Dysregulation of vascular endothelial growth factors and their neuropilin receptors in the eutopic endometrium of women with endometriosis

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This study found reduced neuropilin-1 and absent cyclical variations in neuropilin-1, neuropilin-2, and VEGF-C in the eutopic endometrium of women with endometriosis compared to controls.

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This study examined expression of neuropilins (NRP-1 and NRP-2) and lymphangiogenic factors VEGF-C and VEGF-D in 79 histologically normal uterine tissue samples from women with endometriosis and controls across menstrual cycle phases, using immunohistochemistry with automated cellular imaging quantification. NRP-1 expression was significantly reduced in women with endometriosis, and the normal menstrual-cycle–dependent variation in NRP-1, NRP-2, and VEGF-C was absent in endometriosis; VEGF-D expression was also dysregulated. The authors interpret these dysregulated growth factor/receptor patterns as potentially contributing to altered angiogenesis, lymphangiogenesis, neurogenesis, and immune function, while noting that hormone signal alteration is a proposed linkage. This paper is centrally about endometriosis — it specifically characterizes dysregulation of neuropilin receptors and VEGF-C/VEGF-D in the eutopic endometrium of women with endometriosis.

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Abstract

Despite the importance of neuropilins (NRPs) in a number of processes that are altered in endometriosis, such as angiogenesis and neuronal guidance, these molecules have not been previously studied in the disease. Similarly, potent lymphangiogenic factors, vascular endothelial growth factor C (VEGF-C) and VEGF-D, have not been comprehensively investigated in endometriosis. The objective of this study was to examine their expression in women with and without endometriosis. NRPs and VEGFs were quantified in 79 histologically normal uterine tissue samples (37 control and 42 endometriosis, all menstrual cycle phases) using immunohistochemistry and automated cellular imaging analysis. NRP-1 was significantly reduced in women with endometriosis (P = .004). The normal significant menstrual cyclical variations in endometrial NRP-1, NRP-2, and VEGF-C were absent in endometriosis, and VEGF-D was dysregulated. Dysregulated expression of growth factors and receptors, such as NRPs and VEGFs, likely contribute to altered angiogenesis, lymphangiogenesis, neurogenesis and immune function in endometriosis and may reflect altered hormone signals.
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Abstract

Despite the importance of neuropilins (NRPs) in a number of processes that are altered in endometriosis, such as angiogenesis and neuronal guidance, these molecules have not been previously studied in the disease. Similarly, potent lymphangiogenic factors, vascular endothelial growth factor C (VEGF-C) and VEGF-D, have not been comprehensively investigated in endometriosis. The objective of this study was to examine their expression in women with and without endometriosis. NRPs and VEGFs were quantified in 79 histologically normal uterine tissue samples (37 control and 42 endometriosis, all menstrual cycle phases) using immunohistochemistry and automated cellular imaging analysis. NRP-1 was significantly reduced in women with endometriosis (P = .004). The normal significant menstrual cyclical variations in endometrial NRP-1, NRP-2, and VEGF-C were absent in endometriosis, and VEGF-D was dysregulated. Dysregulated expression of growth factors and receptors, such as NRPs and VEGFs, likely contribute to altered angiogenesis, lymphangiogenesis, neurogenesis and immune function in endometriosis and may reflect altered hormone signals. Similar content being viewed by others

References

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endometriosis

MeSH descriptors

Endometriosis Endometrium Neuropilin-1 Neuropilin-2 Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor D Case-Control Studies Endometriosis Endometriosis Endometrium Endometrium Female Humans Image Processing, Computer-Assisted Immunohistochemistry Lymphangiogenesis Menstrual Cycle Menstrual Cycle Neovascularization, Physiologic Neurogenesis

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