title: Swainsonine induces apoptosis through mitochondrial pathway and caspase activation in goat trophoblasts.
abstract: The indolizidine alkaloid swainsonine (SW) has been reported to impair placentae and ultimately cause abortion in pregnant goats. Up to now, however, the precise effects of SW on goat trophoblast cells (GTCs) are still unclear. In this study, the cytotoxicity effects of SW on GTCs were detected and evaluated by MTT assay, AO/EB double staining, DNA fragmentation assay and flow cytometry analysis. Results showed that SW treatment significantly suppressed GTCs viability and induced typical apoptotic features in a time- and concentration-dependent manner. SW treatment increased Bax protein levels, reduced Bcl-2 protein levels, induced Bax translocation to mitochondria, and triggered the release of cytochrome c from mitochondria into cytosol, which in turn activated caspase-9 and caspase-3, and cleaved PARP, resulting in GTCs apoptosis. However, caspase-8 activity and the level of Bid did not exhibit significant changes in the process of SW-induced apoptosis. In addition, TUNEL assay suggested that SW induced GTCs apoptosis but not other cells in goat placenta cotyledons. Taken together, these data suggest that SW selectively induces GTCs apoptosis via the activation of mitochondria-mediated apoptosis pathway in goat placenta cotyledons, which might contribute to placentae impairment and abortion in pregnant goats fed with SW-containing plants. These findings may provide new insights to understand the mechanisms involved in SW-caused goat's abortion.
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Yong
authors: Y
authors: Huang
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Feng
authors: F
authors: Dong
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Qian
authors: Q
authors: Du
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Hongling
authors: H
authors: Zhang
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Xiaomao
authors: X
authors: Luo
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Xiangjun
authors: X
authors: Song
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Xiaomin
authors: X
authors: Zhao
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Wenlong
authors: W
authors: Zhang
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Dewen
authors: D
authors: Tong
mesh_terms: D000034:Abortion, Veterinary / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D005260:Female; D005434:Flow Cytometry; D006041:Goats; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D017026:Swainsonine / Q000633:toxicity*; D014327:Trophoblasts / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D017026:Swainsonine
keywords: abortion.; apoptosis; caspase; goat trophoblast cells; mitochondrial pathway; swainsonine