Human Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor

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.

Bioinformatics strategy for the screening of key genes to differentiate adenomyosis from endometriosis (Review)

“…NGF mRNA expression has been shown to be increased in the ectopic endometrium of patients with adenomyosis (46) or endometriosis (48) compared to the eutopic endometrium or normal endometrium. E2 promotes NGF production in adenomyosis endometrial stromal cells, but not in control endometrial stromal cells (47).…”

“…We found that the survival and apoptosis-related genes were upregulated or downregulated in the previous studies cited. Thus, the proliferation-and growth-related genes, including IGF1 (16)(17)(18)(19), IGF2 (19), vascular endothelial growth factor (VEGF) (40)(41)(42), hepatocyte growth factor (HGF) (43)(44)(45), nerve growth factor (NGF) (46)(47)(48), platelet-derived growth factor (PDGF) (16,49), epidermal growth factor receptor (EGFR) (16,17,49,50), fibroblast growth factor 2 (FGF2) (49,51,52) and mechanistic target of rapamycin kinase (mTOR) (53,54), were upregulated in both the ectopic and eutopic endometria from subjects with adenomyosis compared with the eutopic endometria from women without adenomyosis, while the anti-apoptotic or autophagy-related genes, such as BCL2 apoptosis regulator (BCL2) (38,(55)(56)(57), beclin 1 (BECN1) (58,59) and programmed cell death 4 (PDCD4) (60,61), were much higher in the ectopic and eutopic endometria than in the control endometria. Furthermore, the decreased expression of BCL2 associated X, apoptosis regulator (BAX) has been observed in adenomyosis, suggesting that the downregulation of apoptotic cell death machinery is a hallmark of adenomyosis (39).…”

Oxytocinergic regulation in pathogenesis of pelvic pain caused by adenomyosis

“…Locally increased estrogen levels and inflammation cause increased nerve growth factor (NGF) production in the uterus of patients with adenomyosis. Nerve growth factor stimulates the proliferation and increased aromatase expression of endometrium stromal cells from adenomyosis foci, suggesting NGF might contribute to the pathology and etiology of adenomyosis [14].…”

Current and Future Medical Treatment of Adenomyosis

“…Myostatin, follistatin, and activin A are hyper-expressed by adenomyotic nodule and may affect proliferation of endometrial glands/stroma and of surrounding myometrial cells (14). Increased expression of interleukin 10 (IL-10) (103) and tumor necrosis factor-α (TNF-α) (101), as well as altered expression of cyclooxygenase-2 (COX-2) (104), suggest an involvement in inflammatory pathway in adenomyosis. Abnormal expression of NGF is also described in adenomyosis, as well as in animal model of adenomyosis (105); endometrial stromal cells express NGF, promoting cell proliferation and aromatase synthesis (106).…”