG was decreased by the proliferator-activated receptor γ (PPARγ) antagonist. Decreased expression of the tissue factor was detected in OHSS-induced rats. Interestingly, the tissue factor concentrations in the follicular fluids of women undergoing in vitro fertilization were correlated with pregnancy but not with OHSS. Conclusions: Collectively, the results indicate that tissue factor and Tfpi-2 expression is stimulated during the ovulatory process in rats; moreover, a correlation exists between the levels of tissue factor and OHSS in rats but not in humans.

scholarly journals Expression of tissue factor and tissue factor pathway inhibitors during ovulation in rats: a relevance to the ovarian hyperstimulation syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
You Jee Jang ◽  
Hee Kyung Kim ◽  
Bum Chae Choi ◽  
Sang Jin Song ◽  
Jae Il Park ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Ovarian Hyperstimulation Syndrome ◽  
Quantitative Polymerase Chain Reaction ◽  
Ovarian Hyperstimulation ◽  
Mrna Levels ◽  
Expression Levels ◽  
Preovulatory Follicles ◽  
Tissue Factor Pathway ◽  
Factor System ◽  
Follicular Fluids

Abstract Background Blood coagulation has been associated with ovulation and female infertility. In this study, the expression of the tissue factor system was examined during ovulation in immature rats; the correlation between tissue factor and ovarian hyperstimulation syndrome (OHSS) was evaluated both in rats and human follicular fluids. Methods Ovaries were obtained at various times after human chorionic gonadotropin (hCG) injection to investigate the expression of tissue factor system. Expression levels of ovarian tissue factor, tissue factor pathway inhibitor (Tfpi)-1 and Tfpi-2 genes and proteins were determined by real-time quantitative polymerase chain reaction (qPCR), and Western blot and immunofluorescence analyses, respectively. Expression levels of tissue factor system were also investigated in ovaries of OHSS-induced rats and in follicular fluid of infertile women. Results The expression of tissue factor in the preovulatory follicles was stimulated by hCG, reaching a maximum at 6 h. Tissue factor was expressed in the oocytes and the preovulatory follicles. Tfpi-2 mRNA levels were mainly increased by hCG in the granulosa cells whereas the mRNA levels of Tfpi-1 were decreased by hCG. Human CG-stimulated tissue factor expression was inhibited by the progesterone receptor antagonist. The increase in Tfpi-2 expression by hCG was decreased by the proliferator-activated receptor γ (PPARγ) antagonist. Decreased expression of the tissue factor was detected in OHSS-induced rats. Interestingly, the tissue factor concentrations in the follicular fluids of women undergoing in vitro fertilization were correlated with pregnancy but not with OHSS. Conclusions Collectively, the results indicate that tissue factor and Tfpi-2 expression is stimulated during the ovulatory process in rats; moreover, a correlation exists between the levels of tissue factor and OHSS in rats but not in humans.

Lysophosphatidylcholine Decreases the Synthesis of Tissue Factor Pathway Inhibitor in Human Umbilical Vein Endothelial Cells

1998 ◽  
Vol 79 (01) ◽  
pp. 217-221 ◽  
Author(s):  
Koichi Kokame ◽  
Toshiyuki Miyata ◽  
Naoaki Sato ◽  
Hisao Kato
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Umbilical Vein ◽  
Mrna Levels ◽  
Down Regulation ◽  
Human Umbilical Vein ◽  
Tissue Factor Pathway ◽  
Umbilical Vein Endothelial Cells

SummaryThrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor pathway inhibitor (TFPI), has the function of regulating the initial reaction of tissue factor (TF)-induced coagulation, we investigated the effect of LPC on TFPI synthesis in cultured human umbilical vein endothelial cells (HUVEC). The treatment of HUVEC with LPC for 24 h decreased TFPI antigen levels in both the culture medium and the cell lysate in a dose-dependent manner. Northern blot analysis revealed that LPC caused a time-dependent decrease in the TFPI mRNA levels. The levels of TFPI antigen and mRNA were decreased to 72% and 38%, respectively, by the incubation with 50 μM LPC for 24 h. The down-regulation by LPC of TFPI mRNA expression was not observed in the presence of cycloheximide, suggesting that protein synthesis was involved in the suppression of TFPI mRNA expression. The TFPI mRNA levels in actinomycin D-treated cells were relatively stable, indicating that the down-regulation of TFPI mRNA by LPC would be partly explained by the enhanced mRNA destabilization. In contrast to the significant down-regulatory effects of LPC on TFPI expression, LPC did not induce TF mRNA expression in HUVEC. These results indicate that LPC accumulated in the atherosclerotic vascular wall would suppress endothelial TFPI synthesis, reducing the antithrombotic property of endothelial cells.

scholarly journals Endometrial HOXA10 mRNA Expression in PCOS Patients at High Risk for Ovarian Hyperstimulation Syndrome

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Arzu Yurci ◽  
Suphan Ersahin
Keyword(s):  
High Risk ◽  
Mrna Expression ◽  
Ovarian Hyperstimulation Syndrome ◽  
Positive Control ◽  
High Risk Group ◽  
Control Group ◽  
Ovarian Hyperstimulation ◽  
Mrna Levels ◽  
Pcos Group ◽  
Infertile Patients

Background: This study was designed to determine whether the risk of ovarian hyperstimulation syndrome (OHSS) contributes to the subfertility in PCOS. Endometrial HOXA-10 mRNA expression, a well-characterized gene essential to endometrial receptivity, was evaluated in PCOS patients whose embryos are planned to be frozen due to the risk of OHSSS. Methods: Twent-five women with PCOS in high risk group for OHSS and age and BMI matched 25 non-PCOS infertile patients were included the study. Five fertile women were accepted as positive control. Following egg collection each group of subject underwent total embryo freezing. After the egg collection, endometrial sampling was performed with a pipella cannula from each gruop of participant and fertile control. Expression levels of HOXA-10 mRNA were determined by RT-PCR. Gene expression results are presented as Ct (cycle threshold), ΔCt, and ΔΔCt. Reults: Average ΔCt value of HOXA-10 mRNA in PCOS, non-PCOS and fertile groups were found to 5.88, 6.77, and 7.79 respectively. Compared to endometrial HOXA-10 mRNA levels of fertile cases, the HOXA-10 mRNA levels of the patients in the PCOS group were found to be significantly lower (ΔCt 7.79 vs. ΔCt 5.88, p<0.002). Similarly, endometrial HOXA-10 mRNA levels in the non-PCOS control group were significantly lower than the HOXA-10 mRNA levels in the fertile group (ΔCt 6.77 vs. ΔCt 7.79, p<0.001). HOXA-10 mRNA levels in endometrial samples taken from patients in the PCOS group were found to be significantly lower than the HOXA-10 mRNA levels in non-PCOS control group. Conclusions: HOXA-10 mRNA levels were found to be lower in PCOS patients with high risk for OHSS compared to both fertile and infertile patients without PCOS. OHSS risk in PCOS decreases endometrial HOXA-10 mRNA expression.

Different protein expression patterns associated with polycystic ovary syndrome in human follicular fluid during controlled ovarian hyperstimulation

2012 ◽  
Vol 24 (7) ◽  
pp. 893 ◽  
Author(s):  
Guo Dai ◽  
Guangxiu Lu
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Protein Expression ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Expression Patterns ◽  
Controlled Ovarian Hyperstimulation ◽  
Ovarian Hyperstimulation ◽  
Mrna Levels ◽  
Ovary Syndrome ◽  
Follicular Fluids

Polycystic ovary syndrome (PCOS) is one of the most common causes of anovulatory infertility, affecting 5–10% of females during their reproductive life. Currently the pathology of PCOS is largely unknown. To identify the differential protein expression in follicular fluids from PCOS and normal subjects during controlled ovarian hyperstimulation, we performed an initial proteomic study including two-dimensional gel electrophoresis (2DE) analysis and mass spectroscopy, and confirmed results by western blot. Thirty-two protein spots were shown to be significantly differentially expressed between PCOS and normal follicular fluids, of which 20 unique proteins were identified to be associated with cellular metabolism and physiological processes; 13 of these proteins were upregulated while seven were downregulated in PCOS follicular fluids. Western blotting analyses confirmed the differential expressions for three randomly selected proteins, i.e. upregulated α1-antitrypsin, apolipoprotein A-I and transferrin in follicular fluid from PCOS patients than normal controls. Furthermore, semiquantitative reverse transcription-polymerase chain reaction (RT–PCR) analyses revealed that mRNA levels of serine palmitoyltransferase 2, serine/threonine-protein kinase male germ cell-associated kinase (MAK) and DNA damage-regulated autophagy modulator protein 2 decreased significantly in granulosa cells of PCOS patients compared with normal samples. These results increase our understanding of PCOS and the identified genes may serve as candidate biomarkers to develop diagnostic and therapeutic tools.

A Histopathological Evaluation of Ovarian Hyperstimulation Syndrome on Reproductive and Vital Organs and the Role of the VEGF-PKA Pathway in a Mouse Model

2021 ◽  
pp. 1-20
Author(s):  
Seda Karabulut ◽  
Oya Korkmaz ◽  
Ceren Erdem Altun ◽  
Ilknur Keskin
Keyword(s):  
Ovarian Hyperstimulation Syndrome ◽  
Expression Profiles ◽  
Periodic Acid ◽  
Ovarian Hyperstimulation ◽  
Expression Levels ◽  
Iatrogenic Complications ◽  
Histopathological Evaluation ◽  
Pka Pathway ◽  
Histopathological Effects

Ovarian hyperstimulation syndrome (OHSS) is one of the most common and iatrogenic complications of in vitro fertilization therapy, which is an exaggerated response to excess hormones resulting in the development of a large number of maturing follicles. Although the complications of and reasons for the condition are well known, the overall histopathological effects on systemic organs and the extent of the damage have not been fully elucidated. Besides, the mechanism that underlies the situation is not very well known. The aim of the present work was to analyse the histopathological effects of OHSS on reproductive (uterus and ovary) and vital organs (liver and kidney) and the possible role of the VEGF-PKA pathway in triggering the condition. Balb/c mice were used to establish an OHSS model. The OHSS group were injected with overdose PMSG while the normal responder group were injected with an optimal dose. Histopathological evaluation was utilised in the liver, kidney, ovary, and uterus stained with hematoxylin and eosin, Masson’s trichrome, and periodic acid-Schiff stain. The expression profiles of VEGF (vascular endothelial growth factor), PKA (protein kinase A), and p-PKA (an activated form of PKA) were detected with immunohistochemistry and Western blotting. OHSS was demonstrated to have a negative histopathological effect on all of the organs analysed. These effects were associated with an overall increase in the expression levels of VEGF, PKA, and p-PKA. OHSS has a serious histopathological negative effect on the systemic and reproductive organs and is proven to affect overall health, and thus should be considered a dangerous complication during ART techniques. The activation of the VEGF-PKA pathway, which is indicated by the expression levels of VEGF, PKA, and p-PKA, is demonstrated to accompany this complication, which should be further elucidated to understand the mechanisms underlying the condition.

scholarly journals Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women

2020 ◽  
Vol 52 (02) ◽  
pp. 104-108
Author(s):  
Roshan Nikbakht ◽  
Mahvash Zargar ◽  
Farideh Moramezi ◽  
Mahnaz Ziafat ◽  
Hamed Tabesh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Ovarian Hyperstimulation Syndrome ◽  
Polycystic Ovary ◽  
Antral Follicle ◽  
Controlled Ovarian Hyperstimulation ◽  
Multivariable Logistic Regression Analysis ◽  
Ovarian Hyperstimulation ◽  
Free Androgen Index ◽  
Preovulatory Follicles

AbstractWe evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p<0.001). The best cut-points for IR, FAI, AFC, AMH, and preovulatry follicles were 2.36, 3.9, 8, 3.3 ng/ml, and 10, respectively. Patients with a higher value of BMI, FAI, HOMA-IR, and preovulatory follicles and the presence of PCOM are more likely to develop OHSS, which are not confined to PCOS patients.

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