title: Cigarette smoke exposure elicits increased autophagy and dysregulation of mitochondrial dynamics in murine granulosa cells.
abstract: Cigarette smoking is a lifestyle behavior associated with significant adverse health effects, including subfertility and premature ovarian failure. Cigarette smoke contains a number of chemicals, many of which are involved in the generation of reactive oxygen species, which can lead to apoptosis and autophagy. Autophagy is a fundamental process that removes damaged organelles and proteins through lysosomal degradation. The relevance of autophagy to toxicant-induced changes in ovarian function is largely unexplored. Previously, we reported that exposure to cigarette smoke causes follicle loss, oxidative stress, activation of the autophagy pathway, and decreased expression of manganese superoxide dismutase, which points to altered mitochondrial function. Therefore, our objective here was to test whether exposure to cigarette smoke results in the dysregulation of mitochondrial repair mechanisms leading to loss of follicles via autophagy-mediated granulosa cell death. In this study, mice were exposed to cigarette smoke or room air for 8 wk. The expression of genes and proteins of autophagy and mitochondrial repair factors was measured using quantitative real-time PCR and Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay. Increased expression of parkin and decreased expression of the mitofusins suggest that exposure to cigarette smoke triggers mitochondrial damage. Moreover, the autophagy cascade proteins, BECN1 and LC3, were upregulated, whereas the antagonist BCL2 was downregulated, following treatment. Taken together, our results suggest exposure to cigarette smoke induces dysfunction of mitochondrial repair mechanisms, leading to autophagy-mediated follicle death.
authors: Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Anne Marie
authors: AM
authors: Gannon
authors: Martin R
authors: MR
authors: Stämpfli
authors: Warren G
authors: WG
authors: Foster
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D014028:Tobacco Smoke Pollution