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論文名稱:四溴雙酚A誘導小鼠GC-1 spg細胞活性氧的產生及細胞死亡
論文名稱(外文):TBBPA Induces Mouse GC-1 spg Cells Reactive Oxygen Species Generation and Cell Death
外文關鍵詞:spermatogoniatetrabromobisphenol Areactive oxygen speciescell death
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四溴雙酚A (tetrabromobisphenol A)為最常用的溴化阻燃劑(brominated flame retardants)之一。前人研究發現四溴雙酚A可藉由胎盤、粉塵、食物、母乳等方式進入人體,研究也發現四溴雙酚A會累積在老鼠組織、影響睪丸中產生睪固酮的萊氏細胞(leydig cells)和孕育精子發育的史托利細胞(sertoli cells)之生長、活化此兩類細胞中細胞激素(cytokine) IL-1alpha和IL-6的基因表現,因此四溴雙酚A被認為對睪丸發育和男性生殖能力具有傷害性。本論文對四溴雙酚A干擾睪丸發育是否會直接透過影響精原細胞(spermatogonia)的生長進行分析。實驗結果指出四溴雙酚A會抑制精原細胞GC-1 spg的細胞生長,抑制程度與處理濃度及處理時間呈正相關性。四溴雙酚A在濃度200 M時會導致細胞死亡,且伴隨細胞膜不對稱性的喪失、粒線體膜電位梯度差的下降、細胞中活性氧的異常累積及caspase 3蛋白酶和caspase 9蛋白酶的酵素活性的被提高,而這些影響皆具有濃度及時間的相關性。四溴雙酚A亦會干擾GC-1spg細胞對雌性素(estrogen)的反應,以四溴雙酚A處理GC-1 spg細胞會降低細胞中雌性素受器beta (estrogen receptor beta)的mRNA量,降低雌性素促進GC-1spg細胞生長的效果。以四溴雙酚A處理GC-1spg細胞數小時後,即可觀察到細胞中細胞激素IL-6的基因表現被活化,顯示四溴雙酚A導致睪丸異常發炎的可能性。綜合以上結果,本論文研究顯示四溴雙酚A可藉由多重方式導致小鼠精原細胞生長與反應的異常,推測將會影響精子形成 (spermatogenesis),對男性生殖力應有潛在的干擾能力。
Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs), used in a variety of consumer products, including electrical equipment and household furniture. The consumption of TBBPA is rising due to its efficacy and in order to meet fire safety standards for products on the market. Previous study indicated that TBBPA might be accumulated in animal tissues via placenta, food, breast milk, and household dust. It has also been reported that TBBPA exhibits binding affinity to estrogen receptors in vitro, inhibit the growth of murine testis cells and activate the gene expression of pro-inflammatory cytokines including IL-1a and IL-6. However, it is unclear that TBBPA would directly affect the development and the growth of spermatogonia cells. In this study, the effect of TBBPA on the growth of GC-1 spg cells was analyzed and the results suggested that TBBPA inhibited the growth of GC-1 spg cells in a concentration dependent manner. Cell death, accompanying parameters including the decline of mitochondrial membrane potential, the accumulation of ROS, and the increased activity of caspase 3 and 9, was detected in GC-1 spg cells treated with TBBPA at 2x10-4 M. The loss of cell membrane asymmetry, as indicated by strong staining of Annexin V to phosphatidyl serine, which frequently serves as an early indication of programmed cell death was also noted in TBBPA-treated cells. The hormonal response of GC-1 spg cells was also impaired by the treatment of TBBPA since TBBPA decreased the mRNA level of estrogen receptor-beta and partially abolished the stimulatory effect of estrogen on the GC-1 spg cell proliferation. The treatment of TBBPA as found to induce the gene activation of IL-6 via NF-kappa B pathway with at least partial involvement of Toll-like receptor 4 in GC-1 spg cells. In conclusion, the results of this study suggested that TBBPA could produce adverse effects on male fertility thought interfering with the physiology of sperm cells directly.

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