Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte

Wen, Xuesong; Tozer, Amanda; Liu, Dong; Docherty, Suzanne M.; Al-Shawaf, Talha; Iles, Ray K.

doi:10.1016/j.fertnstert.2007.03.086

Cited by 17 publications

(13 citation statements)

References 35 publications

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“…Activin A is a member of the transforming growth factorb family that is secreted from the ovary and placenta (Petraglia et al 1987, Wen et al 2008. However, in pregnancy, the main source of secretion is the trophoblast (Petraglia et al 1987).…”

Section: Activin Amentioning

confidence: 99%

Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities

Cartwright¹,

Duncan²,

Critchley³

et al. 2009

Reproduction

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Ectopic pregnancy remains a considerable cause of maternal morbidity and mortality worldwide. Currently, it is diagnosed using a combination of transvaginal ultrasound and serial serum b-human chorionic gonadotrophin levels. Diagnosis is often delayed and these tests are time-consuming and costly, both psychologically to the patient and financially to health services. The development of a biomarker that can differentiate a tubal ectopic from an intrauterine implantation is therefore important. In the pre-genomic era, a one-by-one scientific approach has revealed over 20 candidate biomarkers that could be used as a test to diagnose ectopic pregnancy although at present their clinical utility is very limited. These biomarkers cluster into themes: markers of abnormal embryo/trophoblast growth, markers of abnormal corpus luteum function, markers of a growing pregnancy in the Fallopian tube, markers of inflammation and peritoneal irritation, and uterine markers of normal implantation. It is likely that this thematic approach will facilitate the identification of newer biomarkers using microarray technology and inform the development of investigative paradigms using multiple markers at the time of presentation.

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Section: Activin Amentioning

confidence: 99%

Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities

Cartwright¹,

Duncan²,

Critchley³

et al. 2009

Reproduction

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“…At the tissue level, activin A and FS are expressed in the human oviduct during the different phases of the menstrual cycle, during early pregnancy, and in fallopian tubes bearing an EP [22, 23]. The reported upregulation of the proteins in EP fallopian tubes has been accompanied by a downregulation of the mRNA of these molecules [22, 23], but the serum levels of FS have not yet been studied.…”

Section: Introductionmentioning

confidence: 99%

Activin A and Follistatin as Biomarkers for Ectopic Pregnancy and Missed Abortion

et al. 2013

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Activin A as a predictor of pregnancy failure has been the focus of heated debate, but the value of a combined activin A and follistatin (FS) measurement in serum to predict pregnancy failure has not been reported yet. We assessed whether a single serum measurement of the two physiological antagonists at 6–8 weeks gestation could differentiate ectopic pregnancies (EP) or missed abortions (MA) from healthy intrauterine pregnancies (IUP). activin A concentrations were significantly lower in women with EP (n = 30, median value of 264 pg/mL) and women with MA (n = 30, median value of 350 pg/mL) compared to IUP (n = 33, median value of 788 pg/mL); P < 0.001. At a threshold value of 505 pg/mL, activin A had 87.9% sensitivity and 100% specificity and negative predictive value of 0.974 for discriminating an ectopic pregnancy from viable pregnancies. FS was able to discriminate IUP from EP (ROC curve P < 0.001) as was their ratio (ROC curve P = 0.008), but was unable to discriminate a MA from an EP. In EP, activin A did not correlate with beta HCG levels. The present findings support the thesis that activin A or FS could be considered promising biomarkers for the discrimination between an IUP and a failed pregnancy (MA or EP).

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“…In our experiment, mural granulosa cells were isolated from pooled follicular fluid of women undergoing IVF [9] and stimulated in vitro with metformin. We found a direct and significant effect of metformin on the expression of IR and IGF1R mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…Similar changes occur in the ovary, where insulin and insulin-like growth factor-1 (IGF1) act as co-gonadotropins and affect follicular recruitment, selection and dominance [4]. The improvement in hyperandrogenism signs and symptoms [6] and in ovulation [7], even in patients without significant improvement in metabolic parameters, suggests that metformin has an important effect on the ovary, as previously described for the insulin-IGF system [8] and steroidogenesis [9]. …”

Section: Introductionmentioning

confidence: 99%

Human Granulosa Cells: Insulin and Insulin-Like Growth Factor-1 Receptors and Aromatase Expression Modulation by Metformin

Fuhrmeister

Branchini²,

Pimentel³

et al. 2014

Gynecol Obstet Invest

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Background/Aim: Granulosa cells are the source of the most important ovarian steroids. Even in patients without significant improvement in metabolic parameters, metformin has apparently an important effect on the ovary. The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin. Methods: Luteinized granulosa cells were collected from 27 patients during in vitro fertilization procedures. Cells were isolated, stored in culture for 24 h and divided into four groups: control; metformin for 30 min, and metformin for 30 min plus insulin for 30 or 60 min. Results: IR and IGF1R mRNA expression was significantly enhanced by metformin but was not affected by insulin. Aromatase mRNA expression was significantly reduced in metformin-incubated cells following stimulation with insulin for 30 min. No statistical differences were found in IGF1R and aromatase protein expression, and IR expression was not detected. Conclusion: A direct effect of metformin on the gene expression of IGF1R, IR and aromatase was observed. Further studies should investigate the role of IGF1R, IR and aromatase in ovarian physiology for a better understanding of the effect of metformin.

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Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte

Cited by 17 publications

References 35 publications

Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities

Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities

Activin A and Follistatin as Biomarkers for Ectopic Pregnancy and Missed Abortion

Human Granulosa Cells: Insulin and Insulin-Like Growth Factor-1 Receptors and Aromatase Expression Modulation by Metformin

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