Human Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor

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Adenomyosis stromal cells secrete more nerve growth factor, which is promoted by estrogen and inflammation, and NGF stimulates stromal cell proliferation and aromatase expression in adenomyosis.

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The study investigated why nerve growth factor (NGF) is abnormally expressed in human adenomyosis by culturing endometrium stromal cells (ESCs) derived from adenomyosis (AM) foci and eutopic endometrium from non-AM controls, then exposing them separately to graded 17β-estradiol, TNF, CoCl2 (hypoxia mimic), or H2O2. ESCs were assessed for NGF expression, and when NGF was added, for ESC proliferation, apoptosis, and aromatase expression; 17β-estradiol increased NGF production in AM ESCs but not control ESCs, while TNF promoted NGF production in both groups and CoCl2 inhibited NGF only in controls. NGF increased proliferation and aromatase synthesis in AM ESCs, leading the authors to propose that local estrogen and inflammation drive NGF and that NGF contributes to AM pathology, with the explicit caveat that findings are based on cultured cells from tissue samples. This paper is centrally about endometriosis and/or adenomyosis — it is specifically focused on adenomyosis mechanisms linking estrogen/inflammation to increased NGF in endometrial stromal cells and downstream effects on aromatase.

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Abstract

Abnormal expression of nerve growth factor (NGF) was found in adenomyosis (AM). We collected AM foci from patients and eutopic endometrium from non-AM controls. Endometrium stromal cells (ESCs) were cultured. Different levels of 17β-estradiol, tumor necrosis factor (TNF), CoCl2, and H2O2 were added to the culture system separately, then the expression level of NGF in ESCs was detected. After adding different levels of NGF, the proliferation and apoptosis of ESCs and aromatase expression were detected. We found that 17β-estradiol promoted NGF production in AM ESCs but not in control ESCs; TNF promoted NGF production in both AM and control ESCs; and CoCl2 inhibited NGF production in control ESCs, but had no effect in AM ESCs. Nerve growth factor promoted the proliferation and synthesis of aromatase in AM ESCs. In conclusion, locally increased estrogen levels and inflammation may cause increased NGF production in the uterus of patients with AM. Nerve growth factor stimulated the proliferation and increased aromatase expression of ESCs from AM foci, suggesting NGF might contribute to the pathology and etiology of AM. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Li, Y., Zou, S., Xia, X. et al. Human Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor. Reprod. Sci. 22, 1073–1082 (2015). https://doi.org/10.1177/1933719114561559 Published: Issue date: DOI: https://doi.org/10.1177/1933719114561559

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adenomyosis

MeSH descriptors

Adenomyosis Endometrium Nerve Growth Factor Stromal Cells Adenomyosis Adenomyosis Adult Apoptosis Apoptosis Aromatase Aromatase Case-Control Studies Cell Proliferation Cell Proliferation Cells, Cultured Cobalt Cobalt Dose-Response Relationship, Drug Endometrium Endometrium

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