Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage

Lash, Gendie E.; Innes, Barbara A.; Drury, Josephine A.; Robson, Samuel; Quenby, Siobhán; Bulmer, Judith N.

doi:10.1093/humrep/der376

Cited by 85 publications

(67 citation statements)

References 49 publications

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“…Increased αSMA expression during the secretory phase (22) suggests a correlation between endometrial vascular maturation with αSMA expression. In support of this thesis, the VSMC proliferation index (24) and the number of endometrial vessels enveloped by more than one VSMC layer increases from the proliferative to secretory phase (25). Moreover, αSMA expression is decreased around endometrial microvasculature of Norplant users exhibiting bleeding (23).…”

Section: Discussionsupporting

confidence: 52%

Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

Kayisli

Başar

Guzeloglu‐Kayisli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Molecular mechanisms responsible for abnormal endometrial vasculature in women receiving long-acting progestin-only contraceptives (LAPCs) are unknown. We hypothesize that LAPCs impair vascular smooth muscle cell (VSMC) and pericyte proliferation and migration producing thin-walled hyperdilated fragile microvessels prone to bleeding. Proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (αSMA) double-immunostaining assessed VSMC differentiation and proliferation in endometria from women before and after DepoProvera (Depo) treatment and from oophorectomized guinea pigs (OVX-GPs) treated with vehicle, estradiol (E2), medroxyprogesterone acetate (MPA), or E2+MPA. Wholegenome profiling, proliferation, and migration assays were performed on cultured VSMCs treated with MPA or etonogestrel (ETO). Endometrial vessels of Depo-administered women displayed reduced αSMA immunoreactivity and fewer PCNA (+) nuclei among αSMA (+) cells (P < 0.008). Microarray analysis of VSMCs identified several MPA-and ETO-altered transcripts regulated by STAT1 signaling (P < 2.22 × 10 −6 ), including chemokine (C-C motif) ligand 2 (CCL2). Both MPA and ETO reduce VSMC proliferation and migration (P < 0.001). Recombinant CCL2 reversed this progestin-mediated inhibition, whereas a STAT1 inhibitor abolished the CCL2 effect. Similarly, the endometria of MPA treated OVX-GPs displayed decreased αSMA staining and fewer PCNA (+) nuclei in VSMC (P < 0.005). In conclusion, LAPCs promote abnormal endometrial vessel formation by inhibiting VSMC proliferation and migration.progestin contraceptives | abnormal uterine bleeding | VSMC | impaired vascular maturation | proliferation

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Section: Discussionsupporting

confidence: 52%

Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

Kayisli

Başar

Guzeloglu‐Kayisli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…VEGF-C deals with growth of blood vessels and lymphatics (26). VEGF-A and C binds with a high affi nity to two related receptor tyrosine kinases expressed on vascular endothelial cells (27). The previous study showed the role of VEGF-A and VEGF-C in implantation and placentation (28,29,30).…”

Section: Discussionmentioning

confidence: 99%

“…VEGF functions are mediated via binding to its tyrosine kinase receptors; VEGF receptor 1 (VEGFR1/Flt1) and VEGF receptor 2 (VEGFR2/Flk1/KDR). Expression of VEGF-A and VEGF-C has been demonstrated in the human endometrium throughout the menstrual cycle with an increase in the late proliferative and secretory phases (13,14). In addition, VEGF's expression was found in decidual cells of early pregnancy (15).…”

Section: Introductionmentioning

confidence: 99%

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Bagheri¹,

Kumar²,

Kamath³

et al. 2017

BLL

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INTRODUCTION: Recurrent miscarriage (RM) defi ned as 2 or more spontaneous miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains unexplained. Reduced expression of Angiogenic factors such as: vascular endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND OBJECTIVES: To investigate the relationships between serum level of VEGF-A and VEGF-C with clinical characteristic in women with URM and compare to pregnant and healthy women. MATERIALS AND METHODS: A case-control study, which was conducted between 90 non-pregnant women with history of RM, age-matched with 70 non-pregnant women without history of recurrent abortion with at least one child (controls) and 70 pregnant women without history of recurrent abortion with at least one child (controls). Those with unexplained RM were eligible. Demographic and Anthropometric data were retrieved by pre-test questionnaire and serum level of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87±88.1 vs 238.8±99.6) compared to healthy (239.1±99.7 vs 275.5±133.08) and pregnant (301.5±76.4 vs 402.5±128.6) women as control groups. Univariate analysis demonstrated that clinical characteristic factors were signifi cantly associated with concentration of VEGF-A and VEGF-C in cases and controls. CONCLUSIONS: Our fi ndings suggest that these molecules could be used as potential predictive markers of miscarriage in these women presenting with URM (Tab. 4, Fig. 5, Ref. 40). Text in PDF www.elis.sk.

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“…The processing of tissue and staining of CD56+ cells in the initial experiment was 140 carried out as per the established procedure in each centre detailed below (Tuckerman et al 2007;Tuckerman et al 2010;Quenby et al 2005;Lash et al 2012). …”

Section: Initial Analysismentioning

confidence: 99%

Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure

Lash

Bulmer

et al. 2016

Journal of Reproductive Immunology

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Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage

Cited by 85 publications

References 49 publications

Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure

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