臺灣博碩士論文加值系統

油炸為常見且受歡迎的烹調法，但三酸甘油酯在高溫和含水及氧氣的環境下會發生許多化學反應，使原本非極性的三酸甘油酯產生帶有含氧官能基的極性化合物使油品變質，稱為氧化炸油。已知炸油中極性化合物類似xenobiotics或內分泌干擾物(endocrine disrupting chemicals, EDCs)，皆會誘發peroxisome proliferator-activated receptor α (PPARα)及cytochrome P450酵素加速自我代謝。基於許多環境xenobiotics已知具有內分泌干擾效應，因此我們懷疑炸油可能也具有內分泌干擾作用。為探討炸油飲食對雄性生殖發育影響，本研究分為兩部分，第一部分使用C57BL/6J小鼠於母鼠懷孕期給予炸油極性化合物飲食，結果發現懷孕第17至19天正常出現的雄性胚胎睪固酮波峰消失，且第19天雄性胚胎肛殖距顯著降低的類雌化現象。實驗二使用SD雄性大鼠，從母親懷孕至出生後9週齡性成熟之期間持續給予炸油飲食，觀察炸油對於雄性子代的生殖系統發育之影響。結果發現與新鮮油相比，炸油飲食的雄性子代出生肛殖距較短、包皮分離時間較晚以及血清、睪丸睪固酮濃度較低，還有五個雄激素依賴性組織：腹側前列腺、儲精囊及凝結腺體、提肛肌及尿道球肌、龜頭、尿道球腺重量減輕等結果，而雖然附睪精子數及精子活動力沒有顯著變化，但炸油組的的精子活動力有降低傾向，此外睪丸組織切片發現有生精上皮退化、細胞間隙增大、出現空泡等現象。再進一步發現睪丸中睪固酮合成相關酵素17β-hydroxysteroid dehydrogenase (17β-HSD)以及速率限制酵素steroidogenic acute regulatory protein (StAR)、cholesterol side-chain cleavage enzyme (P450scc)還有負責膽固醇擷取的LDL-receptor之mRNA表現量皆下降，導致睪固酮合成原料-膽固醇的缺乏且直接抑制睪固酮合成而造成上述結果。結論為炸油飲食確實具有抗雄激素作用，會抑制睪丸膽固醇擷取及睪固酮的合成對雄性生殖系統發育有不利影響。

Deep frying is a common and popular cooking method, but triglycerides (TG) in cooking oil undergo many chemical reactions in environments with the presence of high temperature, water and oxygen, so that the oxidized frying oil contains the unaltered components called non-polar compounds and altered components called polar compounds which is characterized by the presence of oxygen-containing functional groups in TG monomer, dimer or polymer. Polar compounds are very similar to xenobiotics or endocrine disrupting chemicals (EDCs) as both can induce peroxisome proliferator-activated receptor alpha (PPARα) and cytochrome P450 enzymes to accelerate their own catabolism. Based on many xenobiotics are known to be EDCs, we suspect that frying oil may have endocrine disrupting effects. In order to investigate the effects of the frying oil on male reproductive development, we conducted two experiments in this study. In the first experiment, C57BL/6J dams were fed with diet containing polar compounds during pregnancy and killed at pregnancy d17, d18 and 19 to measure the testosterone concentration in the whole embryos of males. The testosterone surge normally present at day 18 disappeared in polar compound group. The anogenital distance (AGD) of embryos at day 19 shortened in polar compound group suggesting a feminizing effect occurred. In the second experiment, SD male rats were exposed to frying oil diet persistently from embryo to 9 weeks of age. The results showed that compared with control, frying oil-diet resulted in shortened AGD, delayed age of preputial separation, lowered serum concentration of testosterone, and reducted the androgen-dependent tissue weights, i.e. ventral prostate, seminal vesicles and coagulated glands, bulbourethral gland, levator ani and bulbocavernosus muscle as well as penis glans. Although the sperm count did not change significantly, the sperm motility tended to decrease in the oxidized frying oil group. In addition, histological study showed the abnormalities in seminiferous tubules of testis. The mRNA level of 17β-hydroxysteroid dehydrogenase (17β-HSD) and the rate-limiting enzyme of testosterone synthesis, steroidogenic acute regulatory protein (StAR) and P450scc, as well as LDL receptor were significantly reduced by frying oil-diet, indicating a lowered cholesterol uptake (precursor of testosterone) and testosterone synthesis in testis contributed to the anti-androgenic effects of frying oil. We concluded that dietary frying oil is unfavorable for male reproduction and a suppressed cholesterol uptake and testosterone synthesis may contribute to this effect.

謝誌 ................................ ................................ ................................ ................................ ... 1
摘要 ................................ ................................ ................................ ................................ ... 2
Abstract ................................ ................................ ................................ .............................. 3
目錄 ................................ ................................ ................................ ................................ ... 5
圖目錄 ................................ ................................ ................................ ............................... 7
表目錄 ................................ ................................ ................................ ............................... 8
縮寫表 ................................ ................................ ................................ ............................... 9
第一章 前言 ................................ ................................ ................................ ................... 12
第二章 文獻回顧 ................................ ................................ ................................ ........... 14
第一節 氧化炸油 ................................ ................................ ................................ ..... 14
一、 油脂化學 ................................ ................................ ................................ . 14
二、 炸油生理效應 ................................ ................................ ......................... 14
第二節 內分泌干擾物 (Endocrine disrupting chemicals EDCs) ........................... 16
一、 定義 ................................ ................................ ................................ ......... 16
二、 環境 EDCs ................................ ................................ ............................... 16
第三節 雄性生殖系統 ................................ ................................ ............................. 20
一、 雄性生殖系統發育 ................................ ................................ ................. 20
二、 雄性生殖系統功能 ................................ ................................ ................. 23
三、 精子的生成 – 精子發生作用 (Spermatogenesis) ............................... 28
四、 Spermatogenesis的調控 ................................ ................................ ......... 30
五、 睪固酮生合成 – 類固醇新生作用 (steroidogenesis) .......................... 32
第三章 材料與方法 ................................ ................................ ................................ ....... 42
第一節 氧化炸油製備及極性合物分離 ................................ ............................. 42
一、 氧化炸油製備 ................................ ................................ ......................... 42
二、 極性化合物分離 ................................ ................................ ..................... 42
三、 氧化指標測定 ................................ ................................ ......................... 44
第二節 動物實驗 ................................ ................................ ................................ ..... 47
一、 實驗設計 ................................ ................................ ................................ . 47
二、 飼料配方 ................................ ................................ ................................ . 51
三、 理學檢查 ................................ ................................ ................................ . 53
四、 胚胎性別鑑定 ................................ ................................ ......................... 55
五、 全胚睪固酮測定 ................................ ................................ ..................... 57
六、 血液生化分析 ................................ ................................ ......................... 58
七、 睪丸化學分析 ................................ ................................ ......................... 60
目錄
6
八、 睪丸 mRNA測定 ................................ ................................ .................... 62
九、 睪丸組織切片 ................................ ................................ ......................... 68
十、 西方墨點法 (western blot) ................................ ................................ ..... 69
十一、 統計分析 ................................ ................................ ............................. 75
第四章 結果 ................................ ................................ ................................ ................... 76
第一節 氧化炸油 ................................ ................................ ................................ ..... 76
一、 炸油回收率 ................................ ................................ ............................. 76
二、 PC百分比 ................................ ................................ ............................... 76
三、 TLC點片 ................................ ................................ ................................ . 76
四、 油脂氧化指標測定 ................................ ................................ ................. 76
第二節 動物實驗 ................................ ................................ ................................ ..... 79
一、 胚胎 AGD ................................ ................................ ................................ 79
二、 胚胎性別鑑定 ................................ ................................ ......................... 79
三、 雄性胚胎睪固酮含量 ................................ ................................ ............. 79
一、 雄性子代出生後體重變化 ................................ ................................ ..... 84
二、 包皮分離日齡 ................................ ................................ ......................... 84
三、 雄性子代 AGD ................................ ................................ ........................ 84
四、 尿道下裂及乳頭保留 ................................ ................................ ............. 84
五、 雄激素依賴性組織絕對重量 ................................ ................................ . 85
六、 其他器官絕對重量 、相................................ ............................. 85
七、 睪丸切片 ................................ ................................ ................................ . 86
八、 精子計數及活動力 ................................ ................................ ................. 86
九、 雄性子代血清睪固酮、膽醇濃度 ................................ ..................... 86
十、 睪丸固酮及膽醇含量 ................................ ................................ ..... 87
十一、 雄性子代睪丸 mRNA表現量 ................................ ............................ 87
十二、 雄性子代睪丸蛋白質表現量 ................................ ............................. 88
第五章 討論 ................................ ................................ ................................ ................. 104
一、 炸油的抗雄激素效應 ................................ ................................ ........... 104
二、 炸油抗雄激素的機制 ................................ ................................ ........... 106
第六章 參考文獻 ................................ ................................ ................................ ......... 110

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