INCREASES IN CELL MIGRATION RATE AND AROMATASE EXPRESSION IN HUMAN ENDOMETRIAL STROMAL CELLS INDUCED BY A NEONICOTINOID INSECTICIDE IMIDACLOPRID

MARTINA L; CEBALLOS L; MIRET N; PONTILLO C; RANDI A; CHIAPPINI F

Capital Federal

Congreso; LXVII Reunion Anual de la Sociedad Cientifíca de Investigación (SAIC); 2022

Under the modern lifestyle, humans are exposed to chemicals such as pesticide residuals. These compounds can mimic or influence the action of endogenous hormones acting as endocrine disrupting chemicals (EDCs). Imidacloprid (IMI) is a neonicotinoid insecticide; the most widely used agricultural insecticides. Several studies report that EDCs, such as IMI, affect aromatase expression and activity, and interfere with estrogen signaling. Endometriosis is a chronic disease hormone-dependent which is defined by the presence of endometrial tissue outside the uterus. The EDCs may be involved in the development and progression of disease. Aromatase is the key enzyme in the estrogen biosynthesis and it is essential for establishment and growth of endometriosis lesions. Moreover, the development of endometriosis lesions depends on factors that facilitate migration, adhesion, proliferation and invasion of endometrial cells. The aim of this work was investigate the IMI effect in human endometrial stromal cells (T-HESC) on: cell migration (wound healing assay) and proliferation (PCNA by WB), aromatase expression (WB), and Matrix metalloproteinases 2 and 9 (MMP-2,-9) activities (zymography). T-HESC cells were exposed to different doses of IMI (0.01, 0.1, 1 and 10 μM) for 7 and 24 h. The results showed that IMI increase cell migration ratio (15 and 30% IMI 1 and 10 μM) in a dose response manner. Moreover, we observed that IMI induce Aromatase and PCNA expression (74 and 67%; 30 and 38%; IMI 1 and 10 μM).We also examined the activity of MMP-2 and 9, which are involve in remodeling the extracellular matrix and participate in migration and invasion processes. IMI increased MMP-9 (17, 26 and 23% IMI 0.1, 1 and 10 µM) and MMP-2 activities (41 and 28% IMI 0.01, 1 µM). In conclusion, our results show that IMI exposure could contribute to endometriosis development, affecting migration and invasion parameters, proliferation and disrupting hormonal homeostasis in human endometrial cells.