Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1 alpha activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1 alpha protein stabilization in endometrial stromal cells, and that CS-induced HIF-1 alpha-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1 alpha might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.

Automated summary

Cigarette smoking is a major risk factor for various fatal diseases, including cancers. The study found that smoking induced HIF-1 alpha activation in human endometrial cells, leading to cellular stress, inflammation, and endometrial remodeling. These findings suggest a potential mechanism underlying the detrimental effects of smoking on endometrial health.