Zinc(II) niflumato complex effects on MMP activity and gene expression in human endometrial cell lines

Endometriosis is a chronic inflammatory disease which increasingly affects young women under 35 years of age and leads to subfertility even infertility. Analysis of the cytotoxic effect of zinc(II) niflumato complex with neocuproine ([Zn(neo)(nif)2] or Zn-Nif) on immortalized human endometriotic cell line (12Z) and on control immortalized human endometrial stromal cell line (hTERT) was performed using xCELLigence technology for approximately 72 h following the treatment with Zn-Nif as well as cell viability Trypan Blue Assay. 12Z cell line proliferated more slowly compared to unaffected cells, whereas hTERT cells did not show similar behavior after treatment. The complex probably reduces the effect of pro-inflammatory pathways due to the effect of NSAID, while presence of zinc might reduce the level of ROS and regulate ER2 levels and MMP activity. The observed effects and high selectivity for rapidly proliferating cells with increased inflammatory activity suggest a good prognosis of successful decrease of endometriosis stage with this complex.

Nitric oxide positively affects endometrial receptivity via FAAH and NAPE-PLD invitro

Objective: To determine if models of human “receptive” and “non-receptive endometrium” differ in their responses to nitric oxide (NO) supplementation by measuring the levels of the enzymes of the endocannabinoid system (ECS), [fatty acid amide hydrolase (FAAH) and N-acylphosphatidylethanolamine (NAPE-PLD)], which control the “anandamide tone” essential for successful pregnancy. Design: A study of FAAH and NAPE-PLD expression (using human endometrium) through the menstrual cycle and an in-vitro using a model of “receptive” (Ishikawa) and “non-receptive” (HEC-1A) human endometrial cell lines treated with the NO-donating compound S-nitroso-N-acetylpenicillamine (SNAP). Results: Immunoreactivity measured by optimised H-score for both FAAH and NAPE-PLD was reduced in secretory (receptive) endometrium compared to proliferative (non-receptive) endometrium (p=0.0009 and <0.0001 respectively. FAAH and NAPE transcript levels were significantly higher in untreated Ishikawa cells than in HEC-1A cells (=0.0228 and 0.0001 respectively). Treatment of cultures with SNAP resulted in an increase in the amount of FAAH mRNA produced by Ishikawa cells and a decrease in NAPE-PLD mRNA. No effect of SNAP was observed in HEC-1A cells. Similarly, FAAH protein was significantly decreased in endometria representative of the receptive endometrium. Conclusion: These data suggest that NO most likely affects the expression of ECS enzymes in the implantation site of a receptive endometrium; a phenomenon not seen in a non-receptive endometrium. These effects are most marked with FAAH expression, suggesting that FAAH may play the more critical role in ensuring the correct “anandamide tone” for successful embryo implantation than NAPE-PLD.

Potential use of ellagic acid for endometriosis treatment: its effect on a human endometrial cell cycle, adhesion and migration

EA treatment decreases cell adhesion and migration of endometrial cells and alters the progression of an endometrial stromal cell line cycle.

Hormones and endometrial carcinogenesis

Endometrial cancer (EC) is the commonest gynaecological cancer in the Western World with an alarmingly increasing incidence related to longevity and obesity. Ovarian hormones regulate normal human endometrial cell proliferation, regeneration and function therefore are implicated in endometrial carcinogenesis directly or via influencing other hormones and metabolic pathways. Although the role of unopposed oestrogen in the pathogenesis of EC has received considerable attention, the emerging role of other hormones in this process, such as androgens and gonadotropin-releasing hormones (GnRH) is less well recognised. This review aims to consolidate the current knowledge of the involvement of the three main endogenous ovarian hormones (oestrogens, progesterone and androgens) as well as the other hormones in endometrial carcinogenesis, to identify important avenues for future research.