Changes in circulating levels and ratios of angiopoietins during pregnancy but not during the menstrual cycle and controlled ovarian stimulation

Hurliman, Amanda; Speroff, Leon; Stouffer, Richard L.; Patton, Phillip E.; Lee, Annette; Molskness, Theodore A.

doi:10.1016/j.fertnstert.2009.04.036

Cited by 12 publications

(14 citation statements)

References 37 publications

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“…In addition, Ang-1, a 70 kDa molecule, predominantly exists in high-order multimers [24], which may be speculated to limit its diffusion capacity across the blood-follicle barrier. Our data support earlier findings by Hurliman et al who reported Ang-1/Ang-2 ratios in serum and follicular fluid during controlled ovarian stimulation in a population of oocyte donors [18]. They found similar Ang-1/Ang-2 ratios in serum and follicular fluid to the ones reported in our study.…”

Section: Discussionsupporting

confidence: 93%

Angiopoietin-1 and angiopoietin-2 are altered in polycystic ovarian syndrome (PCOS) during controlled ovarian stimulation

Tal¹,

Seifer²,

Grazi³

et al. 2013

Vasc Cell

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Polycystic ovarian syndrome (PCOS) ovaries are characterized by increased angiogenesis and hypervascularity. While angiopoietin-1 (Ang-1) and its antagonist, angiopoietin-2 (Ang-2), are essential for ovarian function and angiogenesis, the levels of Ang-1 and Ang-2 in PCOS are unknown. This was a prospective cohort study of 14 PCOS women and 14 matched controls undergoing controlled ovarian stimulation (COS). Serum was collected on day 3, hCG and retrieval days. Follicular fluid (FF) was collected on retrieval day. Serum Ang-1 and Ang-2 levels were constant throughout COS, but serum Ang-1 levels were increased at all time points in PCOS women compared with controls (p < 0.05). No differences between groups were found in serum Ang-2 levels or FF Ang-1 levels. However, FF Ang-2 levels were increased almost 2-fold in PCOS women compared with controls (p < 0.01), and correlated positively with number of oocytes retrieved (r = 0.65, p < 0.0001). This study is the first to provide evidence of an alteration in the Ang-1/Ang-2 system in PCOS women. The biological role of Ang-2 in promoting capillary leakage, the increased Ang-2 FF level in PCOS, and its correlation with number of oocytes suggest that Ang-2 may play an important role in the increased risk of ovarian hyperstimulation in PCOS.

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Section: Discussionsupporting

confidence: 93%

Angiopoietin-1 and angiopoietin-2 are altered in polycystic ovarian syndrome (PCOS) during controlled ovarian stimulation

Tal¹,

Seifer²,

Grazi³

et al. 2013

Vasc Cell

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“…The high ANGPT-2:ANGPT-1 ratio in developing follicles in vitro was found in a granulosa cell study, where nonluteinized cells produced more ANGPT-2 than ANGPT-1 during a short-term culture. There is also evidence of similar characteristics in the follicular fluid of "lead" follicles from controlled ovarian stimulation protocols in women [28,29].…”

Section: Angiogenesis and Ovarian Functionmentioning

confidence: 91%

“…Examples have been shown that FGF2 is released by human embryos as well as in gilts. During early human pregnancy, ANGPT-1 mRNA and ANGPT-2 mRNA/protein are also expressed in the syncytiotrophoblast [28], and there is evidence that ANGPT-2 mRNA and protein expression also occur in invasive cytotrophoblast [43]. The ANGPT receptors, Tie-1 and Tie-2, have almost exclusive expression on endothelial cells in humans and other primate species [44].…”

Section: Angiogenesis In Placentation and Embryo Developmentmentioning

confidence: 99%

Molecular regulation and role of angiogenesis in reproduction

Rizov¹,

Andreeva

Dimova

2017

Taiwanese Journal of Obstetrics and Gynecology

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Angiogenesis is an essential process for proper functioning of the female reproductive system and for successful pregnancy realization. The multitude of factors required for physiological angiogenesis and the complexity of regulation of their temporal-spatial activities contribute to aberrations in human fertilization and pregnancy outcomes. In this study, we reviewed the current knowledge of the temporal expression patterns, functions, and regulatory mechanisms of angiogenic factors during foliculogenesis, early implantation/placentation and embryo development, as well as recurrent spontaneous abortions. Angiogenic factors including vascular endothelial growth factors and angiopoietins have documented roles in the development of primordial follicles into mature antral follicles. They also participate in decidualization, which is accompanied by the creation of an extensive network of vessels in the stromal bed that support the growth of the embryo and the placenta, and maintain early pregnancy. During placentation angiogenic and angiomodulatory cytokines, T and B lymphocytes and macrophages affect angiogenesis in a context-dependent manner. Defects in angiogenesis at the maternal-fetal interface contribute to miscarriage in humans. The establishment of more polymorphisms in the genes involved in angiogenesis/vasculogenesis, and their pathological phenotype and expression could give opportunities for prediction, creating a therapeutic strategy, and treatment of diseases related to female reproductive health and problematic conception.

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“…The novel data show that serum levels of Ang-2 are increased during the early stage of gestation while serum levels of Ang-1 and sTie2 are relatively stable throughout the gestation [20], [21], [25], [26], [27], [28].the increase in serum level of Ang-2 during first trimester suggests that Ang-2 is required at the early stage of pregnancy. In addition, this increase of Ang-2 in pregnancy serum coincides with the timing of placental vascularisation and development [18].…”

Section: Discussionmentioning

confidence: 78%

Serum Angiopoietin-2 and β-hCG as Predictors of Prolonged Uterine Bleeding after Medical Abortion in the First Trimester

et al. 2013

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ObjectiveThe combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We evaluate serum Angiopoietin-2(Ang-2) and β human chorionic gonadotropin (β-hCG) in women who had undergone a medical abortion as markers of prolonged uterine bleeding (PUB).MethodsProspective trial involving 2843 women attending an gynecology outpatient clinic who following a medical abortion with mifepristone and misoprostol, the study cohort was divided into women with duration of uterine bleeding >14 days (PUB) and women with duration of uterine bleeding ≤14 days (normal uterine bleeding, NUB). Serum determinations of Ang-2 levels by ELISA and β-hCG levels by electrochemiluminiscence immunoassay. Receiver Operating Characteristics (ROC) analyses were calculated and plotted for the diagnostic accuracy of serum β-hCG and Ang-2 concentration to discriminate PUB and NUB.ResultsBaseline characteristics for both groups were similar, Only duration of bleeding showed a significant difference between the PUB group and NUB group. Ang-2 serum levels moderately correlated with serum β-hCG levels with statistically significant correlation coefficients of 0.536. Serum β-hCG and Ang-2 levels on day 7 and on day 14 after medical abortion were signifcantly higher in PUB group than in NUB group. Plotted as ROC curves, β-hCG area under curve (AUC) was 0.65 (95% CI, 0.53–0.76) on day 7, rising to AUC = 0.83 (95% CI, 0.75–0.92) on day 14. Using Ang-2 on day 7 and day 14 as predictive parameter resulted in an analogous AUC (AUC = 0.61 on day 7, AUC = 0.78 on day 14).ConclusionsBoth parameters are clinically useful as a diagnostic test in predicting PUB after medical abortion, and can be helpful in uncertain clinical situations, but should be considered as supplementary to a general clinical evaluation.

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Changes in circulating levels and ratios of angiopoietins during pregnancy but not during the menstrual cycle and controlled ovarian stimulation

Cited by 12 publications

References 37 publications

Angiopoietin-1 and angiopoietin-2 are altered in polycystic ovarian syndrome (PCOS) during controlled ovarian stimulation

Angiopoietin-1 and angiopoietin-2 are altered in polycystic ovarian syndrome (PCOS) during controlled ovarian stimulation

Molecular regulation and role of angiogenesis in reproduction

Serum Angiopoietin-2 and β-hCG as Predictors of Prolonged Uterine Bleeding after Medical Abortion in the First Trimester

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